A Systematic Review and Meta-Analysis on the Effects of Exercise on the Endocannabinoid System

Overview

Journal Cannabis Cannabinoid Res

Specialty Pharmacology

Date 2021 Dec 6

PMID 34870469

Citations 15

Authors

Shreya Desai

Breanna Borg

Carrie Cuttler

Kevin M Crombie

Christine A Rabinak

Matthew N Hill

Hilary A Marusak

Affiliations

Soon will be listed here.

Abstract

The endocannabinoid (eCB) system plays a key role in maintaining homeostasis, including the regulation of metabolism and stress responses. Chronic stress may blunt eCB signaling, and disruptions in eCB signaling have been linked to stress-related psychiatric disorders and physical health conditions, including anxiety, depression, post-traumatic stress disorder (PTSD), diabetes, and obesity. Pharmacological and nonpharmacological behavioral interventions (e.g., exercise) that target the eCB system may be promising therapeutic approaches for the prevention and treatment of stress-related diseases. In this study, we perform a systematic review and the first meta-analysis to examine the impact of exercise on circulating eCB concentrations. We performed a review of the MEDLINE (PubMed) database for original articles examining the impact of exercise on eCBs in humans and animal models. A total of 262 articles were screened for initial inclusion. Thirty-three articles (reporting on 57 samples) were included in the systematic review and 10 were included in the meta-analysis. The majority of samples that measured anandamide (AEA) showed a significant increase in AEA concentrations following acute exercise (74.4%), whereas effects on 2-arachidonoylglycerol (2-AG) were inconsistent. The meta-analysis, however, revealed a consistent increase in both AEA and 2-AG following acute exercise across modalities (e.g., running, cycling), species (e.g., humans, mice), and in those with and without pre-existing health conditions (e.g., PTSD, depression). There was substantial heterogeneity in the magnitude of the effect across studies, which may relate to exercise intensity, physical fitness, timing of measurement, and/or fasted state. Effects of chronic exercise were inconsistent. Potential interpretations and implications of exercise-induced mobilization of eCBs are discussed, including refilling of energy stores and mediating analgesic and mood elevating effects of exercise. We also offer recommendations for future work and discuss therapeutic implications for exercise in the prevention and treatment of stress-related psychopathology.

Citing Articles

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Endurance Exercise Training Alters Lipidomic Profiles of Plasma and Eight Tissues in Rats: a MoTrPAC study.

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Exercise and PTSD.

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Endocannabinoids and Stress-Related Neurospsychiatric Disorders: A Systematic Review and Meta-Analysis of Basal Concentrations and Response to Acute Psychosocial Stress.

Gowatch L, Evanski J, Ely S, Zundel C, Bhogal A, Carpenter C Cannabis Cannabinoid Res. 2024; 9(5):1217-1234.

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References

Castillo P, Younts T, Chavez A, Hashimotodani Y . Endocannabinoid signaling and synaptic function. Neuron. 2012; 76(1):70-81. PMC: 3517813. DOI: 10.1016/j.neuron.2012.09.020. View

Feuerecker M, Hauer D, Toth R, Demetz F, Holzl J, Thiel M . Effects of exercise stress on the endocannabinoid system in humans under field conditions. Eur J Appl Physiol. 2011; 112(7):2777-81. DOI: 10.1007/s00421-011-2237-0. View

Zou S, Kumar U . Cannabinoid Receptors and the Endocannabinoid System: Signaling and Function in the Central Nervous System. Int J Mol Sci. 2018; 19(3). PMC: 5877694. DOI: 10.3390/ijms19030833. View

Cabral G, Griffin-Thomas L . Emerging role of the cannabinoid receptor CB2 in immune regulation: therapeutic prospects for neuroinflammation. Expert Rev Mol Med. 2009; 11:e3. PMC: 2768535. DOI: 10.1017/S1462399409000957. View

King-Himmelreich T, Moser C, Wolters M, Schmetzer J, Schreiber Y, Ferreiros N . AMPK contributes to aerobic exercise-induced antinociception downstream of endocannabinoids. Neuropharmacology. 2017; 124:134-142. DOI: 10.1016/j.neuropharm.2017.05.002. View

Wolf S, Bick-Sander A, Fabel K, Leal-Galicia P, Tauber S, Ramirez-Rodriguez G . Cannabinoid receptor CB1 mediates baseline and activity-induced survival of new neurons in adult hippocampal neurogenesis. Cell Commun Signal. 2010; 8:12. PMC: 2898685. DOI: 10.1186/1478-811X-8-12. View

