Alkyl Nitrite and the Confusion by US Federal Govt Agencies

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Alkyl Nitrite and the Confusion by US Federal Govt Agencies

Restrictions on the use of amyl nitrite and other alkyl nitrites over time by the FDA and CPSC have been based on confusing, misleading and often contradictory data. Frequently, the data that does exist at the time that decisions are made seems to be completely ignored by the powers that be. This paper will review the history of the US government’s agency actions to control the use of nitrites as inhalants. The current status will also be examined. Finally, necessary actions to be taken to bring about regulatory changes will be explored.

Alkyl nitrites, commonly referred to as “poppers” have been regulated by the U.S. government since the 1960’s at various levels of restriction and for a variety of reasons. Not all of the regulation has been based on solid data, or sound clinical information. Regardless, the impact has been the same. Individuals who desire to use nitrites as inhalants for recreational purposes find themselves up against the law. Restrictions on the use of amyl nitrite and other alkyl nitrites over time by the Federal Drug Administration (FDA) and the Consumer Product Safety Commission (CPSC) have been based on confusing, misleading and often contradictory data. Frequently, the data that does exist at the time that decisions are made seems to be completely ignored by the powers that be, or contradicts the actions that are taken.

This paper will review the history of the US government agency’s actions to control the use of nitrites as inhalants. The various players in the drama will be considered. Available studies and data will be identified and examined as practical. Where possible, arguments on both sides of the issue will be identified when available. The current status will also be examined. Finally, necessary actions to be taken to bring about regulatory changes will be explored. A chronological organization will be presented as a framework for this discussion.

What Are Poppers, and Why Are They Popular?

Alkyl nitrites and similar variants have many brand and street names including: amyl nitrite, butyl nitrite, isobutyl nitrite, TNT, liquid gold, Amy, high-tech, kix, locker room, poppers, ram, rave, rush, clock cleaner, snappers, and thrust.
The term alkyl nitrite covers a number of volatile solvents, most commonly: amyl, butyl, and isobutyl nitrites. They are esters of nitrous acid and are prepared by combining the corresponding alcohol, sodium nitrite, and sulphuric acid. Amyl nitrite was originally used medically to relieve angina, first described in 1859 (Brunton 1867). Today, the only medical uses for amyl nitrite is as an antidote to cyanide poisoning (Baselt and Cravey 1989) and as a diagnostic means for detecting cardiac murmurs (Rosoff and Cohen 1986) since alternative methods of treating angina have been created. Although butyl and isobutyl nitrites have similar effects as amyl nitrite, they have never been used clinically.
Nitrites are volatile liquids that are inhaled by those seeking an effect to produce a near instantaneous “rush” that can last from a few seconds to up to five minutes. In the past, nitrites were sold in glass vials that had to be popped between the fingers to release the vapor; Hence, poppers becoming the slang term for nitrites. They produce a sweet, fruity smell when fresh, but when stale develop a pungent odor. Amyl nitrite evaporates at room temperature releasing a vapor causing veins and arteries to dilate resulting in the blood flowing faster through the heart and the brain. Poppers are used to enhance sensation, awareness of the environment and sexual sensation. They are popular among gay users and others because they trigger an almost immediate jump in the heart rate and a corresponding drop in blood pressure, causing smooth muscle tissue to relax. It is this muscle relaxation that allows for smooth entry during sexual acts.

Brief History of Amyl Nitrite Use
Amyl nitrite had a long history of use for medical treatment for angina as noted above. In the 1960’s use of the compound as an inhalant for the recreational purposes listed above apparently caught the attention of the manufacturer and other who became concerned with the off-label use of the product. Perhaps their concern for their reputation, loss of profits to renegade competitors, and the concern for possible physical side effects lead to their action to call for re classification of the compound. Another possible motivation was that they were concerned by the fact that the high use and popularity was among manly gay men at the time. A 1977 Wall Street Journal article “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, recounts these corporate actions to reclassify amyl nitrite,

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 last 12 months or so, when they suffered a 30% drop.

Sansweet continues that the recreational use expanded, “…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.” Clearly this lobbying by the manufacturer was not substantiated by any claim or data referencing harmful physical effects of recreational use of the product.

