Drug Abuse

A.6 ALCOHOL

INTRODUCTION
Alcohol is one of the most widely used psychoactive drugs known to man; it has apparently been with us since the dawn of civilization. Breweries flourished in Egypt almost six thousand years ago, and there is evidence that Stone Age prehistoric man made alcoholic beverages long before that.", 283 The Roman philosopher Seneca, in an essay on alcohol, observed almost 2,000 years ago that "Drunkenness is nothing but a condition of insanity purposely assumed.1/264 Varying degrees of alcohol use have appeared in most societies throughout recorded history and have traditionally played an important symbolic as well as pharmacological role in many social, religious and medical practices. Just as the use of alcohol has been almost universal, so, apparently, has its misuse. Consequently some degree of opposition to 'drink' appears to have arisen in all indulging cultures, although attempts to eradicate its use have met with almost uniform lack of success.

What is this drug which has been hailed as the "water of life" and "nectar of the gods" by some, and damned by others as "second only to war" as a source of human problems? Ethyl alcohol (C2H5OH) is a colourless, flammable and volatile liquid made up of three common elements, carbon, hydrogen and oxygen. The word "alcohol" is commonly taken to mean ethyl alcohol or ethanol (common beverage alcohol), even though there are a vast number of other substances in the aliphatic alcohol family, many of which are highly toxic in even low doses. Methyl alcohol (wood alcohol) and isopropyl alcohol (rubbing alcohol) are common examples of such toxic substances. Unless otherwise specified, in this report the word "alcohol" is taken to mean ethyl alcohol or ethanol.

Although the technique of producing alcoholic beverages by fermenting fruit, grain, vegetables, and other food-stuffs has been known for the past few thousand years, the biologic process by which the drug is generated was first illuminated by Louis Pasteur in the middle of the 19th century. His investigations revealed that alcohol is produced by single-celled microscopic plants (yeast fungi), which break down certain sugars by metabolic combustion, releasing carbon dioxide (CO2) and ethyl alcohol as by-products. The production of CO2 is responsible for the head on a glass of beer, the popping of champagne corks, and the leavening effect of yeast in the rising of bread. Since yeast cannot digest starch, mash from cereal grains such as barley, rye, corn and rice must be malted (i.e., converted to maltose sugar) prior to fermentation in the production of beer, gin, whisky and other alcoholic beverages.

Under optimal conditions fermentation continues until the sugar supply is exhausted. However, as the amount of alcohol in the fermenting solution increases, the metabolic activity of the yeast is slowed and arrested, and the fungi are killed when the alcohol they produce reaches a level of about 14%. Thus a limit is set on the maximum strength of natural (undistilled) beverages such as beer, wine and cider. The distillation process of boiling off and isolating the more volatile alcohol from the other fluids (mostly water) allows a further increase in ethanol concentration. Although this technique was used in Middle Eastern cultures centuries earlier, the production of 'spirits' by distillation has been known in Europe for less than seven hundred years. Today, alcohol can be produced synthetically.

The pharmacological effects of alcoholic beverages are attributable primarily to the quantity of alcohol they contain. In Canada, beer usually contains about 5% alcohol by volume, natural wine 7% to 14%, fortified wine up to 20%, and distilled spirits or liquor approximately 40% alcohol. In other words, a 12-ounce bottle of beer or 3 to 4 ounces of wine contain about as much alcohol as 1 I ounces of whisky. In the alcohol literature a distinction has frequently been made among beverages on the basis of potency, with more serious consequences often attributed to the use of distilled liquor than to the consumption of weaker drinks such as beer or wine. However, certain studies, including some Commission research, suggest that even though acute toxic reactions may occur more frequently with distilled spirits, the long-term effects of chronic alcohol use are primarily related to the total alcohol consumed, rather than to the form or potency of the individual drinks.89, 151, 222, 279 Further research in this area is clearly needed.

In addition to ethanol and water, alcoholic beverages frequently contain small quantities of substances collectively referred to as congeners. Typical congeners include methanol, higher alcohols (fusel oil), acids, esters, aldehydes and other organic and inorganic compounds. Some of the congeners are important to the flavour and aroma of alcoholic beverages. There is evidence that they also can contribute to certain effects including post-intoxication 'hangover'. After pure ethyl alcohol and water (e.g., Alcool) which has essentially no congeners, vodka has the second lowest congener content of all alcoholic beverages. At equivalent doses of alcohol, after-effects with these beverages are less severe than those produced by drinks with more congeners, such as brandy. 43, 64, 202, 215

The notion of alcohol 'proof' originated centuries ago from a crude but effective analytic technique designed to assess the strength of spirits. If gun powder soaked with the beverage exploded on ignition, this was taken as `proof' that the liquor was more than half alcohol. 'Proof spirit' in the United Kingdom and Canada contains about 57% alcohol, while in the United States proof is calculated as twice the percentage of alcohol per unit volume of the beverage (e.g., 80 proof whisky is 40% alcohol)."

Canada has experimented with alcohol prohibition in varying ways since 1878. Although there are currently some 'dry' localities, alcohol is generally legally available to adults across the country. Over 300 years ago the prohibition of liquor sales to Indians was Canada's first alcohol regulation. 2° Some residual discriminatory policies have only recently been eliminated.

In the United States there was a 15-year period of alcohol prohibition which ended in 1934. Although alcohol consumption and certain related social problems and physiological disorders (such as cirrhosis of the liver) decreased during "prohibition", the program was repealed, apparently because of the unworkable form of the laws, inadequate enforcement, corruption among public authorities and, perhaps most importantly, a general lack of public support. During that period, the elimination of legitimate alcohol outlets resulted in home breweries and distilleries, the production of 'bootleg' liquor, the use of toxic substitutes, smuggling (frequently from Canada), and an economic vacuum which was rapidly filled by organized crime. Many authorities feel that this multi-million dollar illicit market provided the initial capital for the emergence of a network of syndicated criminal and quasi-legal business empires which have considerable economic and political strength in North America today.

Alcohol is now used by approximately three-quarters of the Canadian population over the age of 18. (See Appendix C Extent and Patterns of Drug Use.) Although most alcohol is undoubtedly consumed for its pharmacological properties, there is a significant aspect of alcohol usage which is in some respects independent of direct drug effects. There are many longstanding customs, traditions and superstitions which pervade alcohol use in the Western world. Because it has become an integral part of our culture, the set and setting surrounding alcohol use is substantially different from that associated with the non-medical use of other drugs in Canada.

Drinking alcoholic beverages may have special meanings in various social contexts. Depending on the type and quantity of beverage consumed, alcohol use is often symbolically associated with the acknowledgement of birth, death, marriage and other contracts, adulthood, friendship, and, to some, it may imply virility or masculinity, affluence and cultural refinement (or the opposite). Although it is employed in some religious ceremonies, in other contexts many individuals may approach its use with moral apprehensions and feelings of ambivalence and guilt. Some reject it outright on principle, while others feel that moderate use is morally acceptable. In many social circles abstinence is frowned upon and 'teetotallers' are looked upon with suspicion. But alcohol intoxication is frequently tolerated, condoned, and even expected and encouraged in many situations in North American society. When one considers the fact that these various attitudes interact with the diverse pharmacological potentials of alcohol in determining the overall drug effect, the complexity of the psychopharmacology of alcohol becomes apparent. Because its use is so ingrained at all levels of society, many Canadians do not consider alcohol a drug.

In a wider context Jaffe observed in The Pharmacological Basis of Therapeutics:

The large role that the production and consumption of alcoholic beverages plays in the economic and social life in Western society should not permit us to minimize the fact that alcoholism is a more significant problem than all other forms of drug abuse combined.'

