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Major Studies of Drugs and Drug Policy
The Report of the Canadian Government Commission of Inquiry into the Non-Medical Use of Drugs - 1972


45. The term 'barbiturate' generally refers to drugs which are derivatives of barbituric acid. Barbital, the first drug of this class to be synthesized, was introduced into medicine in Germany in 1903. Barbiturates rapidly gained a wide usage as tranquillizers, sedatives and hypnotics (sleep inducers) which continues to this day. In the past half-century, over 2,000 different barbiturates have been synthesized, although less than a dozen make up the bulk of current use. Among these are amobarbital (Amytal*), pentobarbital (Nembutal*), phenobarbital (Luminal*), and secobarbital (Seconal*). These drugs are frequently referred to as 'barbs', 'nemmies', 'goof balls', 'yellow jackets', 'red devils', 'downers' or 'sleeping pills'.

The barbiturates are often classified by the duration of their sedative or hypnotic action at a standard dose. Since the similarities among these drugs exceed the differences, they will be discussed in general terms as a group.

46. Barbiturates are among the most widely used psychoactive drugs (medically and non-medically) in our society, and are the toxic agents in thousands of accidental or intentional deaths annually in North America. In addition, the barbiturates have considerable potential for producing psychological and physiological dependence, and are probably second only to alcohol in frequency of drug-induced debilitation in modern society. While a considerable body of research exists into the many medical applications of these drugs, there has been relatively little careful investigation of non-medical use.

Although the medical and non-medical use of barbiturates appears to be widespread across age groups and social class, the chronic use of these drugs, as with alcohol, seems to be primarily an adult practice. Good epidemiological data in this area are not available. Since prescription control is only partially effective and possession of these drugs for personal use without medical authorization is not a criminal offence and, perhaps, because the users do not appear to form any homogeneous, cohesive or easily recognized minority, the usual medical and law enforcement statistics are of little assistance in assessing the extent of non-medical use.

47. It has been frequently said that in Canada, the supply of barbiturates lawfully manufactured or imported greatly exceeds the requirements of legitimate medical use. It appears that many current non-medical users were initiated into barbiturate use for medical reasons. Numerous medical users develop dependence and continue use long after the original medical purpose or prescription is absent, and there are indications that most chronic barbiturate users obtain the drugs through legitimate channels.98 Since many physicians do not adequately maintain or monitor prescription records, a patient may be able to arrange an increase in the frequency and/or quantity of drug prescribed. In addition, many chronic barbiturate (and other prescription drug) users obtain 'legitimate' prescriptions from a number of different doctors simultaneously, without the physicians' awareness.79 Because of these patterns, the distinction between medical and non-medical use of barbiturates is often particularly difficult. Essentially all of the medical and non-medical barbiturate supply in Canada is legitimately and professionally manufactured; 'home-made' versions have not been identified.

Medical Use

48. Barbiturates are commonly used in medical practice today and it would seem likely that many households have had first-hand experience with them. Most of the medical uses are based on the sedative, hypnotic, and anti-convulsant effects of the drugs. Barbiturates are widely prescribed where a general depression of nervous system activity is desired. In low doses, they are widely used as day-time sedatives or tranquillizers. The hypnotic effect of these drugs is familiar to thousands of Canadians who use barbiturates in higher dose in the form of the common sleeping pill. Barbiturates are also often administered alone, and in conjunction with other drugs, as anaesthetics in surgical and related medical situations; but they are poor analgesics if used alone. The anti-convulsant effects of certain barbiturates have been very important in the treatment of acute convulsions associated with drug dependence withdrawal symptoms, various neurological disorders (including epilepsy), and poisoning due to the overdose of such stimulants as strychnine, nicotine and cocaine.

