Sex differences in methamphetamine use disorder perused from pre-clinical and clinical studies: Potential therapeutic impacts

Methamphetamine (METH) use, and misuse are associated with severe socioeconomic consequences. METH users develop tolerance, lose control over drug taking behaviors, and suffer frequent relapses even during treatment. The clinical course of METH use disorder is influenced by multifactorial METH-induced effects on the central and peripheral nervous systems. Although these METH-induced consequences are observed in humans of all ages, races, and sexes, sexual dimorphism in these outcomes have been observed in both pre-clinical and clinical settings. In this review, we have provided a detailed presentation of the sex differences reported in human and animal studies. We have therefore presented data that identified the influences of sex on METH pharmacokinetics, METH-induced changes in behaviors, cognitive processes, structural changes in the brain, and the effects of the drug on neurotransmitter systems and molecular mechanisms. Finally, we highlighted the potential significance of sex as a critical variable that should be considered when planning the development of new pharmacotherapeutic approaches against MEH use disorder in humans. •METH use is more prevalent in men who experience more emergency room visit and overdose deaths.•Women suffer from more severe lifetime METH-induced neuropsychiatric complications.•Women are more likely to respond positively to therapeutic interventions.•Female rodents exhibited more METH-induced locomotor activity.•Female animals also showed more METH seeking behaviors during drug withdrawal.