MEDICAL USE

Alcohol is currently recognized as an official drug in the British and U.S. Pharmacopeias, although the various alcoholic beverages, as such, are no longer listed for medical use. Alcohol has been cited over the past few thousand years as a cure for nearly every ailment or disease. Most of the medical benefits were probably indirect, if not more imagined than real, and although it still plays a useful role in medicine, many of alcohol's legitimate therapeutic functions have now been filled by more effective drugs.

Alcohol is often used as a preservative, solvent, and vehicle for other drugs, and is contained in tinctures, elixirs, spirits and many medicinal syrups. External applications are used to cleanse, disinfect and harden the skin, to reduce bed sores, to cool fever, and to decrease sweating (alcohol is included in many antiperspirant deodorants). In concentrations around 70%, alcohol is an effective anti-bacterial agent, although it is not satisfactory for disinfecting open wounds since it damages the raw tissue.74, 237 Alcohol is sometimes injected in the vicinity of nerves to temporarily or permanently block transmission and relieve certain types of pain. Concentrated alcohol may be administered orally in the treatment of fainting, and alcoholic beverages are sometimes used to stimulate appetite and digestion. Alcohol is also sometimes employed as a source of calories and may be administered orally or intravenously in such applications.

Alcohol is still sometimes recommended as a tranquilizer, sedative, or hypnotic and may also serve as a mild mood elevator for some individuals. Used alone it has not been considered a safe surgical anesthetic, since the dose necessary to produce unconsciousness is often dangerously close to the fatal level. However, the use of alcohol, particularly in conjunction with other anesthetic drugs, is being re-evaluated.", 6° In addition, alcohol may reduce pain at moderate doses. Alcohol is still used in household medicine to "treat" the common cold, although its benefits, if any, are probably limited to an improvement in mood and increased relaxation and rest.

CHEMICAL ANALYSIS OF ILLICIT SAMPLES IN CANADA
Most of the alcohol consumed illicitly in Canada comes originally from licensed brewers and distributors. However, thousands of gallons of liquor are illicitly manufactured and consumed in Canada annually. In some instances considerable effort is made to imitate or counterfeit popular brands, and bottles are often prepared complete with bogus labels and Liquor Board stamps.30, 35 (See also Appendix B.6 Sources and Distribution of Alcohol.)

Among the contaminants which have been identified in illicit alcohol are calcium and copper salts, hydrocarbon oils, vegetable debris, dead insects, animal feces and urine. These materials arise from uncontrolled and usually unsanitary conditions, including easy access for insects and rodents, the use of dirty vessels, hard or unclean water, and abnormally high acid content in the brewing mash. Lead from old radiators used as condensors in stills is occasionally found in illicit alcohol. Deliberate additives include sugar, soft drinks, various flavouring and colouring matter, and glycerol. Toxic quantities of methyl alcohol are sometimes added inadvertently (blindness and death may result from such adulteration). Illicit alcohol is typically diluted with water and the strength of such spirits is highly variable, with approximate limits of 30-160 proof.87, 111, 115, 243

ADMINISTRATION, ABSORPTION, DISTRIBUTION AND PHYSIOLOGICAL FATE

Alcohol is usually taken orally and is rapidly and completely absorbed in the gastrointestinal tract. Some absorption takes place in the stomach, although diffusion into the blood stream is typically most rapid from the upper intestine; consequently, the quicker the alcohol passes through the stomach, the shorter its latency of action and the higher the peak blood alcohol level achieved.74, 237 Alcohol in beer or sweet wine is absorbed more slowly than that in equivalent quantities of dry wine or diluted or full strength distilled spirit. Therefore, they result in a lower peak effect than the latter beverages.112, 292 Food eaten before or with alcohol tends to decrease the drug effect by slowing stomach emptying, and a meal before drinking alcohol may reduce the peak alcohol level in the blood by almost one-half compared to that attained by drinking with the stomach empty. Once absorbed, alcohol is distributed quite uniformly in all body fluids; it easily enters the brain, and in pregnant women, crosses the placental barrier into the fetus.305

Approximately 95% of the alcohol entering the body is broken down by oxidation and the rest is excreted unchanged, primarily in the urine and breath. Much smaller quantities of alcohol can be detected in sweat, saliva, tears, milk and other body secretions.237 Unlike many drugs, alcohol is metabolized at a relatively constant rate on a given drinking occasion. The rate of alcohol elimination is roughly proportional to body weight, with the average 150-pound man metabolizing about 9 ml (0.3 oz.) of pure alcohol per hour.74, 305 On various occasions there can be significant differences in the rate at which an individual metabolizes alcohol. Substantial differences in metabolism rates between individuals are frequently observed. Genetic factors are often significant. Differences in response to alcohol among various ethnic and racial groups have been linked to differences in rates of metabolism at various stages in the biotransformation of alcohol.", 231, 313

While certain alcoholic beverages, such as beer, contain very small amounts of protein and carbohydrates, alcohol itself provides only calories when metabolized, but no vitamins, minerals, protein or essential fatty acids needed for adequate nutrition. Depending on the form of alcoholic beverage and possible mixers, an ordinary drink may contain 90 to 150 calories or more. Thus, as little as two 12-ounce servings of beer may make up 10% of the daily caloric needs of a 160-pound individual, and a 25-ounce bottle of 40% distilled spirits may supply over 50% of the needed calories.82, 156, 292

A convenient index of the quantity of the drug in the body (and the intensity of the short-term effects) is the blood alcohol level (b.a.l.), represented in per cent alcohol per unit weight of blood. Since the amount of alcohol excreted in the breath bears a fixed relationship to that in the blood, it is possible to estimate the blood alcohol level from expired air. This principle is utilized in the Breathalyzer tests now employed in the enforcement of driving laws.18. 74, 274, 293 A variety of other related techniques are also available for rapid estimation of blood alcohol level.'" Standard methods of chemical analysis have been developed for the direct determination of alcohol levels in body fluid and tissue.46, 126, 127, 278

SHORT-TERM EFFECTS

Alcohol exerts its primary acute effects through the central nervous system, producing a general sedation or depression of neural activity over a wide dosage range, although in certain circumstances, behavioural and psychological stimulation may result. Little is known as to the specific mechanism by which alcohol produces its psychopharmacological effects. However, in a general sense, alcohol is believed to exert its sedating effects by inhibiting areas of the brain stem reticular formation which control sleep and wakefulness. Behavioural and psychological arousal effects are thought to be related, at least in part, to the release of certain brain areas (including the cortex) from inhibition by the reticular formation. Areas of the brain called the limbic system and the hypothalamus are involved in the neurological basis of mood and emotion; but since the operation of these systems is not at all well understood, it is not possible to speculate how alcohol (or any other drug) might affect them?", 139

As with most drugs, certain effects of alcohol depend to a large extent on the individual and the situation in which the drinking occurs. A drink or two may produce drowsiness and lethargy in some instances while the same quantity might lead to increased activity and psychological arousal in another individual, or in the same person in different circumstances. Furthermore, a dose which is initially subjectively stimulating may later produce seda-
tion.206, 226, 287

In many social settings, alcohol seems to result in a lessening of inhibitions, and in feelings of well-being, sociability and camaraderie in most individuals. For many people alcohol relieves tension and anxiety—the common notion that one 'needs a drink' when worried, irritated or upset, reflects a general acknowledgement of this function. Although alcohol usually elevates mood at first, a general lack of emotional control, including anxiety, withdrawal, self-pity and general depression may occur later or with higher doses.

