Alkyl Nitrites

Rebuttal to “QUEER ADVERTISING” by John Lauritsen

2006-06-20T16:26:00.000-07:00

Rebuttal to “QUEER ADVERTISING” by John Lauritsen

Over six years ago, at the 2000 Queer Studies Symposium at McMaster University in Canada, anti-poppers and anti-AZT activist John Lauritsen gave a speech entitled “Queer Advertising.” The title was surprisingly misleading for a speech more concerned with his allegations of alleged dangers of inhaling alkyl nitrites and their advertisement in the gay press, than any other aspect of queer advertising. Today, nearly seven years later, one wonders if Lauritsen’s arguments are still timely, or if they were ever an honest representation the facts? Over the next pages, this article explores questions concerning the accuracy of Lauritsen’s claims. Lauritsen’s speech tends to jump from topic to topic in a somewhat haphazard fashion; but for ease of clarification, this article has been organized by subject, rather than by how topics were presented in the original speech.

Poppers: Safety and Chemistry

Lauritsen makes it clear from the first paragraph on that he believes poppers are harmful, if not outright dangerous. According to Lauritsen, “they have been and continue to be the cause of suffering and death for tens or hundreds of thousands of gay men.” However, it’s important to note that, contrary to Lauritsen’s claim, the safety of alkyl nitrites or “poppers” as they are commonly called, was no longer being questioned at the time of his speech. Nitrite inhalants have been subjected to numerous scientific studies regarding their possible toxic effects over the past decades. The largest and most definitive of these studies was published in 1979 by a group of respected scientists and doctors, including Dr. John Parker from Queen's University, a specialist in nitrite vasodilators, including alkyl nitrites. Dr. Parker had been the chairman of the Division of Cardiology at Queen's for almost a decade. Also prominent in this study was Mark Nickerson, PhD, MD, professor and past chairman of the Department of Pharmacology and Therapeutics at McGill University in Montreal, who had been the author of the nitrite vasodilator chapter of Goodman & Gillman’s standard textbook of pharmacology for nearly forty years. Their findings were definitive: “No important acute or chronic toxic effects have been demonstrated with the volatile nitrites, and their use in an uncontrolled and unregulated fashion has proven to be safe." Later, the FDA and the Consumer Product Safety Commission (CPSC) confirmed these findings. Add to this the fact that alkyl nitrites have been used to treat angina for over 150 years with no safety concerns whatsoever, and Lauritsen’s claim appears oddly alarmist, with no basis in fact.

Lauritsen goes on to argue that poppers use is unique to the homosexual male population. This is actually quite far from the truth. Alkyl nitrites act in the body by relaxing smooth muscle. Because all the sphincters in the body are comprised of smooth muscle, including the anal sphincter, homosexual males often use poppers to facilitate anal intercourse. However, the vagina sphincter is smooth muscle as well, and many women, straight and lesbian, also find poppers help facilitate intercourse. Nitrites do not act on the pain receptors of the body whatsoever, as Lauritsen claims. However, anecdotal evidence indicates that they do act on pleasure receptors, producing a powerful sense of enhanced orgasm, and lengthened duration of orgasm. As a result, many heterosexual men and women find inhalation of poppers enhances sex. Media reports over past few decades, along with anecdotal evidence, confirms that both homosexual and heterosexual individuals use alkyl nitrites to enhance sexual experience.

Also discussed in Lauritsen’s speech are the biochemical properties of alkyl nitrites. It soon becomes clear from his comments, however, that he lacks a clear understanding of the chemistry behind these compounds. For instance, the activist claims that poppers cause severe burns when spilled on the skin. Chemically speaking, the volatile nature of these compounds makes such burns nearly physically impossible. Alkyl nitrites evaporate so quickly that there simply isn’t time for the compounds to cause a burn before they evaporate into the atmosphere. It’s likely that an individual spilling nitrites on his or her skin wouldn’t even be aware of it, other than for a slight feeling of cold. Of course, poppers might cause a skin burn if they were contaminated with a residual acid, but such an occurrence is extremely unlikely in the higher quality consumer brands of nitrite room odorants.

Lauritsen’s comment linking the flammability of poppers to the “explosion” of the RUSH® factory in San Francisco also warrants clarification. While it’s true that alkyl nitrites are highly flammable, this simply means that you shouldn’t hold a lit match to an open bottle. The fire at the RUSH® factory in San Francisco in 1981 (there was no explosion, as nitrites are flammable, but not explosive), was caused, according to then-San Francisco Fire Chief Andrew Casper, as the result of an employee using an electric space heater next to some piping, which had sprung a leak during a production run.

What about Lauritsen’s comment that “at gay discotheques [in the 1970s] men could be seen shuffling around in a daze, holding little bottles under the nose?” This is an unfortunate case of ‘guilt by association’, in which the activist establishes an unwarranted connection in his audience’s mind. While his comments leave one with the impression that men at discos shuffle about in a daze as a result of inhaling poppers, this is scientifically impossible. Alkyl nitrites relax smooth muscle in the body and that’s all they do. They are 100% chemically incapable of creating a “daze” in anyone. Quite possibly, the miasma of other drugs used at the disco created this daze. This was, after all, the 70s, and the drug culture was a well-established way of life. Lauritsen uses this ‘guilt by association’ technique again when he associates poppers with heroin, cocaine, and whisky. The latter three are mind-altering drugs; alkyl nitrites are not. Yet simply by linking poppers to these drugs, a connection between them is falsely established in the audience’s mind. On a curious note, heroin, cocaine, and alcohol have all been proven to be serious health hazards, while poppers have been proven to be essentially safe through the scientific investigations mentioned earlier.

While we’re discussing vices, exaggeration is another one we can easily add to Lauritsen’s portfolio. What else could a comment such as “some gay men became so addicted to poppers that they snorted nitrite fumes around the clock” be labeled as?

As for his claim that “for some, poppers became a sexual crutch, without which they were incapable of having sex, even solitary masturbation”, if published data exists that supports to such a claim, I’d certainly like to see it. Such unsubstantiated statements seem to be the rule rather than the exception in Lauritsen’s speech. Consider the list of unsubstantiated claims the activist provides in an attempt to depict poppers as dangerous. Why does Lauritsen argue that alkyl nitrites are harmful when he should know there is no scientific basis to his arguments? It’s a difficult question to answer, but let’s look at each of his claims more closely.

Lauritsen claims that alkyl nitrites harm the immune system. Is there any scientific basis to this claim? In fact, there is, but it is an extremely shaky basis built on a framework of faulty research methods. For instance, some studies did conclude that alkyl nitrites could damage the immune system of mice; however, it was later confirmed that the doses were not adjusted for body size. In other words, the mice were given doses that far exceeded the doses and exposure duration of humans inhaling poppers. Thus, mice were exposed to toxic and near toxic levels of the compound. The same argument stands for the lung damage Lauritsen claims poppers cause. In the amount inhaled by humans, there is no risk of such damage. As for the claim that poppers can cause severe anemia, this is possible only if poppers are injected into the blood stream or swallowed, known toxic modes of delivery.

What about the activist’s claim that poppers are mutagenic (cancer causing)? This is based on early speculation that alkyl nitrites had the capacity to form carcinogenic N-nitroso compounds (such as those found in smoked meat), a hypothesis later disproved in scientific studies.

Lauritsen’s further claim that inhalation of poppers can result in death or brain damage due to a heart attack or stroke is similarly unfounded. There has never been a documented case of this happening. Curiously, people are much more likely to suffer a stroke or heart attack when watching a scary movie – a fact that is well documented.

Lauritsen’s argument that poppers have been used successfully to commit suicide is similarly unsupported by documentation. There has never been a case of such a tragedy ever having occurred. However, it is well known that suicide by ingestion of non-prescription drugs, such as aspirin, is quite common. There are numerous ways by which an individual can commit suicide if he has set his mind on it; the availability or non-availability of alkyl nitrites has absolutely no impact on this unfortunate reality.

Along similar lines, Lauritsen tries to link poppers to a bizarre Wisconsin murder case in the 1980s where the victim died as a result of suffocation. The medical examiner and coroner’s report was very clear about the cause of death. According to court transcripts made during the trial, the victim insisted on having a poppers-soaked sock stuffed into his mouth to enhance orgasm while tied up with a rope as part of a sexual fetish. As tragic as this case is, the connection that Lauritsen implies between alkyl nitrites and the man’s death simply does not exist. Death was due to suffocation, nothing more.

Later in his speech, Lauritsen also attempts to link alkyl nitrites to AIDS, and more specifically, to Kaposi’s sarcoma (KS). Yet, as scientific research has progressed over the past decade, these claims have been proven unfounded. Lauritsen is correct in his statement that “for at least five years the top AIDS experts, including Robert Gallo, have known that HIV is not the cause of KS.” We know today that HIV plays a role in development of the disease, but isn’t the causal factor. While a Kaposi’s sarcoma-poppers link was studied early in the AIDS crisis, the evidence supporting this connection was later dismissed as merely correlational. Scientists now know that poppers play no role in the development of Kaposi’s sarcoma. This was verified in the late 1990s when a herpes virus, HHV-8, was isolated as the cause of both AIDS-related and non-AIDS related KS. Coincidently, this data was available before Lauritsen gave his speech in 2000.

Similarly, there is no “disinformation’ coming from government agencies and AIDS organizations. On the contrary, these organizations have contributed tirelessly in the battle against AIDS, and Lauritsen’s comments are a disservice to the dedicated employees and volunteers involved with these groups.

Lauritsen shifts to a new adversary in his war against “toxic” compounds, when anti-AIDS drugs such as AZT and protease inhibitors suddenly join poppers and become his targets as well. AZT and protease inhibitors are not without their side effects, although the side effects of the latter are certainly significantly less, as they reflect recent advances in anti-retroviral therapy. Unfortunately side effects are a reality when it comes to almost all prescription and non-prescription drugs, including ones as seemingly benign as aspirin. AZT and protease inhibitors are not free from risk, yet this risk must always be weighed against the benefits provided by the medication. Since the introduction of protease inhibitors, the number of people who have become ill from AIDS-related opportunistic infections or have died from the disease has decreased by 70%. Lauritsen’s further comments that “there is no basis in reality for the claim that protease inhibitors have reduced AIDS deaths” and that the “sharp drop in new AIDS diagnoses and in AIDS deaths began several years before the protease inhibitors were put on the market” simply do not ring true, as a little research into the subject will quickly reveal. Limits on time restrict a fuller coverage of Lauritsen’s anti-AIDS drug comments in this article, but I urge you take the time to research this topic yourself to determine if Lauritsen’s comments sink or swim. You probably won’t be surprised to find they need a very large life preserver.

Poppers and Politics

Leaving the biochemical laboratory for the political stage, let’s take look at Lauritsen’s comments about government legislation concerning poppers. According to Lauritsen, poppers have been a "banned hazardous product" in the United States since February 15, 1989. This statement, however, is incorrect. Poppers were indeed banned in the United States, but in 1991, not 1989. Curiously, Lauritsen gets it wrong even when he doesn’t have to change the facts to support his argument. This unfortunate disregard for accurate fact-finding seems to pursue Lauritsen throughout his speech. For instance, he goes on to claim the “initiative for regulating poppers came from the gay community itself.” This is yet another misrepresentation of the facts. The initiative for regulating poppers was based on a relentless campaign by Hank Wilson and John Lauritsen himself, two men who are hardly a representation of the gay community. Similarly, his statement that “West Hollywood, the gayest city in the world, took the lead in banning poppers” is incorrect. West Hollywood actually regulated poppers years after other jurisdictions had already done so. Houston, Texas, for instance, had already banned their sale to minors. As such, being a ‘gay city’ is irrelevant to the issue at hand. A more likely reason for singling out West Hollywood is an attempt by Lauritsen to establish poppers use as a solely gay phenomenon, which it clearly isn’t. As for Lauritsen’s reference to “the Committee to Monitor Poppers, founded in 1981 by gay activist Hank Wilson” as the lobbying group responsible for the regulation against poppers, the organization did indeed play a role. However, contrary to being a group, the organization always has been and remains to this day a one-man ‘committee’ headed by Wilson.

Lauritsen shows further bias when he correctly states that the prescription requirement for poppers was eliminated by the Food and Drug Administration (FDA) after 1960, but fails to comment on why the prescription ban was lifted in the first place. It would naturally be rather damaging to his argument to admit that the FDA eliminated the prescription requirement for alkyl nitrites because the compound was found to be perfectly safe for non-prescription use. Lauristen’s anti-poppers bias reveals itself again and again throughout his speech. For instance, the prescription requirement for alkyl nitrites was indeed reinstated by the FDA in 1969; however, this was entirely in response to a conservative push to do so once it became clear that people were using them to enhance sexual pleasure. It was not, as the activist claims, because the compound was dangerous. In fact years later, the FDA definitively stated that there was no more risk in inhaling poppers than there was in using other non-prescription drugs products.

Lauritsen goes on to illustrate “a number of factors [that] help explain why poppers became a mass phenomenon among gay men.” His first point is that poppers were a legal substance, and as such the “the Food and Drug Administration (FDA) looked the other way.” This is a curious claim, considering that the FDA had no jurisdiction over poppers whatsoever when they were sold as ‘room odorants’. The FDA is, after all, the Food and Drug Administration. Instead, jurisdiction over nitrite room odorants fell under the Consumer Product Safety Commission (CPSC), an agency that undertook a yearlong investigation of the poppers industry in 1980, which included an exhaustive review of national data concerned with the use of room odorants as inhalants and the potential dangers of such use. The final outcome: use of nitrite-based room odorants both per label instructions, and even when used as inhalants, was safe. As stated above, the FDA also reported (when poppers fell under their jurisdiction) that poppers use posed little potential health hazard.

Poppers and the Press

What about Lauritsen’s claims regarding the role the gay press played in what he refers to as “one of the most brilliant advertising campaigns of all time?” According to Lauritsen, “within only a few years, hundreds of thousands of men were persuaded that poppers were an integral part of their gay identity.” Let’s look a bit more closely at this claim.

It’s true that new brands of poppers were advertised in the gay press, but no ad campaign in the world, no matter how persuasive or well financed, is able to convince a group of people that a product is part of their identity if it doesn’t deliver what it promises. As such, it was the pleasurable sensations people experienced from inhaling poppers that drove the market, nothing else. Lauritsen misleads his audience by claiming that the gay press was both “odd and deplorable” for the role they played in advertising these compounds to the homosexual population. According to Lauritsen, the “so called gay publications were delighted with the revenues they received from running full-page, four-color ads for the various brands of poppers.’ Well, why wouldn’t they be pleased to gain major advertising revenue? I’ve never heard of a publication that was unhappy when a company purchased advertising space, no matter whether that company sold poppers or popcorn. True to form, Lauritsen fails to mention that Playgirl, Penthouse, Hustler, and many other straight publications were also very pleased to earn revenue when they ran the very same popper ads in their magazines. Poppers were a legal product at the time and contrary to Lauritsen’s innuendo, no conspiracy theory was at work here, only the laissez faire reality of the American free market.

Lauritsen is incorrect again when he claims “there had been no word in the gay press that poppers were harmful.” In fact, the gay press had printed numerous misleading articles, columns, and unsubstantiated opinion/editorial pieces to this effect – nearly all of which originated from Lauritsen and his colleague Hank Wilson. Considering the flawed nature of the studies that reported a health risk associated with alkyl nitrites, it isn’t really surprising that responsible members of the gay press ignored the packets of “medical reports” Lauritsen’s colleague Hank Wilson relentlessly continued to send to the gay press over the years.

As for Lauritsen’s claim that: “in 1982, a scientist sent a letter to the Advocate, describing research which demonstrated that amyl nitrite strongly suppresses the immune systems of mice. The Advocate's editor, the late Robert McQueen, said: We're not interested,” it’s curious that Lauritsen doesn’t identify the scientist. Was this one of the scientists associated with flawed alkyl nitrite research? We will never know.

Lauritsen goes on to further vilify the gay press in his statement that “in 1983, at the request of a poppers manufacturer, the Advocate ran a series of advertisements (Blueprint For Health) which falsely claimed that government studies had exonerated poppers from any connection to AIDS.” The “request” Lauritsen refers to was what is referred to in the advertising industry as an insertion order, the same thing any advertiser uses when they run an advertisement. It is a simple relationship between an advertiser and a publication, nothing more sinister than that. With regard to the statement that the government had exonerated poppers from any connection to AIDS, this was completely accurate. The government, after much research, determined that poppers were not directly causative of AIDS or any related opportunistic infections, including KS.

Along the same vein, Lauritsen’s broad-based comments such as “for most of the gay press, advertising dollars were more important than the lives of gay men” are interesting attempts to bury all members of the gay press in a mass grave of greed. Curiously, this accusation of capitalism at the cost of lives does not seem to include the two sister publications New York Native and Christopher Street, which ran full page popper ads for many years, and both of which bizarrely began relentlessly publishing articles about unsubstantiated dangers of poppers – much like the tabloids that were warning about two-headed space creatures impregnating teenage girls. It will come as no surprise to learn that Lauritsen was closely associated with these papers, both of which saw their readership plummet as a result of the publication of alarmist articles concerning bizarre HIV/AIDS theories and unsubstantiated allegations of dangers supposedly associated with the use of poppers.

Lauritsen also takes aim at Nathan Fain, the health critic of the Advocate, a highly regarded and widely respected gay journalist. The Advocate, which today remains the nation’s largest and most prestigious gay publication, has always been well-known for basing its reporting on facts and good science, and as such was open to slander from anti-poppers AIDS denialists who found their arguments threatened by the publication’s award-winning reporting.

In his closing, Lauritsen also discusses the marketing of alkyl nitrites, claiming “at its peak, the poppers industry was the biggest money-maker in the gay world, grossing upwards of $50 million per year.” This often-repeated statistic, which was first reported in a TIME magazine article in 1978, was simply a guess by the magazine staff and has no basis in fact whatsoever. Why does Lauritsen make use of such unsubstantiated claims? While no one can know for sure, it appears that he has some kind of agenda to marginalize poppers as a compound sold only in the ‘gay world’, perhaps in an effort to support his theory that manufacturers of alkyl nitrites are in some way determined to make a profit at the cost of the gay population’s welfare.

Lauritsen’s final comments are refreshing in this respect, as he finally openly states what he has been hinting at throughout his speech. “Why were these deadly drugs foisted on us?” he asks. “The main reason,” claims Lauritsen “lies in hatred of gay men, including self-hatred. The belief that men who have sex with each other are worthy of death is not new.”

This is certainly conspiracy theory at its worse. To suggest that we should believe Lauritsen’s argument that the U.S. government, along with poppers manufacturers, AIDS organizations and pharmaceutical companies across the United States all banded together in their hatred of homosexuals to market deadly products to the gay population, simply defies logic and belief. Lauritsen argues, “Gay men must recognize the war that is being waged against us, and must fight back. We must stop the poisoning of our brothers”. If there is a “poison”, it is not poppers, as Lauritsen claims. Rather it is the misinformation that Lauritsen provides in his speeches and articles intended to poison the minds of his unsuspecting audience and readers. The antidote to such misinformation? Our own common sense aided by the guidance of peer reviewed, systematic scientific research. A healthy dose of skepticism doesn’t hurt either.

“Some of us have to tell the truth with as much objectivity as possible – some of us with the scientific research-training to evaluate the data at more than its face value.”
~ Dr. Bruce Voeller, Internationally Renowned AIDS Researcher, 1986

HIV & AIDS - Poppers

2006-05-07T23:08:00.000-07:00

Mariposa Occasional Paper #6

IN A SERIES OF ONGOING PROJECTS FOR EDUCATING THE PUBLIC ABOUT "MAKING SEX SAFE" AND "SENSIBLE SEX."

ARE "POPPERS" SAFE? ...By BRUCE VOELLER, Ph.D.

MAY 1986
Mariposa Education & Research Foundation

When mediocre or even plain bad scientific research is politically exploited by AIDS institutions eager to appear to be earning their keep, or by the media -- ever keen to fan any spark of controversy, or zealots riding their favorite hypothesis saddled up as fact, the public is in danger.

Basing public policy on inadequate science is particularly inappropriate.

All this appears to be fueling the hysteria surrounding the use of volatile nitrites or "poppers", especially the issue of whether "poppers" are a factor in causing AIDS or in suppressing the immune system.

As a scientist current with AIDS research and who has reviewed the extensive literature on nitrite use, I can not assure you that "poppers" are harmless, any more than I can assure you aspirin is; but neither have I found grounds to tell you "poppers" are harmful. I can assure you, however, that the existing scientific studies on this topic do not justify the widespread belief that “poppers" have been shown to help cause AIDS, or cause anything else for that matter. My viewpoint is shared by other preeminent and qualified persons, including the prominent cardiologist John 0. Parker, M.D., and James Mosley, M.D., the University of Southern California Medical School professor who heads the federal government's largest, multi-million dollar program studying the AIDS virus and the nation's blood supply. Each of these physicians has provided public testimony in recent months at governmental hearings considering the banning of “poppers". Each had reviewed the evidence and stated under oath that he regards the claims of danger to be ill founded.

============================================================
"When mediocre or even plain bad scientific research is politically exploited by AIDS institutions eager to appear to be earning their keep, or by the media -- ever keen to fan any spark of controversy, or zealots riding their favorite hypothesis saddled up as fact, the public is in danger."
==================================================================

I can also tell you that the intense campaigns against use of volatile nitrites conducted by Hank Wilson in San Francisco, Neil Schram and his Los Angeles City/County Aids Task Force, and John Lauritsen in New York, are slim in scientific merit.

Space limits for this article do not allow reviewing each of the many published papers on "poppers". However, a critical look at three of the most frequently cited ones may whet your awareness of the need for a more substantial weighing of the evidence than has been provided by the "popper"-ban advocates. A look at these three papers is representative, in my view, of the best of what has been published.

Hersh and Newell and their colleagues(1) at M.D. Anderson Hospital in Houston, studied the effect of butyl nitrite (“poppers") on laboratory (in vitro) cultures of white blood cells --cell types important in the body's immune response to infection.

They reported that many of these cells were killed when left for 24 hours in the presence of one percent added butyl nitrite, whereas at 1/2 that concentration (i.e., 0.5 percent) or less the "cell count and viability were unaffected." [emphasis added] In other words, a small change in concentration dramatically eliminated the toxic effect. They also wrote that at 0.5 percent several of the cells' immunological responses were inhibited. However, again only a generally small inhibition could be detected at slightly lower concentration (0.01 percent).

The authors warned of the need for caution in evaluation of the significance of their results in real life application(2): "The data suggest but do not prove that the agents may be immunosuppressive in vivo [in living animals]." Despite their own sound advice, a paragraph later in their text, they ignore their advice stating: "these in vitro studies strongly suggest that the inhalant nitrites may indeed be dangerous, and their use should be condemned by those physicians who treat patients who use these drugs regularly." [Note that they use the term "condemned”, a judgmental, non-scientific word, rather than one such as it cautioned about."]

============================================================
"In other words, a small change in concentration dramatically eliminated the toxic effect."
==================================================================

Although it is true that instructive information about the effect of use of a drug on people is sometimes gained by in vitro (test tube) studies, more often than not such work proves non relevant. Most people are aware, for instance, of the large numbers of “promising" drugs discovered in the lab and reported in the press but which then prove unworkable when tested on live patients. This drug failure, in moving from the test tube to actual people, is often because very high or very low concentrations of drugs were used in the laboratory phase of the study and have little relevance to "real life" testing.

Clearly a small reduction in nitrite concentration dramatically changed the responses Newell and Hersh found. The question logically follows: how relevant is the use of their concentration of poppers to real life"?

============================================================
"The authors warned of the need for caution in evaluation of the
significance of their results in real life applications"
==================================================================

One estimate is to calculate what Newell's one percent nitrite concentration means for an average adult male with 6 liters of blood for even transiently establishing a one percent blood level, never mind for a 24-hour one. CALCULATION: one percent of 6 liters equals 0.06 liters, or 60 milliliters (ml.) of butyl nitrite. A representative bottle contains 10 to 12 ml. of “poppers"; that is to say, about 5 or 6 bottles of "poppers" would have to be injected into a person's blood to briefly attain a one percent level ... a staggering amount of butyl nitrite!

And that's attained only if all the nitrite gets into the person's blood. Unlike adding butyl nitrite directly into Hersh and Newell's laboratory dish where the "poppers" can saturate the culture medium, only a fraction of the chemical will be absorbed at the lungs through inhalation, the common way poppers are used. As with cigarette smoke, most of what is inhaled is immediately exhaled out of the user, thus, many more bottles of butyl nitrite would be needed to achieve an inhalation level comparable to that in the laboratory study, making the bearing of Newell and Hersh's data still more remote in human relevance.

Also, the authors' laboratory results are based on 24-72 hour continuous exposure to butyl nitrite, a condition utterly without parallel in common human usage, even though some might wish that disco-ing or sex lasted that long.

I think it is instructive to consider all this information with regard to a far less politicized compound, such as aspirin. It would not be surprising to find that common household aspirin, used by generations of average Americans, would have had similar inhibitory laboratory effects if Newell and Hersh had tested one percent levels of it, too. In fact, for a rough and ready comparison, as little as 0.325 grams (gm.) of aspirin taken by some persons can cause changes in blood chemistry leading to bleeding for several days, as well as other effects. 0.3 gm. of aspirin in 6 liters of blood represents a concentration of 0.005 percent, even less than the percentage of butyl nitrite needed for an effect.

To conclude, yes, if enough "poppers" are used an effect can be forced... just as household aspirin can be forced to lethal levels.

In another study, the M.D. Anderson Hospital group(3) injected mice with "Rush", a commercial brand of “poppers", in order to see "real life” effects of nitrites. They inoculated the mice twice, each time with 1/4 ml. of a “poppers" solution of about 5.6 percent nitrite. That calculates to about 0.028 ml. of butyl nitrite per mouse.

How does that compare to a man? The average mouse weights about 80 gm., the average man 80,000 gm.; the weight ratio is about 1000 to 1.

Scaling up the nitrite dose used in the mice to a comparable one for a man, would thus require injecting him twice with 14 ml. of "Rush" -- that is a total of 28 ml., or nearly three bottles of "Rush". Adult humans have died from similar amounts (10 to 30 gm.) of aspirin(4). Such a massive dose of aspirin is highly toxic compared to ordinary usage. With this parallel in mind I fail to see what significance a similarly massive dose of butyl nitrite has for comparison to ordinary “popper" use.

============================================================
“ ... about 5 or 6 bottles of "poppers" would have to be injected into a person's blood to briefly attain a one percent level ... a staggering amount of butyl nitrite!

Also, the authors' laboratory results are based on 24-72 hour continuous exposure to butyl nitrite, a condition utterly without parallel in common human usage, even though some might wish that disco-ing or sex lasted that long."
==================================================================

The third research study is one of rare restraint and high integrity. The study by Haverkos et al.(5) has been widely used by "popper"-ban lobbyists to claim a link between "poppers" and AIDS, even though the authors avoid that link. In fact, they argue that of those persons who have already developed immunodeficiency, those who have a history of using substantial amounts of “poppers" more frequently succumb to Kaposi's sarcoma (KS), whereas those with lower or no nitrite use, succumb to pneumocystis pneumonia (PCP). Ironically, the AIDS patients with KS (higher nitrite use) have a considerably longer life expectancy after diagnosis than do those with PCP (lower use).

However, in comparing a rather small sample of 47 men with KS and 20 with PCP, Haverkos found a long list of other statistically significant differences too: Men with KS were more likely to earn over $20,000 per year (!); to have had hepatitis B; use amphetamines, barbiturates, cocaine, ethyl chloride, LSD, marijuana, methaqualone; had more sexual partners. This is a formidable list of statistically significant differences.

Unable to draw any clear conclusions from these direct correlations, the authors resorted to 'multivariate analysis’, a sophisticated, but treacherous technique. It is especially tricky with small numbers of subjects, as in this study. Indeed, Haverkos and his associates themselves state that multivariate analysis only “suggests the relative importance of differences." [emphasis added]

Haverkos et al. cautiously report "Total days of nitrite use more significantly differentiated between the disease groups than any other variable," and "interpreting the results of these analyses requires caution. The numbers of patients enrolled are small," and as the final statement in the 'discussion' section of their paper: "The association of KS with nitrites in this study may only represent correlation. In other words, nitrites may be merely a marker for other behaviors or exposures associated with their use."

Indeed, other published multivariate studies do not confirm Haverkos et al. As the authors forthrightly and candidly admit, Marmor et al.(6) initially reported a KS-“poppers" link, "However, they [Marmor et al.] reanalyzed their data, entering additional factors, and found that still other variables appear to
differentiate KS patients from controls by multivariate analysis," and Jaffe et al., at the Centers for Disease Control.(7) also reported using multivariate analysis and found that nitrite use was NOT significant.

============================================================
"In short, the much vaunted body of research supposedly demonstrating a link between "poppers" and AIDS does not withstand close scrutiny. If a link exists it still remains to be proven."
==================================================================

Elsewhere, in the lead chapter of one of the finest new AIDS research and therapy books(8), J.J. Goedert and W.A. Blattner at the National Cancer Institute draw a very interesting conclusion from their research and that of others. While noting that in one study, "helper T-cell counts were slightly lower with frequent nitrite inhalant use; this suggests the possibility that nitrite use may be a co-factor" for AIDS or for KS, "Neither of these possibilities has been completely evaluated," and, "However, it now appears that frequent use of nitrite inhalants simply may be a surrogate marker of frequent receptive anal intercourse. This sexual activity was associated very clearly with Kaposi's sarcoma in a case-control study of homosexual men and with HTLV-III seropositivity in the cohort studies of homosexual
men in Denmark and New York City, even after statistically adjusting for the number of homosexual partners and the frequencies of nitrite inhalant use and seven other sexual practices.”

In short, the much vaunted body of research supposedly demonstrating a link between “poppers” and AIDS does not withstand close scrutiny. If a link exists it still remains to be proven.

============================================================
“…it now appears that frequent use of nitrite inhalants simply may be a surrogate marker of frequent receptive anal intercourse.”
J.J. Goedert, M.D.
W. A. Blattner, M.D.
National Cancer Institute, NIH
==================================================================

IN analyses of diverse other published works, Goedert et al., Jacobs et al., Gerblish et al., Mathur-Wage et al., and unpublished work by Gangadharam et al., for example, fare even less well than those I have addressed here.

Do I advocate “popper” use? No. Am I paid by the “popper” industry? No. Why do I press the issue?

1) Because I think some of us have to tell the truth with as much objectivity as possible – some of us with the scientific research training to evaluate the data at more than its face value (thus, leaving out most physicians and nearly all journalists and advocate-lobbyists).

2) I feel that the liberties with fact taken by some who act as medical spokespeople in the AIDS crisis can only serve to undermine public trust in the scientific process.

3) I fear the damage which will be done if people are boldly told, as they have been, that “poppers” are ‘the drug linked with AIDS.’ Too many will give up “poppers”, but continue with (or move on to) cocaine, heroin, crystal meth, and other amphetamines, etc. These are drugs more likely in my view to be among the AIDS-cofactors.

In the New York Native(9) a Gay doctor in San Francisco was quoted as saying, “Unfortunately, most of my patients and friends appear to be engaged in an elaborate ritual of denial that there is even a problem here. They make some token sacrifice, such as giving up a drug or sexual practice that they never really liked anyway, and they convince themselves that this sacrifice will get them through the Lenten period for another 40 days or so until the AIDS problem is solved.”

I’m fearful that illegalizing “poppers”, coupled with the media blitz which already exists, makes “poppers” the “token sacrifice”, and “legitimizes” clearly dangerous drugs.

4) I’ve seen gas chromatographic profiles of the purity of street “poppers” and of the largest ‘legitimate’ manufacturer’s. The latter is pure, while the street form is like bathtub gin. Illegalizing “poppers” will knock out the pure forms and make dirty street “poppers” the standard item.

5) We either need to put the issue of “poppers” behind us, or make a valid case against them through better science, so that we can turn our attention to other drugs and other and other cofactors. We’ve been too preoccupied with “poppers” to the exclusion of everything else. By continuing up a wrong path, we lose time finding the right one.

On the AIDS clock, time is measured in deaths.

1 1983 Cancer Research 43; 1365
2 ibid pg. 1371
3 1984 Lotzova, Hersh et al., Cancer Iaununol. Itnmunother. 17; 130-134
4 1985 'Goodman and Gillman', THE PHARMACOLOGICAL BASIS OF TYIERAPEUTICS, 7th ed.
5 1985 Sexually Transm. Dis. 12(4:203-220)
6 1982 Lancet, 1:1083-7
7 1983 Ann. Int Med. 99:145-151
8 Goedert, JJ. and Blattner, W.A. The epidemiology of AIDS and related conditions. IN: AIDS: ETIOLOGY, DIAGNOSIS, TREATMENT, AND PREVENTION. eds.: DeVita, V.T., Hellman, S. and Rosenberg, S.A. 1985 J.B. Lippincott Company. New York
9 No. 102, p. 16

This reprint is provided by the Mariposa Education & Research Foundation as a public service and is #6 in a continuing series on “Making Sex Safe”.
©1986 Bruce Voeller, Ph.D./Mariposa Education & Research Foundation

Much of Dr. Voeller's life work has been archieved for future generations of researhers in the "Human Sexuality Collection" of the 'Rare & Manuscript Collections' at Cornell University Library.

Reprinted From: Mariposa Occasional Paper #6 IN A SERIES OF ONGOING PROJECTS FOR EDUCATING THE PUBLIC ABOUT "MAKING SEX SAFE" AND "SENSIBLE SEX."

Discovering the Cause of AIDS, Stanley B. Prusiner

2006-04-27T17:32:00.000-07:00

It is almost 25 years since HIV was first isolated and identified as the cause of AIDS. In this introductory Viewpoint, Prusiner details the early days of the AIDS epidemic and the huge task of trying to identify its cause. He introduces Viewpoints by Gallo and Montagnier, who describe the different yet complementary paths that each took to discover that HIV, a new human retrovirus, is the cause of AIDS. "Poppers" are not the cause of AIDS.

By Stanley B. Prusiner
Institute for Neurodegenerative Diseases, Department of Neurology and Department of Biochemistry and Biophysics, University of California, San Francisco
Copyright © 2002 by The American Association for the Advancement of Science. All rights reserved.

Great discoveries in science are infrequent, yet they are the grist that motivates every scientist. This source of motivation is critical because most experiments advance our knowledge little, and even when an experiment "works," the step forward is small. Great discoveries happen within different contexts. Some occur when the scientists are not anticipating the outcome--these are genuine gifts of nature. Others occur when clearly defined questions, usually with "yes" or "no" answers, are posed. And often those posing the query are not the ones making the discovery.

In 1981, the initial description of immunodeficiency in very sexually active, young gay men posed the question of causation (1). That report was followed by an alarming rise in the number of new cases of what became known as acquired immune deficiency syndrome, or AIDS. The immunodeficiency associated with AIDS resulted in the appearance of a rare cancer, Kaposi's sarcoma (KS), and a number of opportunistic infections caused by, for example, Pneumocystis carinii and Candida albicans (2-4).

As the clinical descriptions of AIDS widened in the early 1980s, the dramatic reduction in T lymphocytes and a decrease in the ratio of helper T cells to suppressor T cells became the focus of medical investigators searching for a cause. And as the number of AIDS cases exploded to reach epidemic proportions, so did the hypotheses about its possible causation (5). The appearance of AIDS in distinctly different populations including young gay men, intravenous drug abusers, hemophiliacs, Haitians, infants, and blood transfusion recipients argued for an infectious agent. But what kind of infectious agent would destroy the immune system of so many different groups of people?

With more than 20 million deaths from illnesses resulting from AIDS over the last two decades, learning the cause of this fatal illness was a major discovery, enabling the development of a sensitive blood test and effective drugs. Although I never worked in AIDS research, as a neurologist I examined AIDS patients with nervous system complications, and as a scientist I was engaged in defining the enigmatic infectious agent that caused degeneration of the central nervous system of immunocompetent humans and animals. Most scientists would agree that the discovery of the cause of AIDS by Luc Montagnier and his colleagues at the Pasteur Institute and by Robert Gallo and his colleagues at the U.S. National Institutes of Health ranks as a great scientific discovery. However, I became disturbed by the rancor that seemed to engulf Montagnier and Gallo at each stage in the acquisition of new knowledge about this terrifying disease. Some scientists were all too happy to involve the popular press, whose members were ready to write almost any rubbish that their editors would accept. In the mid-1980s, I had my own troubles with the press but because my work did not impact the lives of hundreds of thousands of people infected with a highly communicable, infectious pathogen, I could retreat by simply refusing to speak to reporters. AIDS researchers did not have that option--too many people were dying of this new scourge!

By both reading the literature and speaking to many scientists, I have developed what I believe is a reasonably accurate view of what Montagnier, Gallo, and their numerous colleagues contributed to our understanding of the cause of AIDS. I have taken care to determine which of my views about priority are supported by the dates of submission and subsequent publication of manuscripts in refereed journals. After all, this is the currency by which scientific discoveries have been and will continue to be judged for the foreseeable future. I did not consider abstracts, presentations at meetings, patent applications, or hearsay. In retrospect, there is no doubt that Montagnier and his colleagues were the first to report the discovery of the virus that we now call human immunodeficiency virus, or HIV (6). Equally important were the contributions of Gallo and his co-workers, who showed that the virus reported by Montagnier was the cause of AIDS (7-10). The work of both Montagnier and Gallo was made possible by the earlier discovery by Gallo's laboratory of the cytokine interleukin-2 (11), which is necessary for the growth of cultured T lymphocytes that support HIV replication. The propagation of large quantities of HIV in cultured T cells enabled the development of a blood test for detecting HIV by Gallo's group (9, 10, 12). Not only did the blood test allow the convincing demonstration that HIV causes AIDS but, equally important, it prevented millions of people from becoming infected with HIV through the transfusion of tainted blood. Certainly, the Montagnier and Gallo laboratories were not alone in these early days of AIDS research (13, 14), but their seminal contributions dominate the field. The contemporaneous and independent isolation of HIV by my colleague Jay Levy at the University of California, San Francisco, demonstrated the presence of HIV in AIDS patients and in healthy carriers (13). (Levy managed not to become embroiled in the controversy and so I will not further address his research here.) Despite all of the evidence, more than a decade would pass before there was universal agreement that HIV is the cause of AIDS (6-17).

