Abstract
This review summarizes findings from human and animal research investigating the influence of progesterone and its metabolites allopreganolone and pregnanolone (progestins) on the effects of cocaine and other drugs of abuse. Since a majority of these studies have used cocaine, this will be the primary focus; however, the influence of progestins on other drugs of abuse will also be discussed. Collectively, findings from these studies support a role for progestins in (1) attenuating the subjective and physiological effects of cocaine in humans, (2) blocking the reinforcing and other behavioral effects of cocaine in animal models of drug abuse, and (3) influencing behavioral responses to other drugs of abuse such as alcohol and nicotine in animals. Administration of several drugs of abuse in both human and nonhuman animals significantly increased progestin levels, and this is explained in terms of progestins acting as homeostatic regulators that decrease and normalize heightened stress and reward responses which lead to increased drug craving and relapse. The findings discussed here highlight the complexity of progestin-drug interactions, and they suggest a possible use for these agents in understanding the etiology of and developing treatments for drug abuse.