Poppers

Poppers are recreational drugs belonging to the alkyl nitrite family of chemical compounds. When fumes from these substances are inhaled, they act as potent vasodilators, producing mild euphoria, warmth, and dizziness. Most effects have a rapid onset and are short-acting. Its recreational use is believed to be potentially dangerous for people with heart problems, anaemia, or glaucoma. Reported adverse effects include fainting, retinal toxicity, and vision loss.
As poppers include a broad range of chemical types, their legality differs across different jurisdictions. They are often packaged under the guise of room deodorizer, leather polish, nail polish remover, or videotape head cleaner to evade anti-drug laws.
The term poppers comes from the popping sound made when glass vials of the substance were crushed to release the vapors for inhalation. Amyl nitrite was originally prescribed in the late 1800s for the medical management of angina. Many analogues exist, such as isoamyl nitrite, isopentyl nitrite, isopropyl nitrite, and isobutyl nitrite. These substances are subject to different regulations; for example, isobutyl nitrite is banned in the European Union.
Poppers act as muscle relaxants, causing the relaxation of involuntary smooth muscles such as the throat and anus. Such physiological effects, along with others, have resulted in poppers being used as recreational drugs, sometimes during sexual intercourse, as the effects can heighten arousal and help facilitate acts such as anal intercourse. Poppers were a part of the club culture which began during the mid-1970s disco scene, and surged in popularity during the rave scene of the 1980s and 1990s.

Administration and effects

Administration

Poppers come in liquid form, but this liquid is not directly consumed. When the bottle is opened, the vapors are inhaled, rather than the liquid. This is typically done through the nasal cavities, typically directly from the bottle, without touching the bottle to the skin, or with the help of small inhalers.

Effects

Physiological effects

Inhaling nitrites produces a fast-acting, short-lived and non-specific relaxation of smooth muscles. Blood vessels are surrounded by smooth musculature, which directly influences blood pressure by increasing or decreasing its inward pressure on the blood vessels.
With relaxation of the smooth muscles, the 'inward' pressure on the blood vessels decreases and they dilate, resulting in a drop in blood pressure and an immediate increase in heart rate. Vasodilation may cause giddiness, dizziness, headache, nausea, vomiting and flushing, and may produce a sensation of heat and excitement. Maximum vasodilatory effect is usually reached within 30 seconds, with physiological effects lasting for 5 to 10 minutes.

Psychological effects

Inhaling nitrites produces several psychological effects such as euphoria, increased sensual awareness, lowered inhibitions or increased confidence, and potential for impaired judgement and disorientation.

Interactions

Vasodilators

Alkyl nitrites interact with other vasodilators, such as sildenafil, vardenafil, and tadalafil, to cause a serious decrease in blood pressure, which can cause strokes, and low blood pressure leading to people fainting. Side effects of popper abuse include tachycardia, headaches, migraines, dizziness and fainting.

Toxicity

The Merck Manual of Diagnosis and Therapy reports insignificant hazard associated with inhalation of alkyl nitrites, and British governmental guidance on the relative harmfulness of alkyl nitrites places them among the less harmful of recreational drugs.
If in contact with the skin, butyl nitrite poppers can cause chemical burns and contact dermatitis of the skin around the mouth and nose.
Swallowing poppers may cause cyanosis, methemoglobinemia, unconsciousness, coma, and complications leading to death. Accidental aspiration of amyl or butyl nitrites may cause lipoid pneumonia.

Isopropyl nitrite

Isopropyl nitrite poppers may be a cause of maculopathy, as reported in France and the United Kingdom. Some studies have concluded that there may be increased risk for at least temporary retinal damage with habitual poppers use in certain users; in a letter to the New England Journal of Medicine, an ophthalmologist described four cases in which recreational users of isopropyl nitrite poppers suffered temporary changes in vision. In November 2014, it was observed maculopathy is a rare complication of isopropyl nitrite abuse. A full recovery of visual acuity in longterm abuse could be demonstrated after drug abstinence. Studies have shown that poppers users who have HIV and/or use Sildenafil in combination with poppers are at an increased risk of developing poppers‐associated maculopathy.
Foveal damage has also been described, in six habitual users of isopropyl nitrite poppers. Furthermore, in June 2014, optometrists and ophthalmologists reported having noticed an increase in vision loss in chronic poppers users in the United Kingdom associated with isopropyl nitrite.