In 1969 a citizen petition was filed before the FDA calling for enforcement of the regulations restricting amyl nitrite pursuant to 21C.F.R. 9250.1000. The petitioner cited various commercial products including: the prescription only drug amyl nitrite, aka, isopentyl nitrite, … branded Jungle Juice, Man Scent and otherwise; and as it relates to the inter-net websites www.vhcleaner.com/big-bottles2; www.poppersexpress.com/index. http://getbooked.com/shop/product_in..php/nroducts id/5728; and
www.nitroaroma.com/nremium.html At that hearing the records show, “…the Commissioner of Food and Drugs received reports of the abuse of this drug by those who do not require it for medical purposes. Additionally, comment included a great deal of concern expressed by individual physicians, medical associations, pharmaceutical associations, manufacturers, and State and local health authorities.” (emphasis added). The report does not cite specific studies or professionals, corporations or associations. Their findings continued, “Based on the information available, it is the opinion of the Commissioner of Food and Drugs, concurred in by the Food and Drug Administration Medical Advisory Board, that amyl nitrite inhalant is a drug with a potentiality for harmful effect and that it should be removed from over-the-counter status and restricted to sale on the prescription of a practitioner licensed by law to administer such drug. Thus the recommendation to restrict the sales is based on undiscoverable (at this time) evidence. The outcome was that the products had to be labeled to include the need for prescriptions and hazard warnings. The scope of these hearings also expanded to isobutyl nitrite inhalant products registered to Great Lakes Products of Indianapolis, Indiana.

Data Seems Dependent on Political Position

The controversy continues as to the negative physical effects of use of alkyl nitrites, and the outcome of the assertions seems to be dictated by the political position of the speaker. Negative physical outcomes are cited in the archives of Drugabuse.gov in their 1977 monograph Review of Inhalants: Euphoria to Dysfunction. While citing numerous studies pertaining to the uses and the populations that use nitrites, they then cite the list of potential side effects from the “most commonly used and abused aliphatic nitrite,” amyl nitrite. Interestingly, most citations are for animal studies, which frequently result in mass quantities and extreme results. They report,
The use of amyl nitrite may be accompanied by medical complications. Limited toxicological data have been available. When given to mice by i.p. injection, the LD50 was 130mg/kg. When given by i.v. the LD50 was 51 mg/kg Dewey et. al., 1973). When dogs were administered amyl nitrite i.v., low doses elicited tremors and ataxia, while higher doses produced convulsions and death (Dewey et al., 1973). When these same investigators exposed the dogs to the drug by inhalation, one dog became quiet and another ataxic for a short period. When they were subjected to repeated inhalation doses of amyl nitrite at 20- to 90-second intervals for up to 7 minutes. varying degrees of pharmacologic effects were noted, ranging from no effect to ataxia, gagging, vomiting, urination, defecation, and even brief convulsions. These effects seemed to be somewhat related to the frequency of dose and the number of doses.
Many of us are old enough to remember similar studies involving large doses of artificial sweeteners, that were later discredited because the doses represented significant overexposure to that typically used by humans. The reference to human effects, however, are scant in comparison and do not appear as scientific as the animal studies. They continue, “Other side effects have been noted in people who have used or abused this drug, including dizziness, headache, tachycardia, hypotension, syncope, and increased intraocular pressure (Everett, 1972, 1975b); Gay and Sheppard, 1973; Hollister, 1975a, 1975b; Louria, 1970; Pearlman and Adams, 1970). Nitrites in general have also been associated with methemoglobinemia and rare sudden deaths (Louria, 1970).” Amyl nitrite is contraindicated in certain persons who have cardiovascular problems (Everett, 1975b; Hollister, 1975a, 1975b).” they then opine, “If abuse of such drugs continues to escalate medical complications may be seen more frequently.” (emphasis added) They also discredit their evidence further by stating that, “Few if any investigations have been conducted on the effects of butyl nitrites and related components contained in over-the-counter products such as Locker Room or Rush. Clearly the government agency position clearly promoted the notion that inhaling nitrites has toxicological outcomes

Opponents of the ban cite other evidence. In 1977, the Consumer Product Safety Commission and the manufacturer challenged the belief or assertion that recreational use of nitrites was harmful. According to Sansweet in his Wall Street Journal article, “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.” He also asserted that, “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.” (emphasis added). The agency did prod major manufacturers to include cautionary labels that warn, among other things: Not for human consumption. The manufacture of the prescription product also questioned the validity of concerns over harmful effects.
Sansweet continued, “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. To be fair, “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.’ Still, there haven’t been specific studies on possible adverse effects of frequent use of butyl compounds for recreational purposes over an extended period. Thus you have an exonerating opinion from both the CPSC and the manufacturer of amyl nitrites. Both the government and the pharmaceutical representatives reaffirm that insufficient study of butyl products has been made as late as 1977.

