Pharmacological Adjuncts in the Treatment of Opioid and Cocaine Addicts

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Abstract
Addiction consists of a complex neuropharmacologic behavioral cycle. The positive reinforcement of the drug and the negative reinforcement of withdrawal serve to drive the behavior of obtaining and ingesting the drug. The pharmacological adjuncts that are available today work by interfering with one or another part of the cycle. The alpha 2-adrenergic agonists, such as clonidine and guanabenz, act to block noradrenergic activity in the locus coeruleus and therefore block the negative reinforcement of opioid withdrawal. Naltrexone, on the other hand, works by preventing the positive reinforcement of administered opioids by preventing them from binding to the opioid receptor. In the case of cocaine addiction, most of the adjuncts currently in use focus on decreasing the severity of the immediate withdrawal symptoms. These agents potentiate dopaminergic transmission and in so doing tend to counter the dopamine depletion effect of prolonged cocaine use. Bromocriptine is the best known and probably the most effective member of this class. It may be that neuroleptics or naltrexone will prove to decrease reinforcement of cocaine use. However, the hazards of long-term neuroleptic use make it unlikely that they will be widely used for this purpose. Desipramine and perhaps other antidepressants may have a special role in treating cocaine addiction: They may prove to have some long-term prophylactic value and prevent relapse in recovering addicts. This ability may stem from the antidepressant action or it may involve a more specific action on dopaminergic transmission. These pharmacological agents may be very effective for certain purposes, such as relieving withdrawal symptoms. However, since they only act on one part of the addiction cycle, they can never be considered complete treatment by themselves. Of course, the use of all of these agents requires the voluntary cooperation of the patient. Therefore, the basis of the treatment of addictive illness continues to be the peer group and other types of interpersonal interactions. However, these pharmacological adjuncts may serve to make treatment easier, shorter and less expensive, and they may improve overall success rates. Consequently, they are of great value in the present and they can serve as models for the development of more effective agents in the future.