Hostility and aggression are not at all uncommon in some drinkers, and fights and other forms of violent antisocial behaviour are often reported to accompany bouts of heavy drinking. There is evidence that persons with certain pre-existing psychiatric or neurological disturbances are more likely than others to become aggressive or violent when intoxicated.116, 201, 220, 312 Although delusions, illusions and amnesic 'black-outs' may occur with high doses in some individuals, acute alcohol psychosis (pathological intoxication) in normally moderate drinkers is rare.98, 130, 247, 280

Alcohol does not have a specific aphrodisiac (sex-drive stimulating) effect per se, although the emotionality and general lessening of inhibitions often induced may lead to an increase in sexual activity and other normally restricted behaviour. An increase in desire or opportunity may be countered by acute sexual impotence or difficulty achieving orgasm.237, 266, 292

In moderate amounts, alcohol may increase or decrease heart rate, produce a 'flushing' or dilation of small blood vessels in the skin (giving a sensation of warmth), lower body temperature, stimulate appetite and the secretion of saliva and gastric juices, increase urination, produce a slowing of the electroencephalogram (EEG), increase complex reaction time, and may reduce muscular coordination. The swelling of the minor blood vessels in the eye (conjunctival congestion) may give a 'blood-shot' appearance.6, 74, 237' 306 Alcohol has been reported to narrow the visual field, reduce sensitivity to brightness contrast, and increase the time required for the eye to adjust to darkness,158, 197' 248 but other investigators have not found such effects.

Alcohol generally reduces performance on tests of a wide variety of psychological functions. Tasks requiring a high degree of selective or divided attention are particularly sensitive to alcohol effects,195, 196 and impairment is usually most pronounced on complex and recently learned tasks.37, 74' 132 However, a small amount of alcohol may actually improve performance in some situations.293 The frequently observed impairment of psychomotor performance with moderate doses of alcohol (e.g., 0.04% blood alcohol level)
was confirmed in Commission experiments.58, 164, 196, 233, 234, 293

In high doses, alcohol produces drunkenness with disorientation and confusion, slurred speech, blurred vision, inadequate muscular control and, often, nausea and vomiting. As larger quantities are ingested, depression of respiration, general anesthesia and unconsciousness and, rarely, death due to respiratory and circulatory failure occur.74. 169, 237

Heavy alcohol use is often followed by pronounced 'hangover' symptoms characterized by nausea, fatigue and weakness, dizziness, poor coordination, headache, 'heartburn' and a variety of other aches and pains. Anxiety, guilt and depression may also occur. The number and intensity of these symptoms tend to increase in proportion to the quantity of alcohol drunk.43. 96 Some authorities consider this post-inebriation phase a form of acute withdrawal syndrome.

A number of factors have been shown to influence appetite for alcohol in different species, including age, sex, and various physiological, nutritional and pharmacological variables."' Electrical stimulation and specific lesions in certain parts of the brain have been shown to affect alcohol intake and effects in animals.6, 164. 174 Changes in alcohol self-administration may be mediated by the modification of neurological reactions which reinforce drug use.

Many studies have shown that the use of alcohol is negatively correlated with academic performance in high school and university.272, 308, 309 Heavy or frequent users of alcohol almost invariably have poorer grades than light users or abstainers. While chronic heavy use might have direct effects contributing to this correlation, non-pharmacological factors are thought to be primarily responsible. Similar findings have been reported for most other drugs, and it would appear that certain attitudes and life styles influence both drug use and academic performance.

DRIVING

In moderate to large doses alcohol adversely affects many of the functions thought to be important in automobile driving. In addition, to detrimental effects on various perceptual, attentional, cognitive and psychomotor skills, alcohol may increase risk taking and aggression in driving.47, 162, 284 Commission experimental research has replicated the frequent finding that alcohol in quantities commonly consumed in Canada (0.07% blood alcohol level) reduces driving performance.13, 48, 105, 189

In 1904, data linking alcohol consumption to automobile crashes was published in an editorial in the Quarterly Journal of Inebriety.227 Since then, a considerable amount of evidence has been accumulated which continues to point to alcohol as a major contributing factor in such accidents. A 1969 study of alcohol involvement in fatal motor vehicle accidents in three Canadian provinces presented findings similar to those reported regularly across North America: approximately 70% of drivers killed in single vehicle accidents and 50% of drivers killed in multi-vehicle collisions had been drinking. Among all driver fatalities, alcohol was detected in the blood of 60 to 70% of those considered responsible for their own deaths.26 The majority of such alcohol-related fatalities involve drivers with blood alcohol levels above 0.08%; a much smaller fraction of other drivers on the road at a comparable time show blood alcohol levels of such a magnitude.17. 166 In other words, many of the fatal crashes are caused by a small but distinguishable group of drivers, namely those with blood alcohol levels above about 0.08%.

Although more than half of the adult population in North America at some time drive automobiles after drinking, alcoholics, primarily men, account for a disproportionate number of highway fatalities, even when corrections are made for driving exposure.253, 293, 302 Numerous factors including failure to use seat belts, greater susceptibility to death due to trauma, and possible suicide attempts may contribute to this relationship.86, 287 Another group which accounts for a disproportionate number of highway deaths, often involving high blood alcohol levels, are young adult males (roughly between the ages of 15 and 24).26, 216 However, evidence indicates that all age groups contribute to the traffic safety problem, particularly after heavy drinking 17' 293

The relationship between blood alcohol level and non-fatal automobile accidents has not been extensively studied, partly because drivers involved in such accidents may not consent to being tested for alcohol. Nevertheless, evidence indicates that blood alcohol levels at or above 0.10% are seen in approximately one-quarter of the serious but non-fatal crashes; for various reasons these figures are considered to be underestimates.17, 113 Thus, the overall trend is quite consistent—significant quantities of alcohol are frequently found in drivers (and, incidently, in about 50% of their passengers) involved in fatal single-vehicle crashes, fatal multiple-vehicle crashes, and nonfatal serious crashes, compared to drivers not involved in accidents. On the average, the likelihood of such crashes begins to accelerate at blood alcohol levels of about 0.08-0.10%; above that the chance of an accident increases rapidly as a function of the alcohol level in the blood.17, 119, 186

Alcohol has also been found to be a contributing factor in pedestrian fatalities;100 in the Canadian study cited above, more than half the pedestrians killed were shown to have been recently drirtking.26 Alcohol is also a significant correlate of fatal aviation crashes, and it has also been cited as a contributing factor in rail crashes and home and industrial accidents.22, 54' 199'
107, 159, 293

Although the intensity of the acute effects of alcohol can, to a certain extent, be estimated from the amount of alcohol in the blood, the relationship between the blood alcohol level and the effects produced may vary considerably from individual to individual. Federal legislation prohibits driving with blood alcohol level greater than 0.08%. This concentration may be produced by three or four ordinary drinks, if consumed in a short time. While certain individuals might be capable of driving satisfactorily with this much of the drug, most persons perform less skillfully at even lower levels."5, 189 Although the Breathalyzer can be used to predict the immediate effects of alcohol, there are no simple methods of detecting a 'hangover', and there are indications that this post-inebriation phase can have adverse effects on psychomotor performance and driving.

Recent reviews of the broad area of drugs and traffic safety have concluded that alcohol is a major factor contributing to highway crashes and fatalities. There is little evidence that other drugs are presently significant factors in comparison.145, 208, 269, 303 According to Statistics Canada data, almost a half million automobile accidents were reported in this country in 1971; of these, there were 4,670 fatal accidents (resulting in 5,573 deaths), 192,599 traffic injuries and 358,883 property damage accidents.229 Existing information suggests that alcohol was involved in a large proportion of these occurrences, although Canadian data are not available to allow an accurate estimate of the precise number which could be attributed to alcohol intoxication.276 It has been estimated that alcohol-related mishaps account for 30% of the severe injuries and at least 50% of the deaths from traffic accidents in the United States.211, 293, 299 The Canadian situation is probably not drastically different.

LONG-TERM EFFECTS

Many authorities differentiate between low-risk' (moderate) and 'high-risk' (heavy) drinking in discussing the long-term effects of alcohol. For most otherwise normal individuals, moderate drinking over a prolonged period of time may produce little apparent psychological or physiological change. However, high-risk or heavy drinking (e.g., an average of five or more drinks a day) frequently leads to a variety of psychological and physiological difficulties, many of which are subsumed under the general terms alcoholism or alcohol dependence.