Other medical applications include diagnosis and attempted therapy of certain psychiatric disorders. In these instances the drug is usually administered intravenously in a dose adjusted to keep the patient in a semi-conscious state in which inhibitions are reduced and various suppressed and emotionally charged material may be released. This procedure is essentially that used in the so-called 'truth serum' application in criminal investigations. This effect, then, is really just a carefully monitored dose-response to ordinary short-acting barbiturates and, while this procedure frequently results in information different from that communicated normally, there is little evidence that it really exposes the 'truth' as such.

Administration, Absorption, Distribution and Physiological Fate

49. In crystalline form, barbiturates are odourless, white or yellow powders, with a slightly bitter taste. They are available as powders, elixirs, injections, suppositories, capsules or tablets (both in sustained and delayed release forms). They are frequently marketed for medical use in mixtures with other drugs, such as other sedatives or tranquillizers, analgesics, belladonna alkaloids (e.g., atropine or scopolamine), various stimulants (e.g., amphetamine or caffeine), vitamins and various gastrointestinal agents.

Barbiturates are usually administered orally for both medical and non-medical purposes and are readily and efficiently absorbed by the stomach, small intestine, and rectum. Absorption is more rapid on an empty stomach than if the drug is taken immediately after eating. Both intramuscular and intravenous injections are also effective, but they are more prone to physiological complication and are generally avoided except for special purposes. While most chronic dependent users take barbiturates orally, those who are experienced with self-injections (e.g., opiate narcotic or amphetamine dependents) may use the intravenous route.

After absorption into the bloodstream, barbiturates are initially distributed rather uniformly throughout the body, with the latency of the psychological response being partly a function of the facility of the particular drug in entering the brain. The body eliminates barbiturate activity in several ways. Most barbiturates are broken down or metabolized in the liver into relatively inactive substances which are excreted by the kidney in the urine, along with various quantities of the unaltered drug. Temporary binding of drug molecules by plasma and tissue protein soon after distribution, plus the affinity of certain barbiturates for body tissue fats, may further shorten the initial central nervous system (CNS) effects (and possibly prolong other more subtle reactions). The preceding factors of metabolism, excretion, and distribution are largely responsible for the differences in potency and duration of action among the different barbiturates. Acute and chronic barbiturate use can be identified from blood and urine samples. 198

Psychological Effects

50. Many of the psychological and behavioural effects of hypnotic doses of barbiturates are quite similar to the alcohol inebriation syndrome and consequently do not need much elaboration. While the drug user may be able to discriminate between the alcohol and barbiturate states subjectively, it is extremely difficult to tell the difference from the user's behaviour.

Although high doses invariably produce behavioural sedation, drowsiness, and sleep, the effects of mailer quantities may be quite unpredictable. As with alcohol and other sedatives, barbiturates may initially produce behavioural excitation, stimulation and lack of inhibition (especially at low doses), rather than sedation, depending on the situation and the individual. In certain persons, sedation is not produced until a considerable quantity has been administered, whereas other psychological and behavioural effects may be quite pronounced. The user may become happy, pleasant, euphoric or 'mellow' on one extreme, or possibly hostile, suspicious, aggressive and violent on the other. Emotional depression, self-pity, and withdrawal are also not uncommon, and barbiturate-related suicides are frequently reported. Although low-dose effects are often erratic, moderate to high doses generally slow down reaction time, impair complicated mental functions, and produce a lessening of inhibition, a reduction in emotional control, and an impairment of physical co-ordination as well as a variety of other effects resembling alcohol inebriation. Acute toxic psychoses are rare. The extreme variability in response, even within the same individual over a short period of time, is illustrated by Wikler's report.243

After intravenous injection of 0.25 to 1.0gm of amobarbital, a subject may fall asleep if he lies in bed undisturbed, yet he may be awake and voluble if interviewed by a psychiatrist, or he may exhibit ataxia on attempting to walk back to his bed, but he may 'sober up' promptly when instructed to pose for a motion picture demonstration of ataxia.

