Human sex differences in d-amphetamine self-administration


Craig R. Rush, University of Kentucky College of Medicine, Medical Behavioral Science Building, 1100 Veterans Way, Lexington, KY 40536, USA. E-mail:


Women and men may respond differently to the effects of stimulants such as amphetamine and cocaine.

Aim  In order to assess potential sex differences in the reinforcing effects of d-amphetamine, a retrospective-analysis was conducted on data collected from three studies that employed similar d-amphetamine self-administration procedures and used identical subject-rated drug-effect measures.

Methods  Data from 10 women and 15 men were included in the analysis. In all studies, participants sampled placebo, low (8–10 mg) or high (16–20 mg) dose oral d-amphetamine. Following sampling sessions, participants worked for capsules containing one eighth of the previously sampled dose on a modified progressive-ratio schedule of reinforcement. We hypothesized that women and men would be differentially sensitive to the reinforcing effects of d-amphetamine. A two-way mixed-model analysis of variance (sex and dose) and planned comparisons were used in the statistical analyses.

Results  The low dose of d-amphetamine functioned as a reinforcer in women, but not men, whereas the high dose of d-amphetamine functioned as a reinforcer in men, but not women. Men self-administered significantly more capsules under the high dose condition than women.

Conclusion  The results of this study suggest that men are more sensitive to the reinforcing effects of a high dose of d-amphetamine than women. Future research is needed that determines prospectively the reinforcing effects of weight-adjusted doses of d-amphetamine in women and men while controlling for menstrual cycle phase.