There is considerable disagreement among authorities as to the proper delineation of the concept of alcoholism—definitions may be as general as "a family of disorders accompanying chronic heavy drinking" with various social and economic complications, or they may contain more restrictive specifications of physical dependency and addiction, or psychological and physiological harm.61.13° Jellinek has described five different types of alcoholics which differ in degree and kind of psychological, behavioural and physiological involvement.'30 In some areas of North America, at least 2% to 5% of alcohol users become alcoholics and perhaps twice that many would be considered problem drinkers. The Addiction Research Foundation has estimated that in 1967 there were over 300,000 alcoholics in Canada.1 The number is undoubtedly substantially higher today.

Only a small minority of alcoholics are 'down and out', 'skid row' variety derelicts; there are many alcohol-dependent persons in all levels of society who function in varying degrees of effectiveness in spite of their high alcohol consumption. Psychological and physiological disorders in these individuals vary considerably as a function of general life style and drinking patterns. Some heavy drinkers show little obvious functional impairment for long periods of time.

Some of the consequences of excessive alcohol use include increased physical and mental health problems, earlier death and a greater likelihood of incarceration; discussion of these topics will follow directly. In addition, however, there are other consequences of alcohol use which involve not only the user, but others about him, and society in general.'" A seemingly endless list of such consequences is possible, although those which are clear liabilities to society are the most frequently enumerated. As examples, heavy alcohol users are frequently cited as being responsible for injuring and killing large numbers of persons in automobile crashes and in acts of violence and aggression. Moreover, the legal handling, incarceration and rehabilitation of such individuals involve costs typically paid for by society as a whole. Alcoholics' increased accident rate adds to the costs of medical and automobile insurance, and their greater need for medical treatment decreases available hospital space and services already in short supply. They are more likely to create problems and misery for their families and their productivity while employed is frequently below par, partly due to their increased absenteeism.219

General Physical Health

The physical health of heavy alcohol users is typically poorer than that of the general population.86, 156, 237, 252 Some illnesses result from the direct effects of alcohol, or they may involve other factors such as general life style, nutritional deficiencies, heavy use of other drugs (e.g., tobacco or Aspirin® ), bodily injury due to accidents and other violent mishaps, inadequate hygiene and rest, over-exposure, overcrowding and other forms of stress.

Chronic heavy alcohol consumption often produces a loss of appetite for food and a disruption of normal digestion, absorption and, perhaps, utilization of essential nutrients. Heavy tobacco use, which is typical of alcoholics, often further reduces appetite. In addition, some alcohol-dependent persons choose to spend their limited funds on alcohol rather than adequately balanced meals. A large proportion of the diet of certain alcoholics is made up of alcoholic beverages (in some cases with weeks or even months with little else) and is thus dangerously low in protein, vitamins, minerals and other important food-stuffs. In addition to producing severe nutritional disorders, such diets may result in increased susceptibility to other diseases and infections.

Several liver diseases are related to heavy alcohol use. Cirrhosis of the liver involves a replacement of functional liver cells with scar tissue. Alcoholic liver cirrhosis is reported to develop after 10 to 15 years of heavy drinking and may lead to death.292 Alcohol itself may be directly responsible for cirrhosis although other alcohol-related factors, particularly nutritional deficiencies, are typically most significant.128, 161, 217 A Commission project examining societal factors influencing alcohol dependence in 45 countries replicated and extended the findings of others, showing that the incidence of cirrhosis in certain populations is positively correlated with per capita consumption of alcohol.151, 230, 242, 258, 286 It has been estimated that 65-90% of the liver cirrhosis in certain parts of North America is attributable to heavy alcohol consumption.'• 230 In the United States, alcohol prohibition brought a marked decline in deaths due to liver cirrhosis, compared to the general mortality rates during the same period.147 Cirrhosis fatalities rose gradually after prohibition was repealed and alcohol became freely available again. (See Figure A.1.)

Another serious liver impairment associated with alcohol dependence is alcoholic hepatitis; this illness involves inflammation of the liver with accompanying fever, abdominal pain and jaundice.218 Other liver complications include a narrowing of the blood vessels serving the liver, and frequently, although apparently of lesser consequence, an increase in deposits of fat in the liver.122, 160 Since many drugs are metabolized by the liver, alcohol-related liver damage may result in unusual or prolonged reactions to certain drugs in alcoholics, even when alcohol is not present in the body.

Heart disease is also seen in heavy alcohol users more frequently than in the general population. Although nutritional deficiencies and other factors can add complications, the cumulative effects of chronic alcohol consumption have been shown to impair the functioning of the heart and to result in metabolic and structural abnormalities before any difficulties are noticed by the drinker.70, 232 The progression of the disease to produce heart failure, arrhythmias and other problems is not yet fully clarified, since a number of additional factors such as malnutrition, infections, excess trace metals sometimes found in beer, and the chronic use of other drugs such as tobacco may be involved.1°3, 232 Heart disease has frequently been reported as a major cause of death among alcoholics.148, 288

Alcohol can also adversely influence other parts of the circulatory system. In one study blood cells were found to clump together forming a "sludge" in small vessels in the eye which slowed the rate of blood flow in proportion to the blood alcohol level; some vessels ruptured and others were completely blocked. The authors suggested that such effects may adversely affect many organs including the liver and brain.'"

Gastrointestinal difficulties associated with heavy alcohol consumption include chronic gastritis, an undersupply of hydrochloric acid in the stomach, increased incidence of ulcers, and impaired absorption of various substances in the small intestine including thiamine, folic acid, xylose, fat and vitamin B12.184' 272 Heavy drinkers are also reported to have higher rates of cancer of the mouth, larynx, pharynx and esophagus; although heavy tobacco smoking is thought to add to the likelihood of some of these cancers, alcohol is also believed to be a significant factor.86, 315, 316, 317 Various infectious diseases such as tuberculosis and pneumonia are also more frequently reported in heavy users of alcohol.86

Chronic and acute muscle disorders, involving muscle weakness, swelling, cramps and pain, have been related to heavy alcohol use. Bath nutritional deficiencies and decreased oxygen to the muscles have been suggested as possible causes of these conditions.167. 292 Other diseases associated with alcohol dependence, but due primarily to nutritional deficiencies, include pellagra, scurvy, anemia, brain damage and alcohol neuritis.184. 292 Alcohol-related neurological disorders are discussed in more detail in a separate section below.

Regular, heavy alcohol use has significant effects on the secretion and metabolism of various hormones in the body, and some authors have suggested that many diseases of alcoholism are secondary to alcohol-induced disruption of endocrine function.65 Disorders of the pancreas are frequently noted in alcoholics.249 Low blood sugar and elevated fat content in the blood are also often seen. 184, 292

The majority of the illnesses associated with heavy alcohol use improve when alcohol consumption is discontinued and diet and living conditions are improved. Frequently, recovery is near complete, although in some instances permanent damage or disability results.156. 222 The general area of alcohol-related fatalities is discussed in more detail in a separate section below.

Adverse Psychological and Neurological Reactions

Heavy alcohol consumption is associated with a variety of psychiatric and neurological disorders. As with other drugs, it is often difficult to differentiate cause and effect in such correlations. Some investigators contend that only those individuals with serious psychiatric disorders become heavily involved in alcohol use, while others might argue from the same data that alcohol is primarily responsible for the pathology observed. In many cases it would appear that both factors are operating with considerable interaction.
In addition to the rather ambiguous but significant role of alcohol complications in various common psychiatric disorders, there are some relatively well defined organic conditions involving brain damage which are attributable directly or indirectly to the effects of chronic high-dose alcohol consumption. While the major psychiatric and neurological disorders associated with chronic alcoholism occur primarily in adults, there is considerable concern over the possible effects of heavy alcohol use on the maturation process in adolescents. Little adequately controlled research is available in this latter area, however.