51. Frequent mention is made of a phenomenon called 'drug automatism', associated with toxic barbiturate overdose, although, many observers have expressed doubts as to its significance. In this situation, the individual, in a drug-induced state of confusion or stupor, is said to administer additional doses of the drug without being fully aware of the previous administration.148

52. Although it appears certain that driving skills would be diminished by barbiturate intoxication, little direct investigation has been conducted. Related behavioural studies do suggest such an effect. Low therapeutic doses may not reduce driving ability, however, if the drug is not taken in conjunction with other sedatives such as alcohol.72

53. On the basis of existing evidence it would appear that the long-term psychological effects of moderate barbiturate use are negligible for most users. Some of the complications of chronic high-dose use will be dealt with later.

Physiological Effects

54. The short-term effect of moderate to high doses of barbiturates is a general depression of neural and muscular activity. As with psychological and behavioural effects, the response to low dose is much more variable. Initially, the electroencephalogram (EEG) may suggest cortical activation, although this pattern is usually soon replaced by signs of drowsiness or sleep. The sleep induced by hypnotic doses generally resembles normal sleep with the exception of a marked reduction in the rapid eye movement (REM) stage, the significance of which is only beginning to be understood. Drowsiness or 'hangover' symptoms may follow acute intoxication or drug-induced sleep. Although the sedative action of the barbiturates has frequently been attributed to their effects on the reticular activating system of the brain, little is known of the specific details, and this action might occur through a variety of different pharmacological mechanisms.

A variety of other transient or temporary physiological changes may occur with moderate barbiturate use; the majority of these apparently reflect a general 'slowing down' of physiological activity (in the respiratory, cardiovascular and other systems) normally occurring with behavioural sedation, and are of little clinical significance. After even chronic non-medical use there is generally a fairly complete recovery of psychological and physiological capabilities following withdrawal instances of permanent psychological or neurological disorder, or of irreversible liver or kidney damage are rarely reported. This is a rather surprising picture in light of the vast number of disabilities attributed to chronic alcoholism and the general pharmacological similarities between alcohol and the barbiturates. It may be significant to note here that persons physically dependent on barbiturates seem to be more likely to maintain a reasonable state of nutrition than do chronic alcoholics.

The toxic or poisoned state induced by barbiturate over-dose is characterized by coma, a general shock syndrome (e.g., weak rapid pulse, low blood pressure and cold sweaty skin) and may result in death due to respiratory arrest, cardiovascular collapse or kidney failure. If the over-dose is not fatal, a temporary jaundice due to impaired liver function is likely to follow and skin reactions may result. Some of these responses will also occur to normal doses in individuals allergic to or abnormally sensitive to the barbiturates. Because of the well documented additive or potentiating effects (as well as cross-tolerance) among the sedatives, users of related drugs, such as alcohol, must be especially attentive to dose levels.

Tolerance and Dependence

55. Tolerance to some of the effects of barbiturates can be demonstrated, although the degree and rate of tolerance acquisition varies considerably with the dose, frequency of administration and the individual. The potential for tolerance is much lower with barbiturates than with the opiate narcotics, and appears to level off at a maximum of 1.0 - 2.5gm. per day. (A normal sleep-inducing dose might be around 0.1 - 0.3gm.) While this loss of drug sensitivity is quite general and applies to both sedative and mood effects, no tolerance appears to develop to the lethal toxicity level since chronic users are as susceptible to fatal over-doses as are initiates. In other words, the safety margin decreases with increased tolerance. Several mechanisms operate in producing tolerance. Barbiturates stimulate the body's production of the metabolic enzymes which inactivate the drug. Also, some insensitivity to the depressant effects appears which might reflect a general neurological adaptation. Certain learning processes are also probably involved in changing the character of the response upon repeated administrations. Most aspects of tolerance disappear after a few weeks of abstinence from the drug.

