VOLATILE SOLVENTS

247. Although the inhalation of volatile substances and gases foV non-medical purposes has been known for well over a century, it only been within the last decade that such practices have come to the. regular attention of public health officials. While the recent practice of adolescent 'glue sniffing has 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 witk the sedatives and might be considered in a sub-Class of that category.,
In addition, certain solvents and gases apparently have some psyche..
delic properties.

248. Many of the chemicals used may be described as volatile hydro.v carbon solvents and are highly soluble in 'lipids (fats)—a majd 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 inflammable.

249. There ate literally hundreds of easily accessible sources 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 glue and cements; many paints and lacquers and their corresponding thinners and removers; gasoline, kerosene and-various other petroleum products; lighter fluid, dry cleaning fluid, finger nail polish remover and various aerosol products. Active chemicals in these materials include toluene, acetone, naphtha, benzene, 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, the original inhalant anesthetic, and related nitrites are also highly volatile substances with long histories of non-medical use. It was recently observed that thirty-eight different products containing such substances were available from the shelves of a service station-hardware store in Ottawa.

It is clear that we have in this drug category a large aggregate of, chemically diverse substances fiom 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. In most instances, human studies, if any, have been limited to gross investigations of toxicity in industrial situations and may have uncertain application here.

250. Nitrous oxide, ethyl ether and chloroform, three of the best known inhalant anesthetics, had considerable non-medical recreational use which preceded their general medical acceptance. Over a century _ago, 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, December 10, 1844.
Forty gallons-of Gas will be prepared and administered to all in the audience who desire to inhale.
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 or danger may be entertained. Probably no one will attempt to fight.
The effect of the Gass to make those who inhale it Whet WW1; 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.

Although dccuring several decades before systematic investigation Ad general medical acceptance of nitrous oxide as an analgesic and anesthetic, the promoters of this entertainment showed considerable appreciation for the variety of potential effects of the drug and the importance of the individual personalities of those taking it.

251. During the century prior to its introduction into medical practice, ether 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 A,S sophisticated social circles in North America before the turn of the century.
Ether inhalation parties were not uncommon at that time, 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 unconscious' 'less or sleep induced by large doses of these substances °'

252: Although current non-medical use of volatile solvents has been reported across age groups and spanning social class, recent surveys concur with law enforcement and public health impressions that chronic use is predominantly a phenomenon of youth, reaching a peak in early teens and dropping off soon after. There are no specific
statutes dealing ,with the use of most of the substances discussed, although chronic users may be apprehended, fot example, as juvenile delinquents.

253. The almost unlimited number of potential substances makes specific legislation of questionable value as a deterrent. An alternative approach to control which has frequently been suggested is to add to the products most commonly used, a substance which renders the original material offensive to the user. An irritant chemical or obnoxious odor might serve this purpose, although it might also be unpalatable to the manufacturing staff and the legitimate user of these chemicals as well. 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. Restficting certain substances 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 drug use.

Medical Use

254. Most of the substances included in this category 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, trichloroethylene (Trilene*) and chloroform have been widely used to reduce pain and produce unconsciousness prior to and during surgical and dental work, and at one time were used, as sedatives, and in the treatment- of sleeplessness. Other nitrogenous compounds (e.g., amyl nitrite) are used in the therapy and relief of heart pain and, occasionally, asthma.
Administration, Absorption, Distribution and Physiological Fate

255. Although in many instances the active agents in the substances used would be absorbed if taken orally, inhalation provides a more rapid and effective means of administration, and a sharpening of effects. Techniques used in inhalation are generally designed to maximize the gas concentration in the air. Frequently the substance is emptied 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 applied to the cloth, which is then rolled up and held against the nose and/or mouth and the gases breathed in. In other instances, the drug may be sniffed directly from an open container or inhaled through a tube: Amyl nitrite is also available in ampules or `pearls' which are broken to release the fumes.
As noted earlier, drinking of certain relatively pure substances, such is ether, has also been noted. The effects of oral administration are reported to bd in many ways similar to ordinary alcohol. The somewhat different initial results of inhalation are probably due to the more rapid rate of absorption from the lung as compared to the gastrointestinal tract. These observations would again underline the importance of route and rate of administration in determining drug effects.

