A.9 VOLATILE SUBSTANCES: SOLVENTS AND GASES
The inhalation of volatile substances and gases for non-medical purposes has been known for centuries, although it has only been within the last decade that such practices have come very commonly to the attention of public health officials.11, 17, 34, 36, 46 While recent occurrences of adolescent `glue sniffing' have received the most publicity, a wide variety of other substances and practices have been involved. These drugs have frequently been labelled deliriants, although delirium is only one of many potential effects and is clearly not restricted to these substances. Some of these drugs have much in common with the sedatives (such as alcohol and barbiturates) and might be considered in a sub-class of that group. In addition, certain solvents and gases apparently have some psychedelic or hallucinogenic properties and, in sufficient doses, are anesthetic.
Many of the chemicals used may be described as volatile hydrocarbon solvents and are highly soluble in lipids (fats)—a major component of living tissue. Most of the substances are either gases at room temperature or rapidly evaporate from a liquid phase to a gaseous state when exposed to the air. This property makes them highly desirable, industrially, in the production of materials in which fast drying is essential. The solvents are also usually highly flammable.
There are literally hundreds of easily accessible forms of these materials, which may run from hardware store and cosmetic sundries to clinical drugs and anesthetics. Some common products which may contain large quantities of these chemicals are: fast drying glues and cements; many paints, lacquers and varnishes, and their corresponding thinners and removers; gasoline, kerosene and various other petroleum products; lighter and dry cleaning fluid; fingernail polish remover; and various aerosol products. Active chemicals in these materials include toluene (also called toluol or methylbenzene), benzene, acetone, naphtha, hexane, cyclohexane, trichlorophane, trichloroethylene, perchlorethylene, carbon tetrachloride, chloroform, ethyl ether, and various alcohols, ketones and acetates. Closely related chemically to the solvents are the freon gases which are commonly used as aerosol and refrigerant gases. Nitrous oxide (often called "laughing gas") and related nitrites are also highly volatile substances with long histories of non-medical use. It was recently observed that 38 different products containing such substances were available from the shelves of a single service station-hardware store in Ottawa.
It is clear that we have in this drug category a large aggregate of chemically diverse substances from a wide variety of sources. While this heterogeneity precludes any broad and all-encompassing generalizations, many of the substances have common properties which warrant general consideration.
Most of these drugs have not been investigated individually in much detail, since only a few have had extended medical use. There has been little systematic pharmacological investigation of the deliberate and repeated inhalation of solvents. In most instances, human studies have been limited to gross investigations of toxicity in industrial situations which have limited application in this context.24, 29, 82, 58, 67 Some significant information can be gleaned from individual clinical case study reports of intentional users.
Nitrous oxide, ethyl ether and chloroform, three of the best known inhalant anesthetics, had considerable non-medical recreational use which preceeded their general medical acceptance. In 1844, the following advertisement was circulated in Hartford, Connecticut:
A Grand Exhibition of the effects produced by inhaling Nitrous Oxide, Exhilarating or Laughing Gas! will be given at Union Hall this (Tuesday) Evening, Dec. 10th, 1844.
Forty gallons of Gas will be prepared and administered to all in the audience who desire to inhale it.
Twelve Young Men have volunteered to inhale the Gas, to commence the entertainment.
Eight Strong Men are engaged to occupy the front seats to protect those under the influence of the Gas from injuring themselves or others. This course is adopted that no apprehension of danger may be entertained. Probably no one will attempt to fight.
The effect of the Gas is to make those who inhale it either Laugh, Sing, Dance, Speak or Fight and so forth, according to the leading trait of their character. They seem to retain consciousness enough not to say or do that which they would have occasion to regret.
N.B.—The Gas will be administered only to gentlemen of the first respectability. The object is to make the entertainment in every respect, a genteel affair.17
Although this event occurred before the systematic investigation and general medical acceptance of nitrous oxide as an analgesic and anesthetic, the promotors of the entertainment showed considerable appreciation for the variety of potential effects of the drug and the importance of the individual personalities of those taking it. The non-medical use of nitrous oxide apparently continued on a small scale, and recently seems to be coming back into vogue in North America.
