Exercise as a Prevention for Substance Use Disorder: a Review of Sex Differences and Neurobiological Mechanisms
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.
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.
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.
KeywordsAcquisition Addiction Animal models Biological mechanisms Clinical Drug use initiation Drug use escalation Exercise Gender differences Gonadal hormones Intervention Physical activity Preclinical Prevention Sex differences Sex-specific Substance use disorder
Wendy J Lynch is supported by grants from National Institute on Drug Abuse (grants no. R01DA024716 and R01DA039093). Mark A. Smith is supported by a grant from the National Institute on Drug Abuse (grant no. DA031725).
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance
- 1.Greer TL, Ring KM, Warden D, Grannemann BD, Church TS, Somoza E, Blair SN, Szapocznik J, Stoutenberg M, Rethorst C, Walker R, Morris DW, Kosinski AS, Kyle T, Marcus B, Crowell B, Oden N, Nunes E, Trivedi MH. Rationale for using exercise in the treatment of stimulant use disorders. J Glob Drug Policy Pract. 2012;6(1).Google Scholar
- 7.Tabak I, Mazur J, Zawadzka D. Physical activity as a factor protecting teenage boys from tobacco and marihuana use. Przegl Epidemio. 2015;69(4):795-800–19-22.Google Scholar
- 9.• Engelmann AJ, Aparicio MB, Kim A, Sobieraj JC, Yuan CJ, Grant Y, et al. Chronic wheel running reduces maladaptive patterns of methamphetamine intake: regulation by attenuation of methamphetamine-induced neuronal nitric oxide synthase. Brain Struct Funct. 2014;219(2):657–72. This study showed that terminating exercise sessions prior to methamphetamine self-administration training enhanced rates of acquisition in rats that had a history of unlimited voluntary wheel running indicating that certain exercise conditions enhance vulnerability to drugs of abuse. PubMedCrossRefGoogle Scholar
- 10.Lynch WJ, Abel J, Robinson AM, Smith MA. Part II: exercise as a treatment for substance use disorder: a review of sex differences and neurobiological mechanisms. Curr Addict Reports, (2017) In Press.Google Scholar
- 12.• Veliz P, Boyd CJ, McCabe SE. Nonmedical use of prescription opioids and heroin use among adolescents involved in competitive sports. J Adolesc Health. 2017;60(3):346–9. This study showed high-school participation in certain sports where risk of injury is high (e.g., football, ice hockey, lacrosse, and wrestling) and is associated with increased prescription opioid misuse and heroin. PubMedCrossRefGoogle Scholar
- 18.Gray KM, Squeglia LM. What have we learned about adolescent substance use? J Child Psychol Psychiatry. 2017. https://doi.org/10.1111/jcpp.12783.
- 25.Veliz P, Boyd CJ, McCabe SE. Nonmedical prescription opioid and heroin use among adolescents who engage in sports and exercise. Pediatrics. 2016;138(2) https://doi.org/10.1542/peds.2016-0677.
- 31.World Health Organization. Global recommendations on physical activity for health. Geneva: World Health Organization; 2010. Report No.: 9789241599979Google Scholar
- 38.Darlington TM, McCarthy RD, Cox RJ, Miyamoto-Ditmon J, Gallego X, Ehringer MA. Voluntary wheel running reduces voluntary consumption of ethanol in mice: identification of candidate genes through striatal gene expression profiling. Genes Brain Behav. 2016;15(5):474–90.PubMedPubMedCentralCrossRefGoogle Scholar
- 42.Smith MA, Witte MA. The effects of exercise on cocaine self-administration, food-maintained responding, and locomotor activity in female rats: importance of the temporal relationship between physical activity and initial drug exposure. Exp Clin Psychopharmacol. 2012;20(6):437–46.PubMedPubMedCentralCrossRefGoogle Scholar
- 62.Toy WA, Petzinger GM, Leyshon BJ, Akopian GK, Walsh JP, Hoffman MV, et al. Treadmill exercise reverses dendritic spine loss in direct and indirect striatal medium spiny neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson’s disease. Neurobiol Dis. 2014;63:201–9.PubMedCrossRefGoogle Scholar
- 72.Roberts MD, Ruegsegger GN, Brown JD, Booth FW. Mechanisms associated with physical activity behavior: insights from rodent experiments. Exerc Sport Sci Rev. 2017;45(4):217–222.Google Scholar
- 76.Paukste E, Harris N. Using rap music to promote adolescent health: pilot study of VoxBox. Health Promot J Austr. 2015;26(1):24-6–8-9.Google Scholar
- 77.Schaus JF, Sole ML, McCoy TP, Mullett N, O’Brien MC. Alcohol screening and brief intervention in a college student health center: a randomized controlled trial. J Stud Alcohol Drugs Suppl. 2009;(16):131–41.Google Scholar