Sex- and gender-related differences in the neurobiology of drug abuse

Sex-related responses to drugs of abuse add an important dimension to the larger issue of gender-related differences in epidemiology, prevention strategies and treatment. One of the most important factors in collecting such data is controlling for the many demographic, behavioral, physiological, and hormonal differences that exist between mates and females as these may influence the direct effects of a drug and contribute to a progression from use to abuse to dependence. There are a number of factors that make studying female subjects more challenging. Aside from the obvious hormonal and menstrual cycle differences, there are a variety of gender-related issues that are unique to women and alter the drug abuse profile of certain drugs, regardless of the pharmacological effect. Studies have revealed that the pharmacokinetic profiles (secondary to route of administration) may alter the responses to cocaine and may help explain some of the male/female differences that have been observed, especially via the intranasal route. Sex differences appear to be minimal when cocaine is administered i.v. or by inhalation suggesting that rate of absorption may play an important role in the acute effects of cocaine. In summary, difficulties in conducting studies with females can be overcome with careful planning, time and additional expense. Using controlled laboratory studies, important pharmacokinetic and pharmacodynamic differences in drug effects may modulate male/female expectations about psychoactive drug effects and ultimately play a role in the etiology of drug abuse, dependence and how treatment programs should be structured. Finally, the application of new brain imaging techniques has the potential to reveal the mechanism of these sex-related differences. (c) 2005 Published by Elsevier B.V. on behalf of Association for Research in Nervous and Mental Disease.