Volatile substances drug profile

Volatile substances drug profile

Domestic products such as spray deodorants, glue, lighter refills and spray air fresheners can be used as drugs.

Volatile substance use may be defined as the deliberate inhalation of volatile compounds to produce psychoactive effects. These compounds have few characteristics in common, other than their intoxication effects and the behavioural effects they produce. Such volatile substances are often referred to as inhalants, a term which encompasses a diverse group of psychoactive chemicals that are defined by the route of administration, rather than their mechanism of action on the central nervous system or psychoactive effects.

The use of volatile substances is unlike most other forms of drug use in that it involves various compounds contained in readily accessible domestic or commercial products. These compounds, that are safe when used for their intended purposes, may cause intoxication and in some cases death when their vapours are deliberately concentrated and inhaled.

A specific subgroup of volatile substances — alkyl nitrites — are used on the dance club scene because they cause relaxation of vascular smooth muscle and produce a ‘rush’, or to enhance a sexual experience. They are generally known as ‘poppers’ and can be found on the ‘street’ market in bars and clubs. In some countries, they are available in sex shops and ‘head’ shops.

Chemistry and typical use

Volatile compound CAS Registry Number Use
Butane, iso-butane, propane, liquefied petroleum gas (LPG) 106-97-8 fuel gases, propellants
Chloroform, trichloromethane 67-66-3 solvent, redundant anaesthetic
Diethyl ether, ethyl ether, ether,
60-29-7 solvent, car starter, redundant anaesthetic
Dimethylether, Methyl Ether, Oxybismethane, DME 115-10-6 propellant
Enflurane, 2-Chloro-1-(difluoromethoxy)-1,1,2-trifluoroethane 13838-16-9 anaesthetic
Fluothane, 2-Bromo-2-chloro-1,1,1-trifluoroethane 151-67-7 anaesthetic
Gasoline, Petrol, Benzin mixture automotive fuel (reformulated in Australia to be low in aromatics to minimize misuse)
HFC134a, 1,1,1,2-Tetrafluoroethane 811-97-2 refrigerant, propellant
Helium 7440-59-7 party balloons
Isoflurane, 2-Chloro-2-(difluoromethoxy)-1,1,1-trifluoroethane 26675-46-7 anaesthetic
Nitrous oxide 10024-97-2 propellant, analgesic, anaesthetic
Tetrachloroethene, perchloroethylene 127-18-4 solvent, degreaser, dry cleaning solvent
Toluene, methylbenzene 108-88-3 paints thinners glues
Trichloroethylene 79-01-6 solvent, degreaser, dry cleaning solvent, redundant anaesthetic
Xylene, dimethylbenzene 1330-20-7 paints thinners glues
Amyl nitrite - mixture of isomers chiefly isoamyl nitrite other isomers also present 110-46-3 cyanide antidote, 'poppers'
n-butyl nitrite, nitrous acid butyl ester 544-16-1 'poppers'
isobutyl nitrite 542-56-3 'poppers'
isopropyl nitrite 541-42-4 'poppers'

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Physical form

The compounds used are volatile liquids or gases contained in domestic, industrial or medicinal products often freely available to the public in a range of shops, from the workplace or laboratories.

The nitrite-containing products (‘poppers’) usually contain butyl or isobutyl nitrite and are often impure. The products have suggestive names and are typically packaged in small glass bottles. The smell is distinctive, sweet and sickly — sometimes described as similar to the smell of ‘old socks’.

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The mode of action of these compounds is not well understood as is also the case for the volatile anaesthetics legitimately used in medical practice. It is the physical properties, such as volatility and fat solubility, of the compounds that determine their ability to be used as drugs. The chemical properties and consequently the degree to which they are metabolised may however be important in terms of morbidity because the metabolites may be toxic and cause lasting organ damage.

The intoxication induced by inhalation of volatile substances produces some behavioural effects similar to those due to alcohol. Minutes after inhalation, dizziness, disorientation and a short period of excitation with euphoria are observed, followed by a feeling of light-headedness and a longer period of depression of consciousness.

Marked changes in mental state are induced in people who misuse toluene and other solvents. Most users report elevation of mood and hallucinations. Potentially dangerous delusions can occur, thoughts are likely to be slowed, time appears to pass more quickly, and tactile hallucinations are common. These behavioural effects are accompanied by visual disturbances, nystagmus, incoordination and unsteady gait, slurred speech, abdominal pain and flushing of the skin.

The duration of action varies greatly, depending largely on the volatility of the compound. The effects of butane last only a few minutes — requiring frequent repeated doses —whereas toluene is much longer acting (more like alcohol) requiring less frequent doses. There are indications that toluene activates the brain’s dopamine system that plays a role in the rewarding effects of many psychoactive drugs.

Most deaths are believed to occur from ‘sudden sniffing death syndrome’ (SSDS) an irregular and rapid heart rhythm brought on by the use of volatile substances and anoxia or hypercapnia and a sudden stimulus that produces an epinephrine (adrenaline) release. Unless a defibrillator is available, death can result within minutes from a single session in an otherwise healthy young person. Deaths also may result from asphyxiation, particularly if a plastic bag is used to inhale the compound (e.g. when inhaling glue). Deaths from trauma may occur, particularly with the longer acting compounds, e.g. toluene.

