Exercise as a Prevention for Substance Use Disorder: A Review of Sex Differences and Neurobiological Mechanisms

Abstract

Purpose of review: This report provides an update on clinical and preclinical findings for the efficacy of exercise to prevent substance use disorder with a focus on recent evidence for sex differences and neurobiological mechanisms.

Recent findings: Exercise/physical activity is associated with decreased drug use in humans. Preclinical results further indicate that exercise decreases vulnerability to drug use and the development of features of substance use disorder, and suggest that females have an enhanced sensitivity to its reward-substitution effects. However, certain exercise conditions may sensitize the reward pathway and enhance vulnerability suggesting that parallel observations in humans (e.g., increased prescription opioid misuse and heroin use in high-school athletes) may be biologically-based.

Summary: Exercise is a promising prevention strategy for substance use disorder. Further work is needed to establish its efficacy as a sex-specific strategy using larger samples, and to understand the exercise conditions that induce beneficial versus risk-enhancing effects.

Keywords: acquisition; addiction; animal models; biological mechanisms; clinical; drug use escalation; drug use initiation; exercise; gender differences; gonadal hormones; intervention; physical activity; preclinical; prevention; sex differences; sex-specific; substance use disorder.