Although barbiturates were not recognized as 'addictive' drugs for decades after their general medical acceptance and usage, in chronic users, physical dependence may develop along with tolerance. Barbiturate dependence is in some respects similar to opiate narcotic dependence, although barbiturate (and alcohol) withdrawal symptoms are frequently more severe and are more likely to result in death. The abstinence syndrome following withdrawal of the drug in chronic heavy users may begin with a reduction in intoxication and an apparent improvement in condition. Within a few hours, however, general physical weakness, dizziness, anxiety, tremors, hyperactivity, nausea, abdominal cramps and vomiting may occur. These may be followed after one-and-one-half to five days by muscle spasms and grand mal (epileptic) seizures. Between the third and seventh day, delusions and hallucinations may appear; this psychosis may last for days or even months although recovery usually occurs within a week or two. Death during the convulsive phase occasionally occurs. 111, 89

56. The full picture of barbiturate withdrawal only appears after heavy chronic use, and the effects of abstinence following more moderate consumption are considerably less severe, and may manifest only a few of the classic symptoms. Many regular users of therapeutic doses develop neither significant tolerance nor physical dependence. As is the case with alcohol and opiate narcotics, babies born of mothers physically dependent on barbiturates are also physically dependent on the same drugs.

Psychological dependence also occurs in some users, and anxious or tense individuals may become dependent on even small doses in order to function in a manner which they consider satisfactory. Many persons depend upon the hypnotic effects of the barbiturates and can not sleep without a pill. In other individuals, the drug may be depended upon for a variety of subjective effects which the user considers essential to his well-being. The problem of psychological and behavioural dependence on barbiturates has not been adequately explored, however, and remains in the area of clinical impression and conjecture.

Barbiturates and Other Drugs

57. Because of the many similarities between barbiturates and other sedatives, they are often used interchangeably. A certain amount of cross-tolerance exists among these drugs, and chronic users of barbiturates are generally quite resistant to many of the effects of alcohol, minor tranquillizers and volatile anaesthetics, as well. This cross-tolerance, however, does not appear to affect the lethal dose, and large quantities of alcohol and barbiturates taken simultaneously (acting in an additive fashion) may produce a toxic or fatal reaction. In addition, the sedative drugs have the capacity to be substituted for each other in diminishing withdrawal symptoms, and barbiturates are frequently used therapeutically to reduce the severity of withdrawal in alcoholics. Since the sedatives show this cross-dependence, individuals dependent on one may turn to other sedatives if the supply of the preferred drug is restricted. Consequently, chronic barbiturate dependents are usually heavy alcohol users as well. Such multiple users often refer to the barbiturate intoxication as a 'dry drunk'. Barbiturates have the advantage of producing inebriation without the obvious odour of alcohol.

The relationship between barbiturates and the opiate narcotics is more complicated. These drugs may not show significant cross-tolerance, although barbiturates can be useful in the treatment of opiate narcotic withdrawal symptoms and may effectively reduce the unpleasantness of the abstinence syndrome. The drugs do interact in some sort of complementary way since barbiturates are frequently, used by opiate narcotic dependents to strengthen or reinforce a weak heroin dose or as a substitute in an emergency. Many opiate users, however, avoid barbiturates and consider the barbiturate-dependent person to be at the bottom of the 'addict' community, together with the alcoholics.

  1. Barbiturates are often used in conjunction with amphetamines. Dexamyl*, for example, is a combination of dextroamphetamine and amobarbital which supposedly produces stimulation without certain of the irritation or tension-producing effects of the amphetamines. More important clinically, is the frequently noted alternating cycle of sedation and stimulation which many medical and non-medical drug users demonstrate. A stimulant may be used to overcome the drowsy hangover the day after a hypnotic dose of barbiturate. By evening, another sedative dose may be necessary to overcome the insomnia potentiated by the day's amphetamine. This continuing cycle is apparently not at all uncommon among otherwise socially respectable drug users. A somewhat related pattern has been demonstrated by some amphetamine injecting 'speed freaks' who use barbiturates to terminate the stimulant effect or produce sleep after a 'high' of several days' duration.

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