The neurological complications of alcoholism are usually closely related to nutritional deficiencies which typically accompany chronic heavy alcohol consumption. Deficiencies in the vitamins thiamine, vitamin B6, nicotinic acid and pantothenic acid are primarily responsible for such disorders of the nervous system,'" although alcohol can have direct irreversible damaging effects on nerve tissue as well.

Some of the more serious alcohol-related neurological disorders include peripheral neuritis, Korsakoff's psychosis, Wernicke's syndrome, and Jolliffe's encephalopathy. Typical symptoms of alcoholic brain disorders include disorientation, clouding of consciousness, memory failure, hallucinations, rigidity of the limbs, and certain uncontrollable reflexes. Other frequently noted neuro-psychiatric conditions associated with alcohol dependence include alcoholic hallucinosis, pathological intoxication, delerium tremens and various convulsive disorders or epilepsy complications.

The examination of hospital records provides some epidemiological information regarding the extent of alcohol-related psychiatric problems. As with other drugs however, the reliability and validity of psychiatric diagnoses associated with alcohol-related problems is often not adequate for survey purposes. In many cases, alcoholics may be hospitalized for treatment of their dependence rather than for other specific psychiatric disorders. In any event the number of alcohol-related cases must ultimately be interpreted in terms of the overall patient population, and more importantly, in terms of the extent and patterns of alcohol use in the general population from which the patients were drawn.

In the spring of 1971 the Commission conducted a national survey of the diagnostic records of psychiatric hospitals."° Although alcohol was of interest to the study, primary focus was on other drugs, and consequently, institutions specializing in the treatment of alcoholism were not included in the sample. Because of the frequency of serious non-neurological physical disorders associated with heavy alcohol consumption, many alcoholics are hospitalized in general hospitals rather than in psychiatric institutions. In spite of our a priori exclusion of the majority of alcoholism cases, alcohol was mentioned in the primary or secondary diagnoses of 5.1% of the psychiatric patients in the hospitals surveyed. This figure is three times that reported by the hospitals for all cases with other drug-related diagnoses combined. In British Columbia general hospitals with psychiatric wards were also surveyed. Alcohol was mentioned in the diagnoses of 41 (13.8%) of the 293 patients in the reporting hospitals.[d]

In the 1971 national mental health data published by Statistics Canada, alcoholic psychosis and alcoholism together accounted for 10,071 (17.5% ) of the first admissions and 8,502 (16.5%) of the readmissions to psychiatric wards and institutions in the country.34, [e] The category of alcoholic psychosis includes delirium tremens, Korsakoff's psychosis, other alcoholic hallucinosis, alcoholic paranoia and other or unspecified alcoholic psychoses.32 Alcoholic psychosis was diagnosed in 6.7% of the total alcohol cases. The alcoholism category includes episodic or habitual excessive drinking, alcohol addiction, and other or unspecified alcoholism. Overall, males outnumber females by a ratio of almost six to one in these cases. These data reflect a substantial increase in alcohol admissions from those reported in 1969. However, direct comparison among different years is hampered by the lack of consistency in the number of hospitals reporting from year to year.

Note that the Commission survey and the Statistics Canada data only include cases of alcohol complication of other psychiatric conditions when alcoholism per se is presented in the diagnosis. The total impact of alcohol on general neurological and psychiatric admissions is undoubtedly substantially greater than indicated in these data. (See also Tables A.5, A.6 and A.7 in the Annex to this appendix.)

ALCOHOL AND DEATH

Heavy alcohol users as a group have been shown to have a higher mortality rate than persons of similar age in the general population. Studies in various countries have found that alcoholics are more likely than non-alcoholics to die from various accidents, poisoning with other drugs, suicide, homicide and certain diseases such as pneumonia, tuberculosis, liver cirrhosis, gastrointestinal ulcers, heart disorders and some cancers.22, 45, 86, 100, 143. 163, 209, 241, 252, 277, 281, 304 Some of this literature has been discussed above.

In reports of violent death, it is often difficult to distinguish between acute or chronic effects of alcohol and various associated personality, social and life style factors. The nature of the relationship between alcohol and suicide is often not clear; alcohol use may be responsible for the suicidal state or in other cases heavy alcohol use might be the result of pre-existing emotional depression. The possible role of 'hangover' depression in suicide has not been clarified.

A study of alcoholics in Ontario found that suicide rates were six times the expected figure.252 In another recent report from Ontario, approximately one-half of the males and one-quarter of the females who purposely injured themselves or attempted suicide were heavy drinkers.'" Data from British Columbia indicates that alcohol was associated with more than one-quarter of all attempted suicides.285 Similarly, in an investigation in the U.S. approximately one-quarter of suicide cases involved chronic alcoholics.241

The Federal Poison Control Program has reports of 651 ethanol poisonings or adverse reactions for 1971.2" The majority of the poisonings occurred in persons over 25 years of age; approximately one-tenth involved children under 5 years of age. Males outnumbered females in these data by a little over two to one. It was not indicated whether these alcohol poisonings occurred singly or in combination with other drugs. Of those reports where the disposition of the case was specified, 38% resulted in hospitalization, with a median of 4-5 days institutional care. Of 67 drug death reports in which alcohol was mentioned, only 6 (9% ) were attributed to alcohol alone; the remainder involved drug interactions, with alcohol and barbiturates being the most frequent fatal drug combination reported to the program. None of the alcohol-related deaths involved children.(11

In the national statistics on Causes of death, published by the Federal Government, alcohol deaths may be coded under one of several different categories.33 The following fatalities were reported for 1971: [m]

Alcoholism    350
Alcoholic psychosis (organic)    26
Alcoholic cirrhosis of the liver    739
Toxic effect (overdose)    10
Interaction with other drugs    204
Total    1,329

A little over two-thirds of these persons were males and the vast majority were over 40 years of age at the time of death. Alcohol-barbiturate combinations made up more than two-thirds of the drug interaction deaths.

For various reasons, these official mortality figures must be considered gross underestimates of the actual number of alcohol-related fatalities. Cases noted under the general category of alcoholism typically involve known alcoholics who died of some disease, such as pneumonia, heart attack, or gastrointestinal disorder, which was attributed to their chronic heavy alcohol consumption. The ascription of death to alcoholism or to another disease is often arbitrary, and apparently most alcoholic deaths are coded under various specific diseases rather than under alcoholism in death records.40, 52, 100, 190, 252

Canadian data suggest that approximately 65% of all liver cirrhosis deaths might be attributed to chronic heavy alcohol consumption in this country.23° When this formula is applied to the total number of cirrhosis deaths reported for 1971, an estimate of 1,259 alcoholic cirrhosis fatalities is derived, which is almost double the number officially specified as such.33

The involvement of alcohol in overdose deaths associated with other drugs is apparently much greater than suggested by the above figures. For example, in a Commission study of coroners' reports of drug-related deaths, alcohol was found on autopsy in 44 (48%) of 92 opiate narcotic cases where toxicological findings were reported.'" Death had been coded under opiates without mention of alcohol interaction in many instances.Eo

Dealing with fatalities among heavy alcohol users only, a 1971 report from the Addiction Research Foundation estimated that alcoholism in Canada contributed at least 6,000 deaths annually in excess of the expected mortality.251 We have no accurate epidemiological information on the total number of deaths (among alcohol users and non-users) in Canada due to suicide, homicide or various accidents in which alcohol played a significant role. Existing data indicate that the number of such fatalities which could be attributed to the acute or chronic effects of alcohol would be substantial.