Identifying HIV was the critical first step in defining the cause of AIDS, but, as Robert Koch so elegantly pointed out more than a century ago, showing that a particular infectious agent causes a specific disease can be an arduous process. This process is especially complicated when exposure to the agent is followed by an incubation period of months or even years before symptoms begin to appear. Such is the case with AIDS. Compounding the delayed manifestation of AIDS is the immunodeficiency that allows nonpathogenic microbes to become killers and other latent microbes to erupt. Pneumonia caused by P. carinii is rare in immunocompetent people but common in patients with AIDS; yet, P. carinii is not the cause of AIDS. KS, a rare cancer in immunocompetent people but frequently seen in AIDS patients, is caused by human herpes virus 8, also called KS-associated herpes virus (KSHV), which is transmitted sexually but remains latent in immunocompetent people (18, 19). Clearly, neither KS nor KSHV is the cause of AIDS. About 10% of people infected with HIV also carry HTLV-1, the first human retrovirus causing cancer to be identified (9, 10, 13). Thus, the demonstration that HIV causes AIDS was no small task.

I have suggested to Gallo that the scientific process might be well served if he and Montagnier were to write somewhat dispassionate accounts of how the cause of AIDS was discovered. Although Gallo and Montagnier tried to do this (20, 21), the need for each to be called the codiscoverer of the AIDS virus prevented resolution of the scientific dispute. The codiscoverer status had been a political solution devised by U.S. President Ronald Reagan and French Prime Minister Jacques Chirac in their attempt to resolve the dispute over patent rights covering the blood test for HIV.

The three following essays are a collaborative effort by Montagnier and Gallo that describe the different yet complementary paths that each took to discover the cause of AIDS, and both authors concur with each other's description of events.

References and Notes

M. S. Gottlieb et al., N. Engl. J. Med. 305, 1425 (1981). [Medline]
M. S. Gottlieb et al., Morbid. Mortal. Wkly. Rep. 30, 250 (1981). [Medline]
N. J. Ehrenkranz et al., Morbid. Mortal. Wkly. Rep. 31, 365 (1982). [Medline]
J. M. Karon et al., Morbid. Mortal. Wkly. Rep. Recomm. Rep. 41, 1 (1992). [Medline]
M. Essex, in AIDS: Papers from Science, 1982-1985, R. Kulstad, Ed. (AAAS, Washington, DC, 1986), pp. 3-7.
F. Barré-Sinoussi et al., Science 220, 868 (1983). [Medline]
M. Popovic et al., Science 224, 497 (1984). [Medline]
R. C. Gallo et al., Science 224, 500 (1984). [Medline]
J. Schüpbach et al., Science 224, 503 (1984). [Medline]
M. G. Sarngadharan et al., Science 224, 506 (1984). [Medline]
D. A. Morgan et al., Science 193, 1007 (1976). [Medline]
B. Safai et al., Lancet 1, 1438 (1984). [Medline]
J. A. Levy et al., Science 225, 840 (1984). [Medline]
D. P. Francis et al., J. Natl. Cancer Inst. 71, 1 (1983). [Medline]
J. Coffin et al., Science 232, 697 (1986). [Medline]
B. J. Poiesz et al., Proc. Natl. Acad. Sci. U.S.A. 77, 7415 (1980). [Medline]
Levy called the virus that he isolated AIDS-associated retrovirus or ARV (13), which turned out to be from the same virus family as Montagnier's LAV and Gallo's HTLV-III, all later renamed HIV (15).
Y. Chang et al., Science 266, 1865 (1994). [Medline]
D. Ganem, Cell 91, 157 (1997). [Medline]
R. C. Gallo, L. Montagnier, Nature 326, 435 (1987). [Medline]
------, Sci. Am. 259, 41 (October 1988). [Medline]
I thank F. E. Cohen, R. Gallo, H. Koprowski, J. Levy, L. Montagnier, and N. Nathanson for helpful comments, and H. Nguyen for help with the manuscript.
The author is at the Institute for Neurodegenerative Diseases, Department of Neurology and Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143, USA.

The entire article with all links active can be found here:
Volume 298, Number 5599, Issue of 29 Nov 2002, p. 1726.
Copyright © 2002 by The American Association for the Advancement of Science. All rights reserved.

Reprinted From: aidscience.org

A Rebuttal of "THE POPPERS STORY The Rise and Fall of ‘The Gay Drug' By Ian Young”

2006-04-27T17:28:00.000-07:00

The Poppers Story -- the History of Nitrite Odorants

“Have you brains?” asked the Scarecrow.“ I suppose so. I’ve never looked to see, ”replied the Lion.
--- The Scarecrow and the Lion in The Wonderful Wizard of Oz

Author Ian Young has made some interesting points in his article The Poppers Story, The Rise and Fall of ‘The Gay Drug', but do these points provide the reader with the “complete story” of poppers as the author claims? Are the claims he makes valid? Are the facts he quotes substantiated? Or is the article more like a makeshift saloon in an old Hollywood western, all front but no substance to hold it up? All good questions, but how do we get at the truth?

Well, let’s start with a brief overview of the article itself. There are a few important questions to consider. Who is the author and is he well versed in the subject he is writing about? Is the article original or has it been published before? An Internet search on Ian Young brings up nothing of significance. But interestingly, an article search reveals that Young’s article is not unique. In fact, it is essentially identical to one written by Stan Getchell under a different title. Getchell’s article "THE COMPLETE POPPERS STORY The History of What Some Once Called 'The Gay Drug' By Stan Getchell”, is a mirror image of Young’s article, right down to the opening quote by the arch villain of children’s literature, the Wicked Witch of the West. It even has the same typos. This leaves the burning question in one’s mind: Is Young a real author or a fictionalized character like Frank Baum’s pointy-hatted arch villain? Unfortunately, it’s impossible to know for sure, but one can make a shrewd guess that one of these two authors doesn’t exist. Where does this leave the credibility of this article and its authors? It certainly doesn’t reassure the reader, but let’s set this aside and review the rest of the article with as unbiased a mind as possible.

Unfortunately, even the most unbiased readers are immediately bombarded with an introductory quote designed to shift their bias toward the viewpoint of the author. After all, any article starting with a poison quote from the Wicked Witch of the West herself is sure to be about a most deadly poison. Quietly entering the reader’s mind, such introductory quotes play upon the subconscious as the reader continues the article. In this case, always reminding us that if there were ever a poison worthy of the Wicked Witch of the West, it would be poppers. The next logical question is why did the author(s) find it necessary to vilify poppers with this quote? Doesn’t the quality of the article speak for itself? Aren’t the claims made strong enough to convince the reader that what he or she is reading is fact? Unfortunately for the author, the answer is no. In most cases, the claims made in Getchell’s article are completely without substance. As such, any means of biasing the reader from the onset is a welcome addition. This is a big claim, one that shouldn’t be made lightly when reviewing any article, and one you will want to assess for yourself. What follows is a review of Young’s text that attempts to provide you with a second viewpoint on the claims made in his article. I hope you will use it to weigh the claims made by Young through a less biased set of glasses than those worn by the author, and come to your own conclusions about the validity of the ideas he has proposed as fact.

Leaving the Emerald Kingdom behind, the first claim worth considering in the article is the statement that poppers are back, after "almost dropping from sight in the mid-to-late AIDies." Admittedly, this is a witty pun on words, but that's all it is. Popper use was indeed in its heyday in the 1960 and 70s – and into the mid 1980’s, decreasing, as did most drug use when these psychedelic decades were left behind. However, contrary to the author's claim, use of the compound did not drop out of sight during the late 1980’s, only to resurge in the 1990s when Getchell's article was written. Instead, use has remained consistent to the present day. Retailers of the compound continued to sell it worldwide in regular retail stores, and on the Internet. Young goes on to claim "a friend who used to work in one of the bathhouses here told me their basement was filled with crates of the stuff until just a little while ago." This is quite a claim. Not only is that an incredibly large volume of poppers, but since poppers are not even shipped in crates (rather they are shipped in cardboard shipping boxes like most other consumer products) the claim is even more unlikely. Of course, there is no way of disproving the claim, but it is rather suspicious that Stan Getchell claims a friend told him exactly the same thing in his article. There certainly must be a lot of bathhouses with very full basements in Toronto, or someone is not telling the truth here!

The author goes on to claim that poppers are "not just in the big centers, either. When I visited Saskatoon a few years ago, everyone on the dance floor of the gay bar seemed to be snorting them." But in the next paragraph he further states "of all the drugs, legal and illegal, that have been funneled into the gay ghetto over the years, the cheapest and (apart from alcohol and tobacco) most widely available was poppers." The last time I checked, Saskatoon was certainly not a gay ghetto into which drugs had been "funneled" over the years. If everyone was snorting them at the Saskatoon club, then the dance club was probably selling a legal formulation to patrons directly. As for Young’s claim that poppers are the cheapest and most widely available drug apart from alcohol and cigarettes, one would hope that they would be less regulated than these compounds. Compared to the big bad wolves of cigarettes and alcohol, poppers have a safety record that cannot be competed with. Poppers are a non-addictive compound that do not result in abuse, cancer, hazardous driving, hospital stays or the like. If only alcohol and cigarettes, could boast the same!

In the next paragraph, Young provides what he claims is more background information on poppers, stating that poppers were prescribed "for the occasional use of certain heart patients." With this claim, the author denies over a hundred years of history during which time amyl nitrite (a variety of alkyl nitrite, the scientific name for poppers) was the drug of choice for the treatment of heart pain or angina until it was replaced by nitroglycerine. As such, the compound was both widely prescribed and safely used, with no restrictions such as that intimated by Getchell.

Leaving the annals of medicine and returning to the bar scene, the author reminisces about rampant poppers use in gay bars in Manhattan, stating that "some disco clubs would even add to the general euphoria by occasionally spraying the dance floor with poppers fumes." This urban myth has no place in a serious article. There has never been any proof that a disco or dance club sprayed poppers, a highly flammable compound, onto a dance floor. To do so would be to put their establishment at risk. Young goes on to quote a book by another author, Michael Rumaker, describing gay baths that "permeated with that particularly inert, greasy odor of poppers. Wherever you went, the musky chemical smell of it was constantly in your nostrils." The author, according to Young, was forced to gasp for breath out of a window to escape the permeating odor. Naturally, given that they enhance sex, one would expect poppers to be used in a gay bathhouse; however, to claim that one would have to open a window to breathe freely is clearly an exaggerated claim.

In another walk down memory lane, Young recalls an episode at a party in the 1970s where an acquaintance spilled a bottle of poppers on his leg, causing "a terrible and very unsightly burn." (Once again it seems that twin authors Young and Getchell have attended the same party, having both mentioned the episode in their articles.) In any case, it is a very unlikely story. A search of the Materials Safety Data Sheet on the compound indicates skin irritation is possible, but there is no mention of burns of any nature, severe or otherwise. The only other possibility is that the formulation was very impure and another contaminating chemical caused the burn.

Returning to discuss the original use of alkyl nitrites as a treatment for angina, the author reports that the pharmaceutical company Burroughs Wellcome had both the patent for the compound and a monopoly (incidentally it was also sold be Eli-Lilly) on its sale, providing the company with a healthy profit. Interestingly, in an attempt to vilify poppers by associating them with the gross profits of a pharmaceutical giant, the author a shoots himself in the foot as he leaves the reader wondering why, if so much alkyl nitrite was sold without so much as a peep from the public, the Food and Drug Administration or the medical establishment during over 150 years of amyl nitrite use, are we only hearing about possible safety issues now, from a small group of activists who dissent from the common medical view? Someone must be wrong here, but who? Young goes on to claim that nitroglycerine, the compound that replaced alkyl nitrite for treatment of angina in the 1960s was "better, more convenient, and it didn't give you a headache." While it’s certainly true that nitroglycerin tablets were more convenient, the claim that they don't produce a headache in some patients is false. All nitrite-based heart medications relax smooth muscle, allowing the blood vessels to dilate. The heart pumps faster to compensate for this and the rush of blood to the brain in particular may cause a headache in some cases. No matter whether nitroglycerine or amyl nitrites are used, the resulting headache and physiological changes that cause it are the same.

Young further hints that because alkyl nitrites are marked "poison" (this warning is meant to prevent people from swallowing the compound, which is unsafe, rather than inhaling it, the safe and intended means of use), sales of amyl nitrite began to decline in the 1950s. Contrary to this claim, sales of amyl nitrite ampules continued at a constant level for both for Wellcome and Lilly. At this time, the homosexual and avant guard community were also purchasing the compound for its pleasurable sexual effects. A little more detail and accuracy would go a long way in convincing their readers that the authors' arguments are valid. Unfortunately the authors don't seem to have these at their disposal. Continuing with this historical account, Young(and Getchell) chronicles that at this point in time, "it occurred to someone that there must surely be other lucrative markets for amyl nitrate, with its characteristic throbbing 'rush' and short-lived feeling of euphoria." The true historical background surrounding poppers, revolves around Clifford Hassing, a then young pre-medical school student in Los Angeles, who structurally altered amyl nitrite to create isobutyl nitrite and launched Locker Room®, the first ever bottled popper. This was soon followed by RUSH®, which became and remains today the most popular popper worldwide. Dozens of other brands followed over the years.

The article further argues that "contacts with the US military were sounded out, and before long, poppers had found a new test market in the jungle battlefields of Vietnam" and that "quite a few backline supply sergeants found they could use their Mob contacts from civilian life to transport drugs from Southeast Asia to the US." At this point, the reader needs to ask how much of this conspiracy theory they are willing to endure! If some put the article down at this point and cry "enough", I would be quick to join their cause. Considering that poppers were legal at the time of the Vietnam War (the United States Congress banned the sale of alkyl nitrites in 1991), I have to wonder what role mob contacts would play in shipping room deodorizers to the battlefields of Southeast Asia. You'd think they'd have more lucrative things to do with their time. Young further claims that "For the boys in 'Nam, nitrite inhalants were a welcome addition to the chemical stew. They were legal, they were easy to carry, and they were being shipped in from the States, literally by the crateful - touted as an antidote to gun fumes!" I'm afraid there is no rebuttal for this legation other than to point out that it simply isn’t true. You'll notice though that poppers are again being shipped by the crateful, a fallacy previously addressed.

The next statement the author makes is even more intriguing and outrageous. According to Getchell, "when the surviving GIs returned home, many of them were eager to keep up their poppers habit, and under heavy pressure from the manufacturers, the Food and Drug Administration made a ruling sanctioning over-the-counter sales." Certainly, the FDA did decide poppers were safe enough for over the counter sales, but this decision was based on their belief that they were safe. The idea that one of the largest government departments would risk the safety of consumers in order to satisfy a drug addiction of returning American GI’s (poppers are not addictive) doesn't really warrant consideration, except to mention that the author later claims that poppers were the drug of the gay population, not used by straight people, who in fact made up the majority of American soldiers at the time.

A year later, claims Young, "the first reports of peacetime casualties began to come in." Fortunately, the "terrible skin burns, blackouts, breathing difficulties and blood anomalies" that Young claims to have caused the return of poppers to prescription-only status, are false to begin with. This is a compound that has been safely used for 150 years to treat angina. Why would it suddenly cause a rash of symptoms in consumers a year after becoming available for over-the-counter sales? Logically, even when a prescription was required, similar reports should have come in, if at a lower level, but they didn't. The true story is that poppers were reclassified for prescription sale by the FDA solely based on the request by the drug companies making them, who were concerned about their public image because of the increase in use of the compound by the avant guard and gay communities, both of which were buying them to enhance sex and enjoyment of dancing. In the end, the only side effects that resulted in this change in status were political ones.
In the next paragraph, Young returns to his argument of mafia involvement, claiming that Hassing (recall he made isobutyl nitrite, a variation of amyl nitrite, selling it under the label Locker Room®) was "muscled out of his thoughtful little home-lab operation by organized crime syndicates" who altered the chemical structure of the compound further to create "butyl and isobutyl nitrite - less pure, more toxic, and even faster-acting than the original amyl." This was sold under the name of RUSH®. While it's true that other companies entered the market with varying brands, and one brand – RUSH® – took the lead, there was no involvement of organized crime in the companies that produced and sold any of the major brands. Nor has there been at anytime thereafter. Hassing’s Locker Room® brand consisted of isobutyl nitrite. Butyl and isobutyl nitrite are chemicals that vary slightly in structure from amyl nitrite. Like amyl nitrite, they are pure chemical compounds. They are in no way “less pure” or “more toxic” as Young describes.

Young goes on to claim that “the FDA apparently wanted nothing more than to be done with the whole business, and a modus vivendi was established. The unwritten agreement seems to have been: public distribution of poppers would be permitted - as long as they were labelled ‘room odorizer’ and marketed only to gay men.” This is an interesting claim, considering that the FDA had no jurisdiction over poppers when sold as ‘room odorants’. They are, after all, the Food and Drug Administration. Instead, jurisdiction over nitrite room odorants (poppers) fell upon the Consumer Product Safety Commission (CPSC). In 1980, the CPSC completed a year-long investigation of the industry, including a large-scale review of national data concerning the use of room odorants as inhalants and the potential dangers of doing so. The final outcome of this review was that use of nitrite-based room odorants per label instructions, and as inhalants, was safe. As a result, the CPSC refused to ban alkyl nitrites, and instead, mandated that manufacturers make specific labelling changes. Despite these facts, Young claims that the unwritten agreement with the FDA enabled poppers to become a "multi-million dollar business for the mob.” Again, I find this point to be a curious one. Since poppers were not illegal until 1991, how could the mafia have developed multi-million dollar profits through the sale of legal products that could be bought in any store? The only known connection of the mafia to poppers sales may have been in the 1970s when the mafia controlled many adult books stores. These stores sold poppers, as well other legal products, such as cigarettes and condoms; however, multi-million dollar profits from poppers, a legal product, seem unlikely. The mafia generally made its money off the sale of illegal products, extortion, etc.

Leaving the mafia behind, Young moves on to consider the role of the gay press in poppers advertising in the 1970s and early 1980s. Young’s claim that at this time, "poppers ads appeared only in gay publications” is on shaky ground, as a quick search of most of the popular straight men’s magazines published during those years, such as Playboy, Penthouse, Penthouse Forum and more, shows that these magazines all carried articles about poppers or paid advertisements for the compound. Young’s claim that "poppers became an accepted part of gay sex” as a result of this advertising, also warrants some consideration. Even if one discounts the fact that poppers were and continue to be sold to both homosexuals and heterosexuals, this statement both insults the intelligence of all homosexuals and unrealistically exaggerates the power of advertising through its insinuation that poppers were incorporated into gay sex due to an advertising campaign. Clearly, poppers are part of gay sex because they enhance the sexual experience. Even the best advertising campaign in the world would not overly influence consumer behavior if consumers didn’t believe the product lived up to the claims made by advertisers. How many people would continue to buy Viagra® if it only made their toes curl up? Not many. As such, Young’s claim seems to be more of an attempt to vilify the gay press for whatever reason. (Perhaps it’s because Young and Getchell are associated with the New York Native, the failed gay newspaper that began to rail against poppers when the industry started to cut back on poppers ads in the Native, due to it’s lack of readership.)

Unfortunately for the reader, the author’s claims regarding scientific studies conducted on alkyl nitrites are equally biased. Indeed studies have linked poppers to many of the conditions Young mentions; however, what he fails to tell the reader is that these studies were either in vitro (test tube studies) or conducted on animals. As all trained scientists are aware, it is very rare that findings from in vitro studies can be transferred to human beings. Instead, they are used as a starting point for further studies on animals and humans. Numerous studies were also conducted in which animals were exposed to varying degrees of alkyl nitrites. All studies published in scientific journals are peer reviewed, i.e. other scientists in the field check them for accuracy, repeatability, and validity of findings, etc. The animal studies that produced the findings mentioned by Young had many flaws that he fails to reveal to the reader. Most of these studies were carried out on mice, but the doses given to the rodents were not dose-adjusted for their smaller size. This is a basic tenant of animal research: if you are going to extrapolate findings from animals to humans, you must adjust for differences in lung and body size. This was rarely done in these studies. If fact, most mice were provided with doses that far exceeded the amount inhaled during human use; they were also exposed to the compound for a much longer time period than humans are during inhalation. At such toxic doses and exposure durations, it is no wonder that heart, lung and brain damage (among other symptoms) resulted. Even Aspirin is toxic if a subject is given enough of it. Curiously, most of the studies that found that alkyl nitrites reduced immune function also showed a complete reversal of this suppression when the subject was no longer inhaling the compound, even at near lethal doses! The moral of this story is don’t make scientific claims unless you understand the scientific methods used to evaluate the findings. Interestingly, most prestigious, peer-reviewed journals saw the flaws in the studies Young has quoted and therefore did not publish them. If you look up any of these articles, you’ll find they’ve been published in smaller journals that are often not peer reviewed. None of the articles appear in respected medical journals such as the New England Journal of Medicine or the Journal of the American Medical Association, although these journals have published articles that found inhalation of alkyl nitrites at normal doses and duration to be completely non-toxic.

Young gets it wrong again, when he states in his article that prior to the first reports of AIDS in 1981 “relatively few voices had been raised to question what health problems poppers users might be causing themselves.” Several state regulatory bodies were already studying poppers throughout the 1970’s as numerous petitions to ban them were submitted to federal and state agencies by concerned parties. This issue of safety had been addressed by several distinguished studies in the USA and Canada, all of which reported their safety when used as inhalants. The most well-known of these was published in 1979 by a group of prominent scientists and doctors, including Dr. John Parker from Queen's University, who had been the chairman of the Division of Cardiology there for nearly a decade and was a specialist in nitrite vasodilators, including alkyl nitrites; along with Mark Nickerson, PhD, MD, professor and past chairman of the Department of Pharmacology and Therapeutics at McGill University, in Montreal – who at the time had for nearly forty years been the author of the nitrite vasodilator chapter of Goodman & Gillman’s standard textbook of pharmacology, and who was considered “perhaps the most eminent pharmacologist of the twentieth century”. The result of their findings was clear: “No important acute or chronic toxic effects have been demonstrated with the volatile nitrites, and their use in an uncontrolled and unregulated fashion has proven to be safe."

Returning to Young's article, the author reports that a “few attempts were made to curb sales, but the manufacturers always got around it by changing either the chemical formula or the product name.” Changing product names does not get around product bans. Imagine how many people would be selling marijuana under a pseudonym if it did! Some states, such as Connecticut, did indeed ban the sale of poppers before they were illegalized nationally.

Young also draws attention to the fact that a "researcher contacted Robert McQueen, the Advocate's editor, to warn him that poppers strongly suppress the immune system and could contribute to KS and Pneumocystis pneumonia. But McQueen said he wasn't interested.” Scientists now know that poppers play no role in long-term or significant immune suppression, or in AIDS-related illness. In the late 1990s, a herpes virus, HHV-8, was isolated as the cause of both AIDS-related and non-AIDS related Kaposi’s sarcoma (KS).

Perhaps The Advocate had other reasons for not publishing the warning. As the nation’s largest and most prestigious gay publication, the Advocate's editor was likely aware of ongoing mainstream research that had determined there was no link between poppers and AIDS. The author then continues with what could only be euphemistically called a discussion about poppers advertising in the gay press. I’m not sure what the style of advertisements has to do with the safety of using poppers, so I will leave you to review this section at your leisure and come to your own conclusions. To me this part of the article seems to be some sort of attempt to again place the gay press in a bad light, although the reason remains unclear (however, there may be a connection to the author’s relationship with the New York Native, the failed gay newspaper, as mentioned earlier). The author’s comment that “poppers ads often combined appeals to masculinity and potency with this sort of overt or covered death imagery while at the same time, the political right was sending gays messages that they deserved to die, and information on the deathly effects of poppers was being suppressed” seems both bizarre and unsubstantiated. The author’s claim that a “number of studies of the effects of poppers have strongly suggested a link between poppers use and the appearance of Kaposi's sarcoma in young gay men” is completely true, but both of these findings were correlational rather than causal. These same studies also found that homosexual men with KS tend to have had hepatitis B; use other drugs such as amphetamines, barbiturates, cocaine, LSD, and marijuana to name a few; had a greater number of sexual partners than those without KS; and have an income over $20,000 per year, but the author fails to mention this. As described earlier, the HHV-8 virus was isolated in the late 1990s as the cause of KS, discrediting a poppers-KS connection, yet, this author and his cohorts have refused to publicly acknowledge this and continue to publish anti-popper ramblings.

Further claims by the author that after 1984, “most jurisdictions made poppers illegal - in spite of a well-financed campaign by a leading manufacturer, W.J. Freezer, the 'Pope of Poppers”, is not based on any substantiated facts – it is simply untrue. As for the comment that “the official explanation of AIDS has shown itself to have holes big enough to drive a truck through”, numerous studies have followed HIV-positive individuals and HIV-negative individuals over time. In these studies, many HIV-positive, non-poppers users developed AIDS; none of the HIV-negative poppers users developed AIDS. Case closed. In the early 1980s, there was some investigation into the possible association between inhaling nitrites and the subsequent development of AIDS, but it was quickly shown that no link existed, as was the case with the poppers-KS hypothesis in later years.

Young closes his article with a few personal anecdotes (not surprisingly, the same ones are also shared by Getchell in his identical article). Among his claims are that many gay men can’t enjoy sex or ejaculate without poppers. This is clearly false. Scientific research has shown alkyl nitrites have a transient effect on the human body and are not addictive.

The author also has a tendency to remind the reader that numerous AIDS activists and others that didn't agree with his theory are now dead of AIDS… "George Whitmore, Jerry Mills, Robert McQueen, W.J. Freezer, and Michael Lynch are no longer with us. They all died of AIDS.” Does this intimate that for some reason they died of AIDS because they didn’t agree with his discredited theories that poppers, not HIV causes AIDS? It seems so in Getchell’s mind. If only it were true, the cure for AIDS would already be in our grasp!

Even AZT doesn’t escape Getchell’s closing comments, but rather than being “the highly-toxic 'anti-AIDS' drug” he claims, AZT is a drug that has prolonged the lives of numerous AIDS patients. Like many drugs, it is not without side effects, but it has long been one of our best weapons in the deadly battle against AIDS. That in itself is much more than the ideas of Young (and Stan Getchell) have to offer the millions suffering from the disease.

So, what about our initial questions? Were the claims the author made valid? Were the facts he quoted substantiated? Based on the evidence provided, the answer to both has to be an unequivocal NO. In fact, most lunar landing conspiracy articles provide more substantial evidence to support their arguments than this article does. As such, I would recommend reading anything else published by these authors with a healthy dose of cynicism. The scientific community has long proved the safety of inhaling poppers; it’s about time that anti-poppers activists use their intelligence and graciously put their long dead hypotheses to rest.

“Have you brains?” asked the Scarecrow.
“ I suppose so. I’ve never looked to see,” replied the Lion.

--- The Scarecrow and the Lion in The Wonderful Wizard of Oz

©2006 Ted Bowman

Reprinted From: The Poppers Story -- the History of Nitrite Odorants

Nitrites and Gateway Drugs

2006-04-27T17:26:00.000-07:00

As reported in 1990, alkyl nitrite "poppers" are a relatively minor part of the overall drug abuse problem in the United States. Their use has shown a dramatic decline in the past decade. They do not qualify as gateway drugs either in terms of sequence (e.g., being an initiating drug) or in terms of being widely used.

July 2, 1990
Nitrites and Gateway Drugs
Robert L. DuPont, M.D. President
DuPont Associates
Clinical Professor of Psychiatry
Georgetown University School of Medicine Washington, D.C.

Drugs are chemicals that are used nonmedically to produce feelings that the drug users like. Substances which are drugs, as I use the word in this report, are not necessarily "drugs" as defined in the Federal Food, Drug and Cosmetic Act. Drug use typically begins during the teenage years. The younger drug use begins, in general, the more malignant the course of the drug use. Drug use has a typical pattern beginning with widely used, relatively accepted drugs, and progressing, over time, to less widely used and more dangerous-seeming drugs. Not all users of a particular drug progress to the next drug in the sequence. Those who do progress tend to be the more frequent drug users and the drug users who began drug use at younger ages. The more deviant youth are more likely to progress beyond initial drug use (DuPont, 1989).

Gateway drugs are drugs that are used early in the sequence of drug use. They are widely used in the population and they are considered to be relatively safe. Gateway drugs are thought by drug users not to produce frightening negative effects and their use is thought to be easily controlled. In the United States today the major gateway drugs are alcohol and marijuana. Cocaine showed signs of also becoming a gateway drug in the late 1980s. Tobacco, in the form of cigarettes, while non-intoxicating also qualifies as a gateway drug. These four drugs, with alcohol and marijuana being the prototypes, and cocaine and cigarettes being similar but also different, are the gateway drugs in the United States (DuPont, 1984).

There are many drugs which are commonly used but which are not gateway drugs. The prototypical non-gateway drugs are those that are widely seen as dangerous and therefore used only by the most committed drug abusers. Heroin and PCP are representative of this group. Many psychotropics which have legitimate medical uses are also sometimes abused, but they are not thought of as gateway drugs. Examples include barbiturates, stimulants, analgesics (such as codeine) and the benzodiazepines. LSD and MDMA (or Ecstacy) are also in a special class since they are thought of by some youth to be particularly safe. Nevertheless, they are used by relatively small numbers of youth (compared to alcohol, marijuana, cigarettes, and cocaine). Most youth consider them to be quite dangerous. The volatile solvents are gateway drugs for particular population groups, especially Hispanic youth in the Southwest and in some Native American populations. From time to time even PCP and heroin have been gateway drugs for particular population groups as their use was common for relatively drug-naive youth.

Among the heterogeneous chemicals that are abused by drug abusers the alkyl nitrites (or "poppers") are a special case. There was a time in the early 1970s when their use by youth was relatively common, but their use has declined sharply in the youth population in recent years -- even more sharply than has the use of other drugs, including alcohol and marijuana. Relatively little attention has been devoted to the alkyl nitrites partly because they are seen by drug abuse professionals to pose relatively minor problems. It is rare, if it happens at all, to see a patient in a drug abuse treatment program whose major drug problem is nitrites. When young people do use poppers they generally find the use unrewarding, compared to other drug use, and their nitrite use declines over time.

The Survey Data

The surveys conducted for the National Institute on Drug Abuse (NIDA) in the last two decades document the extent and trends of the use of nitrites and other drugs. The High School Senior survey, the single best data source for information on nitrites, began asking about these substances in 1979 (the survey began in 1975) when 17.3% of high school seniors reported using nitrites at least once in their lives. In that same year 8.9% reported nitrite use in the previous year, and 3.2% reported use in the past month. In 1979 less than 0.1% of high school seniors reported daily use of nitrites (University of Michigan, 1990).

For comparison, the figures for marijuana use rates in that year for high school seniors were: ever used marijuana, 60.4%; past-year use, 50.8%; past-month use, 36.5%; and daily use, 10.3%.

By 1989, the most recent year for which data are available from high school seniors, ever use of nitrates had fallen to 3.3%, past-year use was 1.7%, past-month use was 0.6%, and daily use was 0.3%. Again, for comparison, the figures for marijuana use by high school seniors in 1989 were: ever used, 43.7%; past-year use, 29.6%; past-month use, 16.7%; and daily use, 2.9%.

Focusing on the past-year use figures as the most representative of current general levels of use, nitrate use had fallen by 81% and marijuana use had fallen by 42% over the 10 years from 1979 to 1989. The drop in marijuana use over that decade was the single most dramatic accomplishment of the anti-drug abuse effort in the nation. What is far less widely appreciated is that the fall in nitrite use was the steepest decline in any single abused drug in the United States. Again, for comparison purposes, alcohol, the other commonly used gateway drug, showed a past-year use decline among American high school seniors from 88.1% to 82.7% (a drop of just 6%) from 1979 to 1989.

One of the most striking characteristics of gateway drugs is the tendency for their use to persist once it begins. For example, among high school seniors in 1988 only 7.3% of youth who had ever used alcohol were not still using alcohol in their senior year. Expressed in positive terms that meant that 92.7% of high school seniors who had ever used alcohol were continuing to use it in their senior year of high school. For cigarettes, another gateway drug, only 18.2% of those who had ever used them had stopped by their senior year in high school. For the less widely accepted drugs, those that are not gateway drugs, the rates of stopping were substantially higher. For example, for PCP the rate of stopping was 58.6% and for heroin the rate was 54.5%. For nitrites the stopping rate by the senior year in high school was 46.9% in 1988.

When high school seniors were asked what proportion of their friends were using various drugs, the only two drugs that were used by fewer friends than nitrites were PCP and heroin. In 1988 81.7% of high school seniors said none of their friends was using nitrites. The percentage reporting that none of their friends using marijuana was 24.7% and for heroin it was 87.6%.

In a follow-up of high school seniors it was found that among those ages 19 to 28 the rates of nitrite use in the past year were 2.0% in 1986, 1.3% in 1987, and 1.0% in 1988 (the most recent year for which these data are available) (Johnston, O'Malley, & Bachman, 1989).

Turning to the Household Survey of all Americans 12 years of age and older, there is no category for nitrites, but there is a general category of "inhalants" which has been tracked from 1972 to 1988, the year the most recent survey was conducted. These data show that lifetime inhalant use for Americans aged 12 to 17 had gone from 8.4% in 1972 to 8.8% in 1988. Among Americans 18 to 25 use of inhalants had gone from 9.2% in 1974 (when this question was first asked of this age group) to 12.5% in 1988. Among Americans 26 and older the lifetime inhalant use had gone from 1.2% in 1974 to 3.9% in 1988. Inhalant use in the past 30 days in 1988 for these three age groups was 2.0%, 1.7%, and 0.2%. These data from the household survey are not useful in isolating the use of nitrites, since nitrite use is combined with the use of volatile solvents, a very different drug abuse pattern. Nevertheless, they do establish some boundaries for the use of inhalants as a class (U.S. Department of Health and Human Services, 1989b).

The third major NIDA drug data source is the DAWN (Drug Abuse Warning Network) data on Emergency Room visits and medical Examiner cases (deaths). These data for the end of 1988, the most recent data available, do not list either inhalants or nitrites as special drugs, suggesting that in these contexts, nitrites are a relatively minor problem. In 1986, when DAWN listed the 170 most commonly mentioned drug problems seen in U.S. Emergency Rooms during the year, cocaine was number one followed closely by alcohol and heroin. Aspirin was number 8 and caffeine was number 55. Nitrites were not on the list of 170 drugs (U.S. Department of Health and Human Services, 1987, 1989b).

Conclusions

Nitrites are a relatively minor part of the overall drug abuse problem in the United States. Their use has shown a dramatic decline in the past decade. They do not qualify as gateway drugs either in terms of sequence (e.g., being an initiating drug) or in terms of being widely used.

References

DuPont, R. L. (Ed.) . Stopping Alcohol and Other Drug Use Before It Starts: The Future of Prevention. Rockville, MD: U.S. Department of Health and Human Services, Office for Substance Abuse Prevention. OSAP Prevention Monograph-1, DHHS Publication No. (ADM) 89-1645, 1989.

DuPont, R. L. Gettincr Toucih on Gateway Drugs: A Guide f or the
Family. Washington, D.C.: American Psychiatric Press, 1984.

Johnston, L.D., O'Malley, P.M., and Bachman, J.G. Drucr Use, Drinking, and Smoking: National Survey Results from High School, College, and Young Adults Populations, 1975-1988. Rockville, MD: U.S. Department of Health and Human Services, National Institute on Drug Abuse, DHHS Publication No. (ADM) 89-1638, 1989.

U.S. Department of Health and Human Services, National Institute on
Drug Abuse. Data from the Drug Abuse Warning Network (DAWN) ,
Annual Data 1986. Rockville, MD: National Institute on Drug Abuse, Division of Epidemiology and Statistical Analysis. Statistical Series, Series I, Number 6, DHHS Publication No. (ADM) 87-1530, 1987.

U.S. Department of Health and Human Services, National Institute on
Drug Abuse. Data from the Drug Abuse Warning Network (DAWN) ,
Semiannual Report, Trend Data Through July-December 1988.
Rockville, MD: National Institute on Drug Abuse, Division of Epidemiology and Prevention Research. Statistical Series, Series G, Number 23, DHHS Publication No. (ADM) 89-1620, 1989a.

U.S. Department of Health and Human Services, National Institute on Drug Abuse. Highlights of the 1988 National Household Survey on Drug Abuse, National Institute on Drug Abuse. NIDA Capsules, August 1989b.

University of Michigan, Institute for Social Research (News Release). Drug use continues to decline, according to U-M survey; cocaine down for third straight year. The University of Michigan, News and Information Services, Ann Arbor, MI, February 13, 1990.

"Getting Tough on Gateway Drugs", by Robert L. DuPont, Jr., M.D.

About the Author:

Robert L. DuPont, Jr. has been one of the nation's leaders in drug abuse prevention since the late 1960s when he developed the Narcotics Treatment Administration, the comprehensive program that treated over 15,000 heroin addicts in the District of Columbia between 1970 and 1973 while he was Director. He then moved to the federal government, where he became the first Director of the National Institute on Drug Abuse, serving in that capacity from 1973 to 1978. From 1973 to 1975 he was the White House Drug chief. As NIDA Director, Dr. DuPont visited more than 20 nations to study drug problems. He represented the United States at five consecutive meetings of the United Nations Commission on Narcotic Drugs, and he was Chairman of the Section on Drug and Alcohol Abuse for the World Psychiatric Association.

Since leaving the government, Dr. DuPont has been President of the nonprofit American Council for Drug Education in Rockville, Maryland. Dr. DuPont directs the Center for Behavioral Medicine, which provides clinical psychiatric services from offices in Baltimore, Rockville, Richmond, Norfolk, and Raleigh. He is Vice-President of Bensinger, DuPont, and Associates, Inc., a national firm with offices in Chicago and Rockville, providing consultation on drug abuse prevention in the workplace.

