Gender differences in the behavioral and subjective effects of methamphetamine in healthy humans

Rationale Methamphetamine (MA) use is steadily increasing and thus constitutes a major public health concern. Women seem to be particularly vulnerable to developing MA use disorder, as they initiate use at a younger age and transition more quickly to problematic use. Initial drug responses may predict subsequent use, but little information exists on potential gender differences in the acute effects of MA prior to dependence. Objective We examined gender differences in the acute effects of MA on subjective mood and reward-related behavior in healthy, non-dependent humans. Methods Men (n = 44) and women (n = 29) completed 4 sessions in which they received placebo or MA under double-blind conditions twice each. During peak drug effect, participants completed the monetary incentive delay task to assess reaction times to cues signaling potential monetary losses or gains, in an effort to determine if MA would potentiate reward-motivated behavior. Cardiovascular and subjective drug effects were assessed throughout sessions. Results Overall, participants responded more quickly to cues predicting incentivized trials, particularly large-magnitude incentives, than to cues predicting no incentive. MA produced faster reaction times in women, but not in men. MA produced typical stimulant-like subjective and cardiovascular effects in all participants, but subjective ratings of vigor and (reduced) sedation were greater in women than in men. Conclusions Women appear to be more sensitive to the psychomotor-related behavioral and subjective effects of MA. These findings provide initial insight into gender differences in acute effects of MA that may contribute to gender differences in problematic MA use.