256. 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 odor of the substance may be noticeable on the breath of the user for several hours after administration.

Effects

257. The psychological and physiological effects of the volatile solvents are in many respects similar to the sedatives, alcohol and barbiturates. Low doses can produce 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 drugs exert their action. As with most drugs, the effects of the volatile solvents can be expected to vary considerably with the individual, his mental set and the setting in which the substance is used.

258. 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. Confusitin, 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. As the dose is further increased, the general sedating--anesthetic effects dominate and drowsiness, stupor, respiratory depression and, 'finally, unconsciousness result. Additional quantities may inhibit breathing and produce death.'

259. During the acute phase of intoxication, judgment may be impaired and considerable confusion and laek of behaviotiral control may occur. Some individuals become irritated, tense, or, frightened, and acute psychoses have been reported. There is no evidence of long-term psychotic reactions, however. Possible results of the,se conditions include accidents, self-destructive behaviour and impulsive, aggressive, and other anti-social acts.

260. The effects of. acute intoxication 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. Recreational 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 (Stage 1) 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' 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 map 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 dreamlike 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.

261. 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 anti-social 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 make up the majority of users. Almost no information is available on the long-term psychological outcome of solvent inhalation, although several observers have expressed concern over possible effects of regular drug use by young people coping with the already trying and often troublesome stages of early adolescence.

262. Transient changes or abnormalities resulting from acute intoxication have been reported in kidney and liver function, bone marrow activity, and a variety of psychological and neurophysiological tests. Gastroenteritis, hepatitis, jaundice and blood abnormalities are among the complications reported to be associated with the use of some of these products.' In addition, a_number of chronic users have slow-healing ulcers around the mouth and nose. The frequent loss of appetite and resulting poor eating habits of chronic users complicate the situation further, and various nutritional disorders may also occur. It appears, however, that after discontinuing drug use, complete recovery normally occurs from these disorders and with few exceptions, there is little 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 carefully investigated, however, and generalizations about potential dangers from existing data can not be extended to the vast number of unstudied volatile substances.

263. While the commonly held belief that permanent brain damage is a regular result of glue sniffing can not be supported by scientific data, numerous industrial studies involving related chemicals, as well as certain laboratory animal experiments, suggest that irreversible physiological changes can occur with prolonged exposure to some solvents. In addition, some preliminary results suggest possible chromosome changes in the white blood cells of chronic users of some of these substances, although this effect has not been firmly' established.

264 Recently, a number of deaths have been attributed to volatile solvent use. These fatalities have usually occurred when the user was inhaling alone, and often appear to be a subsequent ° result of the
unconciousness produced by overdose. Such unconsciousness, if of abort duration, might normally be quite harmless since fresh air Usually produces complete and rapid recovery. However, if the users ;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 source after he loses consciousness, he may continue toeathe fumes ând produce further overdose and respiratory arrest
to depression of the brain-stem breathing centers. Other fatalities 'have been attributed to vomitus suffocation, direct cardiac arrest and, 'perhaps, damage to lung tissue.

Tolerance and Dependence

265. Although no tolerance occurs with occasional use, the chronic user may find that after several months he may require two or three. times as much of the active substance to achieve the desired state of intoxication as was necessary in the beginning. The possibility of physical dependence with withdrawal symptoms has not been adequately investigated to date, although existing clinical -reports suggest that this 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 has been suggested by the frequently reported insensitivity of chronic alcohol and barbiturate users to ether anesthesia. it is possible, however, that such factors asthe rapid excretion rates of most volatile solvents and/or the usual intermittent patterns of solvent use make the development of physical dependence unlikely.

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

266. As noted above, cross-tolerance seems to occur between some ; solvents and the sedative drugs. Although some observers entertain the hypothesis that chronic use of solvents in early youth may predispose one to misuse of other drugs in later life, there is, as yet, no empirical evidence linking solvent use with other forms of drug dependence. It has been noted that solvents are taken in conjunction with alcohol by certain individuals. The use of other drugs currently available on the black market, such as marijuana and amphetamines, has also 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.