Despite its continued ban on the sale of alkyl nitrites for recreational purposes on the premise of physical harm, a Consumer Product Safety Commission report from 1983 declined to ban the sale of nitrite poppers due to a lack of evidence of their harm poppers due to lack of injury potential, history of safe use according to their headline. The U.S. Consumer Product Safety Commission, July 1983, Briefing Package on Petition HP82-1 stated, “The staff has not found sufficient data to Support the claim of a behavior disorder associated with volatile nitrite inhalation. Available injury data did not indicate a significant risk of personal injury or illness from room odorizer abuse. These materials were prepared with the assistance of Chemical Hazards Program team members.” Clearly, this government agency did not find justification to ban nitrite poppers because of injury potential. Despite these findings, they continued to control the compound Amyl Nitrite by requiring a prescription for inhalation used, warning labels and the requirement that the product be used for commercial purposes only, such as for cleaners and room odorizers.

In 1988, the assault was extended to include butyl nitrite by amendments to 15 U.S. Code § 2057a – Banning of butyl nitrite. Specifically, the language states, “For the purposes of section 2057 of this title, it shall not be unlawful for any person to manufacture for sale, offer for sale, distribute in commerce, or import into the United States butyl nitrite for any commercial purpose or any other purpose approved under the Federal Food, Drug, and Cosmetic Act [21 U.S.C. 301 et seq.].” They further defined commercial purposes, “The term “commercial purpose” means any commercial purpose other than for the production of consumer products containing butyl nitrite that may be used for inhaling or otherwise introducing butyl nitrite into the human body for euphoric or physical effects.” This Section was enacted as part of the Anti-Drug Abuse Act of 1988 and also as part of the Comprehensive Alcohol Abuse, Drug Abuse, and Mental Health Amendments Act of 1988, and not as part of the Consumer Product Safety Act which comprises this chapter. It is interesting how the various agencies of the federal government take turns handing off responsibility for regulation of the nitrite compounds. This classification as a commercial product will come back to haunt the reputation of nitrite compounds and will be discussed later in this paper in the context of current “studies on inhalants.”

Alkyl Nitrites: A Compendium Of Studies, Abstracts And Analysis About Amyl Nitrate, Isobutyl Nitrite And Poppers, published in 1988 summarized then current findings on the topic. One in particular demonstrates the lack of consistency between data and actions. They presented a reprint 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. The result of this study contradicts the actions to restrict access. (Section 4015), Congress requested that National Institute of Drug Abuse (NIDA), through Health and Human Service, conduct a study of alkyl nitrites to determine the extent and public risk associated with alkyl nitrite use. The report emphasized, “. 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.” 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. This once again shows the disconnect in decision making.

Another resource is a guide highlighting summary statements from professionals regarding adverse effects of using nitrites, and was 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 alkly nitrites. Among the relevant statements were:
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
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
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
Cladd Stevens, M.D., Head of Laboratory of Epidemeology of 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
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
These statements confirm contemporary knowledge in 1988 that use of nitrites as recreational inhalers in not proven to be harmful to the heath of the user.

A ‘Fact Sheet’, originally publish in 1988 by Chemsearch, Ltd, of Indianapolis, IN describes Poppers and their banning. They conclude, “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”. They contend that, “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.” When asked if their use is safe, they opine, “ 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.) Finally, they conclude, “A review of the literature clearly shows that inhalation of the alkyl nitrites poses no significant health hazard.”
Historic Spread of Inaccurate Information

Much of the information disseminated during the 1980’s was based on inaccurate information and research and further served as a catalyst for banning nitrites. Chief among this was the belief that nitrite use caused AIDS in users. This was heralded by advocates for restriction including by Hank Wilson of San Francisco, a gay activist who in 1981 founded the Committee to Monitor Poppers. He along with the main sponsors of the nitrite inhalants provision of the Drug Omnibus Act of 1988 were Representatives Mel Levine and Henry Waxman (Democrats- California). Both are strong supporters of gay rights. They concluded all kinds of things including the cause of AIDS, Karposi Sarcoma, and many other physical ills. As proof they promoted the following beliefs that, “Poppers are immunosuppressive. They cause anemia, lung damage, serious skin burns, and death or brain damage from cardiovascular collapse or stroke. Poppers cause genes to mutate and have the potential to cause cancer by producing deadly N-nitroso compounds. Poppers have been used successfully to commit suicide (by drinking) and murder (victim gagged with sock soaked with poppers). There are strong epidemiological links between the use of poppers and the development of AIDS, and especially Kaposi’s sarcoma (KS). A six-fold decrease in the incidence of KS over the past five years parallels a sharp decline in the use of poppers.” Unfortunately, when incorrect information is disseminated as truth, much of it sticks with uninformed readers. This is the case with much of Wilson’s assertions. Science later disproved much of the information used to form judgments about the negative impact of inhaling nitrites.