During the century before ether was established in medical practice, it was widely used as an industrial solvent and often as an intoxicant. It frequently served as a replacement beverage for alcohol during times of liquor scarcity in numerous areas in Europe, Great Britain and North America in the 19th century. During World War II, ether consumption increased in Germany when alcohol became unavailable. Inhalation of small amounts of ether and chloroform on special occasions is reported to have been accepted practice in certain sophisticated social circles in North America before the turn of the century.46
Ether inhalation parties were not uncommon during the 19th century, especially among students and associates of the healing professions. In fact, it was the observation of one of these ether 'jags' which directly led to the first medical use of ether as a clinical anesthetic by C. W. Long. Soon after, Oliver Wendell Holmes suggested the word anesthesia to describe the state of "insensibility" which accompanies the unconsciousness or sleep induced by large doses of these substances."
Although non-medical use of volatile substances has been reported across age groups and spanning social class, recent surveys concur with the law enforcement and public health impressions that use is predominantly a phenomenon of youth, reaching a peak in early teens and dropping off soon after. (See Appendix C Extent and Patterns of Drug Use.)
(For federal and provincial provisions with respect to volatile substances see Appendix B.8 Sources and Distribution of Volatile Substances: Solvents and Gases.) The almost unlimited number of potential substances makes specific legislation of questionable value as a deterrent. It has often been suggested that manufacturers add to the products most commonly used, a substance which renders the original material offensive to the user. An irritant chemical or obnoxious odour might serve this purpose, although it might also be unpalatable to the manufacturing staff and the legitimate user of these products as well. In Canada, at least one major producer of airplane glue has experimented with mustard oil in this connection.14 The pervasive use of highly volatile, potentially psychoactive substances for largely non-drug purposes in our society makes this approach seem impractical as a general solution. Furthermore, restricting certain chemicals would have little overall effect since many materials, such as gasoline, are easily obtained by any age group. Effective restriction of access to most such substances could not be achieved except at considerable inconvenience to a large segment of the population. This is an area which clearly calls into question the potential of the crimino-legal system in controlling non-medical drug use.
Most of the volatile substances have had no regular medical use although in many instances the general effects produced are similar to those of the clinical inhalant anesthetics. Ether, nitrous oxide, trichloroetheylene (Trilene10) and chloroform have been widely used as anesthetics, to reduce pain and produce unconsciousness prior to and during surgical and dental work, and at one time they were used as sedatives. Other nitrogenous compounds (e.g., amyl nitrite) are used in the therapy and relief of heart pain and, occasionally, asthma.17, 48' 50
ADMINISTRATION, ABSORPTION, DISTRIBUTION AND PHYSIOLOGICAL FATE
In many instances the active agents in the substances used would be absorbed if taken orally, although inhalation generally provides a more rapid and effective means of administration and a sharpening of effects. Techniques used in inhalation are usually designed to maximize the gas concentration in the air. Frequently the substance is emptied or sprayed into a plastic or paper bag, which is held tightly over the nose and mouth, and the fumes inhaled. Alternatively, a cloth may be dipped in a liquid or the active substance otherwise applied to the cloth, which is then rolled up and held against the nose and/or mouth and the vapours sucked in. In other instances, the drug might be sniffed directly from an open container or inhaled through a tube. Aerosol gases have sometimes been sprayed directly into the mouth. Nitrous oxide is often inhaled directly from tanks (such as those used in medical and dental work, or in soda fountain dispensers), and is sometimes sold in balloons for non-medical use. Amyl nitrite is available in ampules or 'pearls' which are broken to release the fumes.
As noted earlier, the drinking of certain relatively pure substances, such as ether, has also been reported. The effects of oral administration are said to be in many ways similar to those of ordinary alcohol. The somewhat different initial effects of solvent inhalation are probably due to the more rapid rate of absorption from the lung, as compared to the gastrointestinal tract. These observations again underline the importance of route and rate of administration in determining drug effects.