The chronic exposure to solvents such as toluene damages the protective sheath around certain nerve fibres in the brain and peripheral nervous system. This extensive destruction of nerve fibres may be similar to that seen with neurological diseases such as multiple sclerosis. Trichloroethylene may cause cirrhosis of the liver, reproductive complications, hearing and vision damage.

There is no evidence of chronic harm caused by butane, which is very volatile and largely excreted unchanged. However, in a young and otherwise healthy population, chronic organ toxicity arising from the use of volatile substances would probably have to be gross in order to become clinically apparent.

The alkyl nitrites cause relaxation of vascular smooth muscle and may be inhaled to enhance sexual pleasure. A side effect of the use of these compounds can be a severe headache. They interact with the drugs used to treat male erectile dysfunction such as sildenafil (Viagra®) and could cause a decrease in blood pressure.

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Synthesis and precursors

The compounds are commercially available so there is no need for them to be synthesised covertly.

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Mode of use

The mode of use depends upon the volatile compound and also the nature of the product that contains it. Gases may be inhaled directly from containers, such as cigarette lighter refills. Aerosols may be discharged when inverted, to enrich the outflow of propellant (usually butane) which may then be sprayed through fabric (e.g. a towel or socks) to further remove the non-volatile components of the product. Solvents, such as toluene, may be poured onto a handkerchief or into a bag and the vapour inhaled. Glue is usually poured into a plastic bag which is palpated as the vapour is inhaled. Helium, often from disposable cylinders purchased from shops selling party balloons can also be fed into a plastic bag covering the head.

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Other names

Names related to the phenomenon: huffing, inhalant abuse, (glue) sniffing, dusting, chroming.

Alkyl nitrites are most commonly known as ‘poppers’, but other names include: locker room, bolt, hardware, room odouriser.

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Analysis of biological specimens (blood, tissue) is most commonly performed using headspace gas chromatography coupled with mass spectrometry (GC-MS) or with flame ionisation (GC-FID) or electron capture (GC-ECD) detection. Precautions need to be taken to prevent the loss of the analyte during sample collection and analysis, particularly for the gaseous compounds, e.g. butane. The blood sample may need to be collected directly into the headspace vial used for the analysis if meaningful quantitative data are to be obtained.

Urine analysis is generally of little value except for the less volatile and more extensively metabolised compounds, such as toluene.

The volatile components of products may be analysed by vapour phase infra-red spectrophotometry (VP-IR) or gas chromatography (GC).

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Typical purities

The products that contain the volatile compounds may also contain other components. For example, aerosols, where the propellant ‘butane’ (a blend of butane, iso-butane and propane) is used, may contain active ingredients such as aluminum hydroxychloride in the case of antiperspirants or they may be essentially ‘pure’ e.g. cigarette lighter refills. The aerosols that are used are those that contain a high proportion of propellant (deodorants/antiperspirants, hair spray, air freshener or paint).

The purity of the volatile compound itself may also vary depending on its intended legitimate use, for example, butane used as a propellant in aerosols is likely to be deodorised (low in sulphur compounds) whereas butane used as a fuel may not be deodorised and may have odorants (sulphur compounds) added. Limits (<0.1 %) are imposed on the carcinogen 1,3-butadiene in butane used in aerosols, but may not be when used for fuel.

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Control status

In Sweden, as of 1 June 1997, ‘poppers’ became regulated through being listed as a legal equivalent to prescription medicines, but this law makes it illegal to import, sell or give them away without a license.

In Romania, amyl-nitrite is controlled by Governmental decision which entered into force on 15 February 2010.

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Price at consumer level

Commercial products and aerosols cost only a few euros.

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Medical use

Some volatile substances are used in human and veterinary medicine as anaesthetics (see Chemistry and typical use table). Amyl nitrite is used as a first aid treatment for cyanide poisoning, whereas the other compounds have no medical uses.

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Bass, M. (1970), ‘Sudden sniffing death’, Journal of the American Medical Association, (JAMA) 212(12), pp. 2075–2079.

Baselt, R. C. (2004), ‘Disposition of toxic drugs and chemicals in man’, 7th edition, Biomedical Publications, California.

Field-Smith, M.E., Butland, B.K., Ramsey, J.D., Anderson, H.R. (July 2007), Report 20, Trends in death associated with abuse of volatile substances, 1971–2005,  ISBN 978-1-8981-8327-3, http://www.vsareport.org/

Lockwood, B., ‘Poppers: Volatile nitrite inhalants’, The Pharmaceutical Journal, Volume 257, 3 August 1996, pp. 154–155.

Neuroscience of psychoactive substance use and dependence, (2004) WHO, Geneva, pp. 100–104.

Wu, L.-T. , Howard, M. O. (2007), ‘Psychiatric disorders in inhalant users: Results from The national epidemiologic survey on alcohol and related conditions’, Drug and Alcohol Dependence 88, pp.146–155.

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