Barbiturates

The barbiturates relieve tension and anxiety at low dose levels without causing drowsiness, although some tendency toward drowsiness may be an initial reaction for the first few days on the drug. These drugs exert a selective action in small amounts on higher cortical (brain) centers, particularly those centers that are involved in the inhibitory or restraining mechanisms of behavior. As a consequence, there is an increase in uninhibitedness such as talkativeness and unrestricted social interaction following the taking of the drug. There is also an impairment of function at low dose levels. All the barbiturates are capable of inducing sleep when given in sufficient amounts. They do not affect the perception of pain as do the analgesics, but they do alter the individual’s response to pain (e.g., decreasing his anxiety) and are useful in this regard. Infrequently, the barbiturates produce undesirable reactions ranging from simple nervousness, anxiety, nausea, and diarrhea to mental confusion, euphoria, and delirium. Some tolerance is developed to these drugs, but no physical dependence occurs in the drug range (100 to 200 mg) normally employed clinically. Prolonged use may lead to drug habituation and psychic dependence. When the drug is used chronically in higher amounts (400 mg per day), physical dependence may develop. Sudden withdrawal of a barbiturate following chronic use is frequently associated with withdrawal symptoms that are more severe than those produced by the opiates. A barbiturate should never be withdrawn abruptly following long continued use. The barbiturate addict shows many of the symptoms associated with chronic alcoholism, including blackouts, irrationality, slurred speech, poor motor coordination, emotional deterioration, mood swings, and psychosis.

Cocaine

Cocaine is an alkaloid derived from the leaves of the coca plant (Erythroxylon coca), a bush that is natural to Bolivia, Chile, and Peru along the western slopes of the Andes Mountains. Cocaine has a pronounced excitant action on the central nervous system and, in small doses, produces a pleasurable state of well-being associated with relief from fatigue, increased mental alertness, physical strength, and a reduction of hunger. In greater amounts, cocaine is an intoxicant that produces excitement, mental confusion, and convulsions. The Incas were acquainted with the ability of cocaine to produce euphoria, hyperexcitability, and hallucinations; the practice of chewing the coca leaf as part of religious ceremonials was an established custom at the time of the Spanish conquest in the 16th century. The natives who worked the mines high in the Andes chewed coca leaves for increased strength and endurance. Coca plants are under cultivation in Sri Lanka, India, and Java. The alkaloid, tropacocaine, is chemically related to cocaine and is obtained from the Java coca plant.

Cocaine is habit-forming and may also be physically addicting in some individuals, but not to the extent of the opiates. Only certain persons display abstinence symptoms on withdrawal. Significant physiological tolerance does not develop. Chronic use is associated with severe personality disturbances, inability to sleep, loss of appetite, emaciation, an increased tendency to violence, and antisocial acts. When a toxic psychosis develops, it is characteristically accompanied by paranoid delusions. Hallucinations are prominent with continued use of cocaine, particularly the tactile hallucinations that give the impression that bugs are under the skin. The drug is a white crystalline powder in pure form and the practice of “snuffing” cocaine was common in Europe at the turn of the 20th century. It is less potent when taken by mouth. When injected by vein the effects are rapid in onset, intense, but of short duration. This is followed by a correspondingly deep depression that prompts the user to repeat the dose to restore the sense of well-being. Cocaine is sometimes mixed with heroin to dampen any extreme excitability produced by the cocaine. The great number of undesired effects that come on continued use frequently prompts the cocaine user to turn to other drugs.

Amphetamines

These stimulants are of three types having closely related actions on the nervous system: amphetamine proper (Benzedrine), one of its isomers (Dexedrine), and methamphetamine (Methedrine). The amphetamines have been used to alleviate depression, fatigue, the hyperkinetic behavior disturbances of children, postencephalitic parkinsonism, enuresis, nausea of pregnancy, and obesity. More recently, the amphetamines have been used in combination with one of the barbiturates, such as amobarbital or phenobarbital, to produce mood elevating effects. It is the effects of the amphetamines on mood that have led to their widespread abuse. A toxic psychosis with hallucinations and paranoid delusions may be produced by a single dose as low as 50 mg if no drug tolerance is present. Although the normal lethal dose for adult humans is estimated to be around 900 mg, habitual use may increase adult tolerance up to 1,000 mg per day.

The ability of amphetamine to produce a psychosis having paranoid features was first reported in 1938, shortly after its introduction as a central stimulant. Sporadic reports of psychosis followed, and in 1958, a monograph on the subject of amphetamine psychosis included these statements:

Psychosis associated with amphetamine usage is much more frequent than would be expected from the reports in the literature.…The clinical picture is primarily a paranoid psychosis with ideas of reference, delusions of persecution, auditory and visual hallucinations in a setting of clear consciousness.…The mental picture may be indistinguishable from acute or chronic paranoid schizophrenia.…Patients with amphetamine psychosis recover within a week unless there is demonstrable cause for continuance of symptoms; e.g., continued excretion of the drug or hysterical prolongation of symptoms.

There have been subsequent attempts to distinguish between amphetamine psychosis and paranoid schizophrenia. Whatever the outcome, amphetamine induces a psychosis that comes closer to mimicking schizophrenia than any of the other drugs of abuse, including LSD. Some behavioral symptoms such as loss of initiative, apathy, and emotional blunting may persist long after the patient stops taking the drug. Methamphetamine was used extensively by the Japanese during World War II, and by 1953 the habitual users of the drug in Japan numbered about 500,000 persons. This large-scale usage created such a serious social problem that the amphetamines were placed under governmental control in Japan in 1954. This Japanese experience provided the opportunity for systematic studies on chronic methamphetamine intoxication. One group of 492 addicts who had been institutionalized showed a 14 percent rate of chronic psychosis with evidence of permanent organic brain damage. In the language of the street, “Meth is death.” The amphetamines produce habituation, drug dependency, physiological tolerance, and toxic effects, but no physical addiction.

Tranquilizers

Serendipity has played a major role in the discovery of tranquilizers (as it has in all facets of medicine). Tranquilizers were unknown to medical science until the middle of the 20th century, when the therapeutic value of reserpine and chlorpromazine in psychiatry was discovered by chance. Reserpine was originally derived in the 1930s from Rauwolfia serpentina, a woody plant that grows in the tropical areas of the world, but it has since been synthesized. Because this drug has many undesirable side effects such as low blood pressure, ulcers, weakness, nightmares, nasal congestion, and depression, however, it has been largely replaced in psychiatric practice by chlorpromazine (Thorazine) and a number of other phenothiazine derivatives synthesized in the 1950s. These phenothiazines are inexpensive, easily available, produce little immediate pleasurable effects, can usually be taken in large amounts without harm, and are not physically addicting. They are used extensively in the treatment of various hyperactive and agitated states, and as antipsychotic agents. These drugs, however, may produce jaundice, dermatitis, or, infrequently, convulsive seizures, and they do not combine well with the drinking of alcohol. Chlorpromazine is effective in reversing “bad trips” such as an LSD-induced panic reaction, but it tends to strengthen rather than reverse the powerful hallucinogenic effects of STP (DOM).

There is a second group of drugs, inappropriately called minor tranquilizers, that has achieved popularity in the management of milder psychiatric conditions, particularly anxiety and tension. The major form is meprobamate (Miltown, Equanil). Although these minor tranquilizers are considered to be entirely safe in terms of side effects, they do produce serious complications, for they are commonly associated with habituation and psychological dependence. Heavy, prolonged use may result in physical dependence and severe withdrawal symptoms including insomnia, tremors, hallucinations, and convulsions.