In certain cases some metabolism occurs in body tissue, although many of these drugs are eliminated, chemically unchanged, by the lungs in gaseous form. Consequently, the odour of the substance may be noticeable on the breath for several hours after use. Some solvents are primarily excreted in the urine. Most of the common volatile substances can be chemically detected in either the urine, blood or breath of users."' 18. 57
The psychological and physiological effects of the volatile solvents are in many respects similar to those produced by alcohol, barbiturates and other sedatives. Low doses can elicit considerable behavioural and psychological arousal, while higher amounts usually result in sedation and a general reduction in activity. Little is known as to the specific mechanism by which these substances exert their action. As with most drugs, the effects of the volatile solvents and gases can be expected to vary considerably with the individual, his mental set, and the setting in which the substance is used.
Little controlled research has been conducted on the psychological effects of the solvents. Frequently reported are a lessening of inhibitions, a feeling of sociability and well-being, and a general elevation of mood. Higher doses may produce laughing and silliness, feelings of floating and being "out of contact", dizziness, perceptual distortions of time and space, and illusions. Certain of these substances are said to have subjective effects which are in some respects similar to those produced by the psychedelic drugs. In addition, confusion, drunkenness, slurred speech, blurred vision, a feeling of numbness, nasal secretion, watering of the eyes, headache, incoordination and, not infrequently, nausea and vomiting may also occur."• 67 As the dose is further increased, the general sedating-anesthetic effects dominate, and drowsiness, stupor, respiratory depression and, finally, unconsciousness result. Extreme quantities may inhibit breathing and produce death.
During the acute phase of intoxication, judgment may be impaired, and considerable confusion, hyperactivity, and lack of behavioural control may occur. Some individuals become irritated, tense, or frightened, and acute psychoses have been noted. There is no evidence of long-term psychotic reactions, however. Reported results of such conditions include accidents, panic, self-destructive behaviour, physical aggression, and other antisocial acts.", 88
The acute effects may be as short as five to ten minutes or last up to an hour, depending on the substance used, the dose administered, and a variety of other factors. Most of these agents are short-acting. Users frequently retain their supply and repeat the administration over several hours, attempting to maintain a balance of intoxication often close to, but below that producing unconsciousness. The state achieved is somewhat analogous to light clinical anesthesia, where mixed stimulation and depression of various psychological and physiological systems occur. Because of the sensitivity of the nervous system to subtle changes in dose, maintaining this level of intoxication is frequently not an easy task, and undesired 'conk-outs' may occur.
Medical anesthetists, in trying to achieve deep anesthesia in a patient with high doses, generally attempt to pass through this early deliriant stage quickly and may use a variety of techniques and other drugs to minimize the erratic stimulating effects of light anesthesia. Many individuals may be able to recall the dream-like experiences and unusual feelings and thoughts which are characteristic of 'going under' with inhalant anesthetics. Such experiences are not unlike the intoxication effects sought by some individuals in the non-medical use of these substances.
The majority of recent reports on volatile solvent inhalation have been concerned with juveniles who had come to the attention of the authorities because of some antisocial or delinquent behaviour, which may or may not have been associated with drug use. Most of these individuals had emotional or behavioural difficulties prior to the use of the drug, and no careful investigation has been done with non-delinquent solvent users, even though there are indications that these latter individuals may make up the majority of users. Little adequate information is available on the long-term psychological outcome of chronic solvent inhalation, although many observers have expressed concern over possible adverse effects of heavy drug use by young people coping with the already trying and often troublesome stage of early adolescence.