A graduate of Emory University and the Harvard Medical School, Dr. DuPont is Clinical Professor of Psychiatry at Georgetown Medical School and Visiting Associate Clinical Professor of Psychiatry at Harvard. Medical School. He is a Fellow of the American Psychiatric Association.

Dr. DuPont maintains an active clinical practice of psychiatry, having worked directly with hundreds of drug-dependent people and their families during the last 15 years. He is married and has two teenage children.

Reprinted From: Nitrites and Gateway Drugs

Poppers in perspective

2006-04-27T17:23:00.000-07:00

The Pink Paper Issue 67 8 April 1989: Poppers in perspective
STEPHEN BURTON

Eighteen months ago I was asked to look into the safety of Poppers (Amyl Nitrite/Butyl Nitrite) by the solicitors representing six men accused of to supplying a noxious substance with intent to harm, injure or annoy". Later on I was one of the the expert witnesses called to their defence in a trial at the Old Bailey.

When first approached I was doing research into the effects of drugs on sleep, and it was a refreshing change of topic. Now, and after reading 300 research papers on poppers, English' (Amyl Nitrite) and ‘American’ (Butyl nitrite and Isobutyl nitrite), and after doing experiments with them on myself, there is a story to be told.

Before chucking over a career in medicine for the loony world of gay publishing no-one could have persuaded me how a body of scientific literature could be so distorted by campaigners (gay and otherwise) with axes to grind. Working for The Pink Paper however, has opened my eyes to the lengths that some will go to, in pursuit of their favourite hobby-horses. Poppers are no exception.

A headline such as "Health Fears Rise As US Bans Poppers", seen by gay men in London last week (Capital Gay), does need to be set in context. No doubt some gay men in the US wanted poppers banned. But did the gay community rise as one? No.

The decision to ban poppers in the US was as a result of a fierce anti-drugs lobby leading to the comprehensive US "Drug Omnibus Act". The decision to include poppers in this legislation was fuelled by certain self-seeking scientists who have been pursuing poppers for 10 or more years as well as politicians sympathetic to a small but vociferous gay anti-poppers lobby.

The main plank of their argument goes as follows: “using poppers causes immune deficiency like that seen with AIDS". Yet, early fears that poppers might cause Kaposi's sarcoma have been found to be groundless, in large well-conducted studies of thousands of gay men. No scientist should be categorical but the evidence just isn't there to show any link at all. At the beginning of the AIDS epidemic in the early 80’s, and before anyone knew that HIV existed, it was natural to look into the lifestyles of the gay men diagnosed with AIDS for reasons as to why they should be so afflicted.

The first several thousand cases ofr KS did have a very significant history of using poppers. But so did thousands of gay men (and probably millions of high school kids) who haven’t gone on to get KS or any manifestation of AIDS. Why?

Because it is now well known that the difference between those who went on to develop KS and those who did not, is that those who did had had a very significant exposure to semen infected with HIV, mostly due to unprotected anal sex. No-one disputes that some men in New York, or for that matter in San Francisco, enjoyed a period of several years having as much sex as they could, in bath houses and elsewhere. This provided ideal conditions for the rapid spread of all sorts of infections.

Once an infection got into that group it got passed around very quickly. The spread of Hepatitis B (causing liver diseases) or Herpes (causing genital sores) or Syphilis was epidemic long before AIDS arrived.

HIV also got into that group, who knows from where, and because it took between five and ten years to show itself - by causing severe immune deficiency or AIDS - it was widely distributed before anyone could change their sexual practices.

KS itself is just one manifestation of AIDS and may be made more likely by repeated infection with different strains of HIV or by other sexually transmitted diseases like Syphilis or Cytomegalovirus (CMV) infection. In fact, KS also occurs rarely in elderly men and has been recorded in patients who have had organ transplants and whose immune systems are suppressed due to drugs.

The common factor is profound immune depression.

KS does not occur in users of poppers who do not have HIV. So the worst thing you can say about poppers is that they make anal sex less traumatic by relaxing the relevant muscles.

That's one of the reasons why they were so popular in the 70's in the US. And, only with the benefit of hindsight, it would have been better for everyone had there been much less anal sex, but, NOBODY KNEW ABOUT HIV.

It is pointless to try and put the blame on poppers for the spread of HIV.

Some people need scapegoats, something to blame for the ills of the world and some, unable to explain the random intrusion of HIV into their world, seek to find something, anything, in themselves, to blame for it. Too much 'unsafe sex' I can accept as reason for self blame (however irrational given everyone's ignorance of what was safe) but to blame a drug which has been used for 150 years by countless millions in the treatment of heart conditions and cyanide poisoning isn't supported by the know facts.

All my researches as presented in evidence in the recent Old Bailey trial point to the following conclusions:

1. There is no link between using poppers and acquiring HIV or KS or AIDS, except if using them makes people forget safer sex guidelines.

2. There is no evidence that sniffing poppers causes significant effects on the immune (or defense) systems of the body. T4 cells (the cells attacked by HIV) may be affected by inhaling poppers but then these cells are known to be affected by the time of day or exercise and a hundred other factors including diet.

3. There is no evidence whatsoever for someone developing AIDS or KS as a result of sniffing poppers independent of being infected with HIV.

4. Poppers inhaled to excess can give you a bad headache, or make you feel sick. In combination with alcohol poppers can do even worse, making users vomit or very rarely faint.

5. All the other effects attributed to poppers by their critics, including anemia, collapse and in extreme circumstances death, have been due to enormous misuse, most often by drinking the stuff.

AIDS, or the fear of it, has made puritans of some people and that's OK for them. What isn't OK is vociferous lobbyists with strong beliefs, unsupported by the evidence, calling for changes in the law that would mean people wouldn't be allowed their own decisions over whether or not to use poppers.

A public debate over poppers is called for and I for one would welcome the chance to discuss the relative merits or risks of poppers in public before any more people are panicked into a monastery by scaremongering headlines.

The moral of this story should be Don't believe everything you read in the newspapers'.

©The Pink Paper Issue 67 8 April 1989 London, England

Reprinted From: Dr. Stephen Burton Writes About the Poppers Trial in London's Pink Paper

"My way with angina victims"

2006-04-27T17:19:00.000-07:00

"Of course, I don't have to tell you that the alkyl nitrites are aliphatic esters of nitrous acid and that amyl nitrite was used first of all for angina by Sir Lauder Brunton in 1867."

MEDICAL NEWS WEEKLY
Volume 12 Number 4
Thursday
January 31, 1980

My way with angina victims
ERIC TRIMMER

After trinitrin and beta-blockers, “what next for angina?" asks Dr P J B Hubner in my latest Prescribers' Journal (vol 19, no 5) and goes on to give "consideration for coronary artery surgery" as the short answer to the question.

But clearly his heart isn't in it, and it is rather nice to see someone providing, in this rather austere little journal, some helpful advice not overflavoured by the credo that so often argues that therapeutics is after all a pretty static science and all those new drugs that the reps try to sell us when trinitrin and beta-blockers fail (like Pexid, Adalat, Cordilox and Synadrin) are just pipe dreams of the pharmacological industry that should be best left on the shelf.

They often can be useful and angina patients are so pleased when you make them feet better.

Recently I've been "Doing It My Way" for angina victims by means of a bit of therapeutic nostalgia.

I mean, of course, dear old amyl nitrite. Not only does it put the local chemist in a flap but in some patients it's really effective.

Let me explain. A few weeks ago I received a book entitled Isobutyl Nitrite and Related Compounds and I would have floor filed it, hadn't I recognized the name of one of its authors - Thomas P Lowry, who is a psychiatrist at the University of California.

Of course, I don't have to tell you that the alkyl nitrites are aliphatic esters of nitrous acid and that amyl nitrite was used first of all for angina by Sir Lauder Brunton in 1867.

But did you know that butyl nitrite and isobutyl nitrite have been used extensively (in the US) as the primary ingredients of room odorizers and they have been claimed to be fantastic olfactory aphrodisiacs.

Now it may have just grazed your consciousness that from time to time some naughty people abuse drugs. In this country when this happens we put a voluntary prescribing ban on them and the shades of CURB can be seen to be falling fast.

Happily in the US when it became wide knowledge that the alkyl nitrites were being used for such wicked purposes as enhancing sexual sensations they decided to sort it out before seeing how fast they could ban these compounds.

To cut a long story short some three thousand odd emergency room specialists and over two hundred forensic pathologists were lobbied for help and statistics. Surprisingly the results were quite disarming.

A few teenagers had got nasty headaches trying to "augment" their orgasms with amyl nitrite. A few more got woozy. One "presumed death" in the Midwest after nitrite inhalation was found to be a multiple drug user.

The conclusion of my old friend Thomas Lowry is that the data suggested "mini morbidity and zero mortality associated with amyl, butyl and isobutyl usage".

One of my patients told me that since he's had his "poppers" he's been a "new man in every way, doc".

I'm beginning to realize what he is hinting at.

©1980 MEDICAL NEWS WEEKLY, London, England

Reprinted From: My way with angina victims

Popper critics lose “credibility” when they drag out their old/ancient/never-documented assertion that “poppers=death”.

2006-04-27T17:16:00.000-07:00

"If “poppers really did equal death” I'd be long dead by now. Once, after having a pleasant dinner with John Lauritsen, I actually indulged myself by “toasting him” with a hit of Rush as he looked on in wide-eyed wonder and/or horror."

Writing on the web, Bruce Mirken has thanked the anti-poppers zealots: "I'd like to thank Lauritsen for laying out in explicit, if unintentional, detail the true nature of the AIDS denialist arguments (and yes, the comparison to Holocaust deniers is indeed apt): A collection of unsupported speculation propped up by carefully selected snippets of data that simply omit anything the "dissidents" find inconvenient."

Lauritsen's claim that the media have censored the views of the denialists is laughable. Nightline did a whole show on the subject a few years ago. They've also gotten extensive coverage in, among other outlets, the London Sunday Times, Spin, numerous gay and lesbian publications and--strikingly--key organs of the right-wing, antigay movement in the U.S., including The American Spectator and the Heritage Foundation's Policy Review.

After all of this attention it's hard to see how the fact that few take their views seriously can be blamed on censorship. Maybe--just maybe--it's because, after carefully looking at all of the data, intelligent observers have concluded that mainstream science, whatever its flaws, pretty much got it right this time.

But the best advice I can give readers is: Don't take my word for it. Look up the references. Read the data--all of it, not just the narrow interpretations of those with an axe to grind--and judge for yourself." (The information is available at the links on this website, both the pros and cons, the anti-popper view, and the opposite view.)

Randy Wicker (short bio) writes of one anti-popper zealot, "However, he totally loses “credibility” when he drags out his old/ancient/never-documented assertion that “poppers=death”. I read his book on that subject and the research simply showed that “if someone was HIV positive, the use of poppers did seem to increase the possibility of their contracting Karposi Sarcoma.” (*This assertion has now been dismissed as never having been valid. KS is not caused by poppers.)

If “poppers really did equal death” I'd be long dead by now. Once, after having a pleasant dinner with John Lauritsen, I actually indulged myself by “toasting him” with a hit of Rush as he looked on in wide-eyed wonder and/or horror."

Writing in NEWSLINE, Volume 3, Issue 1 • February 1997, Stephen J. O'Brien, Ph.D. Director, Laboratory of Genomic Diversity National Cancer Institute National Institutes of Health emphasized: "If AIDS was caused by recreational drugs like nitrate inhalants, also known as "poppers," and prescription drugs like zidovudine, also known as AZT, then how could one account for the millions of cases of AIDS that had occurred in Third World countries?"

Dr. O'Brien went on to say: "With each passing year the evidence that HIV causes AIDS grew more persuasive and less refutable, even at the purely rhetorical level. But even as this evidence mounted, Duesberg and his minions grew increasingly shrill and hectoring. Their unsupported but high-decibel jeremiads garnered some media attention-in 1993, for instance, the London Times labeled the epidemic "a tragic myth"-and even respectable scientific journals felt obliged to address the issue again and again, simply because Duesberg and his outspoken supporters raised the issue again and again."

As Bruce Mirken advises those reviewing the data on poppers: "Don't take my word for it. Look up the references. Read the data--all of it, not just the narrow interpretations of those with an axe to grind--and judge for yourself."

Reprinted From: Popper critics lose “credibility” when they drag out their old/ancient/never-documented assertion that “poppers=death”.

Paul Varnell, Observer's Notebook - Poppers: Less Than Meets the Eye

2006-04-27T17:13:00.000-07:00

"The government's own expert on poppers, Harry Haverkos, has been working on the notion of a poppers-KS link for nearly seven years and still cannot confirm such a link; he always talks in terms of "potential" and "could be" and then calls for more epidemiological and laboratory studies. That's pretty much what he was saying years ago."

Windy City Times/Thursday, March 30, 1989
By Paul Varnell

That body of collective scientific expertise, the United States Congress, has by legislative fiat declared Isobutyl Nitrite (IBN) Poppers a "banned, hazardous product," illegal to manufacture, sell, or distribute. The ban was placed into the 1988 Omnibus Drug Act by Representative Henry Waxman (D California) at the urging of Representative Mel Levine (D-California) who had been heavily lobbied by a self-styled "AIDS activist" hank Wilson, head of the one man committee to Monitor Poppers. However:

- The new law does not forbid possession or use of IBN poppers, so if you can get them, you can use them and even carry them around.
- At this point at least one manufacturer of IBN poppers has gone to court and received a temporary restraining order to keep the law from being enforced against its products.
- Some poppers manufacturers, including Great Lakes Products,Inc have already started manufacturing and selling poppers made with other nitrites (e.g., Isopropyl nitrite), and those are entirely legal to make, buy and sell.
The politics of such a ban, or prohibition, are interesting to contemplate. For instance:
- Do Levine and Waxman and Wilson actually think such a ban will work? IBN poppers are not that hard to manufacture, so we may be in for a supply of "bathtub poppers" by underground network, as well as God-Knows-What substances in plain bottles representing themselves as IBN poppers. Does anyone think this is a clear gain?
- Isn't there some sort of personal liberties issue here? What about the argument that "It's my body" and that I have the moral right to control what goes into it and what stays out of it?
- When cigarettes were shown (shown!) to be harmful, we put warning labels on the package giving the medical evidence and then let people make their own decisions - and the claims against cigarettes are substantially stronger than any claims against poppers. Whatever happened to freedom of choice here?
- Representative Levine has an ADA rating of 95 percent. Scratch a progressive, find a fascist.
The law offers no rationale for its criminalization, only saying that the substance is banned when it is manufactured for use for "euphoric or physical effects. " What everybody knows, however, is that the claims have been repeatedly made that IBN poppers are "somehow" involved as a cause either of AIDS itself (1981-1984) or, the somewhat retrenched position, as a cause of Kaposi's sarcoma (1984-present), or, the even more retrenched position, as a "cofactor" (i.e., not a primary cause) in the development of KS (about 1986-present). These claims seem doubtful because:
- We all know lots of people who have KS who have used little or no poppers in their lives; and we all know heavy poppers users who do not seem to have KS.
- As one physician pointed out to me, if IBN poppers caused KS, lots of people should have KS of the thumb.
- KS is apparently widespread in Africa, an area not known to be a region of heavy poppers use.
- The largest study of gay men I know of, the Multi-Area Cohort Study by the NIH (of which the Howard Brown study is a part) shows no poppers-KS link.
- The government's own expert on poppers, Harry Haverkos, has been working on the notion of a poppers-KS link for nearly seven years and still cannot confirm such a link; he always talks in terms of "potential" and "could be" and then calls for more epidemiological and laboratory studies. That's pretty much what he was saying years ago.
- Haverkos' own summary of all the IBN studies asserts that--at most--a few small studies seem to suggest an association between heavy (heavy!) poppers use and KS, but then says that other studies show no such link.
Much of the work on poppers seems to be of remarkably poor, astonishingly poor, quality, barely within shouting range of standard scientific method. And the conclusions drawn are frequently far in excess of the evidence offered:
- Some of the laboratory work has involved injecting enormous quantities of IBN into small animals. Other studies have forced inhalation of IBN in high concentrations for hours on end. Yet others have used animals with no immune systems to begin with, so it is hard to know what you could learn about IBN's effects on the immune system. Yet others, still, have used animals (and cited people) with rare genetic defects. By and large this is the sort of evidence that Hank Wilson and his Committee to Monitor Poppers has found convincing.
- When a Denver-based researcher a few years ago sent out a press release claiming to have established a poppers-AIDS link, the Illinois Gay and Lesbian Task Force wrote the researcher a long letter asking a number of probing questions about his study and the methods he had employed, control groups, quantity of poppers used, the capacity of his genetically immune-deficient laboratory animals to re-achieve immune-system homeostasis. The researcher refused to provide a copy of his study and wrote an angry letter ("I am upset and angry about your questions," he wrote) in which he more or less acknowledged the inadequacy of his study and wholly and completely withdrew his claim to have established any AIDS-poppers link: "It is not mentioned, nor is it our intention to say, that IBN causes AIDS, nor does it precipitate or intensify the disease status of the AIDS people [sic]." The press release, however, read: "Studies confirm use of drug increases risks of AIDS" and the flamboyant York Native headlined its reprint of the press release, "Researchers Link Poppers to AIDS." It just makes you wonder, doesn't it.
- If some studies suggest an association between heavy poppers use and KS, it is reasonable to be interested. What needs to be inquired into is whether heavy poppers use is causal or, rather, an accompaniment or marker for other behaviors which place people at risk of developing KS. But government researchers seem extremely squeamish about asking gay men details of their sexual behavior. In the past, heavy poppers use tended to accompany anal sex and fisting, for instance. But it is surprising how incurious researchers have been to research these things.
- Nowadays, I am willing to bet, poppers-like pornography-tend to be used as an accompaniment, or enhancement, of the pleasures of private masturbation-just about the safest sort of sexual behavior I know of. To the extent that is true, if poppers do actually make masturbation more pleasant, then instead of banning poppers, the government-if it had a real interest in the health of gay men-should actually provide bottles of them for free at gay bars.
- Wouldn't that just make William Bennett's day.

©Windy City Times/Thursday, March 30, 1989

Reprinted From: Poppers: Less Than Meets the Eye

"The controversy over poppers"

2006-04-27T17:10:00.000-07:00

"By chance it is a topic I found myself having to learn a lot about back in the 1980s when I was doing a great deal of gay activism which then turned into AIDS activism."

Paul Varnell: "The controversy over poppers"

During that time (1982-1990) I served as the Research Director of the Illinois Gay and Lesbian Task Force and served as well on the state of Illinois AIDS Interdisciplinary Advisory Council (appointed by the state Dept. of Health) and the City of Chicago AIDS Advisory Council. Remember that early in the AIDS epidemic, before HIV was discovered by Luc Montagnier's laboratory, people came up with all sorts of theories about what caused AIDS. Noting that gay men disproportionately got the disease, some people thought it must be some fungus in the air conditioning systems of gay bathhouses. Others suggested it might be poppers. Others thought it must be supposedly immune suppressive effects of semen. Or another manifestation of syphilis. And on and on.

Many of these theories and more were proposed and promoted (at the same time) by a gay newspaper in New York which continued to claim that these things caused AIDS even after HIV was discovered. The paper does even not now acknowledge that HIV causes AIDS.

(The same newspaper also promoted various alleged therapies and cures, from Japanese mushrooms, to something made from pond scum, to high doses of penicillin, to repeated shots of typhoid fever vaccine, and so forth.) Those of us at the Illinois Gay and Lesbian Task Force took our obligation seriously and tried to look into all of these theories to see if they had any merit. My job as Research Director was to try to obtain additional information for the board to work with, more than was in the newspapers at the time.

Most of the medical journal articles touching on poppers turned out to be laughable and hardly evidence of immune suppression. Some people were harmed by drinking a bottle, or by falling down and hurting themselves if they inhaled large amounts and became dizzy.

Even studies that supposedly tested for immune suppression all used massive amounts of poppers in tests with mice, giving the poor little mice massive amounts that would be equal (for their body weight) to 100 to 200 times what any gay men would normally use on any occasion.

And the mice were often given the poppers continuously for long periods, so there was no opportunity for their bodies to recover whereas humans use it intermittently and their bodies resume normal condition in a few minutes. Yet other studies used "nude" mice, that is mice that have been genetically altered so that they do not have an immune system to begin with. How any tests using poppers could prove something about immune suppression in mice that do not have an immune system to begin with was beyond us.

In other words, the studies that were being done were not a realistic test of anything that happens in the real world.

Bruce Voeller, the first head of the National Gay and Lesbian Task Force, who later became head of the Mariposa Foundation (and the man who gave AIDS its name), also looked at some of the poppers studies and pointed out how massive the amounts of poppers used in the mice experiments were. If you gave an adult human such proportionately scaled up doses of aspirin, they would die, Voeller pointed out. Ditto most vitamins and even most necessary trace minerals. What, Voeller wondered, was the agenda of these researcher?

One particular study I remember investigating was conducted at a prominent Colorado research facility. The scientist gave massive amounts of poppers continuously over a long period to a few mice and cheerfully reported that the mice got sick. The study was not peer reviewed. It was not published in a peer reviewed journal. It was not published at all. But his institution hired a large public relations firm to promote the study as showing that poppers could cause AIDS. (The New York gay newspaper printed the press release verbatim -- and many other gay and lesbian papers around the country picked up on the story as a result, further spreading misleading information.)

The Gay Task Force wrote to the scientist to ask about the amount of poppers used, the duration of exposure, the pre-trial condition of the mice, the quality of the poppers, what a comparable dose would be if given to a human, &c. the sorts of things that should be included in a published article having any claims to credibility.

When the scientist refused to reply to repeated inquiries, the Task Force wrote to the president of the research facility summarizing its concerns about the integrity of the study. Forthwith came a long, anguished, extremely defensive response, written in broken English, from the researcher who clearly was not happy being challenged.

"I am hurt and angry at your questions" he began, but then refused to give the Gay Task Force much information about his "research," asked how dared we challenge his "findings" and ended up saying, "We did not say, and it was not our intention to say that IBN [iso-butyl nitrite] causes the AIDS disease"-a total reversal of his previous position.

I remember reading this letter to an appalled Task Force board meeting. When I was finished, the board members started laughing and, as I recall, the claim about the immune suppressive tendencies of poppers never came up again. But, of course, the public relations firm never sent out a correction, the research institution never sent out a correction, and the New York gay newspaper never printed a retraction (though we sent them a copy of the researcher's letter).

That long anecdote pretty much summarizes my repeated experience in trying to track down the alleged "scientific" evidence for "the immune suppressive effects" of poppers. Most of it is politics with an agenda combined with misapplied science.

It seems worthwhile to add that in all the years I went to the city and state AIDS advisory council meetings, no one ever brought up poppers as having any impact on AIDS or causing any immune suppression-not public health officials, not gay community physicians, not AIDS researchers, not biochemists, not community activists.

It may be useful to add here what drug expert Andrew Weil, author of The Natural Mind and other books, recently wrote in HotWired Magazine. He notes that all nitrites are poisonous in excess (remember the mouse experiments) but then explains:

"But when inhaled, amyl nitrite breaks down easily and leaves the body quickly. It's been considered one of the safest drugs in medicine. "As with anything else, it's wise not to overdo it. Potential side effects include nausea, headaches, and dizziness. . . . .Be careful not to get it in your eyes, and don't use it in situations requiring muscular coordination (like driving) or in combination with depressants (like alcohol). Finally, make sure you get plenty of fresh air afterward to flush the chemical out of your system."

And that certainly seems like sound cautionary advice no one could disagree with.

I need to be clear here. No one is claiming, and no one needs to claim that poppers are "good" for you, or "wise" to use in the sense that foods have nutritional value or exercise is "good" for you. The conclusion here is simply that poppers are not "bad" for you (as they are ordinarily used by gay men) in the way that some people speculated that they were before HIV was discovered. Despite a great deal of huffing and puffing and some very inflammatory and possibly libelous language to the contrary, the scientific evidence simply is not there in the medical literature.

There are lots of serious problems to worry about in the world, and a lot of things that harm people, and that people do to harm themselves. And there is much that needs to be done to help people with AIDS and to help those who foolishly place themselves at risk for contracting the disease. But running a hostile agenda on poppers contributes nothing to that effort.

©Paul Varnell Chicago

Paul Varnell writes a weekly column for the Chicago Free Press and other gay newspapers.

He has also written for Reason magazine, the Advocate, Lambda Book Report, and the Chicago Reader. Some of his essays were included in Beyond Queer (Free Press, 1996) and The Bedford Guide for College Writers (Bedford, 1999).
Varnell has been involved in gay advocacy for more than two decades. He headed the education committee of the Gay/Lesbian Union in DeKalb, Illinois, 1977-1982, was a board member of Parents and Friends of Gays in Chicago, 1983-84; and chaired the Media Committee of the Illinois Gay and Lesbian Task Force in Chicago, 1983-1990. He was a co-founder of Gay History Month in 1994.
He was a member of the Chicago AIDS Task Force and was appointed to the Illinois Department of Health's AIDS Advisory Committee.His areas of interest include class ical music, gay history, political philosophy, libertarian theory, and socio-economic analysis.

Many of Paul Varnell’s previous columns are posted at the Independent Gay Forum

Reprinted From: Paul Varnell: "The controversy over poppers"

ARE "POPPERS" SAFE?

2006-04-27T17:09:00.000-07:00

Mariposa Occasional Paper #6

IN A SERIES OF ONGOING PROJECTS FOR EDUCATING THE PUBLIC ABOUT "MAKING SEX SAFE" AND "SENSIBLE SEX."

ARE "POPPERS" SAFE? ...By BRUCE VOELLER, Ph.D.

MAY 1986
Mariposa Education & Research Foundation

When mediocre or even plain bad scientific research is politically exploited by AIDS institutions eager to appear to be earning their keep, or by the media -- ever keen to fan any spark of controversy, or zealots riding their favorite hypothesis saddled up as fact, the public is in danger.

Basing public policy on inadequate science is particularly inappropriate.

All this appears to be fueling the hysteria surrounding the use of volatile nitrites or "poppers", especially the issue of whether "poppers" are a factor in causing AIDS or in suppressing the immune system.

As a scientist current with AIDS research and who has reviewed the extensive literature on nitrite use, I can not assure you that "poppers" are harmless, any more than I can assure you aspirin is; but neither have I found grounds to tell you "poppers" are harmful. I can assure you, however, that the existing scientific studies on this topic do not justify the widespread belief that “poppers" have been shown to help cause AIDS, or cause anything else for that matter. My viewpoint is shared by other preeminent and qualified persons, including the prominent cardiologist John 0. Parker, M.D., and James Mosley, M.D., the University of Southern California Medical School professor who heads the federal government's largest, multi-million dollar program studying the AIDS virus and the nation's blood supply. Each of these physicians has provided public testimony in recent months at governmental hearings considering the banning of “poppers". Each had reviewed the evidence and stated under oath that he regards the claims of danger to be ill founded.

============================================================
"When mediocre or even plain bad scientific research is politically exploited by AIDS institutions eager to appear to be earning their keep, or by the media -- ever keen to fan any spark of controversy, or zealots riding their favorite hypothesis saddled up as fact, the public is in danger."
==================================================================

I can also tell you that the intense campaigns against use of volatile nitrites conducted by Hank Wilson in San Francisco, Neil Schram and his Los Angeles City/County Aids Task Force, and John Lauritsen in New York, are slim in scientific merit.

Space limits for this article do not allow reviewing each of the many published papers on "poppers". However, a critical look at three of the most frequently cited ones may whet your awareness of the need for a more substantial weighing of the evidence than has been provided by the "popper"-ban advocates. A look at these three papers is representative, in my view, of the best of what has been published.

Hersh and Newell and their colleagues(1) at M.D. Anderson Hospital in Houston, studied the effect of butyl nitrite (“poppers") on laboratory (in vitro) cultures of white blood cells --cell types important in the body's immune response to infection.

They reported that many of these cells were killed when left for 24 hours in the presence of one percent added butyl nitrite, whereas at 1/2 that concentration (i.e., 0.5 percent) or less the "cell count and viability were unaffected." [emphasis added] In other words, a small change in concentration dramatically eliminated the toxic effect. They also wrote that at 0.5 percent several of the cells' immunological responses were inhibited. However, again only a generally small inhibition could be detected at slightly lower concentration (0.01 percent).

The authors warned of the need for caution in evaluation of the significance of their results in real life application(2): "The data suggest but do not prove that the agents may be immunosuppressive in vivo [in living animals]." Despite their own sound advice, a paragraph later in their text, they ignore their advice stating: "these in vitro studies strongly suggest that the inhalant nitrites may indeed be dangerous, and their use should be condemned by those physicians who treat patients who use these drugs regularly." [Note that they use the term "condemned”, a judgmental, non-scientific word, rather than one such as it cautioned about."]

============================================================
"In other words, a small change in concentration dramatically eliminated the toxic effect."
==================================================================

Although it is true that instructive information about the effect of use of a drug on people is sometimes gained by in vitro (test tube) studies, more often than not such work proves non relevant. Most people are aware, for instance, of the large numbers of “promising" drugs discovered in the lab and reported in the press but which then prove unworkable when tested on live patients. This drug failure, in moving from the test tube to actual people, is often because very high or very low concentrations of drugs were used in the laboratory phase of the study and have little relevance to "real life" testing.

Clearly a small reduction in nitrite concentration dramatically changed the responses Newell and Hersh found. The question logically follows: how relevant is the use of their concentration of poppers to real life"?

============================================================
"The authors warned of the need for caution in evaluation of the
significance of their results in real life applications"
==================================================================

One estimate is to calculate what Newell's one percent nitrite concentration means for an average adult male with 6 liters of blood for even transiently establishing a one percent blood level, never mind for a 24-hour one. CALCULATION: one percent of 6 liters equals 0.06 liters, or 60 milliliters (ml.) of butyl nitrite. A representative bottle contains 10 to 12 ml. of “poppers"; that is to say, about 5 or 6 bottles of "poppers" would have to be injected into a person's blood to briefly attain a one percent level ... a staggering amount of butyl nitrite!

And that's attained only if all the nitrite gets into the person's blood. Unlike adding butyl nitrite directly into Hersh and Newell's laboratory dish where the "poppers" can saturate the culture medium, only a fraction of the chemical will be absorbed at the lungs through inhalation, the common way poppers are used. As with cigarette smoke, most of what is inhaled is immediately exhaled out of the user, thus, many more bottles of butyl nitrite would be needed to achieve an inhalation level comparable to that in the laboratory study, making the bearing of Newell and Hersh's data still more remote in human relevance.

Also, the authors' laboratory results are based on 24-72 hour continuous exposure to butyl nitrite, a condition utterly without parallel in common human usage, even though some might wish that disco-ing or sex lasted that long.

I think it is instructive to consider all this information with regard to a far less politicized compound, such as aspirin. It would not be surprising to find that common household aspirin, used by generations of average Americans, would have had similar inhibitory laboratory effects if Newell and Hersh had tested one percent levels of it, too. In fact, for a rough and ready comparison, as little as 0.325 grams (gm.) of aspirin taken by some persons can cause changes in blood chemistry leading to bleeding for several days, as well as other effects. 0.3 gm. of aspirin in 6 liters of blood represents a concentration of 0.005 percent, even less than the percentage of butyl nitrite needed for an effect.

To conclude, yes, if enough "poppers" are used an effect can be forced... just as household aspirin can be forced to lethal levels.

In another study, the M.D. Anderson Hospital group(3) injected mice with "Rush", a commercial brand of “poppers", in order to see "real life” effects of nitrites. They inoculated the mice twice, each time with 1/4 ml. of a “poppers" solution of about 5.6 percent nitrite. That calculates to about 0.028 ml. of butyl nitrite per mouse.

How does that compare to a man? The average mouse weights about 80 gm., the average man 80,000 gm.; the weight ratio is about 1000 to 1.

Scaling up the nitrite dose used in the mice to a comparable one for a man, would thus require injecting him twice with 14 ml. of "Rush" -- that is a total of 28 ml., or nearly three bottles of "Rush". Adult humans have died from similar amounts (10 to 30 gm.) of aspirin(4). Such a massive dose of aspirin is highly toxic compared to ordinary usage. With this parallel in mind I fail to see what significance a similarly massive dose of butyl nitrite has for comparison to ordinary “popper" use.

============================================================
“ ... about 5 or 6 bottles of "poppers" would have to be injected into a person's blood to briefly attain a one percent level ... a staggering amount of butyl nitrite!

Also, the authors' laboratory results are based on 24-72 hour continuous exposure to butyl nitrite, a condition utterly without parallel in common human usage, even though some might wish that disco-ing or sex lasted that long."
==================================================================

The third research study is one of rare restraint and high integrity. The study by Haverkos et al.(5) has been widely used by "popper"-ban lobbyists to claim a link between "poppers" and AIDS, even though the authors avoid that link. In fact, they argue that of those persons who have already developed immunodeficiency, those who have a history of using substantial amounts of “poppers" more frequently succumb to Kaposi's sarcoma (KS), whereas those with lower or no nitrite use, succumb to pneumocystis pneumonia (PCP). Ironically, the AIDS patients with KS (higher nitrite use) have a considerably longer life expectancy after diagnosis than do those with PCP (lower use).

However, in comparing a rather small sample of 47 men with KS and 20 with PCP, Haverkos found a long list of other statistically significant differences too: Men with KS were more likely to earn over $20,000 per year (!); to have had hepatitis B; use amphetamines, barbiturates, cocaine, ethyl chloride, LSD, marijuana, methaqualone; had more sexual partners. This is a formidable list of statistically significant differences.

Unable to draw any clear conclusions from these direct correlations, the authors resorted to 'multivariate analysis’, a sophisticated, but treacherous technique. It is especially tricky with small numbers of subjects, as in this study. Indeed, Haverkos and his associates themselves state that multivariate analysis only “suggests the relative importance of differences." [emphasis added]

Haverkos et al. cautiously report "Total days of nitrite use more significantly differentiated between the disease groups than any other variable," and "interpreting the results of these analyses requires caution. The numbers of patients enrolled are small," and as the final statement in the 'discussion' section of their paper: "The association of KS with nitrites in this study may only represent correlation. In other words, nitrites may be merely a marker for other behaviors or exposures associated with their use."

Indeed, other published multivariate studies do not confirm Haverkos et al. As the authors forthrightly and candidly admit, Marmor et al.(6) initially reported a KS-“poppers" link, "However, they [Marmor et al.] reanalyzed their data, entering additional factors, and found that still other variables appear to
differentiate KS patients from controls by multivariate analysis," and Jaffe et al., at the Centers for Disease Control.(7) also reported using multivariate analysis and found that nitrite use was NOT significant.

============================================================
"In short, the much vaunted body of research supposedly demonstrating a link between "poppers" and AIDS does not withstand close scrutiny. If a link exists it still remains to be proven."
==================================================================

Elsewhere, in the lead chapter of one of the finest new AIDS research and therapy books(8), J.J. Goedert and W.A. Blattner at the National Cancer Institute draw a very interesting conclusion from their research and that of others. While noting that in one study, "helper T-cell counts were slightly lower with frequent nitrite inhalant use; this suggests the possibility that nitrite use may be a co-factor" for AIDS or for KS, "Neither of these possibilities has been completely evaluated," and, "However, it now appears that frequent use of nitrite inhalants simply may be a surrogate marker of frequent receptive anal intercourse. This sexual activity was associated very clearly with Kaposi's sarcoma in a case-control study of homosexual men and with HTLV-III seropositivity in the cohort studies of homosexual
men in Denmark and New York City, even after statistically adjusting for the number of homosexual partners and the frequencies of nitrite inhalant use and seven other sexual practices.”

In short, the much vaunted body of research supposedly demonstrating a link between “poppers” and AIDS does not withstand close scrutiny. If a link exists it still remains to be proven.

============================================================
“…it now appears that frequent use of nitrite inhalants simply may be a surrogate marker of frequent receptive anal intercourse.”
J.J. Goedert, M.D.
W. A. Blattner, M.D.
National Cancer Institute, NIH
==================================================================

IN analyses of diverse other published works, Goedert et al., Jacobs et al., Gerblish et al., Mathur-Wage et al., and unpublished work by Gangadharam et al., for example, fare even less well than those I have addressed here.

Do I advocate “popper” use? No. Am I paid by the “popper” industry? No. Why do I press the issue?

1) Because I think some of us have to tell the truth with as much objectivity as possible – some of us with the scientific research training to evaluate the data at more than its face value (thus, leaving out most physicians and nearly all journalists and advocate-lobbyists).

2) I feel that the liberties with fact taken by some who act as medical spokespeople in the AIDS crisis can only serve to undermine public trust in the scientific process.

3) I fear the damage which will be done if people are boldly told, as they have been, that “poppers” are ‘the drug linked with AIDS.’ Too many will give up “poppers”, but continue with (or move on to) cocaine, heroin, crystal meth, and other amphetamines, etc. These are drugs more likely in my view to be among the AIDS-cofactors.

In the New York Native(9) a Gay doctor in San Francisco was quoted as saying, “Unfortunately, most of my patients and friends appear to be engaged in an elaborate ritual of denial that there is even a problem here. They make some token sacrifice, such as giving up a drug or sexual practice that they never really liked anyway, and they convince themselves that this sacrifice will get them through the Lenten period for another 40 days or so until the AIDS problem is solved.”

I’m fearful that illegalizing “poppers”, coupled with the media blitz which already exists, makes “poppers” the “token sacrifice”, and “legitimizes” clearly dangerous drugs.

4) I’ve seen gas chromatographic profiles of the purity of street “poppers” and of the largest ‘legitimate’ manufacturer’s. The latter is pure, while the street form is like bathtub gin. Illegalizing “poppers” will knock out the pure forms and make dirty street “poppers” the standard item.

5) We either need to put the issue of “poppers” behind us, or make a valid case against them through better science, so that we can turn our attention to other drugs and other and other cofactors. We’ve been too preoccupied with “poppers” to the exclusion of everything else. By continuing up a wrong path, we lose time finding the right one.

