ADDICTION TO ANALGESICS AND BARBITURATES
Authors: HARRIS ISBELL, H.F. FRASER
Journal: Pharmacological Reviews (1950)

Drug addiction is a condition in which an individual has lost the power of self-control with reference to a drug and abuses the drug to such an extent that the individual, society, or both are harmed. Dependence, either physical or psychic, is not an essential feature of drug addiction.

The most important factor which predisposes to drug addiction is a personality disorder. In addition to the personality disorder, contact with a drug which produces mental reactions that are regarded as pleasurable is necessary. Contact with the drug as a result of curiosity about the pleasurable effects is a much more potent factor in inducing addiction than is contact as a result of legitimate medical administration.

Animal methods have only a limited place in determining the addiction liability of new drugs. Dogs and monkeys are the best species to use for such experiments. The final determination of the addiction liability of any new analgesic drug is dependent upon experimentation or clinical observations with human beings.

There is no drug in the morphine series which is known to be an effective analgesic that does not also possess addiction liability. The addiction liabilities of compounds of the morphine series generally parallel the analgesic potencies of the drugs. However, it is possible that some separation of addiction liability and analgesic potency has been achieved in the compound 6-methyldihydromorphine. N-allylnormorphine does not produce physical dependence in man, but it is not known whether this drug is an effective analgesic.

There are also no known compounds in either the meperidine or methadone series which do not possess addiction liability. Addiction to meperidine is fairly common and physical dependence can be developed in individuals who have never been previously addicted to any other analgesic drug. Addiction to meperidine, because of the toxic effects of the drug, is more undesirable than addiction to morphine.

Recent neurophysiological investigations have shown that the spinal cord, and probably other parts of the central nervous system, are involved in physical dependence on morphine. Physical dependence is not entirely due to changes in the autonomic nervous system.

The theory that the manifestations of abstinence are due to the stimulant effects of morphine outlasting the depressant effects is probably not tenable. The most satisfactory theory of dependence at the present time is that certain homeostatic responses, which oppose some of the actions of morphine, are enhanced by repeated administration of the drug. When morphine is withdrawn, these enhanced physiological counter-responses are still operative and, therefore, signs of abstinence appear. The mechanisms responsible for the enhancement of the homeostatic responses are unknown.

During addiction to morphine and other analgesics, the electroencephalogram is characterized by general slowing. Following withdrawal the electroencephalogram returns to normal.

It has not been established that partial tolerance to certain actions of morphine persists for long periods of time following withdrawal of the drug. Furthermore, it has not been established that individuals who have been addicted to one analgesic drug will develop physical dependence on another analgesic drug any more rapidly than a comparable individual without addiction experience.

There is no real evidence that addiction to morphine produces permanent anatomical damage to the central nervous system. Morphine addiction does not produce any permanent impairment of intelligence.

Treatment of morphine addiction involves withdrawal of the drug followed by a long period of rehabilitative and psychiatric therapy. Withdrawal of morphine is very easy to accomplish provided adequate environmental control of the addict can be achieved. The best and only rational method of withdrawal consists of the administration of decreasing doses of either morphine or some equivalent drug. The results of treatment of addiction, although not completely satisfactory, are much better than is commonly thought.

Barbiturates are addicting drugs no matter how the word addicting is defined. In fact, addiction to barbiturates is far more dangerous and harmful than is addiction to morphine or other analgesic drugs. Barbiturate addiction is apparently increasing in the United States.

The clinical picture of chronic barbiturate intoxication resembles that of chronic intoxication with alcohol and is characterized by impairment of mental ability, impairment of emotional control, psychic regression and dangerous neurological symptoms.

Withdrawal of barbiturates from individuals chronically intoxicated with those drugs is followed by a very definite and severe type of abstinence syndrome which is characterized chiefly by the appearance of convulsions and delirium.

Physical recovery from chronic barbiturate intoxication in man is, so far as can be judged by clinical and psychological examination, complete unless the addict incurs an accidental injury during chronic intoxication or during a convulsion in withdrawal.

The barbiturate abstinence syndrome has been produced experimentally in dogs.

Chronic barbiturate poisoning in animals is accompanied by definite pathological changes in the central nervous system.

The mechanism of symptoms of abstinence from barbiturates is unknown.

Treatment of chronic barbiturate intoxication consists in a very careful gradual withdrawal of the drug followed by a long period of rehabilitative and psychiatric therapy.