Sex differences in the self-administration of cannabinoids and other drugs of abuse

Many studies have provided evidence for important sex-dependent differences in the origins, outcomes and treatment of drug abuse and dependence. Preclinical studies typically have employed animal models of addiction, such as oral or intravenous self-administration, to untangle the environmental, neurobiological and genetic factors that contribute to the shift from occasional, recreational use to compulsive, uncontrolled intake of drugs. Craving and relapse of drug seeking in abstinent individuals have also been found to differ between men and women. Identification of the neurobiological basis of craving and drug dependence continues to pose a challenge to addiction research. Significant sex differences are emerging in substance-abuse-related behavior, which has increased the demand for research on how drug consumption may have different causes, progression and consequences in men and women. In keeping with epidemiological data in humans, differences between the two sexes in drug seeking and intake have been well-documented in animal studies, with most recent findings related to abuse of cannabinoids. Clinical and preclinical findings indicate that sex and gonadal hormones may account for individual differences in susceptibility to the reinforcing effects of addictive substances, and that differences in vulnerability to drug abuse may be mediated by the same biological mechanisms. This review focuses on the differences between males and females in relation to drug self-administration and how such behavior may be affected by hormonal status.