The effects of progesterone pretreatment on the response to oral d-amphetamine in Women

Stimulant abuse continues to be a problem, particularly for women. There is increasing preclinical and clinical evidence showing that the hormone progesterone attenuates the behavioral effects of cocaine, and this effect is primarily observed in females. The purpose of the present study was to determine if progesterone would also alter the behavioral effects of another stimulant, oral d-amphetamine (AMPH) in women. Eighteen normal non-drug abusing women completed eight outpatient sessions over two menstrual cycles. During the follicular phase of each cycle, women were administered AMPH (0, 10, 20 mg); in one cycle they were pretreated with oral micronized progesterone (200 mg) and in another cycle they were pretreated with placebo progesterone. Each session, participants completed a range of tasks including subjective measures of abuse liability, cognitive performance tasks, and behavioral measures of impulsivity and risk-taking. AMPH produced dose-related increases in positive subjective effects and these effects were enhanced by progesterone pretreatment. AMPH alone, or in combination with progesterone, had little effect on performance or behavioral measures of impulsivity. These results are in contrast with previous studies showing that progesterone attenuates the subjective response to cocaine and nicotine. Additional studies are needed to explore the modulatory role of progesterone on the effects of AMPH to determine whether progesterone has any clinical utility for AMPH abuse.