On the AIDS clock, time is measured in deaths.

1 1983 Cancer Research 43; 1365
2 ibid pg. 1371
3 1984 Lotzova, Hersh et al., Cancer Iaununol. Itnmunother. 17; 130-134
4 1985 'Goodman and Gillman', THE PHARMACOLOGICAL BASIS OF TYIERAPEUTICS, 7th ed.
5 1985 Sexually Transm. Dis. 12(4:203-220)
6 1982 Lancet, 1:1083-7
7 1983 Ann. Int Med. 99:145-151
8 Goedert, JJ. and Blattner, W.A. The epidemiology of AIDS and related conditions. IN: AIDS: ETIOLOGY, DIAGNOSIS, TREATMENT, AND PREVENTION. eds.: DeVita, V.T., Hellman, S. and Rosenberg, S.A. 1985 J.B. Lippincott Company. New York
9 No. 102, p. 16

This reprint is provided by the Mariposa Education & Research Foundation as a public service and is #6 in a continuing series on “Making Sex Safe”.
©1986 Bruce Voeller, Ph.D./Mariposa Education & Research Foundation

Much of Dr. Voeller's life work has been archieved for future generations of researhers in the "Human Sexuality Collection" of the 'Rare & Manuscript Collections' at Cornell University Library.

Reprinted From: Mariposa Occasional Paper #6
IN A SERIES OF ONGOING PROJECTS FOR EDUCATING THE PUBLIC ABOUT "MAKING SEX SAFE" AND "SENSIBLE SEX."

Poppers and AIDS: The Story Behind A Prominent AIDS Researcher's Disgust With the Anti-Poppers Campaign

2006-04-27T17:04:00.000-07:00

“We either need to put the issue of ‘poppers’ behind us, or make a valid case against them through better science..."

Charles Stephens MD, Ph.D

The degree of potential hazards associated with widespread misuse of nitrite odorants as poppers has been a contentious issue, most notably since the early 1970's, when their use as the primary ingredient in nitrite-based room odorants began.

Initial concerns centered around general issues of safety, while later concerns, raised immediately after the discovery of AIDS in 1981, centered around whether inhalation of nitrites contributed in any way to AIDS or any of its associated diseases, in particular, a possible link between nitrites and Kaposi's sarcoma – which to this day is still hotly debated.

Prior to 1969 the alkyl nitrites, specifically amyl nitrite, had been used in medicine for the relief of angina pectoris since 1867. In September 1960 the United States Food and Drug Administration (FDA) eliminated the prescription requirement for amyl nitrite because amyl nitrite was considered so harmless it was safe for over-the-counter sales.

But, by the mid-1970's, following an upsurge in the then-unregulated sale of nitrite room odorant products, news mentions about poppers, which typically centered around their use for alleged pleasurable sensations (particularly as aphrodisiacs), began to appear in print and on television, most often questioning their safety. In an October 1977 Wall Street Journal front page article on the poppers industry, Los Angeles bureau chief, Steven Sansweet, wrote that poppers were "a new way to giggle and glow". Several months later, in July 1978, a TIME MAGAZINE feature on poppers suggested that the industry had become a $50 million per-year business.

The controversy accelerated in May, 1977 when the State of Connecticut proposed to ban their sale. The State claimed that there existed a reasonable probability of substantial personal injury resulting from the misuse of these products. The State's concern was the direct concentrated inhalation of these products for the purpose of obtaining a physiological effect.

Based on these concerns, and the then-limited amount of current, consolidated information available, in 1977 a research program was initiated by a group of Canadian and U.S. researchers and medical doctors, some with extensive expertise in the area of the alkyl nitrites. The report remains today as the most authoritative source of credible information on these compounds.

At the onset, objectives were defined and a survey of pertinent literature was conducted. United States Government agencies and private companies with relevant information were questioned. When available data were doubtful or insufficient, a series of research projects was conducted under appropriate auspices.

The research group included Professor Mark Nickerson* of McGill University, in Montreal, Canada. Professor Nickerson was the retired Chairman of the McGill Department of Pharmacology and Therapeutics. In 1977 Dr. Nickerson had, for nearly forty years, been the author of the Nitrite Vasodilator chapter of Goodman & Gillman's standard textbook of pharmacology (The 'Bible" most doctors refer to when treating their patients with drugs). Professor Nickerson has been called "...perhaps the most eminent pharmacologist of the twentieth century". Professor John Parker**, of Queen's University, had at the time been Chairman of the Division of Cardiology for nearly a decade. Nitrite vasodilators, including amyl, butyl, and isobutyl nitrite, had long been a subject of his special study. Dr. Parker is recognized as the world’s leading expert on nitrates and nitrate tolerance. He has published several articles in the New England Journal of Medicine, the Journal of the American College of Cardiology, the American Journal of Cardiology, Circulation, and many other major journals. Professor Thomas Lowry was a psychiatrist who had done extensive research into drugs and sexual behavior. Professor Edward Swenson was a specialist in pulmonary disease who had written more than 80 publications on the subject.

The researchers obtained a great deal of statistical data from epidemiological records which were maintained by agencies of the United States Federal Government, and from the records of Burroughs Wellcome Company and Eli Lilly and Company, both of which in 1977 were the world's largest producers of alkyl nitrites for medicinal use. The research group also obtained much confidential information concerning RUSH® and other similar products, from the files of Pacific Western Distributing Corporation of San Francisco, then the world's largest producer of nitrite-based room odorants.

The research project took nearly two years to accomplish, and resulted in a report consolidating, clarifying, and expanding the pharmacological, toxicological and sociological data regarding these nitrites. (ISOBUTYL NITRITE and Related Compounds, by Mark Nickerson, John O. Parker, Thomas P. Lowry and Edward W. Swenson, ©1979 by Pharmex, Ltd. All rights reserved)

Writing in the "Summary and Conclusions" chapter of their 103-page report, the authors noted that, by 1979, the volatile nitrites had been in use for more than a century. During this entire period of time, their medical use was predominantly in patients with coronary disease. Even in this high-risk group, strict control of frequency of administration was considered unnecessary.

In 1979, reports of the non-medical use of the volatile nitrites dated back nearly fifty years, and during the pervious twenty years, there had been increasing and widespread uncontrolled use of these compounds.

"The nitrites exert short-lived physiological effects, due primarily to their relaxing effect on smooth muscle. The consequent dilating effect on vascular tissue may lead to a transient reduction in blood pressure and increase in heart rate. The unwanted effects of these agents are associated with the vascular effects, but despite the ready availability of the nitrites and their widespread distribution and use, there have been no substantiated reports of serious injury or death secondary to this uncontrolled use. There is no established relationship between the pharmacology or toxicology of the inhalation of the alkyl nitrites and the inhalation of nitrous oxide, or to the suggested carcinogenesis related to the ingestion of inorganic nitrites in foods.

Despite the substantial and increasing uncontrolled sale and use of pharmaceutical amyl nitrite during the decade of the 1960's, no manufacturers received reports of injuries. Based on statistics reported by the United States Government-managed Drug Abuse Warning Network (DAWN) project, during the five-year period ending June 30, 1978, more than 18,036 persons were admitted to hospitals and more than 933 died from "drug abuse" directly attributed to specific prescription drugs. Of these, three admissions and no deaths were attributed to amyl nitrite. During the same period, more than 23,666 persons were admitted to hospitals and 3,754 died from "drug abuse" directly attributed to specific non-prescription drugs ranging from glues and housekeeping aids, to aerosol deodorants. Despite sales estimated at over 12,000,000 bottles during this period, no one was reported injured and no fatalities were reported from consumer products (scents, odorizers) containing butyl or isobutyl nitrite.

During the same 1973-78 period, the National Electronic Injury Surveillance System (NEISS) managed by the United States Consumer Products Safety Commission, estimated that out of 44,658,823 injuries attributable to consumer products, 698,554 injuries were caused by "Home and Family Maintenance Products". In this group, which includes household odorizers and deodorizers, there were estimated to have been 6,627 injuries from chemical deodorizers, and none from odorizers or scents including those containing butyl or isobutyl nitrite.

Amyl nitrite is among the safest medications known to man. The pharmacology and toxicology of the other volatile nitrites, including butyl and isobutyl nitrite, which are in use in consumer or household products, is almost identical. Further Regulation or control would be unnecessary for the protection of the public health. Based on the data, it is difficult to envision any product with a better record of public safety.

The researchers ended the "Summary and Conclusions" chapter of their report by stating: “A definition of safety as being totally free of toxicity has no meaning in toxicology, as all substances are toxic at some level of use. No important acute or chronic toxic effects have been demonstrated with the volatile nitrites, and their use in an uncontrolled and unregulated fashion has proven to be safe."

Also in1979, independent of and entirely unknown to the Isobutyl Nitrite and Related Compounds research project, a report on isobutyl nitrite was presented to Canada’s Product Safety Branch, Consumer and Corporate Affairs agency. In his July 30,1979 cover letter to the Canadian Government, Radhey L. Singhal, Ph.D., the Professor and Chairmen Department of Pharmacology, University of Ottawa said: “As stated in our report, we have concluded that occasional inhalation of isobutyl nitrite for its ‘inebriant’ effect in a recreational context is unlikely to pose a health hazard.”

Two years later, on January 30, 1981, Ray Hamilton, Director of Recall and Litigation, Bureau of Drugs, Food and Drug Administration (FDA), in an official FDA statement clarifying the agency’s feelings on the subject of butyl nitrite, said: “The FDA does not plan to devote resources to a project involving room odorizers containing alkyl nitrites because of the absence of demonstrable hazard.”

Later that same year, on September 9, 1981, following a lengthy investigation, the United States Consumer Product Safety Commission (CPSC) voted unanimously against controlling alkyl nitrites. The Commission found insufficient evidence to support the allegation of behavior disorder associated with alkyl nitrite inhalation. It also found that injury data did not indicate a significant risk of personal injury or illness.

By 1981 the controversy over the potential dangers of poppers seemed to have been settled. Consumer odorizer products containing alkyl nitrites had built a significant record of public safety, a record that was recognized by researchers and government agencies alike.

==The Battle Over the AIDS Connection==

However, and also in 1981, the beginning of the AIDS crisis fueled an hysteria about poppers, around the issue of whether poppers were a factor in causing AIDS or any of it’s opportunistic infections – particularly Kaposi's sarcoma. As a result, during the ten years between 1981 and 1991, a small band of poppers/AIDS-connection proponents waged an intensive war against poppers which ultimately resulted in the United States Congress banning the sale of alkyl nitrite poppers in the U.S. in 1991.

But, was banning nitrite odorants (poppers) justified? Some still believe it was, but there’s a growing consensus that the early concerns over whether poppers caused AIDS or any of its opportunistic infections, including KS, were politically exploited by those ever keen to fan any spark of controversy, or anti-popper zealots riding their favorite hypothesis saddled up as fact.

By 1986 the poppers/AIDS/KS connection had been essentially discounted by most every credible AIDS researcher in the world. However, on the periphery of the AIDS research community, a handful of researchers would continue to write grants to get funding for their never-ending efforts to blame poppers for AIDS and a host of other ills. Seemingly spurred on by anti-popper zealots with a potentially vested interests in an ongoing campaign against poppers, these ‘studies’ would be mostly small scale, non-peer reviewed, never replicated and would provide conflicting results essentially canceling themselves out. But they conveniently served to provide the underpinning of a relentless anti-popper campaign that would push on through the next decade, and beyond. A campaign many would come to view as being based on misinformation and disinformation.

That same year, no less an expert on AIDS than researcher Bruce Voeller, Ph.D., the man who gave AIDS its name, publicly revealed his disgust with the anti-poppers campaign.

As President of the Mariposa Education & Research Foundation, headquartered in Los Angeles, Dr. Voeller addressed the poppers/AIDS controversy in the now famous “Mariposa Occasional Paper #6”, dated May 1986. Titled “Are Poppers Safe?”, the Mariposa document explored the controversy that had been raging over the prior five years, and laid bare the faults inherent in the anti-popper campaign, while explaining the potential dangers in continuing the campaign.

Writing in “Mariposa Occasional Paper #6”, Dr. Voeller said that “when mediocre or even plain bad scientific research is politically exploited by AIDS institutions eager to appear to be earning their keep, or by the media -- ever keen to fan any spark of controversy, or zealots riding their favorite hypothesis saddled up as fact, the public is in danger."

Basing public policy on inadequate science is particularly inappropriate.

All this appears to be fueling the hysteria surrounding the use of volatile nitrites or "poppers", especially the issue whether "poppers" are a factor in causing AIDS or in suppressing the immune system.

As a scientist current with AIDS research and who has reviewed the extensive literature on nitrite use I can not assure you that "poppers" are harmless, any more than I can assure you aspirin is; but, neither have I found grounds to tell you "poppers" are harmful.

I can assure you, however, that the existing scientific studies on this topic do not justify the widespread belief that “poppers" have been shown to help cause AIDS, or cause anything else for that matter. My viewpoint is shared by other qualified persons, including prominent cardiologist John 0. Parker, M.D., as well as James Mosley, M.D., the University of Southern California Medical School professor who heads the federal government's largest, multi-million dollar program studying the AIDS virus and the nation's blood supply. Each of these physicians has provided public testimony in recent months at governmental hearings considering the banning of “poppers". Each had reviewed the evidence and stated under oath that they regard the claims of danger to be ill founded.

I can also tell you that the intense campaigns against the use of volatile nitrites conducted by Hank Wilson in San Francisco and John Lauritsen in New York, are slim in scientific merit.

Space limits for this article do not allow reviewing each of the many published papers on poppers. However, a critical look at three of the most frequently cited ones may whet your awareness of the need for a more substantial weighing of the evidence than has been provided by the "popper"-ban advocates. A look at these three papers is representative, in my view, of the best of what has been published.

Hersh and Newell and their colleagues(1) at M.D. Anderson Hospital in Houston, studied the effect of butyl nitrite (“poppers") on laboratory (in vitro) cultures of white blood cells--cell types important in the body's immune response to infection.

They reported that many of these cells were killed when left for 24 hours in the presence of one percent added butyl nitrite, whereas at 1/2 that concentration (i.e., 0.5 percent) or less the "cell count and viability were unaffected." [emphasis added] In other words, a small change in concentration dramatically eliminated the toxic effect. They also wrote that at 0.5 percent several of the cells' immunological responses were inhibited. However, again only a generally small inhibition could be detected at slightly lower concentration (0.01 percent).

The authors warned of the need for caution in evaluation of the significance of their results in real life applications(2): "The data suggest but do not prove that the agents may be immunosuppressive in vivo [in living animals]." Despite their own sound advice, a paragraph later in their text, they ignore their advice stating: "these in vitro studies strongly suggest that the inhalant nitrites may indeed be dangerous, and their use should be condemned by those physicians who treat patients who use these drugs regularly." [Note that they use the term "condemned”, a judgmental, non-scientific word, rather than one such as “cautioned about."]

Although it is true that instructive information about the effect of use of a drug on people is sometimes gained by in vitro (test tube) studies, more often than not such work proves non relevant. Most people are aware, for instance, of the large numbers of “promising" drugs discovered in the lab and reported in the press but which then prove unworkable when tested on live patients. This drug failure, in moving from the test tube to actual people, is often because very high or very low concentrations of drugs were used in the laboratory phase of the study and have little relevance to "real life" testing.

Clearly a small reduction in nitrite concentration dramatically changed the responses Newell and Hersh found. The question logically follows: how relevant is the use of their concentration of poppers to real life"?

One estimate is to calculate what Newell's one percent nitrite concentration means for an average adult male with 6 liters of blood for even transiently establishing a one percent blood level, never mind for a 24-hour one. CALCULATION: one percent of 6 liters equals 0.06 liters, or 60 milliliters (ml.) of butyl nitrite. A representative bottle contains 10 to 12 ml. of “poppers"; that is to say, about 5 or 6 bottles of "poppers" would have to be injected into a person's blood to briefly attain a one percent level ... a staggering amount of butyl nitrite!

And that's attained only if all the nitrite gets into the person's blood. Unlike adding butyl nitrite directly into Hersh and Newell's laboratory dish where the "poppers" can saturate the culture medium, only a fraction of the chemical will be absorbed at the lungs through inhalation, the common way poppers are used. As with cigarette smoke, most of what is inhaled is immediately exhaled out of the user, thus, many more bottles of butyl nitrite would be needed to achieve an inhalation level comparable to that in the laboratory study, making the bearing of Newell and Hersh's data still more remote in human relevance.

Also, the authors' laboratory results are based on 24-72 hour continuous exposure to butyl nitrite, a condition utterly without parallel in common human usage, even though some might wish that disco-ing or sex lasted that long.

I think it is instructive to consider all this information with regard to a far less politicized compound, such as aspirin. It would not be surprising to find that common household aspirin, used by generations of average Americans, would have had similar inhibitory laboratory effects if Newell and Hersh had tested one percent levels of it, too. In fact, for a rough and ready comparison, as little as 0.325 grams (gm.) of aspirin taken by some persons can cause changes in blood chemistry leading to bleeding for several days, as well as other effects. 0.3 gm. of aspirin in 6 liters of blood represents a concentration of 0.005 percent, even less than the percentage of butyl nitrite needed for an effect.
To conclude, yes, if enough "poppers" are used an effect can be forced...just as household aspirin can be forced to lethal levels.

In another study, the M.D. Anderson Hospital group(3) injected mice with "RUSH®", a commercial brand of “poppers", in order to see "real life” effects of nitrites. They inoculated the mice twice, each time with 1/4 ml. of a “poppers" solution of about 5.6 percent nitrite. That calculates to about 0.028 ml. of butyl nitrite per mouse.

How does that compare to a man? The average mouse weights about 80 gm., the average man 80,000 gm.; the weight ratio is about 1000 to 1.

Scaling up the nitrite dose used in the mice to a comparable one for a man, would thus require injecting him twice with 14 ml. of "RUSH®” -- that is a total of 28 ml., or nearly three bottles of "RUSH®". Adult humans have died from similar amounts (10 to 30 gm.) of aspirin(4). Such a massive dose of aspirin is highly toxic compared to ordinary usage. With this parallel in mind I fail to see what significance a similarly massive dose of butyl nitrite has for comparison to ordinary “popper" use.

The third research study is one of rare restraint and high integrity. The study by Haverkos et al.(5) has been widely used by "popper"-ban lobbyists to claim a link between "poppers" and AIDS, even though the authors avoid that link. In fact, they argue that of those persons who have already developed immunodeficiency, those who
have a history of using substantial amounts of “poppers", more frequently succumb to Kaposi's sarcoma (KS), whereas those with lower or no nitrite use, succumb to pneumocystis pneumonia (PCP). Ironically, the AIDS patients with KS (higher nitrite use) have a considerably longer life expectancy after diagnosis than do those with PCP (lower use).

However, in comparing a rather small sample of 47 men with KS and 20 with PCP, Haverkos found a long list of other statistically significant differences too: Men with KS were more likely to earn over $20,000 per year (!); to have had hepatitis B; use amphetamines, barbiturates, cocaine, ethyl chloride, LSD, marijuana, methaqualone; had more sexual partners. This is a formidable list of statistically significant differences.

Unable to draw any clear conclusions from these direct correlations, the authors resorted to 'multivariate analysis’, a sophisticated, but treacherous technique. It is especially tricky with small numbers of subjects, as in this study. Indeed, Haverkos and his associates themselves state that multivariate analysis only “suggests the relative importance of differences." [emphasis added]

Haverkos et al. cautiously report, "Total days of nitrite use more significantly differentiated between the disease groups than any other variable," and "interpreting the results of these analyses requires caution. The numbers of patients enrolled are small," and as the final statement in the 'discussion' section of their paper: "The association of KS with nitrites in this study may only represent correlation. In other words, nitrites may be merely a marker for other behaviors or exposures associated with their use,"

Indeed, other published multivariate studies do not confirm Haverkos et al. As the authors forthrightly and candidly admit, Marmor et al.(6) initially reported a KS-“poppers" link, "However, they [Marmor et al.] reanalyzed their data, entering additional factors, and found that still other variables appear to differentiate KS patients from controls by multivariate analysis," and Jaffe et al., at the Centers for Disease Control.(7) also reported using multivariate analysis and found that nitrite use was not significant.

Elsewhere, in the lead chapter of one of the finest new AIDS research and therapy books(8), J.J. Goedert and W.A. Blattner at the National Cancer Institute draw a very interesting conclusion from their research and that of others. While noting that in one study, "helper T-cell counts were slightly lower with frequent nitrite inhalant use; this suggests the possibility that nitrite use may be a co-factor" for AIDS or for KS, "Neither of these possibilities has been completely evaluated," and, "However, it now appears that frequent use of nitrite inhalants simply may be a surrogate marker of frequent receptive anal intercourse. This sexual activity was associated very clearly with Kaposi's sarcoma in a case-control study of homosexual men and with HTLV-III seropositivity in the cohort studies of homosexual
men in Denmark and New York City, even after statistically adjusting for the number of homosexual partners and the frequencies of nitrite inhalant use and seven other sexual practices.”

In short, the much vaunted body of research supposedly demonstrating a link between “poppers” and AIDS does not withstand close scrutiny. If a link exists it still remains to be proven.”

Dr. Voeller’s expert analysis of diverse other published and unpublished works on the issue of “poppers” and AIDS (Goedert et al., Jacobs et al., Gerblish et al., Mathur-Wage et al., and Gangadharam et al.), showed that those studies fared even less well then those he’d addressed here.

Voeller went on to say that “some of us have to tell the truth with as much objectivity as possible – some of us with the scientific research-training to evaluate the data at more than its face value”; thus leaving out, he said, “most physicians and nearly all journalists and advocate-lobbyists (such as Hank Wilson, a switchboard operator, and John Lauritsen, a poet and gay journalist, both of whom were the most vocal anti-popper proponents). He felt that “the liberties with fact taken by some who act as medical spokespeople in the AIDS crisis can only serve to undermine public trust in the scientific process.”

In the same 1996 Occasional Paper #6, Dr. Voeller made what would become a prophetic comment when he said he feared “the damage which will be done if people are boldly told, as they have been, that ‘poppers’ are ‘the drug linked with AIDS’. Too many will give up ‘poppers’ but continue with or move on to cocaine, heroin, or crystal meth. These are drugs more likely in my view to be among the AIDS-cofactors.” Twenty years later, Voeller’s fears about an upsurge in the gay community of the use of crystal meth have been borne out; the use of crystal meth has fueled a wave of new HIV/AIDS infection throughout the gay community for the past several years.

He went on to say that he was also fearful that illegalizing “poppers”, coupled with the media blitz which existed at the time, would make “poppers” the “token sacrafice”, and “legitimize” clearly dangerous drugs. Voller indicated that he’d seen gas chromatographic profiles of the purity of street “poppers”, and of the largest legitimate manufacturer’s. The latter, he said, were pure, while the street forms were like “bathtub gin”. “Illegalizing ‘poppers’”, he said, “will knock out the pure forms and make dirty street ‘poppers’ the standard item.” Since the ban on poppers in 1991, unscrupulous parties have been producing impure and potentially dangerous counterfeit copies of the major brands, including RUSH® and HARDWARE®, along with several other leading brands. (Which are still legally sold internationally, and available on the Internet)

The man who gave AIDS its name ended his comments by saying that “We either need to put the issue of ‘poppers’ behind us, or make a valid case against them through better science, so that we can turn our attention to other drugs and other potential cofactors. We’ve been too preoccupied with ‘poppers’ to the exclusion of everything else. By continuing up a wrong path, we lose time finding the right one.”

“On the AIDS clock”, he said, “time is measured in deaths.”

******************************************************
References:
(1) 1983 Cancer Research 43; 1365
(2) ibid pg. 1371
(3) 1984 Lotzova, Hersh et al., Cancer Immunol. Immunother. 17; 130-134
(4) 1985 ‘Goodman and Gilllman’, THE PHARMACOLOGICAL BASIS OF THERAPEUTICS, 7th ed.
(5) 1985 Sexually Transm. Dis. 12(4:203-220)
(6) 1982 Lancet, 1:1083-7
(7) 1983 Ann. Int. Med. 99:145-151
(8) Goedert, J.J. and Blattner, W. A. The epidemiology of AIDS and related conditions. IN: AIDS: ETIOLOGY, DIAGNOSIS, TREATMENT, AND PREVENTION. Eds.: DeVita, V.T., Hellman, S. and Rosenbert, S.A. 1985 J. B. Lippincott Company. New York

* Mark Nickerson, perhaps the most eminent pharmacologist of the twentieth century, was a Professor of Pharmacology and Therapeutics at McGill University. He joined the faculty at McGill in 1967, where he chaired his department from 1967 to 1975. He also held academic positions at the University of Manitoba, the University of Michigan, and the University of Utah. Professor Nickerson died on March 12, 1998, in Ottawa, Canada where he had moved after his retirement.

** John O. Parker, MD is Director of the Cardiovascular Laboratory at Kingston General Hospital, and Professor of Medicine at Queen’s University in Kingston, Ontario, where he also received his medical degree. Dr. Parker is recognized as the world’s leading expert on nitrates and nitrate tolerance. He has published several articles in the New England Journal of Medicine, the Journal of the American College of Cardiology, the American Journal of Cardiology, Circulation, and many other major journals.

Bruce Voeller, Ph.D. was a biologist, researcher, and founder of the Mariposa Education and Research Foundation. Voeller was perhaps best known for coining the acronym AIDS for "acquired immune deficiency syndrome," a term he used in objection to the disease's earlier label, GRID, or "gay-related immune disorder." From 1961 to 1972, he held various positions on the faculty of Rockefeller University. A prominent gay rights activist, Voeller helped found the National Gay Task Force (NGTF) in 1973 and with Jean O'Leary, served as first co-directors. He also served as President of the Gay Activists Alliance in New York City. In 1980, Voeller established the Mariposa Foundation based in Topanga, California to conduct human sexuality research, placing special emphasis on reducing the risks of sexually transmitted diseases. Voeller's research with the Mariposa Foundation centered on the reliability of various brands of condoms in preventing the spread of diseases. A result of this research was a study funded in part by the American Foundation for AIDS Research (AMFAR) and the National Institutes of Health (NIH), that ranked 31 brands of condoms under various conditions. Voeller also conductrf viral leakage studies for the then recently approved "female" condom.

Charles Stephens M.D., Ph.D., has been involved in the study of the molecular basis of immune recognition for over twenty years. He currently resides in the Republic of South Africa. The evolution of the AIDS pandemic has been of special interest to him for many years, including the areas of Kaposi's sarcoma, and the possible association of drug abuse with AIDS.

Reprinted From: Poppers and AIDS: The Story Behind A Prominent AIDS Researcher's Disgust With the Anti-Poppers Campaign

Alkyl Nitrites study

2006-04-27T16:57:00.000-07:00

Alkyl Nitrites study

The following is reprinted from the "REPORT of the Committee on Labor and Human Resources", The Hon. Edward M. Kennedy, Chairman U.S. Senate Washington, D.C. May 4,1988: REPORT of the Committee on Labor and Human Resources, The Hon. Edward M. Kennedy, Chairman U.S. Senate Washington, D.C. May 4,1988
Page -67-

Alkyl Nitrites study -- As part of the Anti-Drug Abuse Act of 1986

(Section 4015), Congress requested that NIDA, through HHS, conduct a study of alkyl nitrites to determine the extent and public risk associated with alkyl nitrite use. For this study, NIDA analyzed data from three ongoing nationwide substance abuse surveys to ascertain trends in alkyl nitrite abuse in the general population and in specific sub-populations. In addition, NIDA conducted a technical review workshop on March 31, 1987 with leading authorities in the area of the alkyl nitrites. The study reviewed such topics as the extent of nitrite inhalant use among adolescents, homosexual men, and intravenous drug abusers; the results of acute toxicity studies in animals; and a review of the epidemiological associations of nitrites with Kaposi's sarcoma in AIDS. Based on the surveys and the workshop, the HHS Report to Congress concluded that nitrites are not a causal factor in AIDS infection. There was consideration during the workshop whether use of large amounts of nitrite inhalants might be a co-factor in Kaposi's sarcoma, but the Report stated that medical studies failed to confirm any such association. The Report also found that there was a 21% decrease in use by high school students in 1985-1986. Because of the lack of significant health risks
associated with nitrite use, and the fact that less than 3% of the population has ever used it, the HHS Report suggested no Federal legislation and recommended that alkyl nitrites not be treated as drugs. Based on these recommendations, the Committee concludes that no further Federal action as to alkyl nitrites is warranted. However, in view of the Report's finding of somewhat increased use by high school students, the Committee recommends that the States consider prohibiting access by minors to alkyl nitrite products.

Reprinted From: Alkyl Nitrites study: The following is reprinted from the "REPORT of the Committee on Labor and Human Resources", The Hon. Edward M. Kennedy, Chairman U.S. Senate Washington, D.C. May 4,1988

"With respect to the issue of the safety of these products, as a member of Congress I was often called upon to vote on ..."

2006-04-27T16:54:00.000-07:00

Robert Bauman

"...every U.S. government study, including those done by the U.S. Senate and the U.S. Consumer Product Safety Commission, (on which my former wife served for six years), have come to virtually the same conclusion."
"With respect to the issue of the safety of these products, as a member of Congress I was often called upon to vote on issues which turned on scientific evidence."

I write this after learning from friends that a debate over the possible health hazards of “poppers” is still going on. I hadn’t considered “poppers” for years, until my friends – remembering my early involvement in the government’s investigation into the “poppers” industry -- reminded me about them, and directed me to the “Poppers Myth” website today.

Very early during the eight years I was honored to serve as a member of the United States Congress from Maryland, I learned that a member, however fierce the disagreement, must never impugn the motives of another member during debate. To do so is to risk immediate censure from the presiding officer, a command to apologize and withdraw the offending words, and possible silencing and expulsion from debate for the rest of the day.

Similar rules apply in private life, and I chose not to personally attack those who are obviously perpetrating falsehoods on the internet about “poppers” – for what may be personal reasons, or to advance some personal agenda.

The "issue" of nitrite room odorants, or “poppers”, a product many people have safely used to augment sexual pleasure in America, and around the world, for many decades, is a long misunderstood, but easily understood phenomenon. There are those who have taken upon themselves the multiple and contradictory roles of research scientist, expert witness, judge and jury -- all with a pre-determined verdict of guilt about the safety of “poppers”.

With respect to the issue of the safety of these products, as a member of Congress I was often called upon to vote on issues which turned on scientific evidence. Many of my decisions directly affected the people I represented, so I never took my scientific inquiry lightly. Because of the brief scare in the early 1980's, alleging "poppers" were somehow the cause of AIDS (or GRID as it was then called), I looked into the possible danger of misuse of these products as inhalants. I came away satisfied that not only was this not the cause of AIDS, but that such use in moderation, absent any proof of specific harm to individual users, was a matter of personal choice which government had no right to dictate or infringe. In the nearly 25 years since, I have seen no proof of harm from these products when used in moderation -- including AIDS or any of it's opportunistic infections. On the contrary, every U.S. government study, including those done by the U.S. Senate and the U.S. Consumer Product Safety Commission, (on which my former wife served for six years), have come to virtually the same conclusion.

But then I am a gay libertarian conservative (and a Republican) who believes in an absolute minimum of government control and interference in our lives and liberty.

It seems to me that the charges made by the anti-popper zealots are, at the charitable least, based on what ABC television reporter John Stossel has called "junk science." In a timely, special one-hour ABC show a few years ago, and in an Op-ed column in The Wall Street Journal, Stossel described his 20-year conversion from a scare-a-day "consumer affairs" reporter, to an intelligent skeptic appalled at the cavalier, even dangerous way in which politicians, the news media and irresponsible individuals use "junk science" to advance their own personal agendas.

Stossel eloquently summed up the problem suffered by charlatans like the anti-popper zealots this way: "Too often, we seize the first plausible explanation that appears to cut through the confusion of life. Once we have formed a belief, we're inclined to dismiss contrary evidence. We like to tell ourselves that we are superior to the people who burned witches centuries ago. People were often killed for no better reason than a neighbor experiencing crop failure or impotence. But we're still prone to the same basic mental errors that killed 'witches': seeing patterns where there are none, finding causes where there is only coincidence, and turning scanty evidence into wide spread panic."

Which brings me back to my starting point: motives.

The late American financier, J.P. Morgan, drawing on his historic business acumen, once said: "A man always has two reasons for doing anything - a 'good reason' and the 'real reason."

Think about that common sense wisdom as it applies to the “poppers” debate. What is the ‘real reason’ the anti-popper zealots continue their relentless barrage? Perhaps some day they may achieve some measure of peace, and accept the common understanding that “poppers” are not inherently harmful.

Robert Bauman

Reprinted From: Robert Bauman "...every U.S. government study, including those done by the U.S. Senate and the U.S. Consumer Product Safety Commission, (on which my former wife served for six years), have come to virtually the same conclusion."

"The inhalable nitrites may be the nearest thing to a true aphrodisiac."

2006-04-27T16:51:00.000-07:00

Thomas P. Lowry, M.D.

Journal of Psychoactive Drugs; Jan-Jun, 1982; Vol. 14(2): 77-79
T.P. Lowry, M.D., Chief, Department of Psychiatry,
Kaiser Foundation Rehabilitation Center,
975 Sereno Drive, Vallejo, CA 94590

The inhalable nitrites may be the nearest thing to a true aphrodisiac. Approximately 250 million recreational doses are consumed yearly in the United States. Six aspects of these remarkable substances will be considered: chemistry, availability, mode of action, social uses, toxicology and legal trends.

The volatile nitrites are yellowish flammable liquids with an odor variously described as fruity or like old gym socks. They are unstable and decompose when exposed to light, heat and oxygen. There are two available forms: amyl nitrite, a prescription item used in cardiology for over a century in conditions such as angina pectoris; and butyl nitrite, which is marketed as a "room odorizer," under a variety of trade names such as Quicksilver and Hardware. There are more than a dozen other trade names commonly found, including Rush, Bolt, Locker Room, Bullet, Aroma of Men, Dr. Bananas, Cum, and Heart-On. The manufacturers avoid any drug claims for these products, relying on word of mouth and product recognition, an easy matter in the homosexual community where nitrite usage is commonplace, but perplexing to most heterosexuals who are unfamiliar with these substances. Among counseling professionals, there has been increasing familiarity with the social uses of the nitrites, based on recent publications and conference discussions.

From 1960 to 1969, amyl nitrite was an over-the-counter item, but was returned to the prescription list following a Food and Drug Administration (FDA) hearing, apparently related to the politics of pharmacy economics, since no evidence of harm was presented at the hearing. Amyl nitrite users in the Southwest travel to Mexico where no prescription is needed for purchase. Butyl nitrite is available at head shops, adult bookstores, by mail and at a few liquor stores. Amyl nitrite is usually sold in 0.3 ml crushable glass ampules ("poppers," "snappers"), while butyl is available in 12 ml screw-top bottles. Both should be stored in cool, dark locations.

The basic pharmacological action of the nitrites is relaxation of vascular smooth muscles. Its beneficial cardiac action is not by direct effect on the heart, but rather by relaxing systemic arterioles, resulting in a fall in blood pressure, reflex tachycardia and a decrease in left ventricular work. The drop in blood pressure is maximal in 30 seconds, averaging 30 mm of mercury systolic, and return to normal is complete in less than two minutes. The user experiences a sense of warmth, giddiness and a pounding heart. The individual's face and chest blush. The psychological response varies with setting, expectation and individual chemistry, ranging from cosmic bliss to mild nausea and headache.

Mental effects of chemicals are produced by action on brain physiology. As with most other psychoactive substances (e.g., alcohol, morphine, LSD), the mode of action is not fully known. A recent review (Lowry 1980) of studies done on amyl nitrite since 1914, shows the major brain effect is dilation of the retinal and pial arteries and veins, an increase in brain volume and an increased cerebral blood flow. There is a brief elevation of cerebrospinal fluid pressure. EEG studies of five normal volunteers (Lowry l979b) showed no pathological changes. The usual reaction was an alerting response, with a shift from alpha to beta waves. Marcus (1979) studied cortical and brain stem auditory evoked responses. There were large changes in amplitude which returned to normal within 15 minutes. The significance of these changes is unknown. Mathews (1981) is studying cerebral blood flow changes in response to butyl nitrite, using radioactive xenon, which should clarify the issues. In short, the volatile nitrites produce a brief drop in systemic blood pressure and an increase in brain blood flow. The mental effects are due to some effect other than anoxia.

The social uses of the nitrites involve dancing and sexuality. In discos (especially gay discos) patrons sniff nitrites on the dance floor, enjoying the combined high of rhythm, lights, drugs and social-sexual excitement.

In explicitly sexual settings, nitrite usage can be divided into two areas: foreplay (that dreadful, cheerless term for one of earth's chief delights) and penetration-orgasm. In foreplay, the nitrites have a disinhibiting effect, enabling the user to experience total skin-surface sensuality. Nitrites are reported by many women to be useful for a chief female sexual dysfunction -- distraction -- in which peripheral thoughts of unfinished business, child care, body self-consciousness and day-to-day domestic annoyances block the abandonment to sensation, vital for a full sexual experience. Of course, no chemical can substitute for trust, intimacy and respect, but in otherwise positive situations, nitrites may facilitate the process of "letting go." A sensation of timelessness mixed with immersion in the immediate moment is described by many users.

Penetration may be facilitated by enhanced perception of both being filled and being grasped; anal penetration becomes easier, probably from a combination of muscular relaxation and decreased pain perception. When inhaled shortly before orgasm, the user may experience a sense of exhilaration and acceleration, a freeing of inhibition of movement and vocalization, and perception of orgasm as prolonged, intense and exalted. The mind's eye may be filled with rapidly changing patterns of color and shape, often containing symbolic representations of the sexual moment.

A frequent visual perception is that of a bright yellow spot with purple radiations. This phenomenon is so consistent that it must reflect some aspect of the neurophysiology of the nitrites.