Isobutyl nitrite

A working group in 2019 from the International Agency for Research on Cancer determined there to be "sufficient evidence" to suggest carcinogenic properties of isobutyl nitrite on experimental animals, and because they could not find any sufficient studies regarding its carcinogenic effects on humans, they determined that isobutyl nitrite is "possibly carcinogenic to humans". The group primarily looked at 2 studies on animals, one on rats and one on mice. Both of these involved the administration of doses of isobutyl nitrite at seemingly low doses 6 hours a day, 5 days a week, for a total of 103 weeks. This is different from the relatively brief exposure to isobutyl nitrite that inhaling poppers recreationally usually provides. Nonetheless, in the studies there was shown to be no increase in death rates for the animals exposed to isobutyl nitrite, but there was shown to be an increase in tumors in the lungs of the males and females of both species in the groups exposed, as well as in the thyroids of the male mice exposed. Isobutyl Nitrite is no longer sold as 'Poppers' having been banned in the EU since 2007 and banned in the US since 1990.

Refuted link with HIV/AIDS

Early in the AIDS crisis, widespread use of poppers among AIDS patients led to the later disproved hypothesis that poppers contributed to the development of Kaposi's sarcoma, a rare form of cancer that occurs in AIDS patients. Modest, short-term reductions in immune function were observed in animal studies, but not replicated in human studies.

Cyanide treatment

Amyl nitrites were part of some kits used to treat cyanide poisoning, containing amyl nitrite, sodium nitrite, and sodium thiosulfate. The nitrites were administered to produce methemoglobin and induce vasodilation. Amyl nitrites were discontinued in 2012 in standard cyanide kits. Cyanide kits now use hydroxocobalamin.

Chemistry

Poppers contain a class of chemicals called alkyl nitrites. To the extent that poppers products contain alkyl nitrites, the following applies.
The following table summarizes alkyl nitrite chemical and physical properties, including chemical structure:

Alkyl nitrite	CAS	Formula	Molecular weight	Physical state	Color	Boiling point
Amyl nitrite	110-46-3		117.15	liquid	yellow
Pentyl nitrite	463-04-7	CH₃₄ONO	117.15	liquid	yellow
Butyl nitrite	544-16-1	CH₃₃ONO	103.12	liquid	yellow
Isobutyl nitrite	542-56-3	₂CHCH₂ONO	103.12	liquid	colorless
Isopropyl nitrite	541-42-4	₂CHONO	89.09	liquid	yellow
Hexyl nitrite	638-51-7	CH₃₅ONO	131.17	liquid	colorless

History

19th-century discovery

The French chemist Antoine Jérôme Balard synthesized amyl nitrite in 1844. Sir Thomas Lauder Brunton, a Scottish physician born in the year of amyl nitrite's first synthesis, documented its clinical use to treat angina pectoris in 1867 when patients experiencing chest pains would experience complete relief after inhalation. Brunton was inspired by earlier work with the same agent, performed by Arthur Gamgee and Benjamin Ward Richardson. Brunton reasoned that the angina sufferer's pain and discomfort could be reduced by administering amyl nitrite—to dilate the coronary arteries of patients, thus improving blood flow to the heart muscle.

Amyl nitrites were originally enclosed in a glass mesh called "pearls". The usual administration of these pearls was done by crushing them between the fingers, followed by a popping sound. This administration process seems to be the origin of the slang term "poppers". It was then administered via direct inhalation of the vapors or inhalation through silk that covered the capsule.
Brunton found that amyl nitrites had effects of dilating blood vessels and flushing of the face. Isobutyl nitrites were also documented around the late 1890s by Brunton and despite being found to have generally the same effects as amyl nitrites, they were never used as a clinical alternative to amyl nitrates. Brunton also found that propyl nitrites had the same effects as well.

20th century

Although amyl nitrite is known for its practical therapeutic applications, the first documented case of recreational use was in 1964. The poppers "craze" began in the early 1970s in the gay male community in bars, discothèques and bathhouses. It was packaged and sold pharmaceutically in fragile glass ampoules wrapped in cloth sleeves which, when crushed or "popped" in the fingers, released the amyl nitrite for inhalation, hence the colloquialism poppers. The term extended to the drug in any form as well as to other drugs with similar effects, e.g. butyl nitrite which is packaged under a variety of trade names in small bottles.
In the late 1970s, Time magazine and The Wall Street Journal reported that poppers use among gay men began as a way to enhance sexual pleasure, but "quickly spread to avant-garde heterosexuals". A series of interviews conducted in the late 1970s revealed a wide spectrum of users.