ALCOHOL AND CRIME116

Of all drugs used medically or non-medically, alcohol has the strongest and most consistent relationship to crime. In addition to over two and one-half million convictions for offences directly related to alcohol in Canada every year (including drunkenness offences; violations of the liquor control laws, such as operating stills, illegal importation and sales; and drunken and impaired driving) many other crimes are also related to alcohol use.', 224 However, many alcohol-associated criminal acts may not necessarily be attributable to the effects of the drug. For example, compared to non-delinquents, delinquents have been found to drink more frequently, and to report more solitary drinking, more drunken instances and less drinking with the family.168, 225 Although drinking may be associated with crime in some such individuals, evidence suggests that alcohol is generally not the cause of their delinquent behaviour. Instead, illegal alcohol use appears to be part of a general delinquent syndrome involving such acts as joy riding, vandalism, and malicious mischief.'°

To some degree it is possible to predict future alcohol problems on the basis of earlier youthful delinquency. In one study 21% of the individuals who appeared at a psychiatric clinic as children were diagnosed alcoholic 30 years later, compared to only 3% of a group of matched control subjects. Forty-five per cent of the individuals with juvenile court records were subsequently diagnosed alcoholic.238

Alcohol use is frequently correlated with certain crimes in the chronic drunkenness offender or 'skid-row' alcoholic. Most of the offences committed by such persons are typically minor non-drug offences (such as vagrancy, trespassing and panhandling) which are often related to their lack of funds for food, shelter or more alcohol. Petty theft is an occasional charge, and it has been suggested that in order to "break into jail" temporarily for food and shelter, some individuals may commit some minor disturbance or crime against property.72

There is an abundance of evidence relating alcohol use to more serious crimes. Homicide is strongly correlated with alcohol use. In one frequently cited study in Philadelphia alcohol was present in either the offender or the victim in 64% of the homicides over a five-year period.314 In 70% of the alcohol-related cases, alcohol was present in both the offender and the victim, while in only 17% and 14% of the cases had only the offender or the victim, respectively, been drinking. Murders were committed by stabbing, kicking, or beating by fists or with a blunt instrument in 70% of the cases, suggesting that serious alcohol-involved crimes tend to be unpremeditated, physical assault. A study of coroners' cases in Victoria found that out of 41 murder victims tested for alcohol, 19 had a blood alcohol level of over 0.15%." A Canadian study of ex-prisoners concluded that an abnormally high proportion of excessive drinkers had committed crimes against the person, and a lower proportion had committed crimes against property. Excessive drinkers also had a higher proportion of sex crimes." A strong relationship between alcohol use and sex crimes such as rape and incest has been demonstrated in many other studies around the world.4, 8, 228, 236
A study of drinking was made in 415 self-referred and 260 court-referred patients to the Winnipeg Psychopathic Hospital between 1956 and 1959.218 Drinking histories were as follows:

Court-referred Patients (N 260) Self-referred Patients (N 415)
Abstainers    8%    44%
Moderate drinkers    17%    22%
Problem drinkers    40%    11%
Alcoholics    35%    22%

A significantly higher percentage of the psychiatric patients who had been in trouble with the law had drinking problems. Of the court-referred patients, 55 were charged with sex offences, and of these, 54% were problem drinkers and 22% were alcoholics. Homicide was contemplated, attempted or committed by 42 of the court-referred patients, and 95% of these were problem drinkers. Seventy-three per cent of these individuals were intoxicated at the time of the offence. Of 43 patients who had committed theft or forgeries, 70% were problem drinkers.

Persons with alcohol problems constitute a considerable proportion of people imprisoned in Canada for serious offences. Of a total of 4,057 males who were committed to penitentiaries for such offences in 1969, 1,053 (20%) were judged to be problem drinkers and 360 (9% ) were alcoholics, making a total of 29% of the admitted male inmates with serious identified drinking problems. Of some selected crimes, alcoholics and problem drinkers were involved in 33% of the murders, 38% of attempted murders, 54% of manslaughters, 39% of rapes, 42% of other sexual offences, and 61% of assaults. Of female admissions for serious crimes, 16 (22%) out of a total of 72 were judged to be problem drinkers."-

TOLERANCE AND DEPENDENCE

Tolerance to most of the immediate effects of alcohol develops with frequent heavy use, although it does not occur as rapidly or to the same degree as with opiate narcotics. For example, tolerance to the lethal effects of morphine may be in the order of 25- to 100- fold, while tolerance to the lethal dose of alcohol may only be doubled under comparable dependence conditions.259 Alcohol is more like the barbiturates and other sedative hypnotics in that limited or "incomplete" tolerance develops."4, 139 The rate of acquisition and extent of tolerance depends on the pattern of use. Regular heavy drinkers may be able to consume two or three times as much alcohol as a novice. In Western culture, some symbolic masculinity frequently accompanies the development of tolerance and the ability to 'hold one's liquor'.

Most intermittent or moderate drinkers show little tendency to increase dose, although regular heavy drinkers may, in order to obtain the desired psychological effects, ingest quantities which lead to symptoms of chronic alcohol toxicity. A decrease in the sensitivity of the nervous system to alcohol is probably more important than metabolic mechanisms in the development of tolerance.139 Learning to function under the influence of alcohol may further reduce some of the acute behavioural effects of intoxication in regular users. As noted above, relatively little tolerance develops to the lethal dose, and acute alcohol poisoning is sometimes noted as a cause of death in alcoholics, although nausea, vomiting and unconsciousness usually prevent self-administration of a fatal overdose. In some alcoholics, tolerance later seems to decline and a special response or oversensitivity to certain effects of alcohol (pathological intoxication) may develop. In such individuals even a single drink may produce profound loss of control and initiate unrestricted further indulgence. Alcohol-related liver damage may play a role in such phenomena.

Physical dependence on alcohol occurs with the development of tolerance in some long-term heavy drinkers. Although alcoholic hallucinosis, delirium tremens (`DT's'), and convulsions Crum fits') were noted and studied in the 19th century, only relatively recently was it demonstrated that these symptoms are essentially part of the physical dependence withdrawal syndrome.

Isbell and Mendelson and their associates have clearly demonstrated that even when diet is controlled, a characteristic severe withdrawal syndrome can occur in individuals who had been heavy drinkers, after only a few weeks of continual drinking of large doses of alcohol.121, 180 The quantities of alcohol ingested in these studies were considerably greater than those normally consumed. With the usual drinking patterns overt physical dependence may not appear until after years of heavy consumption. Some problem drinkers seem never to become physically dependent on alcohol.'"

The overall picture of the alcohol abstinence or withdrawal syndrome is generally similar to that associated with barbiturate dependence. As with other drugs, the number and severity of the withdrawal symptoms varies with the quantity of the drug regularly consumed before use was stopped. The abstinence syndrome typically involves loss of appetite, nausea, anxiety, sleeplessness, severe agitation and irritability, confusion, tremors, sweating and, later, cramps, vomiting, illusions and hallucinations. In severe cases, after several days delirium tremens develops and convulsions, exhaustion and cardiovascular collapse may occur. The delirium tremens stage occurs in about 5% of withdrawal cases Although reports are inconsistent, death may result in 10% of those undergoing severe withdrawal without treatment.° Major recovery in those surviving usually occurs within a week, although certain symptoms continue for a much longer period.'", 298 The full blown alcohol or barbiturate type withdrawal syndrome is considerably more dangerous than that of the morphine type, which is rarely if ever fatal.

Psychological dependence on alcohol occurs in many individuals and such dependence is often accepted and tolerated in contemporary North America. A great number of people regularly turn to alcohol for relief or aid prior to or after facing a stressful situation, to escape worries, troubles or boredom, to relax and enjoy a party, or even to sleep, and many feel they do not function as well in certain situations without a drink or two. There is a strong psychological component in the drinking behaviour of the developing alcoholic as his drinking becomes more and more compulsive in spite of the obvious consequences.

