Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Mayo LM

PROVIDER: S-EPMC6695366 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Publications

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

Mayo Leah M LM Paul Elisabeth E DeArcangelis Jessica J Van Hedger Kathryne K de Wit Harriet H

Psychopharmacology 20190605 8

<h4>Rationale</h4>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.<h4>Objective</h4>We examined gender differences in the acute ef ...[more]

PMID: 31165207

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Project description:Prescription psychostimulants produce rapid changes in mood, energy, and attention. These drugs are widely used and abused. However, their effects in human neocortex on glutamate and glutamine (pooled as Glx), and key neurometabolites such as N-acetylaspartate (tNAA), creatine (tCr), choline (Cho), and myo-inositol (Ins) are poorly understood. Changes in these compounds could inform the mechanism of action of psychostimulant drugs and their abuse potential in humans. We investigated the acute impact of two FDA-approved psychostimulant drugs on neurometabolites using magnetic resonance spectroscopy (1H MRS). Single clinically relevant doses of d-amphetamine (AMP, 20?mg oral), methamphetamine (MA, 20 mg oral; Desoxyn®), or placebo were administered to healthy participants (n?=?26) on three separate test days in a placebo-controlled, double-blinded, within-subjects crossover design. Each participant experienced all three conditions and thus served as his/her own control. 1H MRS was conducted in the dorsal anterior cingulate cortex (dACC), an integrative neocortical hub, during the peak period of drug responses (140-150?m post ingestion). D-amphetamine increased the level of Glu (p?=?.0001), Glx (p?=?.003), and tCr (p?=?.0067) in the dACC. Methamphetamine increased Glu in females, producing a significant crossover interaction pattern with gender (p?=?.02). Drug effects on Glu, tCr, and Glx were positively correlated with subjective drug responses, predicting both the duration of AMP liking (Glu: r?=?+.49, p?=?.02; tCr: r?=?+.41, p?=?.047) and the magnitude of peak drug high to MA (Glu: r?=?+.52, p?=?.016; Glx: r?=?+.42, p?=?.049). Neither drug affected the levels of tNAA, Cho, or Ins after correction for multiple comparisons. We conclude that d-amphetamine increased the concentration of glutamate, Glx, and tCr in the dACC in male and female volunteers 21/2 hours after drug consumption. There was evidence that methamphetamine differentially affects dACC Glu levels in women and men. These findings provide the first experimental evidence that specific psychostimulants increase the level of glutamatergic compounds in the human brain, and that glutamatergic changes predict the extent and magnitude of subjective responses to psychostimulants.

Dataset Information

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

Rationale

Objective

Methods

Results

Conclusions

Publications

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

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