Toxicology begins with the truism, "Anything which feels that good must be bad for you." Happily, the ratio of pleasure to harm is more favorable for the nitrites than for most other psychoactive chemicals. Approximately 250 million recreational doses a year are consumed in this country and there have been no known deaths from inhalation.

The most common toxic effect is headache, reported by 43% of users on at least one occasion. However, most of the users most of the time do not have headaches. In a survey of 255 experienced users (Lowry 1979c), 10% had experienced nasal irritation at least once and five percent had experienced nausea or temporary loss of erection. These negative effects were usually associated with "overuse" or with certain brands, perhaps reflecting a product quality or storage problem. Thirty percent of new workers in a nitrite bottling plant experienced headache; this is similar to the vascular headache reported years ago among workers in nitroglycerine plants.

Using a recording spirometer, Swenson (1978) studied 20 males who averaged four poppers a day for seven years. The results were compared with a nonuser control group. There were no significant differences between the lung function of the two groups, even though the nitrite-using group smoked much more tobacco and marijuana than the control group.

The Drug Abuse Warning Network (DAWN) found that of 1,350,000 drug-related emergency visits, only 67 were related to volatile nitrites. There were no deaths. In a survey of 605 emergency room specialists (Lowry 1979a), 592 had never seen a patient with inhaled nitrite problems. Thirteen respondents reported patients with transient headaches or methemoglobinemia. This author has interviewed 10 users who have used a dozen amyl nitrite ampules or a 12 ml bottle of butyl nitrite in one evening and had no perceptible ill effects. It would seem that even heavy inhalation usage has a very, wide margin of safety.

However, ingestion is a different matter, Shesser (1980) reported death by methemoglobinemia in a 30-year-old man who drank 12 ml of butyl nitrite. Smith (1980), Steiner (1980) and Wason (1980) all reported cases of serious methemoglobinemia following ingestion of butyl nitrite. In these cases, early administration of 10% methylene blue intravenously gave immediate improvement and full recovery. This author has read a newspaper account (reference unavailable) of a man who died several hours after injecting a large amount of amyl nitrite into his jugular vein.

To summarize the evidence on toxicity, both forms of volatile nitrite appear to be relatively safe when inhaled and clearly toxic when swallowed or injected. Since the labeling of butyl nitrite clearly recommends against swallowing and since no authority has recommended the usage of any volatile nitrite by either ingestion or injection, it would seem that only the most reckless disregard of available information would be likely to lead to any serious harm.

The legal status of amyl nitrite is clear: an FDA approved prescription drug. The status of butyl nitrite varies with locale and time. Several states have moved to ban its sale, usually on the basis of danger to public health. At various times in the past five years, the states of California, Wisconsin, Connecticut, Texas and Pennsylvania have made moves to ban the sale of butyl nitrite within their borders, but following hearings or litigation have dropped these attempts when no evidence of medical harm was forthcoming. The FDA has taken no clear position on butyl nitrite. The Consumer Product Safety Commission is reviewing the labeling of several brands, with an eye toward a more explicit warning label.

The psychology and sociology of governmental bans and restrictions on amyl and butyl nitrite is worth considering. The usual allegations are that the substance in question has either no "legitimate usage," could be a "drug of abuse" or "is used solely for recreation." The underlying philosophical assumption is that any chemical whose sole purpose is pleasure is a priori wrong. There is a rich, clear Puritanical vein visible here regarding any activity which is not practical and productive. America has a rich Comstockian heritage of banning activities because they might bring pleasure to some other person. In the field of government regulations, significant exceptions are made for the psychoactive drugs used by the dominant population, including those socioeconomic groups which tend to be active in legislative matters and consumers of such products as alcohol, tobacco and coffee. A "drug of abuse" is almost always one which is not in wide use by the social class which aspires to elected office. The social origins of governmental decisions regarding psychoactive substances are worth continuing examination and reflection.

References

Lowry, T.P. 1980 Neurophysiological aspects of amyl nitrite. Journal of Psychedelic Drugs Vol. 12(1): 73-74.
Lowry, T.P. 1979a. Amyl nitrite: A toxicological survey. In: Nickerson, M. (Ed.) Isobutyl Nitrite and Related Compounds. San Francisco: Pharmex, Ltd.
Lowry, T.P. 1979b. Amyl nitrite and the EEG: A pilot study. Journal of Psychedelic Drugs Vol. 11(3): 239-241.
Lowry, T.P. 1979c. The volatile nitrites as sexual drugs: A user survey. Journal of Sex Education and Therapy Vol. 5: 8-10.
Marcus, M. 1979. Personal Communication.
Mathews, R. 1981. Personal communication.
Shesser, R. 1980. Fatal methemoglobinemia from butyl nitrite ingestion. Annals of Internal Medicine Vol. 92(1): 131.
Smith, M. 1980. Butyl nitrite and a suicide attempt. Annals of Internal Medicine Vol. 92(5): 719.
Steiner, R. W. 1980. Butyl nitrite and methemoglobinemia. Annals of Internal Medicine Vol. 92: 570-571.
Swenson, E. 1979. Spirometry in men who regularly inhale butyl or isobutyl nitrite. In: Nickerson, M. (Ed.). Isobutyl Nitrite and Related Compounds. San Francisco: Pharmex, Ltd.
Wason, S. 1980. Isobutyl nitrite toxicity by ingestion. Annals of Internal Medicine Vol. 92(5): 637-638.

Reprinted From: Psychosexual Aspects of the Volatile Nitrites

"‘Poppers’ and AIDS: Researchers haven’t found a link between them."

2006-04-27T16:49:00.000-07:00

Kinsey Report
Dr. June Reinisch

Friday, April 1, 1988

‘Poppers’ and AIDS
Researchers haven’t found a link between them.

Dear Dr. Reinisch,

What are the effects of using the liquids commonly referred to as “poppers” during sexual activity? These are sold in small bottles and one inhales or sniffs the aroma. I think they contain amyl nitrite or butyl nitrite, and their use is common practice among some groups.

Recently I heard a rumor connecting poppers with an increased risk of AIDS. Is this true? What are the risks if a person used poppers two or three times a month?

Dear Reader,

Recent research compiled for a federal government study concluded that “the use of nitrites (poppers) does not cause AIDS.”

The question has been raised as to whether use of nitrite vapors may be linked to the incidence of Kaposi’s sarcoma (a usually rare type of skin tumor) among people who already have AIDS, but the answer is not yet clear. One study suggested a link, but other—larger--studies have not supported this.

Remember that the AIDS virus does not usually kill patients directly. Instead it weakens the body’s immune system so that a patient is much more susceptible to a wide array of serous diseases (Kaposi’s sarcoma is only one of these.)

Both amyl nitrite (sold as a prescription drug to treat some heart problems) and butyl nitrite or isobutyl nitrite have been widely used for years because of the belief that they enhance sexual response. Physically, the nitrite vapors produce a brief drop in blood pressure and an increase in blood flow I the brain. Called “poppers”, these nitrites have been popular among some groups.

Regardless of what research concludes about poppers, a person should follow safer sex guidelines to reduce the risk of exposure to HIV (the virus that causes AIDS). These include the use of condoms.

Reprinted From: ‘Poppers’ and AIDS Researchers haven’t found a link between them.

The HIV-AIDS Debate Is Over: What to tell your patients when they ask if HIV causes AIDS

2006-04-27T16:42:00.000-07:00

"With each passing year the evidence that HIV causes AIDS grew more persuasive and less refutable, even at the purely rhetorical level. But even as this evidence mounted, Duesberg and his minions grew increasingly shrill and hectoring. Their unsupported but high-decibel jeremiads garnered some media attention-in 1993, for instance, the London Times labeled the epidemic "a tragic myth"-and even respectable scientific journals felt obliged to address the issue again and again, simply because Duesberg and his outspoken supporters raised the issue again and again."

"If AIDS was caused by recreational drugs like nitrate inhalants, also known as "poppers," and prescription drugs like zidovudine, also known as AZT, then how could one account for the millions of cases of AIDS that had occurred in Third World countries?"

NEWSLINE, Volume 3, Issue 1 • February 1997
Stephen J. O'Brien, Ph.D. Director, Laboratory of Genomic Diversity
National Cancer Institute National Institutes of Health Frederick, MD

Epidemiologists have documented the presence of the human immunodeficiency virus (or antibodies to HIV) in more than 95% of the world's AIDS patients (1-6). Scientists who have examined the clinical data collected from AIDS patients are convinced that it is HIV, and no other etiologic agent, which causes the gradual decline in CD4 cell counts that leads to severe immunosuppression and AIDS. Why, then, is there any lingering doubt about the cause of AIDS? Why, in spite of overwhelming evidence to the contrary, do a small number of scientists-and a larger number of infected individuals-continue to insist that HIV does not cause AIDS?

A decade ago, when a highly regarded molecular virologist named Peter Duesberg first suggested that AIDS was caused not by HIV but by a combination of recreational drugs, hyperstimulation of the immune system, and possibly even antiretroviral drugs themselves (7), the scientific community felt obliged to respond to Duesberg's hypothesis. The fact that his argument was largely rhetorical, and was unsupported by the preponderance of the data then available, made Duesberg's claim dubious, but it did not altogether rule out his theory. Erring on the side of excessive caution, respected members of the scientific community gave Duesberg's hypothesis more serious consideration than the data alone seemed to merit-and they rejected his theory as untenable (1, 4, 8-10).

On the face of it, Duesberg's counter-theory made little sense. If AIDS was caused by recreational drugs like nitrate inhalants, also known as "poppers," and prescription drugs like zidovudine, also known as AZT, then how could one account for the millions of cases of AIDS that had occurred in Third World countries, where these drugs were not available? And how did one explain AIDS in hemophiliacs, transfusion recipients, and infants born to HIV-infected mothers-none of whom had used poppers or AZT?

Duesberg's answer was, frankly, bizarre. He simply announced that these AIDS patients-the vast preponderance of those infected worldwide-did not actually have AIDS. They had something, of course-and they were dying of it. But it wasn't AIDS, Duesberg insisted. The fact that these patients tested positive for the presence of HIV or antibodies to HIV, that they had declining CD4 cell counts, and that they developed the opportunistic infections that are regarded as AIDS-defining illnesses did not seem to trouble Duesberg, whose principal research had been with cancer-causing retroviruses in chickens.

Duesberg's assault on the epidemiology and clinical pathology of AIDS-an assault mounted by someone who had little experience in either discipline-blindsided workers in the field. Initially, at least, they were disconcerted by the volume and volubility of Duesberg's attacks on their data, and they were temporarily disarmed by this scientist who disdained reasonable scientific argument and scientific proof.

With each passing year the evidence that HIV causes AIDS grew more persuasive and less refutable, even at the purely rhetorical level. But even as this evidence mounted, Duesberg and his minions grew increasingly shrill and hectoring (11-15). Their unsupported but high-decibel jeremiads garnered some media attention-in 1993, for instance, the London Times labeled the epidemic "a tragic myth"-and even respectable scientific journals felt obliged to address the issue again and again (8-10, 16-18), simply because Duesberg and his outspoken supporters raised the issue again and again.

In a singularly sensational and reckless response to this furor, a 65-year-old Florida clinician actually inserted a syringe into the finger of an AIDS patient and then injected himself with the same syringe-to emphasize his conviction that HIV infection does not cause AIDS (19). In the same vein, Duesberg himself once proposed to let Robert Gallo inoculate him with HIV. That Duesberg never went through with this publicity-generating ploy leads one to wonder if he has reservations about his own theory.

The HIV-AIDS debate grew more acrimonious, and more futile, with each exchange, and it eventually became apparent that no amount of scientific evidence, no matter how unimpeachable, would silence the naysayers. Indeed, the decade-long controversy culminated last year with the publication of Duesberg's 772-page polemic, Inventing the AIDS Virus, a farrago of rhetorical hubris, unsupported speculation, and selective critiques of the tens of thousands of papers written by scientists who are persuaded that HIV is the etiologic agent in AIDS.

In the end, Duesberg's alternative explanation for the AIDS epidemic was little more than an indictment of a certain kind of gay lifestyle, one that is popularly perceived as consecrated to casual sex and equally casual drug-taking (16). As such, his hypothesis was but a variant of the mean-spirited fundamentalist belief that people with AIDS are victims of their own vices.

Over the past decade Duesberg's counter-theory has found two natural audiences, neither with rigorous scientific training. First, he has found an evergreen audience among certain voracious investigative journalists of the lay press. Controversy and conspiracy theories sell better than sobersided factual analysis, especially in fringe publications, and Duesberg has provided those publications with more than his share of both. But even redoubtable journals like Science and Nature have repeatedly featured Duesberg's arguments, generally under the rubric of point-counterpoint (8-11, 16, 17, 20-22). The controversy surrounding Duesberg's claims has doubtless been perceived as good copy by the publishers and the readers of all of these publications.

Duesberg's second, and far larger, audience is men and women who know (or strongly suspect) that they are infected with HIV. There is a certain irony in this, of course, since these adherents to Duesberg's counter-theory are implicitly joining in his condemnation of their life-style choices. But there is also pathos in this situation. Antibody-positive individuals have been given a near-certain death sentence... if HIV causes AIDS. But if something else-poppers, prescription drugs, African swine fever virus-causes AIDS, and if that causative agent can be identified, then maybe, just maybe, their prognosis is less grim.

Denial is a device for coping with death-dealing illnesses, and it is hardly limited to patients with HIV infection-as any clinician who has ever treated a chronic smoker can attest. The dilemma here is that the form of denial that is manifested by the HIV-infected individuals who espouse Duesberg's views thwarts our best efforts to prevent the spread of HIV and treat those who are infected.

How HIV fulfills Koch's postulates

The mainstay of Duesberg's counter-theory is that HIV cannot be the etiologic agent in AIDS because it does not satisfy Koch's famous postulates-postulates that must be fulfilled before it can be concluded that a particular bacterial agent causes a particular disease. Robert Koch, the discoverer of the anthrax bacillus, first posited his three postulates in the late nineteenth century (23), and although minor modifications have been suggested over the years-chiefly to accommodate technological advances (24, 25)-the basic tenets remain essentially unchanged. For more than a century Koch's postulates have served as the litmus test for determining the cause of any epidemic disease:

Epidemiological association: the suspected cause must be strongly associated with the disease Isolation: the suspected pathogen can be isolated-and propagated-outside the host Transmission pathogenesis: transfer of the suspected pathogen to an uninfected host, man or animal, produces the disease in that host

During the early years of the AIDS epidemic, both defenders and critics of the theory that HIV causes AIDS agreed that HIV failed to completely fulfill Koch's postulates (1, 7, 13, 14, 25). As defenders of the theory were quick to point out, a number of other diseases, notably typhoid fever, diphtheria, and leprosy, also fail to meet these stringent tests of causality-yet there is no controversy about what causes these illnesses. We know the pathogens that produce these diseases; what we cannot do with consistency is culture those pathogens in vitro.

This was the problem with HIV as well, until recently. There was little question, even among the counter-theorists, that HIV clearly satisfied the first and second of Koch's postulates, but it proved considerably harder to show that HIV also fulfilled the third. Today, however, overwhelming epidemiological and experimental data have been assembled to fulfill all three of Koch's postulates, establishing to a virtual certainty that HIV causes AIDS (26).

Demonstrating the epidemiological concordance of HIV exposure and AIDS was relatively straightforward, once the etiologic agent had been identified. Numerous studies have shown, for example, that prompt and progressive depletion of CD4 lymphocytes-and a subsequent diagnosis of AIDS-follows HIV seroconversion in the vast majority of HIV-infected hemophiliacs (27, 28), and HIV antibodies have been detected in more than 90% of transfusion recipients who received blood from donors who were HIV-positive. In the latter group seroconversion has likewise led to progressive depletion of CD4 cells and the onset of AIDS (27-29).

Two recent prospective cohort studies of HIV-positive hemophiliacs have provided an even more direct link between HIV infection and mortality: They show a ten-fold increase in deaths among antibody-positive patients compared to uninfected individuals, irrespective of the severity of the subjects' hemophilia (30, 31). Significantly, since the screening of donated blood for the presence of HIV was instituted, new infections have dropped almost to zero among hemophiliacs and transfusion recipients-further proof that HIV is the cause of AIDS.

The fact that HIV itself (or antibodies to the virus) can be detected in more than 95%-but less than 100%-of AIDS patients worldwide is explained by the relative insensitivity of the early tests for the presence of HIV in patients' peripheral blood. By the more sensitive HIV RNA assays now used to detect the virus, it is possible to confirm the presence of HIV in individuals who have as few as 20 viral particles per mL of blood (see "The HIV RNA Assay: A Valuable New Diagnostic Tool," Vol. 2, No. 2, pages 27-30).

Sensitive as these new diagnostic tests are, they will not detect HIV in all profoundly immunocompromised patients-not because the virus fails Koch's test for pathogenicity but because other disorders cause the body's immune system to collapse (32, 33). Certain drugs also produce immune suppression, as do chemical carcinogens, irradiation, and cigarette smoke.

The isolation component of Koch's postulates has been repeatedly demonstrated since the discovery of HIV. Scores of isolates have been cultured from AIDS patients; the virus has been cultivated in fresh human T lymphocytes; and cultured-cell lines have been developed for in vitro propagation (10, 34). This leaves only Koch's third postulate-transmission pathogenesis-as a matter of contention. Ethical considerations preclude the experimental inoculation of uninfected individuals with HIV, and this makes empirical verification of Koch's last postulate exceedingly difficult.

Difficult, but not impossible. For while we cannot deliberately infect anyone with HIV merely to satisfy Koch's postulates and Duesberg's curiosity, we can examine the evidence that has been gathered on healthcare workers who were accidentally infected with HIV in the course of their professional work. Take, for example, the cases of three laboratory technicians who were inadvertently exposed to the HTLV-IIIb strain of HIV-1 while working with that strain in their laboratories (35). All three of these technicians developed antibodies to HIV, and within five years all three showed marked CD4 lymphocyte depletion. Two had their CD4 counts fall to less than 200 cells/mm3, and one of those developed PCP.

In all three of these cases it was possible to establish the precise phylogenetic type of the virus that had infected the laboratory workers. When genetic sequencing tests were performed on the laboratory virus and on viral samples taken from the three workers, the sequence divergence was less than 3% (36). This low level of divergence is equivalent to the variation observed in cases of HIV transmission from mothers to their infants-and it is less than one third as great as the extent of variation seen when viral samples from unconnected patients are compared (37, 38). Thus, these three unfortunate individuals provide prima facie evidence of transmission pathogenesis, Koch's third postulate.

This same high level of genetic concordance was also seen when the C.D.C. compared viral samples taken from a Florida dentist who died of AIDS with samples taken from five of his patients who tested positive for HIV and who had no HIV risk factors other than multiple visits to the dentist for invasive procedures (39, 40). Two independent research groups reached the same conclusion after examining the HIV gene sequences of these six individuals: the dentist had almost certainly infected his patients in the course of those invasive procedures, although the experts could not say exactly how those infections had occurred (41-44).

It is unlikely that we will ever learn how transmission occurred in this unique cluster of infections, but the genetic data gathered from the victims of this tragedy teach us an important lesson: They establish, as conclusively as science can establish such things, that when HIV is inadvertently transferred from a person with AIDS to an uninfected host, it does indeed produce AIDS in that host (45). And thus it satisfies the last, and most rigorous, of Koch's postulates.

Pathogenesis has also been demonstrated in various animal models. HIV-2, a less virulent strain of HIV largely restricted to West Africa, causes CD4 depletion and AIDS-like pathology in yellow baboons (46), and at least 12 strains of simian immunodeficiency virus, a close cousin of HIV, induce CD4 depletion and cause AIDS-defining illness in Asian macaques (47-51). Given that Koch's third postulate can be fulfilled by transmission to either man or animal, these examples offer strong supplemental evidence that HIV causes AIDS.

Conclusion

The last year has seen dramatic breakthroughs in the treatment of HIV infection, and these advances reinforce the causal role of HIV in AIDS. Triple-drug combination therapy has resulted in dramatic reductions in viral burden, sometimes to undetectably low levels, and these reductions are generally accompanied by increases in CD4 cell counts.

The discovery that certain chemokines are crucial secondary receptors for HIV infection (52) led to the discovery, in my laboratory and others, of a deletion mutation in the CKR5 gene that confers protection against HIV infection (53). In homozygous individuals this mutation prevents infection, and in heterozygous individuals it delays disease progression by several years (see "Genetic mutation appears to confer immunity to HIV," Vol. 2, No. 5, pages 114-115). If HIV were not the cause of AIDS, the new antiretroviral "cocktails" would not work and CKR5, a key receptor for HIV infection, would not delay the onset of AIDS.

It is time to recognize that the HIV-AIDS debate is over, as an academic exercise and as a practical matter. This decade-long debate may have been constructive at first, because it obliged scientists to give careful consideration to the epidemiological and clinical data they were gathering, but it has become a dangerous diversion. The doubt that it has fostered, particularly among our patients, carries the potential for great harm: it can lead those at high risk of infection to ignore prevention messages, and it can keep those who are infected from benefiting from recent advances in therapy. The debate should cease, and all energies should be directed toward developing an effective vaccine against HIV and curative treatments for those who are infected.

References

1. Blattner W, Gallo RC, Temin HM. HIV causes AIDS. Science 1988 Jul 29;241(4865):515-6.

2. Fauci AS. Multifactorial nature of human immunodeficiency virus disease: implications for therapy. Science 1993 Nov 12;262(5136):1011-8.

3. Gallo RC, Sarin PS, Gelmann EP, Robert-Guroff M. Isolation of human T-cell leukemia virus in acquired immune deficiency syndrome (AIDS). Science 1983 May 20;220(4599):865-7.

4. Weiss RA. How does HIV cause AIDS? Science 1993 May 28;260(5112):1273-9.

5. Schechter MT, Craib KJ, Gelman KA, Montaner JS, Le TN, O'Shaughnessy MV. HIV-1 and the aetiology of AIDS. Lancet 1993 Mar 13;341(8846):658-9.

6. Piot P. AIDS: a global response. Science 1996 Jun 28;272(5270):1855.

7. Duesberg PH. Retroviruses as carcinogens and pathogens: expectations and reality. Cancer Res 1987 Mar 1;47(5):1199-220.

8. Weiss RA, Jaffe HA. Duesberg, HIV, and AIDS. Nature 1990 Jun 21;345(6277):659-60.

9. Cohen J. The Duesberg phenomenon. Science 1994 Dec 9;266(5191):1642-4.

10. Moore J. A Duesberg, adieu! Nature 1996; 380: 293-4.

11. Duesberg PH. HIV is not the cause of AIDS. Science 1988 Jul 29;241(4865):514, 517.

12. Duesberg PH. Does HIV cause AIDS? J Acquir Immune Defic Syndr 1989;2(5):514-7.

13. Duesberg PH. Human immunodeficiency virus and acquired immunodeficiency syndrome: correlation but not causation. Proc Natl Acad Sci U S A 1989 Feb;86(3):755-64.

14. Duesberg PH. AIDS epidemiology: inconsistencies with human immunodeficiency virus and with infectious disease. Proc Natl Acad Sci U S A 1991 Feb 15;88(4):1575-9.

15. Duesberg PH. AIDS acquired by drug consumption and other noncontagous risk factors. Pharmacol Ther 1992;55(3):201-77.

16. Dickson D. As UK prepares for Mullis encounter. Nature 1994 May 26;369(6478):265.

17. Anon. More conviction on HIV and AIDS. Nature 1995 Sep 7;377(6544):1.

18. Evans AS. Does HIV cause AIDS? An historical perspective. J Acquir Immune Defic Syndr 1989;2(2):107-13.

19. Weiss R. And now for something completely different. The Washington Post, Washington, D.C., November 1, 1994: 7.

20. Duesberg PH. HIV and AIDS. Science 1993 Jun 18;260(5115):1705-6.

21. Hodgkinson N. AIDS plagued by journalists. Nature 1994 Mar 31;368(6470):387.

22. Anon. New-style abuse of press freedom. Nature 1993; 366: 493-4.

23. Koch R. Ueber bakteriologische Forschung. In: Verhandlungen X Int Med Congr Verlag von August Hirschwald, 1891: 35-37

24. Rivers TM. Viruses and Koch's postulates. J Bacteriol 1937; 33: 1-12.

25. Evans AS. Causation and disease: effect of technology on postulates of causation. Yale J Biol Med 1991 Sep-Oct;64(5):513-28.

26. O'Brien SJ, Goedert JJ. HIV causes AIDS: Koch's postulates fulfilled. Curr Opin Immunol 1996 Oct;8(5):613-8.

27. Goedert JJ, Biggar RJ, Weiss SH, Eyster ME, et al. Three-year incidence of AIDS in five cohorts of HTLV-III-infected risk group members. Science 1986 Feb 28;231(4741):992-5.

28. Goedert JJ, Kessler CM, Aledort LM, Biggard RJ, Andes WA, et al. A prospective study of human immunodeficiency virus type 1 infection and the development of AIDS in subjects with hemophilia. N Engl J Med 1989 Oct 26;321(17):1141-8.

29. Sullivan JS, Learmont JC, Geczy AF, Dyer W. HIV and AIDS. Nature 1995 Nov 2;378(6552):10.

30. Darby SC, Ewart DW, Giangrande PLF, Dolin PJ, et al. Mortality before and after HIV infection in the complete UK population of hemophiliacs. Nature 1995 Sep 7;377(6544):79-82.

31. Goedert JJ. Mortality and hemophilia. Lancet 1995; 346: 1425-6.

32. McKusick VA, ed. Mendelian Inheritance in Man. (Baltimore: Johns Hopkins University Press, 1993.)

33. Dixon FJ, Fisher DW. The Biology of Immunologic Disease. (Sunderland: Sinauer Associates Incorporated, 1983.)

34. Myers G, Berzofsky JA, Korber B, Smith RF, Pavlakis G. Human Retroviruses and AIDS. (Los Alamos: Los Alamos National Laboratory, 1991.)

35. Weiss SH, Goedert JJ, Gartner S, et al. Risk of human immunodeficiency virus (HIV-1) transmission among laboratory workers. Science 1988 Jan 1;239(4835):68-71.

36. Reitz MS Jr, Hall L, Robert-Guroff M, et al. Viral variability and serum antibody response in a laboratory worker infected with HIV-1 (HTLV-IIIB). AIDS Res Hum Retroviruses 1994 Sep;10(9):1143-55.

37. Wain-Hobson S, Vartanian JP, Henry M, Chenciner N, Cheynier R, et al. LAV revisited: Origins of the early HIV-1 isolates from Institut Pasteur. Science 1991 May 17;252(5008):961-5.

38. Wolinsky SM, Wike CM, Korber BTM, Hutto C, et al. Selective transmission of human immunodeficiency virus type-1 variants from mothers to infants. Science 1992 Feb 28;255(5048):1134-7.

39. Palca J. The case of the Florida dentist. Science 1992 Jan 24;255(5043):392-4.

40. Palca J. CDC closes the case of the Florida dentist. Science 1992 May 22;256(5060):1130-1.

41. Ou CY, Ciesielski CA, Myers G, Bandea CI, Luo CC, et al. Molecular epidemiology of HIV transmission in a dental practice. Science 1992 May 22;256(5060):1165-71.

42. Hillis DM, Huelsenbeck J. Support for dental HIV transmission. Nature 1994 May 5;369(6475):24-5.

43. Smith TF, Waterman MS. The continuing case of the Florida dentist. Science 1992 May 22;256(5060):1155-6.

44. DeBry RW, Abele LG, Weiss SH, Hill MD, et al. Dental HIV transmission? Nature 1993 Feb 25;361(6414):691.

45. Holmes EC, Brown AJL, Simmonds P. Sequence data as evidence. Nature 1993 Aug 26;364(6440):766.

46. Barnett SW, Murthy KK, Herndier BG, Levy JA. An AIDS-like condition induced in baboons by HIV-2. Science 1994 Oct 28;266(5185):642-6.

47. Desrosiers RC. The simian immunodeficiency viruses. Annu Rev Immunol 1990;8:557-78.

48. Johnson PR, Myers G, Hirsch VM. Genetic diversity and phylogeny of nonhuman primate lentiviruses. Ann Rev AIDS Res 1991; 1: 47-62.

49. Hirsch VM, Johnson PR. Pathogenic diversity of simian immunodeficiency viruses. Virus Res 1994 May;32(2):183-203.

50. Kestler HW, Kodama T, Ringler D, Marthas M, et al. Induction of AIDS in rhesus monkeys by molecularly cloned simian immunodeficiency virus. Science 1990 Jun 1;248(4959):1109-12.

51. Hirsch VM, Dapolito G, Johnson PR, Elkins WR, London WT, et al. Induction of AIDS by simian immunodeficiency virus from an African green monkey: Species-specific variation in pathogenicity correlates with extent of in vivo replication. J Virol 1995 Feb;69(2):955-67.

52. D'Souza MP, Harden VA. Chemokines and HIV-1 second receptors. Nat Med 1996 Dec;2(12):1293-300.

53. Dean M, Carrington M, Winkler C, Huttley GA, Smith MW, Allikmets R, Goedert JJ, Buchbinder SP, Vittinghoff E, Gomperts E, Donfield S, Vlahov D, Kaslow R, Saah A, Rinaldo C, Detels R, O'Brien SJ. Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Science 1996 Sep 27;273(5283):1856-62.

Copyright ©1990, 2001. ÆGiS. All materials appearing on ÆGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of ÆGIS, or the party credited as the provider of the content.

"A collection of unsupported speculation propped up by carefully selected snippets of data that simply omit anything the "dissidents" find inconvenient."

Pen Points
Letters to
Gay Today

AIDS Denial Isn't Realism

John Lauritsen covered the AIDS crisis for the New York Native As one of the "flacks," referred to in John Lauritsen's "AIDS Realism vs. the HIV Hypothesis," I'd like to thank Lauritsen for laying out in explicit, if unintentional, detail the true nature of the AIDS denialist arguments (and yes, the comparison to Holocaust deniers is indeed apt): A collection of unsupported speculation propped up by carefully selected snippets of data that simply omit anything the "dissidents" find inconvenient.

Lauritsen's claim that the media have censored the views of the denialists is laughable. Nightline did a whole show on the subject a few years ago. They've also gotten extensive coverage in, among other outlets, the London Sunday Times, Spin, numerous gay and lesbian publications and--strikingly--key organs of the right-wing, antigay movement in the U.S., including The American Spectator and the Heritage Foundation's Policy Review.

After all of this attention it's hard to see how the fact that few take their views seriously can be blamed on censorship. Maybe--just maybe--it's because, after carefully looking at all of the data, intelligent observers have concluded that mainstream science, whatever its flaws, pretty much got it right this time.

But the best advice I can give readers is: Don't take my word for it. Look up the references. Read the data--all of it, not just the narrow interpretations of those with an axe to grind--and judge for yourself.
Sincerely, Bruce Mirken
San Francisco

AIDS, Poppers & HIV Theories

I read John Lauritsen's article attacking the theory that HIV was the cause of AIDS. While I disagree with some of his ideas, most of them actually, I think you should be applauded for expanding the dialogue about AIDS.

I found many of Lauritsen's arguments intriguing. He does a damn good job of making his case strongly and convincingly. However, many modern-day "snake-oil salesmen" are plugging into this vital debate.

I found Lauritsen's assertion that AIDS in America was a different disease than AIDS in Africa "reasonable" and considered. Having been exposed, possibly, hundreds of times to American HIV as a "top" and never having been infected, I wonder why it is so easily transmitted from female to male in Africa..

Related Stories from the GayToday Archive:
AIDS Realism Versus the HIV Hypothesis

Answering the AIDS Denialists: CD4 (T-Cell) Counts, and Viral Load

A Rose by Any Other Name…

Related Sites:
Virus Myth

GayToday does not endorse related sites.

However, he totally loses “credibility” when he drags out his old/ancient/never-documented assertion that “poppers=death”. I read his book on that subject and the research simply showed that “if someone was HIV positive, the use of poppers did seem to increase the possibility of their contracting Karposi Sarcoma.”

If “poppers really did equal death” I'd be long dead by now. Once, after having a pleasant dinner with John Lauritsen, I actually indulged myself by “toasting him” with a hit of Rush as he looked on in wide-eyed wonder and/or horror.

I think the “questions” raised by Lauritsen and others are commendable. He does a great job pointing out how “money flows” behind certain ideas and excludes others. Even if he is totally in error, his criticisms force the “consensus advocates” to prove their case.
Randy Wicker
New York City
©gaytoday.badpuppy.com

Reprinted From: EDITORIAL: The HIV-AIDS Debate Is Over: What to tell your patients when they ask if HIV causes AIDS

What About the Relationship Between Alkyl Nitrite Poppers and KS?

2006-04-27T16:39:00.000-07:00

Aids and Poppers: is there a connection?

What About the Relationship Between Alkyl Nitrites and KS?

Named after Dr. Moritz Kaposi who first described the condition in 1872, Kaposi’s sarcoma has been with us for many years. Until the 1980s, the sarcoma (a cancer that effects the connective tissue such as bone, cartilage, fat, muscle, blood vessels and ligaments) was considered a rare disease. In the past it occurred in three main populations: elderly men of Mediterranean or Jewish heritage, organ transplant recipients receiving immune suppression therapy, and young people in Africa (American Cancer Association, 2006). It will probably strike you that these are not populations that typically use nitrites. With the advent of AIDS, Kaposi’s sarcoma reached epidemic proportions in the homosexual male population. Prior to the AIDS epidemic, the cancer occurred in only 0.02 to 0.06 individuals per 100,000 (Oettle 1962). By 1984, never-married men in the San Francisco area were 2000 times more likely to develop the disease than they were in the previous decades (Williams et al. 1994). Fortunately, as new AIDS treatments evolved, the number of cases of Kaposi’s sarcoma has fallen by about 85% (American Cancer Association 2006). These numbers and dates are interesting as they correspond directly with the emergence and treatment of the HIV virus, not with use of poppers, which was at it height in the 1960s and 1970s, prior to the AIDS epidemic (Lau et al. 1992; Stall and Purcell 2000) Scientists suggesting a connection between KS and alkyl nitrites often refer to the fact that KS occurs about 20 times more frequently in homosexual men with AIDS than in heterosexual individuals suffering from the disease (Beral 1989), citing that these findings support the hypothesis that alkyl nitrites may be a cofactor of KS (Wikipedia 2006). While the hypothesis is interesting, I find continued claims of this nature surprising, considering that they were refuted by the MACS study (reviewed earlier in the text) in 1987 (Polk et al. 1987), among other studies (Voeller 1990). In fact, researchers from the Johns Hopkins School of Hygiene and Public Health reanalyzed data from the MACS study and actually found that higher use of alkyl nitrites corresponded with lower incidence of KS (Palenicek et al. 1992).

This leaves us with the million-dollar question: If alkyl nitrites are not causing KS, what is? Many recent studies support the hypothesis that KS is caused by a sexually transmitted herpes virus, HHV-8, also called KSHV (Kaposi’s Sarcoma Associated Herpes Virus) (Whitby et al. 1995; Ziegler and Katongole-Mbidde 1996; Gnann et al. 2000). This hypothesis supports data that shows a low prevalence of KS among intravenous drug users and blood product recipients suffering from AIDS, as these individuals typically contract HIV through non-sexual (blood to blood) means. As a herpes virus, HHV-8 travels through nerve endings, and although it is sexually transmissible, it is unlikely to be transmitted through the blood (Gnann et al. 2000). Many studies support the HHV-8 hypothesis. As early as 1989, the Centers for Disease Control recognized that if an infectious agent caused KS, it was likely transmitted by some form of homosexual contact rather than by blood (Beral 1989). Six years later in a 1995 study by Whitby et al., HHV-8 was consistently detected in the biopsy samples of patients with both AIDS related and non-AIDS related (classical) KS. Further, HHV-8 was detected in the blood cells of over half of the KS patients, but not in those of the non-KS patients used as controls. Further studies support these findings (Bobroski et al. 1998; Gnann et al. 2000). In a 1996, study of children in Uganda published in the International Journal of Cancer, Ziegler and colleagues studied 100 cases of KS in children under age 15. They reported that the incidence of childhood KS in Uganda in 1996 was 40 times as great as it was in the pre-AIDS era. DNA from HHV-8 was found in all cases of childhood KS tested. Distribution patterns of the tumors suggested the virus entered during birth or breast-feeding (Ziegler 1996).

But what about the correlational findings linking high use of alkyl nitrites to KS? When reviewing these findings, it’s important to bear in mind that correlation does not equal cause. An interesting case in point comes from a 1985 study by Haverkos et al. that is widely cited in support of the KS-alkyl nitrite connection. While the authors found a correlation between the high levels of nitrite use and KS, they also found many other statistically significant correlations. For instance, homosexual men with KS tend to have had hepatitis B; use drugs such as amphetamines, barbiturates, cocaine, LSD, and marijuana to name a few; had a greater number of sexual partners than those without KS; and have an income over $20,000 per year (Haverkos et al. 1985).

Not surprisingly, correlation is easily confused with fact. I’ve found that a semi-ridiculous analogy often helps bring the point home. For instance, while homosexual men with KS may also be more likely to own a three-legged dog than those without KS, there is no proven causal link between KS and three-legged dog ownership. It’s the same with alkyl nitrite use. Because we cannot prove the link is more than a correlation, the conclusions remain unclear. Often upon further analysis, as was the case with a reanalysis study done by Marmor et al. in 1982, when other variables are controlled for, nitrite use is shown to no longer be a significant factor.

Reprinted From: What About the Relationship Between Alkyl Nitrites and KS?

Poppers and AIDS or AIDS and Poppers: Is There a Connection?

2006-04-27T16:29:00.000-07:00

Aids and Poppers: is there a connection?

The Art of Scientific Scrutiny: Investigating the Poppers-AIDS Hypothesis By Christine Weber, B.Sc.

