Differential subjective effects of D-amphetamine by gender, hormone levels and menstrual cycle phase

Estrogen and progesterone interact with monoamines in ways that suggest the potential modulation of responses to psychoactive drugs by endogenous steroids, both between menstrual phases and between the sexes. The present study assessed the subjective and physiological effects of a single dose of D-amphetamine (AMPH; 15 mg oral) in healthy, normally cycling women (n=13), who received amphetamine and placebo (PL) during both the follicular and luteal phases of a single menstrual cycle, and in healthy men (n=7). Females reported greater amphetamine-induced subjective stimulation [Addiction Research Center Inventory (ARCI)-A, ARCI-MBG; Drug Effects Questionnaire (DEQ) Feel Drug, Feel High, Want More] during the follicular phase than the luteal phase. Within the follicular phase, the magnitude of individuals' AMPH-induced stimulation was positively associated with baseline (predrug) salivary estradiol [r=+.55-.78; Profile of Mood States (POMS) Vigor, Positive Mood, Elation], and negatively associated with salivary progesterone [r=-.66-.68; POMS Friendliness; Subjective States Questionnaire (SSQ) Pleasant Sedation]. Sex differences also emerged. Males reported feeling greater AMPH-induced stimulation (ARCI-A, ARCI-MBG; DEQ Feel Drug, Want More) than females in the luteal phase. Thus, higher levels of estrogen and lower levels of progesterone are associated with greater subjective stimulation after AMPH in women, and these hormonal influences contribute to sex differences in amphetamine responding.