In one of the first systematic studies of adolescent glue sniffers, Massengale and associates were unable to find any evidence of significant effects of solvent use on physical health.43 Although the authors discovered no neurological or intellectual abnormalities, they felt that glue use was a prominent complicating factor in the delinquency of many of their 27 patients. The majority of the solvent users were poorly adjusted to school, had few friends, were generally withdrawn, and were similar psychologically to adult alcoholic patients. Other investigators have also failed to find evidence of irreversible effects on intellectual functioning in chronic glue sniffers.22
Temporary changes or abnormalities resulting from acute intoxication with some solvents have been reported in kidney and liver function, bone marrow activity, and a variety of psychological and neurophysiological tests. Gastroenteritis, hepatitis, jaundice, blood abnormalities and peptic ulcers are among the complications reported to be associated with the use of some of these products. In addition, some chronic users have developed slow-healing
ulcers around the mouth and nose.4, 9, 39, 42, 49, 67, 68, 71 The frequent loss of
appetite, and resulting poor eating habits, in chronic users may complicate the situation further, and weight loss and various nutritional disorders have also been reported. It appears so far, however, that after discontinuing drug use, complete recovery from these disorders usually occurs. There is little unequivocal evidence of permanent brain damage or other nonreversible psychological or physiological abnormalities due to the deliberate inhalation of these chemicals. Many solvents have not yet been investigated, however, and generalizations about potential dangers from existing data cannot be extended to the vast number of unstudied volatile substances. We have found no evidence that volatile substances are responsible for a significant number of psychiatric admissions in Canada.
While the commonly held belief that permanent brain damage is a reuglar result of glue sniffing is not supported in the scientific literature, numerous industrial studies involving related chemicals, as well as certain laboratory animal experiments, suggest that irreversible physiological and psychological changes might occur with prolonged exposure to some solvents. As noted earlier, gases (such as freon) are sometimes sprayed directly into the mouth and throat from aerosol cans. The hazards of such practice include the possible freezing of lung tissue and anoxia."
In the past few years, a number of deaths have been attributed to volatile solvent use.45, 68 The majority of these fatalities have occurred when the user was inhaling alone, and appear to be due to mechanical suffocation which was subsequent to unconsciousness produced by the drug. Simple unconsciousness, if of short duration, might be quite harmless since fresh air usually produces complete and rapid recovery. However, if the user's mouth and nose is covered by a plastic bag, as is often used for inhalation, suffocation may occur. Also, if the user's face remains close to the vapour source after he loses consciousness, he may continue to breathe fumes which could produce further overdose and respiratory arrest due to depression of the brain-stem breathing centres. A few fatalities have been attributed to vomitus suffocation and, perhaps, damage to lung tissue. In addition, a small number of solvent sniffers in North America have died suddenly and unexpectedly without suffocation, general CNS depression, or gross organic injury.' Such infrequent but clearly identified sudden sniffing deaths can result after only a few deep inhalations and have generally occurred under conditions of considerable physical activity or stress. Direct cardiac arrhythmia and arrest may be responsible in some cases.3, 4' 52' 59, 60
The Commission has investigated in considerable detail reports of volatile solvent poisoning and death in Canada." The Federal Poison Control Program has records of 174 cases of solvent sniffing poisonings occurring in 1971.M Six of these were fatal. The most common materials involved were nail polish remover (84 cases), glue (68 cases) and paint thinner (18 cases). Males outnumbered females by two to one in these data, and most of the cases involved persons between 10-24 years of age. The Commission's study of provincial coroners' reports provided detailed information on ten deaths attributed to deliberate solvent inhalation in Canada during the years 1968-71.31,[x] Eight of the ten cases occurred in Ontario, nine were males and all were between 10 and 18 years of age. In nine of the cases, the deceased was found with a plastic bag over his face. Asphyxia and pulmonary edema were commonly noted. It would appear that the vast majority of solvent deaths in North America would have been avoided if some method of administration not involving plastic bags had been employed.
TOLERANCE AND DEPENDENCE
Although no tolerance occurs with occasional use, the chronic user of some volatile substances may require several times as much of the active material to achieve the desired state of intoxication as was originally necessary in the beginning.28 The possibility of physical dependence with withdrawal symptoms has not been adequately investigated to date, although existing clinical reports suggest that it does not occur. This is somewhat surprising given the pharmacological similarities between the volatile solvents and the sedatives, which do produce both tolerance and physical dependence. Furthermore, cross-tolerance between the sedatives and solvents has been suggested by the frequently reported insensitivity of chronic alcohol and barbiturate users to ether anesthesia. It is possible that such factors as the rapid excretion of most volatile solvents and/or the usual intermittent patterns of use make the development of physical dependence unlikely, since sustained tissue concentration is very probably an indispensable factor in the establishment of such dependence.