As a science writer and researcher, I recently became interested in a scientific controversy I thought had been put to bed many years earlier. In the 1980s, when HIV/AIDS research was in its earliest and possibly most feverish stages, a relationship was discovered between the incidence of AIDS-like symptoms in homosexual men, the largest portion of the population displaying these symptoms at the time, and the use of alkyl nitrites, more commonly called “poppers”. This relationship was later extrapolated to link popper use to Kaposi’s sarcoma, a cancer frequently seen in immunocompromised individuals, including those with AIDS. Mainstream science and soon to be dissident AIDS researchers alike investigated this relationship, and while the former found it to be purely correlational, the latter continue to this day, ardently supported by members of the alternative press, to vigorously argue that a link exists between drug and disease. To this group, AIDS was not caused by the HIV retrovirus, a hypothesis now accepted as near fact by mainstream science, but by a popular recreational inhalant. A brief review of the controversy left me with more questions than I had begun with. For instance, why do two groups of scientists, both educated in universities on the basic tenants of science and established in their fields of research, continue to disagree about the cause of what is possibly the most researched disease of our generation? And more importantly, which of these two hypotheses best stands up to the scrutiny of science?

The case isn’t as unusual as you may think. The history of science is littered with such disagreements over opposing hypotheses. Scientists wouldn’t be practicing good science if they were not questioning their hypotheses every step of the way. That is what hypotheses are there for after all, to either stand or crumble under scientific scrutiny. By definition, a hypothesis is an educated guess, and it’s considered scientific only if it is a) testable and b) falsifiable. Its interesting, I find, that the very foundation science sits upon is designed to be tested and, if the case, proven wrong. But this is the safety net that science needs to operate. Without it scientists would only discover exactly what they were looking for, stubbornly sticking to their favorite hypothesis even if the data indicates that they should turn in a new direction. Often it’s only by identifying the wrong path that we stumble upon the right one. And I do mean stumble. Some of science’s greatest discoveries were a direct result of such happy accidents, possibly the most famous being the discovery of penicillin. Coming back to the AIDS hypothesis, let’s consider our two groups of scientists. One argues that the HIV virus causes AIDS; the other argues that it is linked to poppers. Which is correct? Many more scientists support the first hypothesis, but try to keep that out of your assessment. I can think of more than one scientist who was discredited by his peers, only to later win the Nobel Prize. Instead, clear your mind of bias and follow me on a journey of scientific analysis where logic, scientific procedure and experimental design act as our only guides.

Getting to Know Poppers

To begin with, what are alkyl nitrites, the drugs at the center of this controversy? Essentially, alkyl nitrites are any chemical with the general formula R-O-N=O, where the R is any organic (carbon containing) subgroup. Admittedly, this is a rather dull description of a drug with a long and colorful history. Unbiased Internet sources reviewing the history of alkyl nitrites are, as I quickly found, few and far between. A two-hour search on the subject still left much to the imagination. Fortunately for the frustrated researcher, there is always Wikipedia. According to the cyberspace encyclopedia, amyl nitrite, the most familiar form of the chemical, has been used for over 150 years as a treatment of angina, or heart pain (Wikipedia 2006). It was also used as part of the treatment protocol for cyanide poisoning. While other drugs have replaced amyl nitrite for this medicinal use, for the last 50 years alkyl nitrites have been used mainly as a component of room odorant products (Wikipedia 2006). Sold in small glass bottles or capsules nostalgically referred to as poppers, in reminiscence of the glass capsules that housed amyl nitrite as a heart medication, these compounds are also widely used as a recreational inhalant to enhance sexual experience (Wikipedia 2006). Because of their ability to relax smooth muscle tissue in the body, which includes the anal sphincter (their success as an angina treatment was based on their ability to dilate the blood vessels), their use has long been popular in the male homosexual population to enhance sensation during anal intercourse and to prolong and intensify orgasm (Wikipedia 2006).

Many of us were first introduced to poppers through Hollywood, which depicted the drug in such cult classics as Score and Fear and Loathing in Las Vegas, and through the mainstream media, which was awash with stories concerning the use of the inhalant in the 1970s and 80s (Wikipedia 2006). Although more popular with adults than youths, the drug has been widely used in rave subculture to enhance the experience of lights and music on the dance floor since the insurgence of the phenomenon in the 1980s (Wikipedia 2006). Currently illegal in the United States after a long and particularly convoluted legal history, poppers are still easily accessible through the Internet and other adult sources (Wikipedia 2006). While the concern over a possible poppers-AIDS connection has certainly lapsed since the near hysteria surrounding this issue in the 1980s, it nonetheless still lingers, albeit under a new guise. Where researchers once looked for a direct connection between compound and disease, findings are more recently presented to support the idea that alkyl nitrites act as a co-factor in the development of Kaposi’s sarcoma in AIDS patients, and also as an immune suppressant accelerating the progression of AIDS. Is it possible that the majority of the world’s AIDS researchers erroneously discounted a link between poppers and AIDS? It’s an interesting possibility, but does the link stand up to scientific scrutiny?

A Brief History of the AIDS-Alkyl Nitrite Hypothesis

Before looking at the studies that support or deny the AIDS-alkyl nitrite hypothesis, I found it helpful to gather some background information about the emergence of AIDS to put the dispute into context. AIDS burst onto the scene in 1981, when clinical investigators became aware that some very rare diseases were occurring in unusually high rates in young homosexual men with no previous health problems. These diseases included Kaposi’s sarcoma (KS) (CDC 1981b; CDC 1982a,e), a rare connective tissue cancer that previously had been seen mainly in older men of Mediterranean or Jewish origin, in Africa among young people and children (American Cancer Society 2006), and in transplant patients receiving immunosuppressive therapy to reduce organ rejection (Gange and Jones 1978; Safai and Good 1981). Opportunistic infections such as Pneumocystis carinii pneumonia (PCP), a rare form of pneumonia, and chronic enlargement of the lymph nodes were also present in many instances (CDC 1981a,b, 1982a; Masur et al. 1981; Gottlieb et al. 1981). With further research, it became clear that that these men had one thing in common: Their immune function was compromised because the cell-mediated aspect of their immune system was impaired by a loss of T-helper cells bearing the CD4 marker on their surface (Gottlieb et al. 1981; Masur et al. 1981; Siegal et al. 1981; Ammann et al. 1983a).

Such rare diseases in young men with no history of illness or immunosuppressive therapy had never been seen before in the history of medicine. Thus began the long and frustrating search for a cause. Not surprisingly, in the early stages of this research, scientists came to the rational conclusion that, because initially only homosexual men displayed this unique set of symptoms, some aspect of the gay lifestyle might be playing a role in the development of this disease (Goedert et al. 1982; Sonnabend et al. 1983; Mavligit et al. 1984). Many young men with AIDS symptoms also reported using poppers, a popular recreational inhalant among homosexuals at the time. As one of several behavioral aspects unique to the homosexual lifestyle, poppers were investigated during these early stages as a possible link to the syndrome. It was an interesting hypothesis, but one that would be ruled out relatively quickly. The first cracks in the hypothesis occurred when clinicians began to see the syndrome in populations outside of the homosexual community. Hemophiliacs and other recipients of blood products, injection drug users, female sexual partners of bisexual males, and infants born to females with the syndrome or a past history of injection drug use—all of these cases pointed to a new hypothesis that the disease was caused by a blood borne agent, such as a virus (CDC 1982b,c,d,e, Masur et al. 1982; 1983a; Ammann et al. 1983b; Davis et al. 1983; Elliot et al. 1983; Harris et al. 1983; Poon et al. 1983; Rubinstein et al. 1983).

Despite these findings, scientists continued to pursue the AIDS-alkyl nitrite hypothesis by completing a series of large and well-designed research studies that investigated the link. Although it may seem counterintuitive, it is simply good science to investigate a hypothesis until it is either repeatedly shown to be false or continues to stand up under continued scientific scrutiny. In this case, the hypothesis failed to stand up to the scrutiny of several studies. The results of the largest of these studies, referred to as the MACS (Multicenter AIDS Cohort Study) Project, were published in the prestigious New England Journal of Medicine in 1987 (Polk et al. 1987). This study investigated 1835 HIV positive homosexual men, 59 of which developed AIDS in the course of the 15-month study. One of many aspects studied in this long-term investigation was the possible role of alkyl nitrites in both AIDS and KS; no link was found (Polk et al. 1987; Voeller 1990). Another large-scale study by the New York Blood Center supported these findings (Stevens et al. 1986), as did other smaller studies (Vandenbroucke 1989; Schechter et al. 1993). The Schechter study was particularly definitive. In this study, 715 homosexual men were studied for nearly nine years. Of the 365 HIV-positive men, 136 subsequently developed AIDS. No cases of AIDS occurred in the HIV-negative men, even though they reported considerable use of alkyl nitrite inhalants (Schechter et al. 1993).

In my mind, these studies cleanly sever any possible link between AIDS and inhalation of alkyl nitrites. Science has confirmed what my mind had already surmised: a compound used for over 150 years by countless people to treat angina and cyanide poisoning could not be a casual factor in a disease that first appeared 25 years ago. It simply doesn’t make sense. It seems that many proponents of the alkyl nitrite-AIDS connection also saw the light. Leaving this initial hypothesis behind, researchers soon began to entertain new questions: Could alkyl nitrites accelerate the progression of AIDS by further compromising the immune system? Could they play a role in the development in KS, a disease seen mainly in the homosexual AIDS population? Here are two more interesting questions in the quest for definitive answers. How would the research findings deal with these new questions? Would well-designed studies support or refute these hypotheses?

Taking the Alkyl Nitrite-AIDS Hypotheses One Step Further

I approached these studies with an unbiased mind, searching for both solid and faulty logic, and for strength and weakness in experimental design. I urge you to do the same as you follow me through this further analysis of the AIDS-alkyl nitrite hypotheses. First on the list is the hypothesis that alkyl nitrites suppress the immune system, thereby either encouraging the development of AIDS in HIV-positive individuals or increasing the likelihood that an individual will become infected with the AIDS virus in the first place.

How does the data either support or refute this hypothesis? The first thing that struck me in researching the numerous studies on this topic was that while some immune suppression was found, numerous factors have confounded these findings to the point where they cannot be considered scientifically valid. On first glance, a large number of studies seem to support the immune suppression hypothesis, but further study of the experimental design used in these studies, as well as other shortcomings reveal these claims are on very shaky ground. I began my analysis by looking more closely at a problem found in most of the studies I came across, that of proper dosing.

Not surprisingly, most of these studies are experiments where either mice or cells were exposed to varying concentrations of alkyl nitrites, through various means of delivery. The first question that popped into my mind was how relevant are these experiments to real life? While helpful information is sometimes gained from these types of studies, more often, the findings cannot be transferred to human beings. Many new drugs are studied outside of the human context and, while the lab reports show they are a promising means of treatment, the drug fails to act the same way in human patients (Voeller 1986). Contrasting these experiments to the MACS Project and other studies where humans were studied, I found it impossible to compare the two. The next question that came to mind was how did the researchers adjust for the fact that they are using mice or cells, which differ from human subjects in many ways? Perhaps the most obvious difference is one of scale. Mice and cells are much smaller than human beings. How were doses adjusted to account for this size difference? Most frequently, I discovered, they weren’t.

Let’s look at a study completed by a group of researchers at M.D. Hospital in Houston, Texas (Hersh et al. 1983). The researchers investigated the effects of butyl nitrite (a type of alkyl nitrite) on laboratory cultures of white blood cells. So far, so good. We know the limitations of such an experiment, but let’s continue and look at the dosing regime. Hersh and colleagues reported that when exposed to a 1% concentration of butyl nitrite for 24 hours, many of these cells were killed, while at 0.5%, the cell number and viability were unaffected. What do these findings mean for an average human being? To establish a 1% concentration of butyl nitrite in an average human with six liters of blood even from a brief moment (we are not considering the 24 hour time period here yet), 60 mL of butyl nitrite needs to be added to the blood. A bottle of poppers contains 10 to 12 mL of the compound. This means that five or six bottles of the compound would have to be injected into a human to replicate the conditions of the experiment. Since nitrites are inhaled rather than injected (injecting nitrites is toxic) and only a small fraction of the compound is actually absorbed by the lungs, this study tells us nothing in reality except that a 1% concentration of butyl nitrite kills cells in a test tube. (Voeller 1986)

Numerous experiments conducted on mice also fail to adjust the doses for differences in lung size or body weight. Adjusting dose for body weight is a fundamental aspect of studies using experimental animals. When non-physiological doses (higher or lower than the comparable human dose) are used in animal studies, the results cannot be meaningfully compared to humans. Interestingly, many of the studies I reviewed administered doses that were at near lethal levels, so that it’s also unclear if the observed effect was due to toxicity (Lotzova et al. 1984; Gaworski et al. 1992; Soderberg et al. 1996a; Soderberg and Barnett 1996; Soderberg 1998; Tran et al. 2003). Imagine administering a near lethal dose of any compound, such as aspirin. Would the research findings tell us anything about the behavior of the compound at the normally consumed dose? I’m afraid not. Although it is clear that such data in no way test the hypothesis that alkyl nitrites impair the human immune system, I was completely taken aback to see how many advocates cite numerous studies of similar design to support the AIDS-poppers hypothesis.

In addition to dosing problems, many of the experiments that advocates reference in support of the AIDS-poppers hypothesis report changes in immune function only after administering the compound for an extended duration that simply does not reflect human use. For instance, in the 1983 study by Hersh et al. mentioned earlier, the cells in the experiment were exposed to butyl nitrite continuously for 24-72 hours. I was surprised that this and other studies (Gaworski et al. 1992; Tran et al. 2003) did not administer the compound for a briefer duration to better mimic human inhalation of the compound. Interestingly, I did come across one study that exposed mice to 300 ppm of alkyl nitrites for 6.5 hours a day for five days over 18 weeks, a level and duration that better reflects human use (Lewis 1985). No changes in immune function were observed.

In review, what did these experimental findings say about the effect of alkyl nitrites on immune function? In general, most of the findings stated that immune impairment occurred, but the doses were administered in a manner that rendered the findings invalid. This of course is a matter of scientific opinion. Suppose you don’t agree that the experimental designs were flawed? If so, I have a last point that may interest and surprise you. Many of the studies that saw immune impairment at near toxic doses of alkyl nitrites also reported that these effects were entirely reversible within days of stopping the dose (Soderberg and Barnett 1993; Dax et al. 1991; Soderberg et al. 1996b). Another interesting point to consider is that when immune cell function was compromised, the data often revealed that other cell types experienced cytotoxic effects, showing that nitrites did not act selectively against immune cells, but were harmful to other cell lines as well, suggesting that lethal doses of the compound were administered (Hersh et al. 1983). Additionally, published results were often contradictory. For instance, in 1996 Soderberg and Barnett (Soderberg et al. 1996a) repeated experiments that they had previously published in 1995 (Soderberg and Barnett 1995). The results of these experiments were opposite to those obtained when the same steps were followed previously. In science it’s important to repeat experiments to either support or invalidate a hypothesis. In this case, inconsistent findings help us see that the original hypothesis was invalid.

What About the Relationship Between Alkyl Nitrites and KS?

Named after Dr. Moritz Kaposi who first described the condition in 1872, Kaposi’s sarcoma has been with us for many years. Until the 1980s, the sarcoma (a cancer that effects the connective tissue such as bone, cartilage, fat, muscle, blood vessels and ligaments) was considered a rare disease. In the past it occurred in three main populations: elderly men of Mediterranean or Jewish heritage, organ transplant recipients receiving immune suppression therapy, and young people in Africa (American Cancer Association, 2006). It will probably strike you that these are not populations that typically use nitrites. With the advent of AIDS, Kaposi’s sarcoma reached epidemic proportions in the homosexual male population. Prior to the AIDS epidemic, the cancer occurred in only 0.02 to 0.06 individuals per 100,000 (Oettle 1962). By 1984, never-married men in the San Francisco area were 2000 times more likely to develop the disease than they were in the previous decades (Williams et al. 1994). Fortunately, as new AIDS treatments evolved, the number of cases of Kaposi’s sarcoma has fallen by about 85% (American Cancer Association 2006). These numbers and dates are interesting as they correspond directly with the emergence and treatment of the HIV virus, not with use of poppers, which was at it height in the 1960s and 1970s, prior to the AIDS epidemic (Lau et al. 1992; Stall and Purcell 2000) Scientists suggesting a connection between KS and alkyl nitrites often refer to the fact that KS occurs about 20 times more frequently in homosexual men with AIDS than in heterosexual individuals suffering from the disease (Beral 1989), citing that these findings support the hypothesis that alkyl nitrites may be a cofactor of KS (Wikipedia 2006). While the hypothesis is interesting, I find continued claims of this nature surprising, considering that they were refuted by the MACS study (reviewed earlier in the text) in 1987 (Polk et al. 1987), among other studies (Voeller 1990). In fact, researchers from the Johns Hopkins School of Hygiene and Public Health reanalyzed data from the MACS study and actually found that higher use of alkyl nitrites corresponded with lower incidence of KS (Palenicek et al. 1992).

This leaves us with the million-dollar question: If alkyl nitrites are not causing KS, what is? Many recent studies support the hypothesis that KS is caused by a sexually transmitted herpes virus, HHV-8, also called KSHV (Kaposi’s Sarcoma Associated Herpes Virus) (Whitby et al. 1995; Ziegler and Katongole-Mbidde 1996; Gnann et al. 2000). This hypothesis supports data that shows a low prevalence of KS among intravenous drug users and blood product recipients suffering from AIDS, as these individuals typically contract HIV through non-sexual (blood to blood) means. As a herpes virus, HHV-8 travels through nerve endings, and although it is sexually transmissible, it is unlikely to be transmitted through the blood (Gnann et al. 2000). Many studies support the HHV-8 hypothesis. As early as 1989, the Centers for Disease Control recognized that if an infectious agent caused KS, it was likely transmitted by some form of homosexual contact rather than by blood (Beral 1989). Six years later in a 1995 study by Whitby et al., HHV-8 was consistently detected in the biopsy samples of patients with both AIDS related and non-AIDS related (classical) KS. Further, HHV-8 was detected in the blood cells of over half of the KS patients, but not in those of the non-KS patients used as controls. Further studies support these findings (Bobroski et al. 1998; Gnann et al. 2000). In a 1996, study of children in Uganda published in the International Journal of Cancer, Ziegler and colleagues studied 100 cases of KS in children under age 15. They reported that the incidence of childhood KS in Uganda in 1996 was 40 times as great as it was in the pre-AIDS era. DNA from HHV-8 was found in all cases of childhood KS tested. Distribution patterns of the tumors suggested the virus entered during birth or breast-feeding (Ziegler 1996).

But what about the correlational findings linking high use of alkyl nitrites to KS? When reviewing these findings, it’s important to bear in mind that correlation does not equal cause. An interesting case in point comes from a 1985 study by Haverkos et al. that is widely cited in support of the KS-alkyl nitrite connection. While the authors found a correlation between the high levels of nitrite use and KS, they also found many other statistically significant correlations. For instance, homosexual men with KS tend to have had hepatitis B; use drugs such as amphetamines, barbiturates, cocaine, LSD, and marijuana to name a few; had a greater number of sexual partners than those without KS; and have an income over $20,000 per year (Haverkos et al. 1985).

Not surprisingly, correlation is easily confused with fact. I’ve found that a semi-ridiculous analogy often helps bring the point home. For instance, while homosexual men with KS may also be more likely to own a three-legged dog than those without KS, there is no proven causal link between KS and three-legged dog ownership. It’s the same with alkyl nitrite use. Because we cannot prove the link is more than a correlation, the conclusions remain unclear. Often upon further analysis, as was the case with a reanalysis study done by Marmor et al. in 1982, when other variables are controlled for, nitrite use is shown to no longer be a significant factor.

Summing It All Up

Bringing our scientific analysis to an end, we’ve learned a good deal about scientific research methods and how a scientific hypothesis can either stand against or fall under the weight of solid research. The main problem with the research supporting the alkyl nitrite-AIDS hypotheses is that many of the standards of experimental design are simply not upheld. Most experiments are in vitro (test tube) or involve mice. Results of these studies are then used by advocates to support the poppers-AIDS hypotheses, disregarding the fact that doses were not adjusted for body weight and lung size in mice, and were often administered at near toxic levels over a duration that failed to reflect human alkyl nitrite use. Under these conditions, it is simply impossible to extrapolate the findings to human beings. Not to mention that results derived from the same experimental design were often inconsistent. Even if one fails to consider these experimental design flaws, the small number of studies supporting a connection between poppers and AIDS or KS still do not stand up under the tremendous weight of the large number of well-designed research studies incriminating viruses, not poppers or other compounds, as the causal agent in both AIDS and KS. Advocates of the poppers hypotheses seem to want to sweep this burgeoning body of research under the carpet. To prove something is true in science, you also need try to show that the alternative is false. There are numerous web sites on the Internet that support the popper-AIDS/KS connection. I haven’t seen one that braves the waters to explore the data gathered by mainstream AIDS/KS research. The current is simply too strong to risk a swim.

“By continuing up a wrong path, we lose time finding the right one.
On the AIDS clock, time is measured in deaths.”

~ Dr. Bruce Voeller, Internationally Renowned AIDS Researcher (Voeller 1986)

Literature Cited

Ammann AJ, Abrams D, Conant M, Chudwin D, et al. 1983a. Acquired immune dysfunction in homosexual men: immunologic profiles. Clinical Immunology and Immunopathology. 27(3):315-25.

Ammann AJ, Cowan MJ, Wara DW, Weintrub P, et al. 1983b. Acquired immunodeficiency in an infant: possible transmission by means of blood products. Lancet. 1(8331):956-8.

American Cancer Society. 2006. Detailed Guide: Kaposi’s Sarcoma, What is Kaposi’s Sarcoma? Retrieved on March 21, 2006. http://www.cancer.org/docroot/cri/content/cri_2_4_1x_what_is_kaposis_sarcoma_21.asp?sitearea=cri

Beral V, Peterman TA, Berkelman RL, Holmberg SD, Jaffe HW. 1990. Kaposi's sarcoma among persons with AIDS: a sexually transmitted infection? Lancet. 335(8682):123-8.

Bobroski L, Bagasra AU, Patel D, Saikumari P et al. 1998. Localization of human herpesvirus type 8 (HHV-8) in the Kaposi's sarcoma tissues and the semen specimens of HIV-1 infected and uninfected individuals by utilizing in situ polymerase chain reaction. Journal of Reproductive Immunology. 41(1-2):149-60.
CDC (Centers for Disease Control). 1981a. Epidemiologic notes and reports Pneumocystis pneumonia - Los Angeles. Morbidity and Mortality Weekly Reports. 30:1-3.
CDC. 1981b. Kaposi's sarcoma and pneumocystis pneumonia among homosexual men - New York City and California. Morbidity and Mortality Weekly Reports. 30:305-8.
CDC. 1982a . Epidemiologic notes and reports persistent, generalized lymphadenopathy among homosexual males. Morbidity and Mortality Weekly Reports. 31:249-51.
CDC. 1982b. Current trends update on acquired immune deficiency syndrome (AIDS) - United States. Morbidity and Mortality Weekly Reports. 31:577-80.
CDC. 1982c. Epidemiologic notes and reports Pneumocytsis carinii pneumonia among persons with hemophilia A. Morbidity and Mortality Weekly Reports. 31:365-7.
CDC. 1982d. Epidemiologic notes and reports possible transfusion-associated acquired immune deficiency syndrome (AIDS) - California. Morbidity and Mortality Weekly Reports. 31:652-4.
CDC. 1982 e. A cluster of Kaposi’s sarcoma and Pneumocystis carinii pneumonia among homosexual male residents of Los Angeles and Range counties, California. Morbidity and Mortality Weekly Reports 31:305-307.

Davis KC, Horsburgh CR Jr, Hasiba U, Schocket AL et al. 1983. Acquired immunodeficiency syndrome in a patient with hemophilia. Annals of Internal Medicine. 98(3):284-6.

Dax EM, Alder WH, Nagel JE, Lange WR et al. 1991. Amyl nitrite alters human in vitro immune function. Immunopharmacology and Immunotoxicology, 13(4):577-87.

Elliott JL, Hoppes WL, Platt MS, Thomas JG et al. 1983. The acquired immunodeficiency syndrome and Mycobacterium avium-intracellulare bacteremia in a patient with hemophilia. Annals of Internal Medicine. 98(3):290-3.

Gange RW, Jones EW. 1978. Kaposi's sarcoma and immunosuppressive therapy: an appraisal. Clinical and Experimental Dermatology. 3(2):135-46.

Gaworski CL, Aranyi C, Hall A 3rd, Levine BS et al. 1992. Prechronic inhalation toxicity studies of isobutyl nitrite. Fundamental and Applied Toxicology. 19(2):169-75.

Gnann JW Jr, Pellett PE, Jaffe HW. 2000. Human herpesvirus 8 and Kaposi's sarcoma in persons infected with human immunodeficiency virus. Clinical Infectious Diseases. Suppl 1:S72-6.

Goedert JJ, Neuland CY, Wallen WC, Greene MH et al. 1982. Amyl nitrite may alter T lymphocytes in homosexual men. Lancet. 1(8269):412-6.

Gottlieb MS, Schroff R, Schanker HM, Weisman JD et al. 1981. Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: evidence of a new acquired cellular immunodeficiency. New England Journal of Medicine. 305(24):1425-31.

Harris C, Small CB, Klein RS, Friedland GH et al. 1983. Immunodeficiency in female sexual partners of men with the acquired immunodeficiency syndrome. New England Journal of Medicine. 308(20):1181-4.

Haverkos, H W. Pinsky, P F. Drotman, D P. Bregman, D J. 1985. Disease manifestation among homosexual men with acquired immunodeficiency syndrome: a possible role of nitrites in Kaposi's sarcoma. Sexually Transmitted Diseases. 12(4):203-8.

Hersh EM, Reuben JM, Bogerd H, Rosenblum M et al. 1983. Effect of the recreational agent isobutyl nitrite on human peripheral blood leukocytes and on in vitro interferon production. Cancer Research. 43(3):1365-71.

Jaffe HW, Choi K. Thomas PA, Haverkos HW et al. 1983. National case-control study of Kaposi's sarcoma and Pneumocystis carinii pneumonia in homosexual men: part 1. epidemiologic results. Annals of Internal Medicine. 99(2):145-51.

Lau RK, Jenkins P, Caun K, Forster SM et al. 1992. Trends in sexual behaviour in a cohort of homosexual men: a 7 year prospective study. International Journal of STDs and AIDS. 3(4):267-72.

Lewis DM, Koller WA, Lynch DW, Spira TJ. 1985. Subchronic inhalation toxicity of isobutyl nitrite in BALB/c mice. II. Immunotoxicity studies. Journal of Toxicological and Environmental Health. 15(6):835-46.

Lotzova E, Savary CA, Hersh EM, Khan AA et al. 1984. Depression of murine natural killer cell cytotoxicity by isobutyl nitrite. Cancer Immununology Immunotherapy. 17(2):130-4.

Marmor M, Friedman-Kien A E, Laubenstein L, Byrum RD et al. 1982. Risk factors for Kaposi's sarcoma in homosexual men. Lancet. 1(8281):1083-7.

Masur H, Michelis MA, Greene JB, Onorato I et al. 1981. An outbreak of community-acquired Pneumocystis carinii pneumonia: initial manifestation of cellular immune dysfunction. New England Journal of Medicine. 305(24):1431-8.

Masur H, Michelis MA, Wormser GP, Lewin S et al. 1982. Opportunistic infection in previously healthy women. Initial manifestations of a community-acquired cellular immunodeficiency. Annals of Internal Medicine. 97(4):533-9.

Mavligit GM, Talpaz M, Hsia FT, Wong W et al. 1984. Chronic immune stimulation by sperm alloantigens: support for the hypothesis that spermatozoa induce immune dysregulation in homosexual males. Journal of the American Medical Association. 251(2):237-41.

Oettle AG. 1962. Geographical and racial differences in the frequencies of Kaposi's sarcoma as evidence of environmental or genetic causes. Acta Unio Internationalis Contra Cancrum. 18:330-63.

Palenicek J, Fox R, Margolick J, Farzadegan H et al. 1992. Longitudinal study of homosexual couples discordant for HIV-1 antibodies in the Baltimore MACS Study. Journal of Acquired Immune Deficiency Syndromes. 5(12):1204-11.

Polk BF, Fox R, Brookmeyer R, Kanchanakaksa S et al. 1987. Predictors of the acquired immunodeficiency syndrome developing in a cohort of seropositive homosexual men. New England Journal of Medicine. 316(2):61-6.

Poon MC, Landay A, Prasthofer EF, Stagno S. 1983. Acquired immunodeficiency syndrome with Pneumocystis carinii pneumonia and Mycobacterium avium-intracellulare infection in a previously healthy patient with classic hemophilia. Clinical, immunologic, and virologic findings. Annals of Internal Medicine. 98(3):287-90.

Rubinstein A, Sicklick M, Gupta A, Bernstein L et al. 1983. Acquired immunodeficiency with reversed T4/T8 ratios in infants born to promiscuous and drug-addicted mothers. Journal of the American Medical Association. 249(17):2350-6.

Safai B, Good RA. Kaposi's sarcoma: a review and recent developments. 1981. CA: A Cancer Journal for Clinicians. 31(1):2-12.

Schechter MT, Craib KJ, Gelmon KA, Montaner JS et al. 1993. HIV-1 and the aetiology of AIDS. Lancet. 341(8846):658-9.

Soderberg LS. 1998. Immunomodulation by nitrite inhalants may predispose abusers to AIDS and Kaposi's sarcoma. Journal of Neuroimmunology. 83(1-2):157-61.

Soderberg LS. 1999. Increased tumor growth in mice exposed to isobutyl nitrtite. Toxicology Letters. 104(1-2):35-41.

Soderberg LS, Barnett JB. 1993. Inhaled isobutyl nitrite compromises T-dependent, but not T-independent, antibody induction. International Journal of Immunopharmacology. 15(7):821-7
Soderberg LS, Barnett JB. 1995. Inhalated exposure to isobutyl nitrite inhibits macrophage tumoricidal activity and modulates inducible nitric oxide. Journal of Leukocyte Biology. 57(1):135-40.

Soderberg LS, Barnett JB. 1996. Leukopenia and altered hematopoietic activity in mice exposed to the abused inhalant, isobutyl nitrite. Experimental Hematology. 24(7):848-53.

Soderberg LS, Chang LW, Barnett JB. 1996a. Elevated TNF-a and inducible nitric oxide production by alveolar macrophages after exposure to a nitrite inhalant. Journal of Leukocyte Biology. 60(4):459-64.

Soderburg LS, Flick JT, Barnett JB. 1996b. Acute inhalation exposure to isobutyl nitrite causes nonspecific blood cell destruction. Experimental Hematology. 24(5):592-6.

Sonnabend J, Witkin SS, Purtilo DT. 1983. Acquired immunodeficiency syndrome, opportunistic infections, and malignancies in male homosexuals. A hypothesis of etiologic factors in pathogenesis. Journal of the American Medical Association. 249(17):2370-4.

Siegal FP, Lopez C, Hammer GS, Brown AE et al. 1981. Severe acquired immunodeficiency in male homosexuals, manifested by chronic perianal ulcerative herpes simplex lesions. New England Journal of Medicine. 305(24):1439-44.

Stall R, Purcell DW. 2000. Intertwining epidemics: a review of research on substance use among men who have sex with men and its connection to the AIDS epidemic. AIDS and Behavior. 4(2):181-92.

Stevens CE, Taylor PE, Zang EA, Morrison JM et al. 1986. Human T-cell lymphotropic virus type III infection in a cohort of homosexual men in New York City. Journal of the Americam Medical Association. 255(16):2167-72.

Tran DC, Yeh KC, Brazeau DA, Fung HL. 2003. Inhalant nitrite exposure alters mouse hepatic angiogenic gene expression. Biochemical and Biophysical Research Communications. 310(2):439-45.

Vandenbroucke JP, Pardoel VP. 1989. An autopsy of epidemiologic methods: the case of "poppers" in the early epidemic of the acquired immunodeficiency syndrome (AIDS). American Journal of Epidemiology. 129(3):455-57.

Voeller B. 1986. Are poppers safe? Mariposa Occasional Paper 6. Mariposa Education and Research Foundation, Topanga, California.

Voeller B. 1990. Personal letter to Hon. Henry Waxman, Chairman, Health and Environmental Subcommittee. May 23, 1990.

Whitby D, Howard MR, Tenant-Flowers M, Brink NS et al. 1995. Detection of Kaposi sarcoma associated herpesvirus in peripheral blood of HIV-infected individuals and progression to Kaposi's sarcoma. Lancet. 346(8978):799-802.

Wikipedia. 2006. Retrieved Mar 21, 2006. http://en.wikipedia.org/wiki/Alkyl_nitrites

Williams CKO et al. 1994. AIDS-associated cancers. In Essex M, et al., eds. AIDS in Africa. New York, Raven Press, pp. 325-71.

Ziegler JL, Katongole-Mbidde E. 1996. Kaposi's sarcoma in childhood: an analysis of 100 cases from Uganda and relationship to HIV infection. International Journal of Cancer. 65(2):200-3.

Dr. Bruce Voeller, Internationally Renowned AIDS Researcher
“By continuing up a wrong path, we lose time finding the right one.
On the AIDS clock, time is measured in deaths.” (Voeller 1986)

Reprinted From: The Art of Scientific Scrutiny: Investigating the Poppers-AIDS Hypothesis By Christine Weber, B.Sc.

A Critical Review of the Anti-Popper Research Bibliography

2006-04-27T16:17:00.000-07:00

The articles referenced in Hank Wilson’s bibliography of research do not support his claim that nitrite use causes risky sexual behavior and a decrease in immune function that may lead to HIV infection or Kaposi's sarcoma. "Wilson has not carefully read the references he is using to support his claims or he would not use them."

A Critical Review of Hank Wilson’s Bibliography of Anti-Popper Research
By Lisa Ringold, PhD pharmacology

The articles referenced in Wilson’s bibliography of research do not support his claim that nitrite use causes risky sexual behavior and a decrease in immune function that may lead to HIV infection or Kaposi's sarcoma. An important problem is that out of 90 references, 13 are listed twice and one is listed three times. This is an obvious attempt to make the body of evidence appear larger. The list contains typographical errors, an indication of a lack of attention to detail, which is an essential component of scientific evaluation. Some of his references are merely data presented at meetings as posters or informal talks, which are preliminary data that has not been confirmed or published. Finally, one of the references was submitted, but not accepted for publication. Articles that have been rejected for publication are never cited in credible reference lists.

The primary issue concerning the articles referenced by Wilson is that they are very weak in terms of data presented. The results are not repeated by other scientists. In fact, there are contradictory results both by the same researcher and between different researchers.

A major weakness of the report by Wilson is that for the immune function research (an important part of his claims), nearly every reference is work performed by Soderberg. When one investigator is primarily the only one cited, it indicates that his work has not been replicated by others. This is extremely important to establish validity of claims and the fact that other researchers are not cited is very suspect. If experimental results have not been replicated and thus confirmed by another researcher, the results are most likely not valid.

A limitation of Soderberg's work is that minimal data is presented in each of his papers and the same work is presented in more than one publication. Occasionally researchers will do this to increase their publication volume and it does not reflect that a large amount of data has been generated. In many of Soderberg’s articles, Hank Wilson is acknowledged for providing the nitrites, which indicates bias. It appears that Wilson and Soderberg are associates and considering Wilson’s zeal against nitrites, the research by Soderberg is very suspect. Hank Wilson formed the one man Committee to Monitor Poppers. Wilson's has publicly stated that his boyfriend, who always used poppers with sex and had KS, died of AIDS. Wilson has also publicly acknowledged that he himself was diagnosed with AIDS in 1987. Therefore, it is likely that Wilson has a personal vendetta against nitrites.

Another very important discrepancy is that Soderberg does not obtain consistent results between research summarized in his own papers. The fact that he publishes conflicting data without explanations for this illustrates his inability to establish a connection between nitrite use and AIDS and KS. Furthermore, Soderberg’s results are not consistent with other researcher’s results. This makes it impossible to draw any conclusions from the research that is presented. Wilson has not carefully read the references he is using to support his claims or he would not use them.

In addition to these issues, another extremely serious problem in Wilson’s articles is that the mice or rats used in the experiments are given massive doses that are not relative to a typical human exposure. In fact, in some of the studies, the doses used are lethal. Adjusting a drug dose for a particular body weight is a fundamental pharmacological paradigm for treating experimental animals and it is impossible to determine the effects of nitrites when a toxic dose is used. Therefore, the animal studies are meaningless when comparing them to humans. It is not clear how these articles were published with this blatant oversight. Furthermore, the excessive doses could explain the discrepancies in the results.

Yet another criticism of the immune function research is that the alterations in immune function were reversible. Therefore, it is likely that there are no long-term effects of nitrites, particularly considering the exceedingly high doses used. Lower doses may not have any effect on immune function.

The references cited by Wilson have a scarcity of studies utilizing human subjects. More human studies would dramatically enhance Wilson's argument and they could easily be performed. Perhaps these types of studies have been done, with no negative results, and thus have not been published.
One of the most serious problems with the behavioral studies is that they cannot establish a causal relationship between nitrite use and HIV infection. Only associations between the two can be shown, and because two behaviors occur together, this does not mean that one causes the other. The most logical explanation for the association between nitrite use and unsafe sex is that it results from an underlying personality characteristic that predisposes some men to risky behaviors, and that sexual risk-taking and substance use are just two such behaviors observed in men with risk-taking behavior. Furthermore, nitrites are readily available in places of higher risk behavior, such as pornographic theaters and bookstores.

It is also likely that the immune status of those who use drugs may already be compromised as a result of an unhealthy lifestyle or other psychological factors. To further complicate the issue most of the men who abuse nitrites also use other substances. Therefore, it is impossible to determine the effect of each substance separately. It is of particular consequence if injected drugs are used in conjunction with nitrites. The sharing of needles is a well-established route of HIV infection.

Finally, Wilson’s cited behavioral studies are derived from self-reports, which is subject to recall bias. The validity of the research relies on the accuracy of the reporter and if they are using drugs or alcohol, they may not remember specific drug use or have an altered perception of their actions.