Tanner M, Hake H, Bouchet C, Greenwood B . Running from fear: Exercise modulation of fear extinction. Neurobiol Learn Mem. 2018; 151:28-34. PMC: 6557445. DOI: 10.1016/j.nlm.2018.03.021. View

Stensson N, Grimby-Ekman A . Altered relationship between anandamide and glutamate in circulation after 30 min of arm cycling: A comparison of chronic pain subject with healthy controls. Mol Pain. 2019; 15:1744806919898360. PMC: 6964246. DOI: 10.1177/1744806919898360. View

Patel S, Roelke C, Rademacher D, Hillard C . Inhibition of restraint stress-induced neural and behavioural activation by endogenous cannabinoid signalling. Eur J Neurosci. 2005; 21(4):1057-69. DOI: 10.1111/j.1460-9568.2005.03916.x. View

10.

Mayo L, Asratian A, Linde J, Morena M, Haataja R, Hammar V . Elevated Anandamide, Enhanced Recall of Fear Extinction, and Attenuated Stress Responses Following Inhibition of Fatty Acid Amide Hydrolase: A Randomized, Controlled Experimental Medicine Trial. Biol Psychiatry. 2019; 87(6):538-547. DOI: 10.1016/j.biopsych.2019.07.034. View

11.

Mechoulam R, Parker L . The endocannabinoid system and the brain. Annu Rev Psychol. 2012; 64:21-47. DOI: 10.1146/annurev-psych-113011-143739. View

12.

Charytoniuk T, Zywno H, Konstantynowicz-Nowicka K, Berk K, Bzdega W, Chabowski A . Can Physical Activity Support the Endocannabinoid System in the Preventive and Therapeutic Approach to Neurological Disorders?. Int J Mol Sci. 2020; 21(12). PMC: 7352563. DOI: 10.3390/ijms21124221. View

13.

Forteza F, Giorgini G, Raymond F . Neurobiological Processes Induced by Aerobic Exercise through the Endocannabinoidome. Cells. 2021; 10(4). PMC: 8072750. DOI: 10.3390/cells10040938. View

14.

Koltyn K, Brellenthin A, Cook D, Sehgal N, Hillard C . Mechanisms of exercise-induced hypoalgesia. J Pain. 2014; 15(12):1294-1304. PMC: 4302052. DOI: 10.1016/j.jpain.2014.09.006. View

15.

Sparling P, Giuffrida A, Piomelli D, Rosskopf L, Dietrich A . Exercise activates the endocannabinoid system. Neuroreport. 2003; 14(17):2209-11. DOI: 10.1097/00001756-200312020-00015. View

16.

Nakagawa T, Koan I, Chen C, Matsubara T, Hagiwara K, Lei H . Regular Moderate- to Vigorous-Intensity Physical Activity Rather Than Walking Is Associated with Enhanced Cognitive Functions and Mental Health in Young Adults. Int J Environ Res Public Health. 2020; 17(2). PMC: 7014044. DOI: 10.3390/ijerph17020614. View

17.

Crombie K, Leitzelar B, Brellenthin A, Hillard C, Koltyn K . Loss of exercise- and stress-induced increases in circulating 2-arachidonoylglycerol concentrations in adults with chronic PTSD. Biol Psychol. 2019; 145:1-7. DOI: 10.1016/j.biopsycho.2019.04.002. View

18.

Kendall D, Yudowski G . Cannabinoid Receptors in the Central Nervous System: Their Signaling and Roles in Disease. Front Cell Neurosci. 2017; 10:294. PMC: 5209363. DOI: 10.3389/fncel.2016.00294. View

19.

Fernandez-Aranda F, Sauchelli S, Pastor A, Gonzalez M, de la Torre R, Granero R . Moderate-vigorous physical activity across body mass index in females: moderating effect of endocannabinoids and temperament. PLoS One. 2014; 9(8):e104534. PMC: 4125187. DOI: 10.1371/journal.pone.0104534. View

20.

McPartland J, Guy G, Di Marzo V . Care and feeding of the endocannabinoid system: a systematic review of potential clinical interventions that upregulate the endocannabinoid system. PLoS One. 2014; 9(3):e89566. PMC: 3951193. DOI: 10.1371/journal.pone.0089566. View