Case in point for sound research practice is 1989’s A Critical Review of Hank Wilson’s Bibliography of Anti-Popper Research, in which Lisa Ringold, PhD pharmacology provides a critical review of the bibliography used to discredit nitrite use. She asserts, “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.’ Chief among her claims is that the data do not support the claims made, and that many of the studies are animal studies that result in massive doses that skew interpretation of results. She also finds numerous holes in the research process and validity.
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.
Despite setting the record straight for scholars who will take the time to read the research, the damage to the credible arguments about negative impact of nitrite use have already been tarnished by the inaccurate science of advocates like Wilson and others. Like a bad rumor, the inaccurate information sticks and can’t be struck from the record.

Problems Created by FDA Shifting Compliance to the CPSC

The FDA shifted the responsibility for monitoring and controlling use of nitrites to the commercial sector, and thus the Consumer Product Safety Commission. This action allowed producers to continue to manufacture “poppers” as commercial cleaners and air fresheners. This shifted the governmental oversight from controlling nitrites used as pharmaceuticals, and as inhalants to nitrites used for other commercial uses. The coincidence that recreational users might use the products as inhalants for recreational/sexual uses then is shifted to an off label use. The manufacture still gets to make the product and the inhaler still gets to use the product, and the government slides out of the picture. That is all well and good until you get to the science of the matter.

Attempt to find definitive research about the impact of inhaling alkyl nitrites becomes nearly impossible because research focuses on all of the other commercial products that are inhaled for a “kick” or a rush. Drugabuse.gov’s 1992 monograph Inhalant Abuse: A volatile Research Agenda addresses this difficulty, “The study of the abuse of volatile solvents is hampered by a number of factors not usually found in the study of other drugs of abuse. Consequently, the quality of the research data is very uneven, and many contradictory findings appear in the literature.” Among these is that most drugs are classified and discussed by the effects they create on the user: uppers, downer, psychedelics, tranquilizers, etc. The monolith clarifies,
The term “inhalants,” however, has come to encompass a group of psychoactive chemicals that are defined by the route of administration rather than by their experienced effects or central nervous system (CNS) action. Thus, such diverse substances as toluene, ether, and the nitrites have been included under the rubric of inhalants because they are all taken in through the nose. This can lead to a great deal of confusion, since not only may the psychoactive properties be different, but the profiles of the typical users of the various substances are quite diverse.
The importance of this argument becomes clear when one attempts to research impact of inhalant use because the products studied are typically household and commercial products that are inhaled in many instances for the high, without regard to potential dangers. The monograph continues,
The most common case of overinclusion occurs with amyl and butyl nitrites. These are very often considered the equivalent of industrial and household solvents and little distinction is made between the users of each type of substance. In a very large national data base collected over the past 3 years, we have been able to show significant differences between nitrite users and those who use common household solvents.
While this study was concerned about defining users and how many teens are inhaling, what substances, the argument holds for determining what is inhaled and the physical impact. This becomes a significant challenge for researchers trying to isolate the physical effects, if any, of inhaling nitrites. You will see later that a search for impact of nitrites proves difficult because of this inclusion.

Drugabuse.gov, in May of 1999 and republished in 2012, further describes the problem of identifying inhalants abuse in a letter from the National Institute of Drug Abuse director Nora D Volkow, MD:
Inhalants are volatile substances that produce chemical vapors that can be inhaled to induce a psychoactive, or mind-altering, effect. Although many parents are appropriately concerned about illicit drugs such as marijuana, cocaine, and LSD, they often ignore the dangers posed to their children from common household products that contain volatile solvents or aerosols. Products such as glues, nail polish remover, lighter fluid, spray paints, deodorant and hair sprays, whipped cream canisters, and cleaning fluids are widely available yet far from innocuous. Many young people inhale the vapors from these sources in search of quick intoxication without being aware that using inhalants, even once, can have serious health consequences.
Even gasoline is included in the list of substances inhaled. Many products readily found in the home or workplace—such as spray paints, markers, glues, and cleaning fluids—contain volatile substances that have psychoactive (mind-altering) properties when inhaled. She continues, “Parents and children need to know that even sporadic or single episodes of inhalant abuse can be extremely dangerous. Inhalants can disrupt heart rhythms and cause death from cardiac arrest, or lower oxygen levels enough to cause suffocation. Regular abuse of these substances can result in serious harm to vital organs, including the brain, heart, kidneys, and liver.” One can see from the list that many of these items are extremely toxic and dangerous.