Although Wilson proposes that nitrite use can facilitate HIV infection and Kaposi’s sarcoma, one of his references listed three articles for and three against association of nitrite use with HIV seropositivity and KS. When conflicting data is presented, one cannot conclude that nitrite use is involved in these illnesses.

Therefore, even though Wilson’s reference list might look impressive to the untrained eye, he does not have a case for his claim that nitrite use causes HIV infection or Kaposi’s sarcaoma.

Wilson's "Nitrite Poppers" Section
Most of the work in the first section has experimental design flaws, one of which is that the sample sizes are too small. It is important to utilize a large enough sample in experiments to accurately represent a true population. Furthermore, in many of the studies, most of the tests are not repeated. This is an extremely crucial element of experimental design that is necessary in establishing statistical significance for a particular result. It is essential to repeat experiments because it is possible to obtain contradictory data between different tests, resulting from factors such as researcher error.

Soderberg (1999) Increased tumor growth in mice exposed to inhaled isobutyl nitrite. Toxicology Letters, 104:35.
This article is one of the many Soderberg references listed by Wilson. All of this researcher's studies using mice suffer from a very serious flaw, which is that the mice are exposed to extremely large doses of nitrites when their body size is taken into account.
Earlier work by Soderberg (J. of Immunopharmacology, 15(7):821) reported the, effects of nitrite inhalation on antibody induction of mice were tested. They saw no changes in antibody responsiveness after administering a dose of 300 ppm isobutyl nitrite for 45 minutes a day over a 14-day period. Soderberg only saw decreases in antibody production at 750 and 900 ppm isobutyl nitrite. Even at this dose, there was full recovery within seven days, once again demonstrating reversibility of nitrite effects on immune function, despite the high dose. Since Soderberg's group did not observe their desired effects at a dose which might not be toxic to the animals, this probably explains why they chose this dosing paradigm for their future work.
Although Soderberg reported an increase in incidence and size of tumors, the dose was too high to make any claims. Furthermore, the exposures did not significantly affect body weight, spleen weight, or spleen cellularity, which was reported in other articles. There are many contradictory research results published on a variety of different parameters, making it difficult to ascertain the actual effects of nitrites.

Dax et al. (1991) Amyl nitrate alters human in vitro immune function. Immunopharmacology and Immunotoxicology, 13:557.
In this study, the effects of volatile nitrite inhalation on the immune system of gay male volunteers was examined. However, the amyl nitrate was administered in an unusual manner. The apparatus used consisted of a 4 liter flask connected by tubing to a rubber inflatable breathing bag. Another tube connected the flask to room air and a mouthpiece was attached to a side opening of the flask. Amyl nitrite pearls covered in gauze were broken and dropped in the bottom of the flask. Thirty seconds later, the subject exhaled, and then inhaled the air from the flask until the rubber bag collapsed and completed inspiration with room air (via the flask). The inspiration was held for 5 seconds before exhaling. The drug dose was varied by altering the number of nitrite pearls dropped in the flask. This method of drug administration is very complicated and it does not represent the actual exposure that occurs when the drug is inhaled from a vial. As everyone has a different lung capacity, it is impossible to standardize dose using this flask apparatus. Because of this dilemma, it is not understood why the nitrite was not inhaled directly from a vial to more accurately depict a physiological dose. Surprisingly, the authors claim that "the experimental protocol simulated the common episodic pattern of nitrite abuse." Since the drug was given three times a day (over a nine hour period) for either three or nine days using a complicated device, it does not follow that this protocol simulates nitrite abuse.
Another major flaw in this study is that there were only nine participants in each of the studies (short term or long term, consisting of three or nine day treatments, respectively, with drug administered three times a day) and the study was not repeated. This is a very low sample number and the experiments should have been repeated at least twice. Since the effects that were observed were readily reversible (see below) the same participants could have been used in an effort to replicate the data. Another approach could have been to recruit other volunteers for this study.
In these experiments, there were no changes in the number of T or B cells (which is considered to be an indicator of general immune function) in either the three or nine day experiments. The only statistically significant effect of nitrites observed was a 30% decrease in natural killer cell activity. This effect only occurred in the long-term study and returned to baseline within four days after cessation of drug exposure. This reversibility indicates that nitrite use may not have long term effects. Other immune function tests were not performed and nitrite exposure had no effect on cell proliferation. These results are not compelling evidence for a major effect of nitrite inhalation on the immune system.

Soderberg, et al (2004) Production of macrophage IL-1β was inhibited both at the levels of transcription and maturation by caspase-1 following inhalation exposure to isobutyl nitrite. Toxicology Letters, 152:47.
Soderberg reported a 15% reduction in IL-1β mRNA transcription from inhalant exposed mice. “Such a minor decrease in transcriptional activity is not likely to be solely responsible for 37–55% decrease in secreted protein.” Thus began the search for multiple mechanisms.
The authors state that exposure to isobutyl nitrite reduced the induction of specific cytotoxic T-cells and macrophage tumoricidal activity and “signaling through the macrophage NF-κB pathway was impaired following inhalant exposure. NF-κB-dependent induction of macrophage nitric oxide synthase (NOS2) and subsequent production of nitric oxide were consequently inhibited. The present study examined the effects of nitrite inhalant exposure on another macrophage product important in innate immunity, IL-1β. The production of IL-1β was inhibited at both transcriptional and post-translational level.” Although this sounds impressive, it is very unlikely that one compound can have this many effects that are not a result of toxicity from excessive doses.

Ponappan et al (2004) Inhaled isobutyl nitrite inhibited macrophage inducible nitric oxide by blocking NFκB signaling and promoting degradation of inducible nitric oxide synthase-2. International Immunopharmacology, 4:1075.
Soderberg is an author on this paper, again demonstrating bias. The reasoning of this paper was very difficult to follow but essentially it is a repeat of a previous paper with the exception that they demonstrated nitrite effects in 5 days instead of 14 days. Phosphorylation of IκBα is a prerequisite for ubiquitination and proteasome-dependent degradation of IκBα, freeing NFκB to move into the cell nucleus and affect gene expression. They could not demonstrate an inhalant-associated decrease in IκBα degradation and they stated that it is likely that inhalant exposure inhibits activity of the IκBα kinase or it may act on an upstream component in the signaling cascade. However they did not measure these parameters to demonstrate that these are a mechanism of action.
The researchers state “data suggested that inhalant exposure likely inhibited macrophage (nitric oxide) NO production by blocking NFκB-mediated activation signaling and promoting poly ubiquitination of NOS2.” It is astounding that researchers can publish this much data that is conflicting and obviously does not show target selectivity of nitrites.

Tran et al (2003) Inhalant nitrite exposure alters mouse hepatic angiogenic gene expression Inhalant nitrite exposure alters mouse hepatic angiogenic gene expression. Biochemical and Biophysical Research Communications, 310:439.
The dose for mice was 1400 ppm for four hours, which is even higher exposure than Soderberg. The utilization of this high dose negates any results that may be observed. The authors give as a rationale for performing the research that organic nitrites (NO donors) in vitro studies have shown
NO to stimulate vascular endothelial growth factor (VEGF) protein and mRNA expression. VEGF is essential for tumor growth and metastasis.
In the discussion of this paper, another Soderberg article is referenced (not included in Wilson’s reference list) presenting the fact that NO is liberated by nitrite but exogenous NO does not produce the immunotoxicity observed following exposure to isobutyl nitrite. This does not make sense because NO mediates macrophage tumoricidal activity, so NO liberation would be beneficial.
Other conflicting data presented was that inhalant nitrite exposure also significantly suppressed the gene expression of Smad5 and Smad7 in mouse liver. Smads regulate transforming growth factor-β-dependent (TGF-β) gene expression, which controls cell proliferation, differentiation, apoptosis, migration, and extracellular matrix production. Smad5 plays an important role in angiogenesis and Smad7 is important in negative feedback regulation of TGF-β. Since these Smads have opposite effects on cancer proliferation, one would not expect both to be suppressed if nitrite had carcinogenic effects.
Another area of concern is that they authors do not address why there were no changes in lung VEGF expression, the increase was seen in the liver. “This observation is somewhat counter-intuitive, since the nitrite exposure concentration is expected to be higher in the lung than in the liver.“ This statement indicates that the authors are unclear about the meaning of their results.

Ponnappan and Soderberg (2001) Inflamatory macrophage nuclear factor-κB and proteasome activity are inhibited following exposure to inhaled isobutyl nitrite. J of Leukocyte Biology, 69:639.
Although the authors demonstrate a reduction of nuclear NFκB in activated macrophages (an immune response), nitrite exposure also reduces un-activated macrophage NFκB, which could be an indication of toxicity. A clear demonstration of nitrite’s reduction in immune response would have been shown had the nitrites had no affect on un-activated macrophages.
The discussion of this paper is very confusing, as they attempt to make sense of contradictory data. They report that although isobutyl nitrite was shown to liberate NO, inhaled NO at a concentration equivalent to that produced by 900 ppm isobutyl nitrite did not alter resident macrophage tumoricidal activity. NO liberation would not affect macrophage tumoricidal activity, because NO liberation is macrophage’s mechanism of action. Since they also claim that isobutyl nitrite inhibits macrophage inducible NO, which could be a feedback mechanism because nitrites liberate NO. They also demonstrate that inhalant exposure inhibits macrophage NFκB activation, which is important in HIV replication. This is another contradiction. Actually, the final sentence of the paper states “conflicting influences may be induced by inhalant exposure.” The authors admit the contradictions in their own paper.

Keilbasa and Fung (2000) Nitrite Inhalation in Rats Elevates Tissue NOS III Expression and Alters Tyrosine Nitration and Phosphorylation. Biochem and Biophysic. Res. Comm, 275:335.
In these experiments, rats were exposed to 109 and 1517 ppm isobutyl nitrite for four hours, which is excessive and does not represent human exposure. They did not find alterations in NOS expression in the lungs or spleen, which according to Soderberg’s hypothesis they should find. They reported an increase in the kidney and liver, which are organs of detoxification and it is unclear what an increase in NOS expression in these organs means. They do not address why there is differential expression. Also it is not understood why they do not measure macrophage NOS expression, which is the proposed tumoricidal mechanism of macrophages. If nitrites diminish NOS in macrophages, it would support a role for nitrites in depressing tumoricidal activity.

Guo, et al. (2000) Acute exposure to the abused inhalant, isobutyl nitrite, reduced T cell responsiveness and spleen cellularity. Toxicology Letters, 116:151.
This work was performed in Soderberg’s lab, yet another reference by him. Guo states there is no change in body or spleen weight, yet spleen cells are decreased. In another paper, Soderberg reported no change in spleen cell cellularity, yet in this publication it is decreased. Although there was a decrease in spleen cells, there was no reduction in CD4 and CD8 helper cells, or in differential lymphocytes. This would indicate that nitrates are not selectively reducing immune function. Although a single 45 min exposure to the inhalant inhibited T cell proliferative responsiveness, it was not sufficient to overtly impair major immune mechanisms. Also, they report that only after the 14 day exposure do they see a decrease in T-dependent antibody responses. These results are not definitive.

Soderberg and Flick (1997) Acute blood toxicity of the abused inhalant, cyclohexyl nitrite. Int J Immunopharmac, 19:305.
In this report cyclohexyl nitrite produced anemia and leucopenia. Two important issues must be noted: there were no dose related effects noted and there was a nonspecific cell reduction. A dose response relationship is essential in pharmacology to establish an effect. Generally when this is not the case, toxicity is evident. The nonspecific cell reduction also is an indication of toxicity.
Cyclohexyl nitrite did not decrease macrophage tumoricidal activity, which contradicts a previously published report. Soderberg states in another paper that there are differential effects of cyclohexyl and isobutyl nitrite, yet he is obtaining different results with the same compound.

Soderburg, et al (1996) Acute inhalation exposure to isobutyl nitrite causes nonspecific blood cell destruction. Experimental Hematology, 24:592.
This is also cited as a 1996 poster. Although he reported in an earlier paper that results were seen in 5 days, he continued to use 14 days. Perhaps he only saw certain effects at excessive doses. An indicator of this is the nonspecific blood cell destruction, a likely result of toxicity.
They found a decrease in both red and white blood cells at 24 hours after acute exposure. It is possible that this decrease is a result of lung hemorrhage, with subsequent blood loss, induced by the high dose of nitrite. Regardless, the observed changes in blood cell count were reversed by 72 hours, which again demonstrates that nitrite effects are reversible. The study also described a decrease in spleen cellularity and speculated that spleen cells are mobilized to provide replacement white blood cells. If this is true, then the spleen can overcome any loss in immune function that may occur as a result of transient white blood cell loss and serve as a compensatory mechanism to maintain homeostatic immune function. Therefore, even if nitrites do cause a decrease in white blood cells, there is a rapid response to correct the imbalance.
"Others have not found similar epidemiologic correlations (abuse of nitrate inhalants correlated with seropositivity to HIV and Kaposi's sarcoma among AIDS patients”. These kinds of statements represent the lack of congruence between researchers.

Soderberg, and Barnett (1995) Inhaled exposure to isobutyl nitrite inhibits macrophage tumoricidal activity and modulates inducible nitric oxide. Journal of Leukocyte Biology, 57:135.
This paper is a repeat of experiments in another reference by the same author, except the tumoricidal activity of peritoneal rather than lung macrophages was measured. Interestingly, Soderberg obtained the opposite results between the two publications. For instance, in these experiments, there was a decrease in tumoricidal activity that returns in two weeks, which contradicts their 1996 publication showing an increase in tumoricidal activity of macrophages. Other data presented by Soderberg demonstrated that nitrite exposure increased TNF-a production by itself or in combination with interferon, but caused no change in response to lipopolysaccharide or interferon and lipopolysaccharide (stimulators of TNF- a production). In contrast, the other report stated that there was no effect of nitrite treatment on TNF-a production in either the absence or presence of interferon, but an increase in TNF-a production in the presence of lipopolysaccharide or lipopolysaccharide and interferon. Finally, the 1995 study reported a decrease in nitric oxide production stimulated by lipopolysaccharide and interferon, which contradicts the 1996 study. Interestingly, the author did not discuss these discrepancies. When an investigator publishes results that are the opposite of each other, one cannot derive conclusions from their work.

Soderberg, et al (1996) Elevated TNF-a and inducible nitric oxide production by alveolar macrophages after exposure to a nitrite inhalant. Journal of Leukocyte Biology, 60:459.
The reference that Soderberg gave establishing human exposure as 7000 ppm (Soderberg, et al, Experimental Hematology, 24, 846-853, 1996) does not reflect human doses. In this article, which he used as a reference, Soderberg claimed that abuser doses exceed 1500 ppm, which is much lower than 7000 ppm. In yet another publication by Soderberg (Fundamental and Applied Toxicology, 17:821, 1991), he stated that the actual dose levels of nitrite abusers are unknown. From these disparate statements, it appears that Soderberg has no concrete data to establish the amount of an abuser dose. However, he arbitrarily set the treatment dose for mice at 900 ppm for 45 minutes over a 14 day period. This paper included a dose-response curve showing that a single exposure of this amount to mice caused lung hemorrhage and prolonged treatment caused emphysema-like changes. Doses as low as 300 ppm also caused lung hemorrhage in mice. Furthermore, Soderberg did not account for the difference in lung size between humans and mice. This is a very serious error and because of this, he is probably utilizing a treatment dose that is toxic to mice. Perhaps Soderberg did not get his anticipated results when exposing animals to lower doses and nitrites are not harmful at more physiological doses. Surprisingly, this group continued to publish studies using a dose that is clearly excessive.
Another major problem with this article is that it reported opposite results from Soderberg's previous studies. For example, this article showed an increase in tumoricidal activity of mice lung macrophages, whereas there was a decrease in tumoricidal activity in humans in another paper by Soderberg (see below). If different results are obtained between humans and animals, this would imply that there is a difference between the two species and invalidate the use of animals in experiments. Other work presented in the study showed an increase in TNF-a production of lung macrophages in response to interferon. Activated macrophages release TNF-a, which would indicate an increase in tumoricidal activity. Since macrophages kill both virally infected and cancerous cells, it follows that an increase in macrophage function would be a preventive of HIV infection and KS.
In regards to the data showing an increase in tumoricidal activity, Soderberg stated that this result is unexpected and may be a caused by increased lung inflammation in response to tissue damage. This is further evidence that the researcher is using an excessive nitrite dose. Also, when the same investigator publishes opposite results, it is impossible to establish the true effects of nitrite use.
Soderberg and Barnett (1996) Leukopenia and altered hematopoietic activity in mice exposed to the abused inhalant, isobutyl nitrite. Experimental Hematology, 24:848.
In this paper, after five mice were treated with 900 ppm isobutyl nitrite for 14 days, they exhibit a 36% decrease in white blood cell count and a 7% increase in red blood cells. The later result is unusual because nitrites have been shown to cause a decrease in red blood cells (Fundamental and Applied Toxicology, 19:169, 1992). All observed blood cell changes return to baseline one week after cessation of drug, demonstrating reversibility of nitrite effect.
This report and other articles by Soderberg suffer from the same problems as previously mentioned. These experimental design flaws include the administration of an excessive drug dose to the mice, low sample size, and no replication of experiments to confirm results. These protocol errors, in combination with the contradictory results from different experiments by the same and other authors, make it impossible to develop firm conclusions about the effects of nitrites on the immune system.

Soderberg and Barnett (1996) Exposure to inhaled isobutyl nitrite reduces T cell blastogenesis and antibody responsiveness. Fundamental and Applied Toxicology, 24:821.
In an earlier paper, Soderberg obtained results after treating mice for five days, yet is these experiments mice were 900 ppm isobutyl for 14 days. A similar study with a lower dose, up to 300 ppm for 18 weeks (J. Toxicol Environ. Health 15:823, 1985) reported no change in immune parameters.
In this study, he found a reduction in mice body weight and spleen cells, in contrast to his previous work. He also finds new parameters that nitrites effect. “The frequency of T-dependent plaque forming cells (PFC) was inhibited by 63% and the total number of PFC per spleen was reduced by 72% in nitrite-exposed mice.” Again, these results are meaningless because of the high dose.

Dunkel, et al (1989) Mutagenicity of some alkyl nitrites used as recreational drugs. Environmental and Molecular Mutagenseis, 14:115.
In this study, five of six different alkyl nitrites, including isobutyl nitrite, tested positive for mutagenicity. Since it is not known what the actual dose of nitrite is after inhalation, it is difficult to know if the concentration used in these mutagenecity studies is anywhere near the physiological dose of nitrite. Furthermore, these types of studies do not account for metabolism of the drug, which occurs in the intact animal.
Lotzova et al (1984) Depression of murine natural killer cell cytotoxicity by isobutyl nitrite. Cancer Immununology Immunotherapy, 17:130.
These researchers claimed that isobutyl nitrite causes a decrease in natural killer cell activity in mice when injected intraperitoneally or inhaled. They injected 0.25 mls of isobutyl nitrite twice before assay, which is not a physiological administration of this drug. In addition, this is the same amount that a human would inhale, not inject directly into the body. The metabolism of the nitrite could be very different when given as an intraperitoneal injection rather than the usual inhalation route. For inhalation experiments, mice were placed twice a day for two=three minute (for seven days) in a beaker containing a petri dish with two ml of isobutyl nitrite. They did not attempt to calculate the dose that was given by this exposure, although again, this amount more closely approximates a human dose. Lotzova's group claims to use the maximal dose tolerated by the mice, which implies that these doses were near lethal.
Another flaw in the design of these experiments is that they were not replicated. It is not understood why such a standard scientific procedure was not utilized, unless a replication of the studies did not confirm the initial results.
Finally, these investigators obtained results that contradict work by Soderberg. Lotzova found a decrease in tumor-binding capacity of natural killer cells, whereas Soderberg found no change in this parameter. Considering this discrepancy and more importantly, the dosing regimen utilized, these studies do not establish a role for nitrites in a decrease in tumoricidal activity.

Wilson's "Poppers and Immunosuppression" Section
Soderberg (1999) Increased tumor growth in mice exposed to inhaled isobutyl nitrite. Toxicology Letters, 104:35.
Soderberg contradicts himself again: “Previous studies (Soderberg, 1994) suggested that nitrite inhalant inhibition of T cell activity was through alteration of accessory cell function, although the present data on the effects on tumor growth indicate more immediate effects on immune function.”
“The cumulative effects of multiple exposures were apparently necessary to impair immune mechanisms. The inhibition of T-dependent antibody responses apparently required the cumulative effects of more exposures to the inhalant, since 14, but not five (or one, exposures to the inhalant caused inhibition. Other immune activities, such as T cell responses to concanavalin A, also required the cumulative effects of repeated inhalant exposures for inhibition. Thus, while a single inhalant exposure directly inhibited T cell proliferation, multiple exposures may affect other components of activation, such as accessory cell function”. Again this is very confusing, there are no conclusive results and Soderberg appears to keep publishing new effects that nitrites have without confirmation from other researchers.

Soderberg (1998) Immunomodulation by nitrite inhalants may predispose abusers to AIDS and Kaposi's sarcoma. J Neuroimmunology, 83:157.
This is a review article. In the conclusions Soderberg mentions that chronically impaired immunity could reduce resistance to HIV infections, but research by Soderberg shows the nitrite immune suppression is reversible.
Soderberg states that the LD 50 for mice is 1033 ppm for one hour, which means that at this dose, half of the mice will die, so giving 900 ppm for 45 minutes is approaching the lethal dose. Furthermore, other researchers
cited are using near lethal doses. This supports my claim that differences in body weight between humans and mice were not considered.
Another discrepancy is that he references work by others that does not show a change in human CD4 and CD8 ratios after nitrite exposure, which occurs in AIDS or immonocompromised individuals.
Although in one of his publications he shows a decrease in mouse natural killer (NK) cell activity and proposes it as a nitrite mechanism for immunotoxicity, he states that two other laboratories (including his) were unable to substantiate this alteration.
Dax et al. (1988) Effects, of nitrites on the immune system of humans. Health Hazards of Nitrite Inhalants. National Institute of Drug Abuse Research Monograph Series. #83, 75.
In this study using eight HIV- male volunteers, the investigators found that amyl nitrite inhalation caused an initial suppression in immune function that was followed by an overshoot seven days after cessation of drug. This study had a low sample number and was not repeated.
These results are also contradictory to results obtained by other research groups. If the work presented in this paper is accurate, one could interpret the overshoot in immune activity as evidence for nitrite use causing an increase in immune function. This conclusion refutes Wilson's proposal that nitrites are harmful to the immune system.
Soderberg (1996) Inhaled isobutyl nitrite produced lung inflammation with increased macrophage TNF-a and nitric oxide production. AIDS, Drugs of Abuse, and the Neuroimmune Axis, Ed. Friedman et al., Plenum Press, New York, 187.
This article contains the same information as a previously discussed Soderberg publication (Toxicology Letters, 104:35) with the same flaws. This is an example of an investigator increasing the volume of their work by publishing duplicative results.
Soderberg and Barnett (1995) Inhalation exposure to isobutyl nitrite inhibits macrophage tumoricidal activity and modulates inducible nitric oxide. Journal of Leukocyte Biology, 57:135.
This paper is a repeat of experiments (Toxicology Letters, 104:35) by the same author, except the tumoricidal activity of peritoneal rather than lung macrophages was measured. Interestingly, Soderberg obtained the opposite results between the two publications. For instance, in these experiments, there was a decrease in tumoricidal activity that returns in two weeks, which contradicts their 1996 publication showing an increase in tumoricidal activity of macrophages. Other data presented by Soderberg demonstrated that nitrite exposure increased TNF-a production by itself or in combination with interferon, but caused no change in response to lipopolysaccharide or interferon and lipopolysaccharide (stimulators of TNF-a production). In contrast, the other report stated that there was no effect of nitrite treatment on TNF-a production in either the absence or presence of interferon, but an increase in TNF-a production in the presence of lipopolysaccharide or lipopolysaccharide and interferon. Finally, the 1995 study reported a decrease in nitric oxide production stimulated by lipopolysaccharide and interferon, which contradicts the 1996 study. Interestingly, the author did not discuss these discrepancies. When an investigator publishes results that are the opposite of each other, one cannot derive conclusions from their work.

Soderberg et al (1991) Inhaled isobutyl nitrite impairs T cell reactivity. Drugs of Abuse, Immunity, and Immunodeficiency, Ed. Freidman et al., Plenum Press, New York, pp. 265.
This is a short paper with only one figure, demonstrating the effects of isobutyl nitrite after treating mice for 45 minutes per day for 14 days. After 24 hours, this treatment caused an impairment of T cell reactivity, but no effect on B cell function or hematopoeisis. Other than this group's usual experimental design problems, they did not measure at any other time points to determine reversibility of nitrite effects.
Interestingly, other studies have shown that mice exposed to 300 ppm of nitrite for five days a week for 6.5 ours (over an 18 week period) had no changes in immune parameters (J. of Toxicology and Environmental Health, 15:828,1985 and J. of Toxicology and Environmental Health, 15:835, 1985). Perhaps giving a smaller dose over a longer time period allows for recovery of the nitrite effects, or the drug is metabolized to non-harmful products.
Lotzova, et al. (1984) Depression of murine natural killer cell cytotoxicity by isobutyl nitrite. Cancer Immununology Immunotherapy, 17:130.
These researchers claimed that isobutyl nitrite causes a decrease in natural killer cell activity in mice when injected intraperitoneally or inhaled. They injected 0.25 mls of isobutyl nitrite twice before assay, which is not a physiological administration of this drug. In addition, this is the same amount that a human would inhale, not inject directly into the body. The metabolism of the nitrite could be very different when given as an intraperitoneal injection rather than the usual inhalation route. For inhalation experiments, mice were placed twice a day for two-three minutes (for seven days) in a beaker containing a petri dish with two ml of isobutyl nitrite. They did not attempt to calculate the dose that was given by this exposure, although again, this amount more closely approximates a human dose. Lotzova's group claims to use the maximal dose tolerated by the mice, which implies that these doses were near lethal.

Another flaw in the design of these experiments is that they were not replicated. It is not understood why such a standard scientific procedure was not utilized, unless a replication of the studies did not confirm the initial results.
Finally, these investigators obtained results that contradict work by Soderberg. Lotzova found a decrease in tumor-binding capacity of natural killer cells, whereas Soderberg found no change in this parameter. Considering this discrepancy and more importantly, the dosing regimen utilized, these studies do not establish a role for nitrites in a decrease in tumoricidal activity.
Gaworski, et al (1992) Prechronic inhalation toxicity studies of isobutyl nitrite. Fundamental and Applied Toxicology, 19:169.
This article was cited by Soderberg as supporting his work, although it provides evidence that refutes the validity of Soderberg's model for treating mice with isobutyl nitrite. In addition, Soderberg's results from experiments measuring white blood cells are the opposite of Gaworski's. Gaworksi's group investigated the toxic effects of isobutyl nitrite in short-term and chronic inhalation studies. Rats and mice were exposed to doses of isobutyl nitrite ranging from 0-800 ppm. They found that 12 exposures of greater that 600 ppm for six hours (five days a week) caused 100% mortality in rats and mice. Rats exposed to 200 or 400 ppm exhibited lethargy and a hunched posture. Furthermore, these lower drug concentrations caused hyperplasia of the bronchiolar and nasal epithelia. Doses of 300 ppm induced a decrease in red blood cells and an increase in white blood cells, which contradicts Soderberg's previou studies. Gaworski concluded that the highest exposure for chronic inhalation tests should not be higher than 150 ppm. Although Soderberg and Gaworski were administrating similar doses, Soderberg exposed animals to nearly 10 times the amount that Gaworski recommends for long term studies over a much shorter time period. Since nitrites rapidly decompose, the lower dose over a longer time interval amounts to a final concentration that is much lower than the high dose over a short time. Furthermore, considering that the dose-response curve for isobutyl nitrite is rather steep, a higher dose has a sharply increase toxicity.
Morgan, et al. (1992) Possible roles for nitric oxide in AIDS and associated pathology. Medical Hypothesis, 38:189.
The nitrites are capable of conversion to nitric oxide, which is thought to the active intermediate in the action of nitrites. This review article by Morgan, et al. speculated that exogenous nitric oxide has a potential role in the epidemiology of AIDS. However, there is no evidence cited that supports this claim, most likely because these studies have not been performed. There are articles referenced proposing association of nitrite use with AIDS, which does not demonstrate a role for nitric oxide in the etiology of AIDS. Furthermore, the articles all utilize a low sample number (seven-eight) in their experiments and the tests are not repeated.
In contrast, Morgan cited other studies demonstrating that variables other than nitrite use differentiated AIDS patients from controls. Similarly, another study listed indicated that sexual activity was the best marker for AIDS and that the abuse of nitrite inhalants appeared unimportant in distinguishing AIDS patients from controls. No firm conclusions can be drawn from conflicting population studies.
Finally, this review article gave contradictory mechanisms for nitric oxide action. At the beginning of the article, they claim that nitric oxide released by inhaled nitrites may be involved in HIV neuropathogenesis. In contrast, they state that exogenous nitric oxide released from inhaled nitrites may cause a down-regulation of endogenous nitric oxide production, which is a mediator of tumoricidal macrophages. Thus, Morgan is claiming that an increase and decrease in nitric oxide can have two different pathological effects. This is not logical reasoning.
Mirvish, et al. (1993) Mutagenicity of isobutyl nitrite vapor in the Ames Test and Some relevant chemical properties, including the reaction of isobutyl nitrite with phosphate. Environmental and Molecular Mutagenesis, 21:247.
In this study, the effects of a saturated vapor of isobutyl nitrite and a saturated aqueous solution were tested for mutagenicity using the Ames test (an indicator of cancer-causing agents). The researchers demonstrated that the vapor was 11 times more mutagenic than the aqueous solution. This follows because isobutyl nitrite is not stable in an aqueous solution. Isobutyl nitrite is prepared for commercial distribution in an alcohol solution. Because of this and the rapid breakdown of nitrites upon inhalation, this study is irrelevant to the question of mutagenicity of isobutyl nitrite as it is administered to humans. Furthermore, there is no other data supporting the mutagenicity of this drug.

Khaled (1986) Inactivation of B12 and folate coenzymes by butyl nitrite as observed by NMR: implications on one-carbon transfer mechanism. Biochemical and Biophysical Research, 135:201.
Khaled tested the effects of isobutyl nitrite on coenzymes of B12 and folic acid, which are important in growth and proliferation of mammalian cells. The rationale for the experiment is that nitric oxide, a breakdown product of isobutyl nitrite can oxidize and inactivate these cofactors. Therefore, they measured the effects of isobutyl nitrite on the structures of the coenzymes using nuclear mass resonance spectroscopy. Interestingly, they see no effects when isobutyl nitrite is solublized in alcohol and changes in structure when isobutyl nitrite is added to these compounds in water, in which isobutyl nitrite is virtually insoluble. They do not address this discrepancy. Furthermore, these studies do not replicate an in vivo situation, in which inhaled isobutyl nitrite may not encounter these cofactors, especially in concentrations high enough to be effective.

Hersh, et al. (1983) Effect of the recreational agent isobutyl nitrite on human peripheral blood leukocytes and on in vitro interferon production. Cancer Research, 43:1365.
In these studies, isobutyl nitrite in solution incubated with human white blood cells had a nonspecific cytotoxic effect. They state that a 1% solution was highly toxic to the leukocytes. There was no rationale for the dosing regimen, and considering that nitrites decompose rapidly, it is highly unlikely that this concentration of drug reaches blood cells.
Hersh claims that the effects of isobutyl are not reversible by washing it out of the cultures, which is not in agreement with the in vivo studies referenced by Wilson that demonstrate reversibility of nitrite effect. In addition, in Hersh's work, nitrite had cytotoxic effects on other cell types, including a breast cancer cell line, which indicates that the nitrite is not selective for immune cells. These provide further evidence that the doses used in the experiments are too large.
Another criticism of this work is that it is performed in vitro, which is not a physiological situation. This is a non-physiological situation.

Lycka (1987) Amyl and Butyl nitrites and telangiectasia in homosexual men. Annals of Internal Medicine, 106: 476.
This article is actually a letter to the editor that suggests that nitrites may cause telangiectasia (vascular dilations seen in many diseases) on the chests of homosexual men. Lycka claims that since nitrites are vasodilators, that they may induce this condition. This is not a scientific article and does not belong in a reference list.
Watson (1982) The use of amyl nitrite may be linked to current epidemic of immunodeficiency syndrome. Unpublished paper submitted to the Journal of the American Medical Association and the Advocate (the largest national gay magazine).
Citing a paper that was submitted, but not published, is an example of Wilson's inability to provide substantiated evidence supporting his claim. Papers that are rejected from scientific journals (and non-scientific publications) are not valid research. Such articles are not worthy of inclusion in a document attempting to establish a claim. Furthermore, such references erode the credibility of the author.

Soderberg et al (2004) Increased tumor growth in mice exposed to inhaled isobutyl nitrite. Toxicology Letters, 152:35.
The investigators chose the PYB6 tumor, a syngeneic, virus-induced sarcoma, but it does not have the unique growth characteristics of KS and they state that it “might respond differently to changes in immunocompetence”. Since they are not measuring the effects of nitrite on KS, the logical choice, the results could be irrelevant.
They state studies of immune function using PYB6 cells as target cells in vitro were not fruitful, as the PYB6 cells were not suitable for in vitro cytotoxicity assays, so they could not determine if altered immune function affects PYB6 tumor growth (what they are claiming.)
They end with “it is generally acknowledged that specific CTL are important in controlling HIV replication in the early stages following infection. The nitrite-induced immunosuppression reported here was not as profound as occurs in the late stages of AIDS and was transient, recovering to normal levels within 14 days after termination of exposure”. This also does not correlate with their claim that nitrite use is important in AIDS.

Wilson's "Poppers and Seroconversion" Section
Wilson's theories about seroconversion are as similarly weak, as are most of his other theories. Here, Wilson tries to convince the reader that "poppers" increase the chance of seroconverting. However, as Dr. Steve Harris reminds us, among many other credible studies that also dispute Wilson, are the results of a huge San Francisco study, began in the mid-1980's, which clearly demonstrated that "poppers" appear to have no effect on seroconverting: "Readers will remember that once men were infected with HIV, subsequent use of poppers, and subsequent numbers of partners, made no impact on future risk of developing AIDS. That is one important way epidemiologists know they have the cause of a problem. If many things correlate with risk of getting a diseases, but all things stop correlating after one of the variables changes, then that is likely to be the causal variable of interest. We now have studies showing such a relationship between HIV and AIDS, and between KSHV and KS."

Steve Harris, M.D.

Ruiz, et al (1998) Risk factors for human immunodeficiency virus infection and unprotected anal intercourse among young men who have sex (YMSM) with men. Sexually transmitted diseases, 25: 100.
Ruiz relied on self reporting, the reliance of which from YMSM is unknown. He also did not distinguish between frequency of use, thus the analysis treated those having used a drug once the same as those who used that drug daily. He also grouped nitrite use with another stimulant, crack, which further confounds his results.
Although Ruiz found a slight positive association between recent use and recent UAI, the association between lifetime use and HIV infection is much larger. The first result would indicate no relationship between UAI and nitrite use and the second result is unexplained.

Chesney, et al (1998) Histories of substance use and risk behavior: Precursors to HIV seroconversion of homosexual men. Amer J Public Health, 88:113.
This is a report generated from data from surveying the San Francisco Men's Health Study cohort. Although they do not discuss the implications of this, history of consistent use of amyl nitrite or amphetamines strongly affected seroconversion, while current use of these drugs did not. The data does not support a role for nitrite use in seroconversion.
Chesney did not measure whether substance use occurred at the time of sexual activity that may have caused seroconversion, this is an important factor.
McFarland, et al. (1997) Estimation of human immunodeficiency virus (HIV) seroincidence among repeat anonymous testers in San Francisco. American Journal of Epidemiology, 146:662.
In this study, the investigators claimed that nitrite use was significantly associated with seroconversion. However, only 42 out of 789 men who reported nitrite inhalation during sex in the last year were HIV-positive. Since the incidence of seropositivity in nitrite users is so small, one cannot establish a statistical significance using this data.

