Exercise as a Sex-Specific Treatment for Substance Use Disorder

Abstract

Purpose of Review Exercise is a promising treatment for substance use disorder that may reduce withdrawal symptoms and prevent relapse. In this review, we discuss recent evidence from clinical and preclinical studies for its efficacy, from a behavioral to a molecular level, in order to understand the exercise conditions that lead to beneficial effects. We also highlight the few recent findings of sex-specific differences. Recent Findings Clinical and preclinical findings show that exercise decreases withdrawal symptoms, including craving, in both males and females. Evidence from clinical studies support the efficacy of exercise to prevent relapse to smoking, although further research is needed to examine sex differences, establish long-term efficacy, and to determine if effects extend to other substance use disorders. Preclinical findings also support the potential utility of exercise to prevent relapse with evidence suggesting that its efficacy is enhanced in males, and mediated by blocking drug-induced adaptations that occur during early abstinence. Summary Sex differences and timing of exercise availability during abstinence should be considered in future studies examining exercise as an intervention for relapse. A better understanding of the neurobiological mechanisms underlying the efficacy of exercise to reduce withdrawal symptoms and prevent relapse is needed to guide its development as a sex-specific treatment.

Effects of voluntary exercise and sex on multiply-triggered heroin reinstatement in male and female rats

“…Rather, it appears that drug-and cue-primed reinstatement functioned as an establishing operation (Michael 1982) that increased the reinforcing efficacy of wheel running in female rats. Collectively, the results of the present study add to a growing body of literature on exercise as an effective treatment for drug abuse (e.g., Zlebnik et al 2010;Lynch et al 2017). For human drug abusers, these results suggest a benefit of voluntary physical activity to reduce drug-seeking and increase the likelihood of an individual to engage in physical activity instead of relapsing into drug abuse.…”

“…In the present study, there was no relationship between the change in active lever responses from the control to priming session and the number of wheel revolutions during the priming session in either sex. This lack of concordance has also been found in the past by several other studies that employed either inor out-of-session wheel access and all reported a lack of correlation between wheel revolutions and drug-seeking behavior (Smith and Pitts 2012;Zlebnik et al 2014a;Zlebnik and Carroll 2015b; see review by Lynch et al 2017). One potential explanation is that the time spent in the running wheel is a better predictor of the treatment effects rather than the intensity (i.e., revolutions/min).…”

“…Physical activity (i.e., exercise) has emerged as a treatment for drug abuse (see reviews by Bardo and Compton 2015;Lynch et al 2017). The majority of human studies have examined exercise to treat tobacco dependence, and they have generally found that exercise reduces nicotine withdrawal symptoms and craving severity (Haasova et al 2013), and it can produce abstinence levels comparable to standard smoking cessation treatments (Zschucke et al 2012).…”

Mechanisms underlying the efficacy of exercise as an intervention for cocaine relapse: a focus on mGlu5 in the dorsal medial prefrontal cortex

“…Exercise shows promise as a non-pharmacological intervention for addiction in both humans and animal models (Lynch et al 2017;Wang et al 2014a). In humans, exercise during abstinence reduces craving for cocaine and other drugs of abuse (Abrantes et al 2011;Wang et al 2014a), and recent findings provide preliminary support for its ability to reduce relapse (De La Garza et al 2016;Trivedi et al 2017).…”

Effects of a Dosed Exercise Intervention in Craving and Anhedonia: A Secondary Analysis from the STRIDE-CTN 0037 Clinical Trial

“…These results have motivated to develop more studies in polysubstance users, however such studies are currently in conduction (Ellingsen, Johannesen, Martinsen, Dahl, & Hallgren, 2020). In addition to these studies, preclinical evidence suggest that participant characteristics such as age and gender could be associated with the positive results of exercise in craving (Lynch, Abel, Robinson, & Smith, 2017).…”