Lumping nitrites into this mix is obviously inappropriate and any comparison with the negative side effects absurd. The report states,
The chemicals found in solvents, aerosol sprays, and gases can produce a variety of additional effects during or shortly after use. These effects are related to inhalant intoxication and may include belligerence, apathy, impaired judgment, and impaired functioning in work or social situations; nausea and vomiting are other common side effects. Exposure to high doses can cause confusion and delirium. In addition, inhalant abusers may experience dizziness, drowsiness, slurred speech, lethargy, depressed reflexes, general muscle weakness, and stupor. For example, research shows that toluene can produce headache, euphoria, giddy feelings, and the inability to coordinate movements.
These are clearly not the outcomes from inhaling nitrite compounds.

The NIDA reports outcomes that are reminiscent of the early days of Wilson, including blaming wild sex orgies on the inhaling of nitrite compounds. While they acknowledge the common knowledge that Inhaled nitrites dilate blood vessels, increase heart rate, and produce a sensation of heat and excitement that can last for several minutes, and that other effects can include flush, dizziness, and headache, they describe the unique risks associated with nitrite abuse:
Nitrites are abused mainly by older adolescents and adults. Typically, individuals who abuse nitrites are seeking to enhance sexual function and pleasure. Research shows that abuse of these drugs in this context is associated with unsafe sexual practices that greatly increase the risk of contracting and spreading infectious diseases such as HIV/AIDS and hepatitis.
Animal research raises the possibility that there may also be a link between abuse of nitrites and the development and progression of infectious diseases and tumors. The research indicates that inhaling nitrites depletes many cells in the immune system and impairs mechanisms that fight infectious diseases. A study found that even a relatively small number of exposures to butyl nitrite can produce dramatic increases in tumor incidence and growth rate in animals.
They even reference the animal studies that may or may not reflect outcomes in humans.

Certainly, the point of this paper is not to deny that inhaling other inappropriate commercial products on the list is in anyway safe. The outcomes of abusing genuine commercial products can be devastating. Remember that pharmaceutical nitrites are inappropriately described as commercial solvents for government agency expediency, and they are realistically not classifiable as such. These outcomes are noteworthy for anyone who would consider inhaling gasoline, toluene, benzene and other caustic gases!
What are the other medical consequences of inhalant abuse?
Inhalant abusers risk an array of other devastating medical consequences. The highly concentrated chemicals in solvents or aerosol sprays can induce irregular and rapid heart rhythms and lead to fatal heart failure within minutes of a session of prolonged sniffing. This syndrome, known as “sudden sniffing death,” can result from a single session of inhalant use by an otherwise healthy young person. Sudden sniffing death is associated particularly with the abuse of butane, propane, and chemicals in aerosols. Inhalant abuse also can cause death by—
• asphyxiation — from repeated inhalations that lead to high concentrations of inhaled fumes, which displace available oxygen in the lungs;
• suffocation — from blocking air from entering the lungs when inhaling fumes from a plastic bag placed over the head;
• convulsions or seizures — from abnormal electrical discharges in the brain;
• coma — from the brain shutting down all but the most vital functions;
• choking — from inhalation of vomit after inhalant use; or
• fatal injury — from accidents, including motor vehicle fatalities, suffered while intoxicated.
Based on independent studies performed over a 10-year period in three different states, the number of inhalant-related fatalities in the United States is approximately 100–200 per year.
There is no data on how many, if any can be attributed to nitrites because of the research issues noted above.

In 2006, the UK government commissioned psychopharmacologist Professor David Nutt and neuroscientist Professor Colin Blakemore to rank recreational drugs by their dangerousness. According to the author, “The list has just been published in today’s The Independent and gives some surprising results. Unusually, the list contains both legal and illegal drugs.”
The drugs were ranked by ratings which took into account a combination of their physical damage, social harm and addictive properties.
In rank order of harmfulness:
1. Heroin
2. Cocaine
3. Barbituates
4. Street methadone
5. Alcohol
6. Ketamine
7. Benzodiazepines (e.g. Vallium)
8. Amphetamines
9. Tobacco
10. Buprenorphine
11. Cannabis
12. Solvents
13. 4-MTA
14. LSD
15. Methylphenidate (Ritalin)
16. Anabolic steroids
17. GHB
18. Ecstasy
19. Alkyl Nitrites (poppers)
20. Khat
The author continued, “Apparently, the government were a little reticent to publish the report, considering the legal classification is completely out of whack with this analysis.” As seen, poppers are ranked at the bottom of severity.