Ostrow, et al. (1995) A case-control study of human immunodeficiency virus
type I seroconversion and risk-related behaviors in the Chicago MACS/COS cohort. American Journal of Epidemiology, 142(8):875.
This study found that seroconversion correlated with marijuana, cocaine, and nitrite, but not alcohol use. This contradicts other studies finding that a relationship of alcohol use with HIV infection. Furthermore, it was not reported if subjects used other drugs in conjunction with nitrates, which they likely did and that would confound the issue such that nitrite use can be directly correlated with seroconversion.
Seage, et al. (1992) The relation between nitrite inhalants, unprotected receptive anal intercourse, and the risk of human immunodeficiency virus infection. American Journal of Epidemiology, 135:1.
This article attempted to determine whether nitrite use is an independent risk factor for HIV infection and if it interacts with unprotected receptive anal intercourse to further increase that risk. They collected self-reports from homosexual male couples and performed a number of statistical tests to obtain odds ratios for associations between different behaviors and HIV infection.
The ratio of unprotected anal sex in participants who never used nitrites during sex (9.0) was higher than the number for those who sometimes used nitrites during sex (7.1), which refutes the theory that nitrite use leads to unsafe sex. Although the number for those who always used poppers during sex was higher (31.8), it is likely that a group that always uses any drug during sex may be a skewed population.
The odds ratio was similar when comparing the association of HIV seropositivity with use of several different recreational drugs (a range of 1.7 for cocaine use to 2.9 for nitrite use) or HIV seropositivity with nitrite use and unprotected anal sex. The similarity of these numbers implies that any type of drug use can be correlated to HIV seropositivity. The overall odds ratio for HIV infection in all study participants who used nitrites was only 1.6, which is very low.
An important control that was not included is the incidence of systemic bleeding during unprotected anal sex was not available. This could be the most important risk factor for HIV infection.
In their conclusion, they state that "It did appear that the relation between nitrite use and HIV infection was confounded, since the odds ratio decreased from 2.9 to 1.7 after we controlled for confounding variables as well the presence of a study partner. We suspect that the remaining increased risk associated with nitrite use results from residual confounding. We reanalyzed the data with nitrite use recoded into eight exposure categories using Rosner's model and found that nitrite use was no longer significantly associated with HIV infection." Thus, controlling for confounding factors eliminates the associations between nitrite use and unprotected sex.
Finally, it is stated in the article that this group has never found an association between nitrite use and Kaposi's sarcoma. These results refute the proposed hypothesis that nitrites have an epidemiological role in ks.
Messiah (1993) Factors correlated with homosexually acquired human immunodeficiency virus infection in the era of "safer sex". Sexually Transmitted Diseases, 20:51.
This study also has a disparate sample size (n=201 for seronegative participants and n=45 for seropositive participants). Secondly, although inhalation of nitrites was significantly related to seropositivity, upon multivariate analysis, there was no significant difference between the two parameters. Once again, after controlling for other risk factors, there is no correlation between nitrite use and seroconversion.
Penkower (1991) Behavioral, health and psychosocial factors and risk for HIV infection among active homosexual men: the multicenter AIDS cohort study. American Journal of Public Health, 81:194.
This report contains only one table and has the same flaw as the one that was previously discussed, which is that the number of seronegative (463) versus seropositive (181) participants is extremely disparate, making accurate conclusions difficult. Regardless of this limitation, the data presented indicates that there is a similar increase in seroconversion for alcohol, cigarette, and recreational drug use, with heavy alcohol consumption being the most strongly associated with subsequent seroconversion. Although the researchers claim that nitrite use had the highest risk factor for seropositivity of all other drugs tested, they do not list the drugs that were studied or show the data for these drugs. They also state that drug users were more likely to engage in anonymous sex and had more partners, which are definitely confounding factors.
Burcham et al. (1989) Incidence and risk factors for human immunodeficiency virus seroconversion in a cohort of Sydney homosexual men. The Medical Journal of Australia, 150:634.
In this study, the researchers state that the relative risk of seroconversion was significantly higher among subjects who abused nitrite inhalant during the seroconversion period and that there was a significant relationship between nitrite use and anal receptive intercourse. From these two correlation's, a causal relationship cannot be demonstrated between nitrite use and seroconversion. Furthermore, the author claimed that the drug use may have been a correlate of high-risk behavior and this is the only conclusion that can be accurately formed.

van Griesven et al.(1987) Risk factors and prevalence of HIV antibodies in homosexual men in the Netherlands, American Journal of Epidemiology, 125:1048.
Seropositive respondents took several more drugs than seronegatives, thus confounding results. Additionally, these drugs may lead to a more intensive contact and in that way to a higher probability of transmission and since there was more than one used, it is impossible to tell which one, if any, is responsible for seroconversion.

(1992) The relationship between nitrite inhalants, unprotected anal intercourse, and the risk of Human Immunodeficiency Virus Infection, American Journal of Epidemiology, 135:1.
The role of nitrite use was evaluated between 1984 and 1988 in a study of sexual transmission of HIV among homosexual male couples in Boston. Even though the OR for HIV and unprotected receptive anal intercourse was higher than the OR for HIV and nitrite use, they administered a supplemental questionaire to determine if nitrite use might be a marker for unprotected receptive anal intercourse. The OR for those who always used nitrites during unprotected receptive anal intercourse was 31.8, compared with men who sometimes used nitrites (OR=7.1) or never (OR =9). Their conclusion was “the results of this study suggest that use of nitrate inhalants interacts with unprotected receptive anal intercourse to increase the risk of HIV infection. This is faulty logic, primarily because the OR for those who do not use nitrites is higher that those who sometimes use them.
Also, the confidence intervals are high, ranging from 1-76.7. The width of the confidence interval gives an idea about the uncertainty of the unknown parameter. A very wide interval may indicate that more data should be collected before anything very definite can be said about the parameters.

Wilson's "Poppers and Unsafe Sex" Section
A problem with Wilson’s references that lessens credibility is that many of the articles are not published in peer review journals. It is much easier to publish scientific articles in these types of journals, because the data and conclusions are not reviewed by experts in that particular field. In addition, some of the journals referred to are somewhat obscure and not found in medical school libraries, which carry a large number of the best and most used medical journals. An additional infirmity of the references listed by Wilson is that some of them are data presented at meetings as posters or informal talks. These types of presentations are usually not referenced in scientific publications because they are not peer reviewed and nearly always are preliminary data that has not been confirmed or published. It is difficult to critique these references because they are not published or found in easily obtainable publications. Finally, one of the references was submitted, but not accepted for publication. Articles that were rejected for publication are never cited in credible reference lists.

Woody, et al (1999) Non-injection substance use correlates with risky sex among men having sex with men: data from HIVNET. Drug and Alcohol Dependence 53:197.
Associations between substance use and sexual behavior were examined among 3220 seronegative men. The odds ratio (OR) was low for nitrite inhalants (some use-OR= 1.6, heavy use-OR= 2.18). This is in dramatic contrast to other studies, some of which give OR’s as high as 33. The large range of OR’s indicates a lack of consistency between results.
Although there appears to be a relationship between alcohol or drug use and an increased sexual risk among MSM, it is clear that these relationships are complex and difficult to evaluate. Disparate findings can be explained in many ways including inability to evaluate substance use patterns in the context of the sexual encounter, comparing populations with different ages or cultural features, and limitations in power resulting form small sample sizes which make it impossible to evaluate possible confounds such as demographic contributions of different substances of levels of use. Here the respondents state nitrate use is 29%, compared to marijuana use 49% and alcohol use 89%, nitrite use is the lowest percentage, suggesting that it is less related to risky sex than other substances.

Ekstrand, et al. (1999) Gay men report high rates of unprotected anal sex with partners of unknown or discordant HIV status AIDS, 13:1525.
This paper examined patterns and factors that correlate with unprotected anal intercourse (UAI) practices among 510 San Francisco gay men. They reported that 52% of high transmission risk men (those who reported having sex with a partner of unknown or discordant HIV antibody status) used nitrate inhalants in the previous 12 months, compare to 20 and 25% of no and low transmission groups and 14% (compare to 4% of low and no transmission groups) using at least once-a-month. All groups reported two-three drugs used and alcohol use again which precludes accurate interpretation.

Strathdee, et al (1998) Determinants of sexual risk-taking among young HIV negative gay and bisexual men. J of Acquired Immune Deficiency Syndrome and Human Retrevirology,19:61, 1998.
Independent predictors of sexual risk-taking were low education, nitrite use, low social support, nonconsensual sex. This study reported an OR of 1.6 for nitrite use, which is not very high.
The relationship between sexual risk and inhalant use may represent a decision that is made about how a sexual relationship will be carried out rather than a pharmacological effect of the inhalant.
Stall, et al. (1986) Alcohol and drug use during sexual activity and compliance with safe sex guidelines for AIDS: The AIDS behavioral research project.
This study stated that men who increased their risky sexual behavior also increased their alcohol and drug use and those who decreased their risky behavior also decreased their .alcohol and drug use. Again, nitrite use was not isolated from other drugs. Furthermore, a change in correlative behaviors may simply reflect an overall lifestyle change in a direction that may or may not promote health.
Kalichman (1997) Continued high-risk sex among HIV seropositive gay and bisexual men seeking HIV prevention services. Health Psychology, 16(4):369.
In this article, only 19% of the HIV-positive men surveyed used nitrite inhalants, with the average frequency of use over a three month period being 1.9 times. Furthermore, of the men who engaged in unprotected anal sex, the average frequency of nitrite use over a three month period was only 3.3 times, compared to a mean frequency of use of 0.6 times for those who did not have unsafe sex. Although the author used statistics to show a significant difference between those who did and did not have unprotected anal sex, the raw data indicates an extremely low use of nitrites among any of the men. It is highly unlikely that using a drug 3.3 times over a three month period can cause unsafe sex. This is a good example of how statistics can be used to mislead the reader.
As a final note, the nationwide prohibition on sales of volatile nitrites in the United States in 1991 has not had an appreciable effect on either the use of inhalant nitrites by men in the Chicago MACS/C. Since nitrites are readily available by mail order and in pornographic bookstores and movie theaters, it appears that legal prohibition does not change abuse behaviors. In fact, use of these "street drugs" could be more dangerous because they may have harmful impurities.
This drug is probably one of the safer drugs of abuse that are available, particularly because the effects are transient. In addition, this drug is inexpensive compared to other drugs of abuse, and use of nitrites rather than the more expensive drugs may actually decrease crime and prostitution, which are commonly used by drug abusers to obtain drugs. A lower incidence of prostitution may lead to lower levels of unsafe sex in these groups, which may be a better preventative of HIV infection than other intervention methods.

An Epidemiologic Survey of HIV Risk Behaviors Among MSM ins a Resort Area: the South Beach Health Survey, Miami, Florida oral report presented at the Northwest Regional Workshop on HIV Preventions Approaches for Alcohol and Drug Use Among Men Who Have Sex With Men Webster. Popper use during sex was the only drug significantly related to unprotected anal intercourse in this sample of MSM p=.0495
A potential mechanism is that both substance use and sexual behavior may occur within the context of long-standing social networks. Correlational data do not prove causality.
Ostrow, et al. (1995) A case-control study of human immunodeficiency virus type I seroconversion and risk-related behaviors in the Chicago MACS/COS cohort. American Journal of Epidemiology, 142(8):875.
This study found that seroconversion correlated with marijuana, cocaine, and nitrite, but not alcohol use. This contradicts other studies finding that a relationship of alcohol use with HIV infection. Furthermore, it was not reported if subjects used other drugs in conjunction with nitrates.
Ostrow, et al. (1994) Recreational drugs and sexual behavior in the Chicago MAC/CCS cohort of homosexually active men. Journal of Substance Abuse, 5(4):311.
This study stated that stopping nitrite use was unrelated to improvement in safer sexual behavior, which again refutes Wilson's claim. In addition, they reported that nitrite use was associated with failure to use condoms during receptive anal sex among non-monogamous men only. If inhalation of nitrites was truly a causative factor in unsafe sex, it would prevail in monogamous as well as non-monogamous relationships. More importantly, a cessation of drug use would lead to safer sex.
Ostrow, et al. (1990) Recreational drug use and sexual behavior change in a cohort of homosexual men. AIDS, 4:759.
This article reported that homosexual men who use nitrites are in a higher risk category for sexual behavior. They stated that 80.6% of the highest risk group was nitrite users. However, 72.5% of the same risk group did not use drugs. These percentages are not very different, particularly when one takes into account experimental variability.
deWit, et al. (1994) Time from safer to unsafe sexual behavior among homosexual men. AIDS, 8{1):123.
In this short communication (a type of article that presents preliminary data), the authors state that both a younger age and nitrite use were predictors of a shorter time to unsafe sexual behavior. No other drugs were studied. Perhaps younger men tend to have more unsafe sex and this group also uses drugs more frequently, which is not necessarily correlative with the incidence of unsafe sex.
Letup, et al. (1994) Seroprevalence of HIV and risk behaviors among young homosexuals and bisexual men. Journal of the American Medical Association, 272(6):449.
Homosexual and bisexual men recruited for this study were located in public places in San Francisco and Berkely, including street corners, dance clubs, bars, parks, and other public venues frequented by homosexuals, which is not a random sampling of homosexual and bisexual men. Of the respondents who did not use nitrites during (n=371), 30% had unprotected anal sex, whereas of the 35 men who claimed to use nitrites during sex, 60% engage in unsafe sex. They claimed that nitrite use is a predictor of unsafe anal sex. From this bit of data, one cannot make such a claim.
Finally, the author gives the disclaimer that is predominant in the studies presented by Wilson: "However, our data cannot distinguish whether this represents a causal association, with abuse leading to impaired judgment or disinhibition, or a marker of lifestyle among persons at high risk."
Hogg, et al. (1993) Sociodemographic correlates for risk-taking behaviors among HIV seronegative homosexual men. Canadian Journal of Public Health. 84:423.

In this paper, the majority of the men in this study were white and part of a large urban gay community, which is a homogenous population of homosexual and bisexual men. The investigators found that 55% of risk takers (n=31) used nitrite inhalants compared with 30% of the control group (n=108). It is interesting that only about half of the risk-takers use nitrites. Of the non-risk-takers, a relatively large percentage used nitrites (30%), from which one could imply that the use of this drug is also associated with safe sex. In addition, they found no differences between risk and non-risk takers for cocaine, marijuana, or other drugs, which contrasts from other studies. Finally, the author states that this type of behavior should not be taken to identify all people who take risks.
Paul, et al. (1994) Correlates of sexual risk-taking among gay male substance abusers. Addiction, 89:971.
This paper reported that of the men in this study who have unprotected anal sex, 19.9% used nitrites in the past 90 days. One cannot establish a role for nitrites in unsafe sex. using this data. If nitrite inhalation caused unsafe sex, this percentage would be much higher. At meeting of the Center for Disease Control on the connection between KS and poppers, this investigator discussed the complexities of classifying events as "risky" or "safe". There are many confounding effects among sexual behavior, drug use, and other likely health risks. He emphasized that one could never conduct a controlled study (survey) to answer the question of causality.
Robins, et al. (1997) Do homosexual and bisexual men who place others at potential risk for HIV have unique psychosocial profiles? AIDS Education and Prevention 9(3):239.
This article has very little data (two tables). Although they claim that HIV-positive (n=369) homosexual and bisexual men exhibit more frequent nitrite use than HIV-negative (n=156) men, there is not a significant difference between the two groups.
Men engaging in risky sexual practices reported more popper use than men practicing safer sex, although his effect was not significant. They also tended to use more alcohol than the safer sex group. This study reported that for the variables they studied (demographics, social support, psychological status, coping, substance use) the correlates of risky behaviors were the same in HIV positive and negative men. The study's cross-sectional design does not allow one to draw causal inferences and this article does not support Wilson's hypothesis.

Tabet, et al. (1998) Incidence of HIV and sexually transmitted diseases (STD) in a cohort of HIV-negative men who have sex with men (MSM). AIDS,12:2041.
This provides no useful information. It was performed with 578 HIV negative men in Seattle. The authors compared risk factors for STD with nitrite use (OR =2.3) and STD with UAI (OR =2.6). Tabet found urethritis the most common STD did not compare nitrite use with AIDS.

Barett, et al. (1998) Redefining gay male anal intercourse behaviors: implications for HIV prevention and research. The J of Sex Research 35:381.
Data comes from a multivariate analysis study of HIV risk behaviors in 1001 males who self-identified as homosexual or reported unprotected oral or anal sex with another man in the previous five years. This another example of non-related research.

Myers, et al (1996) Sexual risk and HIV-testing behaviour by gay and bisexual men in Canada. AIDS CARE, 8:297.
This article is irrelevant to the subject. Only the abstract was available and no mention of nitrite use was made. Self reports of 4803 men identified from gay venues focused on unprotected sex and test taking.

Seigel, et al. (1989) Factors distinguishing homosexual males practicing risky and safer sex. Social Science Medicine, 28:561.
Again, the author does not distinguish what type of drug use is associated with risky behavior, which invalidates any assumption that nitrites are involved. In addition, they survey men from street corners, dance clubs, bars, parks, and other public venues frequented by homosexuals, which is not a random sampling of homosexual and bisexual men. Of the respondents who did not use nitrites during (n=371), 30% had unprotected anal sex, whereas of the 35 men who claimed to use nitrites during sex, 60% engage in unsafe sex. They claimed that nitrite use is a predictor of unsafe anal sex. From this bit of data, one cannot make such a claim.
Finally, the author gives the disclaimer that is predominant in the studies presented by Wilson: "However, our data cannot distinguish whether this represents a causal association, with abuse leading to impaired judgment or disinhibition, or a marker of lifestyle among persons at high risk."
Martin, (1990) Drug use and unprotected anal intercourse among gay men. Health Psychology, 9(4):450.
Results are reported from a longitudinal study of 604 NYC gay men spanning four 12-month periods from 1980 to 1987 indicating that as the acquired AIDS epidemic progressed, the link between drug use and high risk-sex diminished. Furthermore, initiation of drug use with sex is not associated with subsequent increases in lower rates of unprotected anal intercourse.
In this report, participants were asked how many times they used drugs in conjunction with unsafe sex over the past year. This type of question is obviously subject to recall bias. Another problem with this study is that respondents who used one type of drug were likely to use other drugs as well, which confounds the issue of nitrite use being directly related to unsafe sex.
The author found that there was a correlation between men using drugs (including nitrites) with unsafe sex and that both behaviors decline over a seven year period. These behaviors declined to the point that none of the associations between any specific drug use and unprotected receptive anal intercourse were statistically significant, which Wilson failed to mention.
Interestingly, within this article, the author reported contradictory results. They found that there is no consistent pattern associating initiation of drug use with sex and high-risk intercourse, either receptive or insertive. This type of data further refutes the hypothesis that nitrite use influences risky behavior.
Finally, the authors stated that "We have evidence that favors (but that no means confirms) a causal interpretation of the link between drug use and high-risk sex among gay men.
On the other hand,...noncausal interpretations of the link between drug use and risk taking may be more parsimonious." In the discussion section of the paper, they say that "conclusions based on an epidemiologic field study of the kind we have conducted are subject to threats to validity, particularly to drawing causal inferences." These kinds of statements do not support Wilson's hypothesis.

"If “poppers really did equal death” I'd be long dead by now. Once, after having a pleasant dinner with John Lauritsen, I actually indulged myself by “toasting him” with a hit of Rush as he looked on in wide-eyed wonder and/or horror."
AIDS, Poppers & HIV Theories

I read John Lauritsen's article attacking the theory that HIV was the cause of AIDS. While I disagree with some of his ideas, most of them actually, I think you should be applauded for expanding the dialogue about AIDS.

I found many of Lauritsen's arguments intriguing. He does a damn good job of making his case strongly and convincingly. However, many modern-day "snake-oil salesmen" are plugging into this vital debate.

I found Lauritsen's assertion that AIDS in America was a different disease than AIDS in Africa "reasonable" and considered. Having been exposed, possibly, hundreds of times to American HIV as a "top" and never having been infected, I wonder why it is so easily transmitted from female to male in Africa..

Related Stories from the GayToday Archive:
AIDS Realism Versus the HIV Hypothesis

Answering the AIDS Denialists: CD4 (T-Cell) Counts, and Viral Load

A Rose by Any Other Name…

Related Sites:
Virus Myth

Stop Dr. Laura.com
GayToday does not endorse related sites.

However, he totally loses “credibility” when he drags out his old/ancient/never-documented assertion that “poppers=death”. I read his book on that subject and the research simply showed that “if someone was HIV positive, the use of poppers did seem to increase the possibility of their contracting Karposi Sarcoma.”

If “poppers really did equal death” I'd be long dead by now. Once, after having a pleasant dinner with John Lauritsen, I actually indulged myself by “toasting him” with a hit of Rush as he looked on in wide-eyed wonder and/or horror.

I think the “questions” raised by Lauritsen and others are commendable. He does a great job pointing out how “money flows” behind certain ideas and excludes others. Even if he is totally in error, his criticisms force the “consensus advocates” to prove their case.
Randy Wicker
New York City

©http://gaytoday.badpuppy.com/garchive/penpoints/052900pp.htm

After all of this attention it's hard to see how the fact that few take their views seriously can be blamed on censorship. Maybe--just maybe--it's because, after carefully looking at all of the data, intelligent observers have concluded that .....
Letters to
Gay Today

AIDS Denial Isn't Realism

John Lauritsen covered the AIDS crisis for the New York Native As one of the "flacks," referred to in John Lauritsen's "AIDS Realism vs. the HIV Hypothesis," I'd like to thank Lauritsen for laying out in explicit, if unintentional, detail the true nature of the AIDS denialist arguments (and yes, the comparison to Holocaust deniers is indeed apt): A collection of unsupported speculation propped up by carefully selected snippets of data that simply omit anything the "dissidents" find inconvenient.

Lauritsen's claim that the media have censored the views of the denialists is laughable. Nightline did a whole show on the subject a few years ago. They've also gotten extensive coverage in, among other outlets, the London Sunday Times, Spin, numerous gay and lesbian publications and--strikingly--key organs of the right-wing, antigay movement in the U.S., including The American Spectator and the Heritage Foundation's Policy Review.

After all of this attention it's hard to see how the fact that few take their views seriously can be blamed on censorship. Maybe--just maybe--it's because, after carefully looking at all of the data, intelligent observers have concluded that mainstream science, whatever its flaws, pretty much got it right this time.

But the best advice I can give readers is: Don't take my word for it. Look up the references. Read the data--all of it, not just the narrow interpretations of those with an axe to grind--and judge for yourself.
Sincerely, Bruce Mirken
San Francisco

AIDS, Poppers & HIV Theories

I read John Lauritsen's article attacking the theory that HIV was the cause of AIDS. While I disagree with some of his ideas, most of them actually, I think you should be applauded for expanding the dialogue about AIDS.

I found many of Lauritsen's arguments intriguing. He does a damn good job of making his case strongly and convincingly. However, many modern-day "snake-oil salesmen" are plugging into this vital debate.

I found Lauritsen's assertion that AIDS in America was a different disease than AIDS in Africa "reasonable" and considered. Having been exposed, possibly, hundreds of times to American HIV as a "top" and never having been infected, I wonder why it is so easily transmitted from female to male in Africa..
Related Stories from the GayToday Archive:
AIDS Realism Versus the HIV Hypothesis

Answering the AIDS Denialists: CD4 (T-Cell) Counts, and Viral Load

A Rose by Any Other Name…

Related Sites:
Virus Myth

However, he totally loses “credibility” when he drags out his old/ancient/never-documented assertion that “poppers=death”. I read his book on that subject and the research simply showed that “if someone was HIV positive, the use of poppers did seem to increase the possibility of their contracting Karposi Sarcoma.”

If “poppers really did equal death” I'd be long dead by now. Once, after having a pleasant dinner with John Lauritsen, I actually indulged myself by “toasting him” with a hit of Rush as he looked on in wide-eyed wonder and/or horror.

I think the “questions” raised by Lauritsen and others are commendable. He does a great job pointing out how “money flows” behind certain ideas and excludes others. Even if he is totally in error, his criticisms force the “consensus advoca//gaytoday.badpuppy.com/garchive/penpoints/052900pp.htm

Reprinted From: A Critical Review of Hank Wilson’s Bibliography of Anti-Popper Research

This is a List of Statements about Poppers and Nitrites from Government Officials, Researchers, and Others...

2006-04-27T15:50:00.000-07:00

A Guide to Alkyl Nitrites and Poppers: Statements of Fact

This guide has been prepared for the assistance of those seeking accurate and timely information on the subject of nitrite-based room odorants (often called “poppers”). It does not cover exhaustively the subject which it treats, but is intended to answer some of the more important, broad questions which may arise. This guide does not recommend or endorse any specific application for the chemical compounds discussed, including amyl nitrite, isobutyl nitrite, or other alky nitrites.

James Curran, M.D.
the CDCs Chief AIDS Investigator
In a letter to the one-man, San Francisco-based 'Committee to Monitor Poppers' Dr. Curran responded to the committee’s request that he take an anti-popper position by telling the committee that "Current data does not warrant an anti-popper campaign." May 6,1985

Mark Novitch, M.D.
FDA Commissioner
In a letter to the White House said that, based on existing data, "...there is very little evidence of acute toxicity related to use of butyl nitrite." “...relative to lifetime use by homosexuals, although some groups contend that the possibility exists that repeated use among homosexuals may produce adverse effects, there is virtually no direct evidence to support that." April 18, 1984

P.R.J. Gangadharam
Researcher
Six months after being widely reported in the media to have 'linked' nitrite inhalation to AIDS and its diseases, in a letter to Paul Varnel, Research Director for the Illinois Gay and Lesbian Task Force, reverses himself when saying: "It is not mentioned, nor is it our intention to say, that isobutyl nitrite causes AIDS, nor does it precipitate or intensify the disease status of the AIDS people." February 24, 1986

Ray Hamilton
Director of Recall and Litigation, Bureau of Drugs
Food and Drug Administration (FDA)
In an official FDA statement clarifying the agency's feelings on the subject of butyl nitrite, Mr. Hamilton said: "...the FDA does not plan to devote resources to a project involving room odorizers containing alkyl nitrites because of the absence of demonstrable hazard." January 30,1981

John A. Liddle, Ph.D.
Public Health Service(PHS)
Centers for Disease Control (CDC)
In a letter to the New York Consumer Protection Board Dr. Liddle told the Board, "No positive correlation between the use of organic nitrites and the onset of AIDS was ever demonstrated." May 10, 1985

Radhey L. Singhal, Ph. D., Professor and Chairman Department of Pharmacology, University of Ottawa
In a letter to Canada's Product Safety Branch, Consumer and Corporate Affairs, says, "As stated in our report, we have concluded that occasional inhalation of isobutyl nitrite for its 'inebrient' effect in a recreational context is unlikely to pose a health hazard..." July 30,1979

J.J. Goedert, M.D. & W.A. Blattner, M.D.
National Cancer Institute, NIH
In the lead chapter of one of the finest new AIDS research and therapy books(l), Dr. Goedert and Dr. Blattner at the National Cancer Institute discuss inhalation of nitrites and say, "...it now appears that frequent use of nitrite inhalants simply may be a surrogate marker of frequent receptive anal intercourse."

(1)Goedert, J.J. and Blattner, W.A. The epidemiology of AIDS and related conditions. W: AIDS: ETILOLOGY, DIAGNOSIS, TREATMENT, AND PREVENTION. eds.: DeVita, V.T., Heuman, S. and Rosenbert, S.A. 1985 J.B. Lippincott Company. New York

Cladd Stevens, M.D., Head of Laboratory of Epidemeology
The New York Blood Center
While conducting one of this nation's largest ongoing studies of gay men and AIDS, during a meeting with J.F. Miller, President and CEO of Great Lakes Products, Inc., Dr. Stevens said: "Based on the data I've accumulated over the past five years, there appears to be no correlation between inhalation of butyl nitrite and AIDS or any of its infections." February 26, 1986 *Meeting held in Dr. Steven's offices at New York Blood Center, New York City

Bruce Voeller, Ph.D. President, Mariposa Foundation, Nationally-known AIDS researcher who gave AIDS its name, co-founder National Gay Task Force
In a major article on AIDS and "poppers" printed in the California newspaper, SAN DIEGO UPDATE: "...the intense campaigns against the use of volatile nitrites conducted by some, are slim in scientific merit. We need to get off poppers", or make a case against them through better science. We've been too preoccupied with "poppers" (as a possible co-factor) to the exclusion of everything else. By continuing up the wrong path, we loose time finding the right one." April 30, 1986

U.S. Department of Health and Human Services (HHS) Memorandum to National Institute on Drug Abuse (NIDA)
"...data would seem to indicate that the abuse of nitrites is relatively unlikely to result In a medical emergency." March 8, 1984

James W. Mosely, M.D.
University of Southern California Medical School professor who heads the U.S. government's largest, multi-million dollar program studying the AIDS virus and the nation's blood supply
In sworn testimony before a state legislative committee, stated that he had reviewed the evidence regarding isobutyl nitrite and AIDS, and that he regarded the claims of danger to be ill-founded. December 1985

U.S. Government Findings: Alkyl Nitrite Misuse by High School Students is Not a Problem in the U.S.
Although abuse of nitrite-based room odorants was never a significant problem with minors, National Institute on Drug Abuse statistics have shown a "substantial drop in the use of the amyl and butyl nitrites..."
NIH and NIDA publication: DRUGS AND AMERICAN HIGH SCHOOL STUDENTS 1975-1983

D. Lewis, of the National Institute for Occupational Safety and Health
As reported in U.S. Medicine, while speaking in an AIDS session at the Public Health Service (PHS) annual meeting, reported his animal research with isobutyl nitrite indicated the substance is not immunotoxic for mice.
June 15, 1983

Cable News Network (CNN)
During a segment on AIDS: "In another development this week, federal investigators did a study of the stimulant isobutyl nitrite ... which was thought to have a depressing effect on the immune system. Studies on mice indicate the compound doesn't directly harm the body's defenses. September 8, 1983

A ‘Fact Sheet’, originally publish in 1988 by Chemsearch, Ltd, of Indianapolis, IN

"Poppers"... What are they?

1. "Poppers" is the street term used for nearly 30 years to describe the misuse of any alkyl nitrite (including amyl nitrite, isobutyl nitrite and butyl nitrite) as inhalants for recreational purposes.

2. Although "Poppers" have only recently come to the public attention, alkyl nitrites have been inhaled for over one hundred years. They have had a long and well-documented history of public safety. This record is strongly reinforced by the fact that during the past 20 years a very high probability has existed that a large percentage of all nitrite odorants sold were misused as "poppers".

Who Wants Them Banned and Why?

1. Despite that long safety record of alkyl nitrites, the AIDS phenomenon opened the door of opportunity for certain self-serving individuals to promote themselves as “experts" on the study of "poppers" and to condemn their use as unsafe. These self-proclaimed "experts" did not have the knowledge of immunology or epidemiology to make informed judgments about AIDS or its cause. Real experts now tell us that AIDS is caused, not by "poppers", but by a virus and that the misuse of nitrites as "poppers" appears rather clearly NOT to be causally associated with AIDS or any of its opportunistic infections. In 1987, the large MCS study, among others, confirmed that no such connection exists.

Are They Really Safe?

1. Anti-"popper" individuals suggest "poppers" are unsafe because they are not regulated by any government agency. This is simply not true. Of the compounds most commonly used as "poppers", amyl nitrite is regulated by the FDA and nitrite-based room odorizers are regulated by the Consumer Product Safety Commission. Within the past few years, the CPSC has twice been asked to restrict isobutyl nitrite products and has twice, after thorough investigation, decided that the safety record of these products did not indicate that such action was necessary. Although responsible nitrite odorant manufacturers have never encouraged or promoted the misuse of their nitrite odorants as "poppers", they have long recognized the high probability of such misuse. They, therefore, have shared a deep concern and responsibility toward each responsible adult user of these products. (in much the same manner that responsible children's crayon manufacturers recognize that their crayons will be eaten and thus assure that they are safely edible.)

2. A review of the literature clearly shows that inhalation of the alkyl nitrites poses no significant health hazard.

©1988 by Chemsearch, Ltd
Reprinted from "Guide to Alky Nitrites - Poppers Statements"

A 1977 Front Page Story on Alkyl Nitrites, Amyl Nitrate, Isobutyl Nitrite and Poppers Appearing in The Wall Street Journal

2006-04-27T14:36:00.000-07:00

'A New Way to Glow And Giggle, and Get A Headache Besides. “Poppers", Legally Sniffable, Becoming a Big Business; The FDA isn’t Interested.'

By Stephen J. Sansweet, Staff Reporter of the Wall Street Journal

At a chic New York nightclub, a trendy East Side couple take turns sniffing a colorless liquid from a small bottle, then start to giggle as a warm red glow suffuses their faces.

A Los Angeles businesswoman, in the middle of a particularly hectic public-relations job, confides “I could really use a ‘popper’ now.”

And at San Francisco’s latest “in” disco, young men pass around metal inhalers, breathe in deeply and start dancing even more frenetically to the pounding musical beat.

All of these people are using a chemical designed to imitate a drug that has been prescribed by doctors for more than a century. In the last year or so this chemical has caught fire as the latest and one of the cheapest ways to get an instant high. Unlike many other “recreational” drugs, this one is legal. It is also becoming a big business nationwide, much to the dismay of some physicians and regulatory authorities.

The prescription drug that is being copied so successfully, amyl nitrite, (mistakenly referred to by most users as nitrate), was introduced in 1867 to ease the pain of angina attacks for people with heart conditions. Amyl, as it is commonly called, has long been marketed as a prescription drug in thin-walled glass ampules covered by cotton mesh.

When a user crushes the ampule to inhale the fumes of the volatile liquid, the ampule makes a popping sound, hence the term ”poppers”. That nickname is used today even for the non-ampule variety sold legally over the counter in thousands of bars, bookstores, boutiques and bead shops.

“Very Profitable Item”

These “poppers” are sold in half-ounce or smaller bottles under such names as Locker Room, Rush and Bullet. The chief ingredient in most of these products is butyl nitrite, a chemical first cousin to amyl. Manufacturers are extremely tight-lipped about sales figures, but an educated guess is that sales of the main brands total as much as $15 million a year at retail prices of $4-$10 a bottle. “It’s a very, very profitable item” says Jim Beale, owner of the Main Line Gift Shop in San Francisco.

In addition to the main brands, at least half-dozen more are being turned out by other small manufacturers. Observers also say that street sales of a homemade variety so-called “bathtub amyl” may account for another several million dollars a year.

“It’s a great kick” says one west Coast user. “You take a sniff, and right away you get this rush. You get all warm and tingly and you feel like you’re strapped to the side of a rocket ship that’s just blasted off.” The sensation, he says, lasts about a minute to 90 seconds.

That “kick” isn’t surprising, given the properties of amyl and butyl nitrite. Richard D. Kramer, a San Francisco pharmacist who has studied the phenomenon, says the chemicals relax involuntary muscles and blood vessels. When the vessels dilate, there is an instantaneous drop in blood pressure. In a reflex action, the heartbeat increases dramatically to bring the pressure back up. A common side effect is headaches, which may last for hours. Mr. Kramer says that other side effects can include blushing, heavy sweating and some dizziness.

Into the Cracks

Unlike amyl, butyl nitrite has fallen into the cracks of the federal regulatory system. The Food and Drug Administration isn’t interested primarily because the products are sold as “room odorizers” or “liquid incense,” not as drugs. A spokesman for the federal Consumer Product Safety Commission says the agency’s Bureau of Biomedical Sciences feels the chemicals are hazardous and should be banned, “but you have to come up with substantial data on injuries to do that, and so far there just isn’t any.” The agency did prod major manufacturers to include cautionary labels that warn, among other things: Not for human consumption.

At a recent hearing, a West Haven, Conn., church organist testified that he and some friends have indeed used butyl nitrite as a room odorizer. They may be a select few. Most of the products have a cloyingly sweet odor that would put off even the most dedicated hedonist, but it isn’t as bad taken in small whiffs directly from the bottle or from an inhaler that contains a cotton wad soaked with the chemical.

A major lure of Rush, Locker Room and the others is their reputed value as aphrodisiacs. The chemicals are said to heighten and prolong sensation, and one product recently was advertised with the line “When the nitrite-dispersed, non-aerosol aroma fills the room, sex is in the air.” Mr. Kramer says, however, that “the nitrites are nonsexual drugs in themselves and can have quite the opposite effect on someone who doesn’t like them.”

All of this activity astonishes Burroughs Wellcome Co., the drug company that has sold pharmaceutical-grade amyl nitrite since the 1920’s. It was a prescription drug until 1960 when the FDA decided to make it over-the-counter. “Around 1964 we started getting reports of non medical abuse of amyl, and we and others wrote the FDA asking that it be made a prescription product again,” a spokesman for the company says. The FDA complied four years later, but sales of the prescription drug remained reasonably level until the last12 months or so, when they suffered a 30% drop.

That is when the entrepreneurs entered what some of them like to call “the aroma market.” Amyl has been big in the homosexual community and among users of other drugs since the 1960s, but the sale of nitrite really took off when butyl nitrite was developed in the early 1970’s by Clifford Hassing, now 34 years old and the president of West American Industries of Los Angeles.

“It all started because I wanted a room odorizer for my own personal use and couldn’t find one on the market.” Mr. Hassing says, carefully choosing his words. “So I slipped into a chemistry lab (he was a pre-medical student) and whipped up a product to meet my needs.” That’s how Locker Room®, which to Mr. Hassing smells like a men’s gymnasium, was born. At first sold to friends and neighbors, the ubiquitous amber bottle (three-tenths of an ounce for $5) became a word-of-mouth marketing sensation.

The main competition comes from Pacific Western Distributing Corp. of San Francisco. W. Jay Freezer, chairman, claims his company’s Rush® now has at least 60% of the total market (a figure Mr. Hassing disputes) after only a year in business. Rush has been aided by a large advertising campaign in specialized newspapers and magazines and an aggressive marketing program. Besides being available at the regular outlets, Rush now is sold in a few record stores and pharmacies and is promoted at boutique and gift trade shows. Mr. Freezer says:

“If Safeway supermarket customers want the product, I don’t see why it couldn’t eventually be sold there.”

The biggest legal challenge to the nitrites comes from the Connecticut Department of Consumer Protection. Commissioner Mary Heslia has proposed a statewide ban on all butyl products under authority of the state’s child protection act. “This is a harmful product that police have reported is being sniffed by children to get high,” the commissioner says. “The primary intention certainly isn’t to use it as a room odorizer and there isn’t any labeling adequate to protect the public health and safety.”

As of now, the safety question is unresolved. A Burroughs Wellcome official says long-term clinical experience with amyl nitrite shows that the product doesn’t have any harmful effects, and a Canadian cardiologist testified on behalf of the makers of Rush® at a Connecticut hearing, that he has seen only “minor complications” in years of clinical experience with nitrites. Still, there haven’t been specific studies on possible adverse effects of frequent use of butyl compounds for recreational purposes over an extended period.

Dr. Richard R. Hamilton, a San Francisco physician, is concerned with abuse of nitrite products. “Some people go through an entire bottle in one evening,” he says, “and that amount of stress can put them in jeopardy, particularly if there are some heart or artery problems.”

Dr. Hamilton tells his patients with Asthma or hepatitis that the use of “poppers” can cause further health problems; he has treated people who have spilled the liquid in their eyes or nose. Curiously, in an informal survey, Dr. Hamilton found that of 500 men using nitrite products at least a few times a month, 50% believed that the chemicals were dangerous to their health.

Reprinted From: Wall Street Journal – October 10, 1977 A New Way to Glow And Giggle, and Get A Headache Besides. “Poppers, Legally Sniffable, Becoming a Big Business; The FDA isn’t Interested By Stephen J. Sansweet, Staff Reporter of the Wall Street Journal