ALCOHOL AND OTHER DRUGS

Pharmacological Interaction

The psychological, physiological and biochemical effects of alcohol can be modified by the presence of other drugs; likewise, alcohol can influence the effects of many other substances. Although research regarding drug interactions has been considerably less extensive than that involving the effects of single drugs, knowledge in this important area is increasing at a rapid rate. Because of the prevalance of alcohol consumption in our society, the interaction of alcohol with other drugs used medically and non-medically is of considerable significance.", 78. 292 The preparation of this summary was greatly facilitated by the annotated bibliography on alcohol interactions prepared by Eric Polacsek and associates of the Addiction Research Foundation.221

Barbiturates. The combination of alcohol and barbiturates may result in effects which are greater and longer lasting than that produced by either drug alone. Under certain conditions sedation is potentiated, resulting in a greater effect than that expected by simply adding the reactions produced by each drug when administered alone. Toxic reactions and death can result from doses of alcohol and barbiturate in combination which, administered singly, are well below the lethal range.50, 71. 133. 169 The mechanisms for these effects are not yet fully understood, but it has been found that the presence of alcohol in the body can decrease the rate of barbiturate metabolism.'"

Alcohol and barbiturates also demonstrate cross-tolerance; it has long been recognized that regular heavy users of alcohol have a diminished response to barbiturates, and vice versa. This cross-tolerance appears to be primarily due to changes in the responsiveness of the brain following regular heavy use of either drug.114, 189, 192 Thus, heavy alcohol users are less sensitive to barbiturates when taken alone, but become increasingly responsive after consuming alcohol. The development of cross-tolerance does not appear to significantly affect the lethal dose, and large quantities of alcohol and barbiturates taken simultaneously may produce a toxic or fatal reaction, even in individuals with high tolerance to other effects. Alcohol and barbiturates also show a considerable degree of cross-dependence, and barbiturates are frequently used therapeutically to reduce the severity of withdrawal in persons physically dependent on alcohol.

Non-barbiturate sedatives and minor tranquilizers. Alcohol combined with certain non-barbiturate sedatives and minor tranquilizers may, under certain circumstances, produce a more intense and prolonged sedation than is produced by either drug alone, although the literature is not consistent in this respect. In only a few studies have such combinations resulted in a potentiation of effects. Minor tranquilizers such as chlordiazepoxide (Librium®), diazepam (Valium()) and meprobamate (Equanil®) did not increase the sedation produced by alcohol in some investigations.38. 80, 78, 140

Cross-tolerance and cross-dependence have been demonstrated between alcohol and some non-barbiturate sedatives and minor tranquilizers.

Since the minor tranquilizers are frequently used by non-hospitalized patients, some of whom are likely to drink alcohol and drive automobiles, there has been considerable interest in evaluating the effects that these drug combinations might have on skills related to driving. Such interaction studies have included only limited measures of psychomotor, intellectual and perceptual functions, but the results are generally comparable to those investigating general sedation: enhanced impairment has been found with some substances, no effects with others, and, under some conditions, certain of these drugs may reduce the response to alcohol.", 39, 79, 99, 140, 153, 185, 199, 319 Similarly complex interaction may be expected for combinations of alcohol, and certain antihistamine and anticholinergic drugs. Many such substances are available and relatively little human research has been done in this
regard.62, 117, 265, 300

Volatile solvents. Volatile solvents are sometimes taken in conjunction with alcohol by certain individuals, who report that some of the subjective effects produced by these drugs are thereby enhanced. Also, alcohol has been shown to augment the adverse effects of the volatile anesthetic, trichloroethylene, on visual-motor performance." Furthermore, cross-tolerance between alcohol and solvents has been suggested by the frequently reported insensitivity of chronic alcohol users to ether anesthesia.104

Major tranquilizers. Numerous studies suggest that many of the major tranquilizers, including phenothiazines, thiozanthines, butyrophenones and rauwolfia alkaloids (all of which are used primarily in the treatment of psychosis) may produce an increase in sedation when taken concomitantly with alcohol.", 191 Since many patients receive such medication on an outpatient basis, some researchers have expressed concern regarding automobile driving and social interactions if alcohol is taken concomitantly.149, 213

Anti-depressants. Certain drugs used to treat severe depression (especially the monoamine oxidase inhibitors such as Parnate®) may exaggerate the toxic effects of alcohol and vice versa when the drugs are taken together. The mechanism of such effects is uncertain. Some other anti-depressants, such as imipramine (Trofranil®) and amitriptyline (Elavil®) may also alter the effects of alcohol, but the interaction is not as consistent or pronounced as with the former class of compounds."' 11°

Opiate narcotics. Surprisingly little human research has been done regarding the interaction of alcohol and the opiate narcotics, such as codeine, morphine, heroin and methadone. On the basis of evidence obtained in animal experiments and from studies of death due to overdose of opiate narcotics and alcohol in humans, it is clear that the dose of either of these drugs which produces sedation, toxicity and death is substantially lower when they are used
together.62, 68, 203, 801

Alcohol does not exhibit significant cross-tolerance or cross-dependence with the opiate narcotics. However, opiate narcotics can reduce or mask some of the symptoms of alcohol withdrawal or 'hangover'. There is almost no evidence regarding other potentially important psychological and physiological interactions resulting from opiate narcotic and alcohol combinations in humans. This is clearly a high priority research area.

Stimulants. The results of research regarding the interaction of alcohol and stimulants such as caffeine and amphetamine are, in general, complex, conflicting, and incomplete, but it does appear that some of the sedative effects of alcohol can be reduced by certain stimulants. Amphetamines have been reported to reverse the impairment due to alcohol on some, but not all tests involving mental addition and the learning of new materia1.282. 3" In another investigation, amphetamines overcame alcohol-induced changes in certain minor involuntary eye movements."- However, in a series of studies involving motor skills and verbal performance under stress, amphetamines did not antagonize the detrimental effects of alcohol even when the subjects were fatigued.117, 141 Amphetamines have been reported to reduce the gross behavioural signs of alcohol intoxication in alcoholics and to decrease some of the symptoms of 'hangover'.23, 186, 235

Some researchers, but not all, contend that caffeine decreases certain symptoms resulting from high doses of alcohol, including potentially fatal depression of respiration.", 237 With moderate doses of caffeine there may be some transient improvement in feelings of alertness, but caffeine has not been shown to improve psychomotor coordination impaired by alcohol." Smoking tobacco in combination with alcohol or with alcohol and coffee may enhance the detrimental effects of alcohol on psychomotor coordination.124, 208, 215

Cannabis and hallucinogens. The interaction between alcohol and cannabis has only recently begun to be systematically explored. Cannabis increases certain alcohol effects on behaviour in mice,13. 97 but apparently does not affect the lethal toxicity of alcohol.69 It has been shown in Commission research and in studies of another group that cannabis and alcohol can have additive effects on certain psychomotor and physiological functions, and that marijuana may intensify the sedative properties of alcohol under some conditions.172, 173, 189, 233 On the other hand, the two drugs may have antagonistic effects on some subjective variables such as visual imagery.233 In the Commission study, cannabis altered the alcohol effects without changing the rate of alcohol metabolism or disappearance from the blood (as measured by the Breathalyzer).

Alcohol interactions with LSD and related drugs have not been systematically explored, but antagonism of certain effects has been reported by illicit users. Alcohol enhancement of the sedative properties of PCP is to be expected.

Non-psychotropic drugs and antagonists. Alcohol may also interact with a number of drugs which have little or no psychotropic effect, or are rarely used for such purposes. Of primary interest here are substances which may reduce or eliminate the acute effects of alcohol, post-intoxication hangover, or withdrawal symptoms in alcohol-dependent persons. Some other drugs used in conjunction with the medical management of alcoholism are discussed as well.