2015
The Code of Federal Regulations continues to enforce the ban on amyl nitrite by reaffirming the position they took in 1967 without reference to additional evidence or studies. They reiterated their prior position by publishing in the register:
(a) Amyl nitrite inhalant has been available over-the-counter for emergency use by the patient in the management of angina pectoris for a number of years. As a result of a proposed policy statement published August 25, 1967 (32 FR 12404), the Commissioner of Food and Drugs received reports of the abuse of this drug by those who do not require it for medical purposes. Additionally, comment included a great deal of concern expressed by individual physicians, medical associations, pharmaceutical associations, manufacturers, and State and local health authorities. Based on the information available, it is the opinion of the Commissioner of Food and Drugs, concurred in by the Food and Drug Administration Medical Advisory Board, that amyl nitrite inhalant is a drug with a potentiality for harmful effect and that it should be removed from over-the-counter status and restricted to sale on the prescription of a practitioner licensed by law to administer such drug.
(b) Therefore, amyl nitrite inhalant will be regarded as misbranded unless the labeling on or within the package from which the drug is to be dispensed bears adequate information for its safe and effective use by physicians, in accordance with 201.100(c) of this chapter, and its label bears the statement “Rx only.”

Thus, no additional evidence of its efficacy or dangers was considered before reaffirming the position. The information on this page posting the register is current as of April 1 2015.

Other 2015 affirmations of the potential for physical harm from the use of poppers comes from the Mayo Clinic in their Drugs and Supplements publication, Amyl Nitrite (Inhalation Route).
Amyl nitrite is related to the nitrate medicines and is used by inhalation to relieve the pain of angina attacks. It works by relaxing blood vessels and increasing the supply of blood and oxygen to the heart while reducing its workload. Amyl nitrite may also be used for other conditions as determined by your doctor. This medicine comes in a glass capsule covered by a protective cloth. The cloth covering allows you to crush the glass capsule between your fingers without cutting yourself. On the street, this medicine and others like it are sometimes called “poppers.” They have been used by some people to cause a “high” or to improve sex. Use in this way is not recommended. Amyl nitrite can cause serious harmful effects if too much is inhaled. Amyl nitrite is available only with your doctor’s prescription.
They go on to caution patients to discuss the use of nitrites if the patient takes certain medications or has existing physical conditions that could be impacted by the sudden drop in blood pressure. They also advise how to use properly for chest pain.

State of Current Research
This researcher attempted to locate current research on the negative impacts of inhaling alkyl nitrites in the US governments research system. Several searches were undertaken through the Research Participation Programs at the U.S. Food and Drug Administration (FDA) using the Search Parameters: Amyl nitrites, Alkyl nitrites, nitrite inhalants for the years from 2010 to 2016 in order to assess the current state of research on this topic. Each successive search achieve a “no results” response. Clearly, no one in the federal level of scholarship is researching the negative impacts of inhaling nitrites.

Conclusion
In this paper we examined many facets of the use and misuses of data to make policy decisions about use and purchases of amyl and alkyl nitrites for use as inhalants and for other labeled commercial purposes. We have shown that restrictions on the use of amyl nitrite and other alkyl nitrites over time by the FDA and CPSC have been based on confusing, misleading and often contradictory data. Frequently, the data that did exist at the time that decisions were made seemed to be completely ignored by the powers that be, or contradicted the actions that were taken. We examined the current status which only serves to maintain the status quo. We attempted to identify current research that would demonstrate that the use of nitrites as inhalants does not present the physical dangers portrayed and typical of inhaling caustic chemicals and compounds. We demonstrated that current research is not focused on the topic on the government level. Finally, we have determined that the only remedy to correct this problem would be to petition the Department of Health and Human Services, FDA and CPSC to examine objectively, data which shows that amyl nitrite and alkyl nitrites are misclassified as commercial products and should be considered on their merits independent of other chemical and compounds that are inhaled for recreational and/or sexual enhancement purposes. Only by receiving an objective review, can the truth prevail about the impact of their use.

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