Symptoms of psychological dependence and compulsive use have been recorded, although chronic use is not frequent. Certain regular users reportedly become restless, irritable and depressed if they cannot have access to the drugs.
SOLVENTS AND OTHER DRUGS
As noted above, cross-tolerance seems to occur between some solvents and the sedative drugs. It has been noted that solvents are taken in conjunction with alcohol by certain individuals.5 Alcohol has been shown to augment the adverse effects of trichloroethylene on visual-motor performance.23 Barbiturates also intensify the effects of certain solvents.37, 38 Interaction with other CNS depressant drugs would also seem likely, but little research in this area has been conducted. Ether and cannabis did not show significant interaction in a study with mice.25
The use of drugs currently available on the illicit market, such as marijuana and amphetamines, has been reported in some youthful solvent users. Adult users of solvents often have a history of heavy alcohol consumption and may switch from one drug to the other. Although some observers entertain the hypothesis that chronic use of solvents in early youth may predispose one to the misuse of other drugs (especially alcohol) in later life, there is, as yet, no empirical evidence to confirm or deny a causal link between solvent use and the use of other drugs. It would appear that solvents are often the substances chosen for non-medical use by very young people primarily because of their ready availability to anyone. Subsequent drug preferences and use patterns may merely reflect an expansion of the options available.
Nevertheless, in view of the generally accepted psychological principle that early significant life experiences tend to be more persistent and to play a more important role in the formation of future behavioural tendencies than later experiences, e.g., during or after adolescence, it would seem reasonable to assume that children who have been repeatedly exposed to the exciting and subjectively rewarding effects of repeated manipulation of mood and consciousness with chemical substances might be at higher-than-average risk to become predisposed to indiscriminate multiple-drug use in later life. (See also Appendix C Extent and Patterns of Drug Use.)
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4. Baerg, R. D., & Kimberg, D. V. Centrilobular hepatic necrosis and acute renal failure in "solvent sniffers". Annals of Internal Medicine, 1970, 73: 713-720.
5. Barker, G. H., & Adams, W. T. Glue sniffers. Sociology and Social Research, 1962-63, 47: 298-310
6. Barman, M. L., Sigel, N.B., & Beedle, D. B. Acute and chronic effects of glue sniffing. California Medicine, 1964, 100: 19-22.
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8. Beecher, H. K. Anesthesia's second power: Probing the mind. Science, 1947, 105: 164-166.
9. Blatherwick, C. E. Understanding glue sniffing. Canadian Journal of Public Health, 1972, 63: 272-276.
10. Bloomquist, E. R. Addiction, addicting drugs, and the anesthesiologist. Journal of the American Medical Association, 1959, 171: 518-523.
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12. Brozovsky, M., & Winkler, E. G. Glue sniffing in children and adolescents. New York State Journal of Medicine, 1965, 65: 1984-1989.
13. Chapel, J. L., & Thomas, G. Aerosol inhalation for 'kicks'. Missouri Medicine, 1970, 67: 378-380.
14. Chapman, R. A. (Formerly Director General, Food and Drug Directorate, Ottawa) Letter to the Commission, May 10, 1971.
15. Choy, T. Laboratory studies of inhalation anaesthetics. British Journal of Anaesthesia, 1969, 41: 827-833.
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19. Connell, K. H. Ether drinking in Ulster. Quarterly Journal of Studies on Alcohol, 1965, 26: 629-653.
20. Corliss, L. M. A review of the evidence on glue-sniffing-A persistent problem. Journal of School Health, 1965, 35: 442-449.
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23. Ferguson, R. K., & Vernon, R. J. Trichloroethylene in combination with CNS drugs. Archives of Environmental Health, 1970, 20: 462-467.
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30. Harms, E. (Ed.) Drug addiction in youth. New York: Pergamon, 1965.
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37. Lal, H., Puri, S. K., & Fuller, G. C. Enhanced toxicity of carbon tetrachloride inhalation after phenobarbital pretreatment. Pharmacological Research Communications, 1970, 2: 143.
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