Pharmacotherapy, current and potential, for the treatment of cocaine dependence

Before the 1980s, cocaine was viewed as producing a psychological, rather than physiological, dependence. Treatment of cocaine addiction was concentrated primarily on psychological intervention. There is now an improved understanding of the impact of long-term cocaine use on neurophysiological adaptation. Cocaine appears to exert its reinforcing effects through dopamine reuptake inhibition. The role of the five dopamine- receptor subtypes in this process is still under exploration. This new knowledge, coupled with the failure of many patients to respond to psychological treatment, has intensified the search for medications that reduce cocaine craving and abuse. There has been an acceleration of such research in the past decade; more than 30 agents have been investigated, and more than 100 reports have been published. These trials have yielded contradictory results, and, in some cases, the study designs have been inadequate. New agents with different mechanisms of action are being investigated, and they may yield better results. For progress to be made in the pharmacotherapy of cocaine abuse, future trials must be adequately designed with regard to dose and duration of medication, and nonpharmacological interventions must also be rigorously defined. Outcome criteria must be specific and objective. The diversity of the population of cocaine abusers suggests that different medications may be needed for different subgroups of patients. Until more effective pharmacotherapies are developed, it may be necessary to accept the use of agents that diminish, rather than eliminate, cocaine use.