A substance which could reverse the short-term effects of alcohol would be of considerable practical importance in both medical and social contexts. Unfortunately, at present there is no known pure alcohol antagonist, although a number of substances have been shown to reduce some of the acute effects of alcohol. One report noted that multiple vitamins (B1, riboflavin, pyridoxine and calcium) can reduce alcohol subjective effects and impairment of reaction time.142 Diarginine ketoglutarate has been reported to lower blood alcohol levels after drinking, and to reduce alcohol effects on certain psychological and physiological measures.44 In one study carbamazepine almost entirely compensated for errors caused by alcohol in a visual field test.257 Intravenous infusions of fructose (a sugar obtained from fruit sources) have recently been reported to increase the rate of alcohol elimination in alcoholics by 25%, thereby presumably resulting in quicker recovery.24 Antacids taken during or after drinking reduce nausea and other gastrointestinal symptoms of alcohol intoxication and hangover."

Mendelson and associates"' recently reported that alcoholics who were given propranolol displayed smaller alcohol-induced decrements in performance than control subjects on assessments of reaction time, hand steadiness, manual dexterity, flexibility of attention, and ability to change perceptual motor sets. Alcohol-induced mood change was reduced as well. The antagonism of alcohol effects in this study was small but consistent. In addition, propranolol has been used to reduce mild alcohol withdrawal symptoms such as trembling, nausea, stomach cramps, and vomiting, and to temporarily reduce craving for alcohol.289 Apomorphine has also been shown to at least temporarily decrease craving for alcohol.289

Disulfiram (Ant abuse()) and calcium carbimide (Temposil®) are often used to encourage abstinence in alcoholism therapy. Antabuse® was developed in Denmark in the late 1940s102 and Temposil® in Canada in the early 1950s.87 Both drugs alter the process by which the body metabolizes alcohol, but have little other relevant pharmacological activity. They are sometimes mistakenly discussed as alcohol antagonists. Under normal drinking circumstances ethyl alcohol breaks down into acetaldehyde when it is oxidized in the body. Acetaldehyde is highly toxic but is usually destroyed so quickly that its effects are minimal and rarely noticed. But with the introduction of disulfiram or calcium carbimide, the metabolism of the acetaldehyde is retarded so that intensely unpleasant effects occur (called the acetaldehyde syndrome) which may include nausea and vomiting (and, in severe cases, dangerous cardiovascular effects). A patient given maintenance doses of disulfiram, for example, can not use alcohol without becoming immediately sick.'" In order to provide a long-lasting deterrent to drinking, long-acting implantable disulfiram preparations have been developed which are effective for six to eight months. In one study, 20 of 22 patients achieved total abstinence over a period of 8 months after such treatment, while 11 of 12 non-implant patients returned to drinking within two months following discharge.12° Further research with such implants is clearly warranted.

Patterns of Multiple Drug Use

Alcohol is currently used by the majority of the Canadian population. Most of these individuals also use other psychotropic drugs non-medically, with caffeine and nicotine being most frequently mentioned. Heavy users of alcohol are almost invariably heavy tobacco smokers and as noted earlier, this high correlation is a frequent complicating factor in interpreting studies of the physical effects of alcohol.

In general, alcohol users are more likely than abstainers to be users of barbiturates, tranquilizers, opiate narcotics, volatile solvents, amphetamines, cannabis and other hallucinogens, and a variety of other prescription and non-prescription drugs. (See Appendix C Extent and Patterns of Drug Use.) Alcoholics are frequently heavy users of other sedative-hypnotics such as barbiturates and minor tranquilizers.56' 57 Likewise, heavy users of barbiturates, minor tranquilizers and opiate narcotics generally turn to alcohol if the supply of the preferred drug is restricted. Most opiate narcotic-dependent persons have histories of heavy illicit alcohol use as adolescents.240, 275 Alcoholism is one of the most serious problems regularly associated with opiate narcotic dependence, and heavy alcohol consumption is common among many former heroin users and patients in methadone maintenance programs.88, 100, 295

The relationship between cannabis and alcohol use has been the subject of much controversy. Some have suggested that cannabis may be a cure for society's alcohol ills. In general, survey studies indicate that those who use alcohol are much more likely than 'teetotallers' to use cannabis, and that most cannabis users still drink alcohol. In addition, heavy users of cannabis tend to drink more alcohol than light or infrequent users.12, 15, 27, 94, 150, 170, 246, 271, 273, 290 However, in a recent survey in Toronto, heavy users of alcohol used less cannabis than more moderate drinkers.272 In a retrospective study of black males in St. Louis, a higher incidence of alcoholism and related problems was found among cannabis users than non-users.239 However, we have no information from most of these studies as to the effect cannabis had on an individual's drinking behaviour and overall alcohol intake.

Many researchers have mistakenly assumed that cross-sectional survey data indicating a positive between-subject correlation of cannabis and alcohol use, at a single point in time, implies a positive relationship between the use of the two drugs within an individual over time, which is the relationship of ultimate interest. This extrapolation is unjustified logically and statistically.4' Evidence of an association (either positive or negative) between the use of two drugs in a population at a given time provides little information as to the relationship (if any) between the levels of use of the drugs within the individual members of the group. Changes in behaviour over time, within an individual, must be studied directly. Even then, other secondary data in addition to drug use patterns must be considered in order to determine causal factors.

The bulk of the limited retrospective within-subject data now available suggest that cannabis use may reduce or interchange with alcohol consumption to some extent in the user population. In many surveys, including several Commission studies, a substantial proportion of cannabis users claimed that they have significantly reduced their consumption of alcohol or quit it
since using cannabis.94, 95, 99, 101, 150, 179, 214, 207, 318 There is a reported tend-
ency, with cannabis use, for a greater reduction in the use of hard liquor than of the milder forms of alcohol. The combined consumption of cannabis with wine or beer is common in some social circles. Anecdotally, in certain parts of the United States, alcohol sales in university areas reportedly declined as marijuana use increased, in spite of generally spiralling alcohol sales across the country.207 Also of interest, five fraternities on a mid-western U.S. campus reported that the proportion of social funds spent annually on alcohol had been reduced considerably since marijuana use became common No indication of alcohol abstinence appeared in these fraternities, however.187 None of these reports present definite, verifiable evidence of a reduction in alcohol use, so conclusions must be guarded.

Some cannabis users claim that alcohol effects dominate and, for that reason, they refuse to mix the drugs even if they enjoy each one separately. However, in several studies, including Commission experiments, where alcohol and cannabis were given separately or together in low doses under `blind' conditions, some experienced cannabis users were not particularly proficient at identifying the predominant drug action.105, 135, 233 Differentiation is easier at higher doses, however, and alcohol does appear to reduce some of the psychedelic aspects of cannabis.55, 233

Comparing the benefits and harms of alcohol and cannabis has become a popular and engaging activity. Due to the profoundly different social connotations, patterns of use, and scientific knowledge of these drugs, such a comparison must be made on limited and tenuous grounds. As discussed in the Commission's Cannabis Report, only a few experiments have been done comparing cannabis and alcohol in humans.28, 198 Two such studies were conducted by the Commission.105, 189, 233

It would appear that individuals who actually quit alcohol use because of cannabis constitute a minority of users, and their choice of drugs may have more to do with their particular value systems than with the pharmacological properties of the drugs. The hostile attitude towards alcohol expressed in the past by some cannabis-using youth is clearly not reflected in the majority of cannabis users today. Combined use is becoming increasingly common 93 Systematic prospective studies have not been done, and it is not clear from the data whether, on a large scale, cannabis would tend to replace alcohol as an intoxicant in the user population, or whether the use of these drugs would be additive without significant interaction, or if the use of one might potentiate or increase the consumption of the other. As measured separately, the use of alcohol and cannabis are both increasing in Canada, especially among young people.13°. 272 (See also Appendix C Extent and Patterns of Drug Use for further discussion of multiple drug use.)