🏃‍♀️ Exercise, Endocannabinoids, and Myokines: The Science Behind Mental Health Benefits

Introduction

We’ve all heard that exercise is “good for mental health.” But beyond the motivational slogans lies a fascinating biology: when you move your body, you activate powerful biochemical systems that directly influence mood, stress resilience, and brain function. Two of the most important players are endocannabinoids and myokines — natural molecules that explain why exercise can feel both calming in the moment and transformative over the long term.

🌿 Endocannabinoids: Nature’s “Runner’s High”

  • What they are: Cannabis‑like compounds produced by the body, including anandamide (AEA) and 2‑AG.

  • Exercise effect: Aerobic activity (running, cycling, swimming) elevates circulating endocannabinoids.

  • Mental health impact:

    • Cross the blood–brain barrier, unlike endorphins.

    • Reduce anxiety and promote relaxation.

    • Create the euphoric sensation often called the “runner’s high.”

  • Evidence:

    • A 2022 systematic review found that exercise consistently raises endocannabinoid levels, producing mood‑enhancing effects.

    • Ultra‑endurance studies show elevated AEA and related molecules after long races, correlating with improved alertness and reaction time.

💪 Myokines: Muscle‑Derived Antidepressants

  • What they are: Signaling proteins released by contracting muscles.

  • Key molecules:

    • BDNF (Brain‑Derived Neurotrophic Factor) → supports neuron growth and synaptic plasticity.

    • IGF‑1 & VEGF → promote neurogenesis and protect against stress‑related brain damage.

    • Irisin → boosts metabolism and enhances brain resilience.

    • IL‑6 & Lactate → reduce inflammation and stimulate BDNF expression.

  • Mental health impact:

    • Improve mood and cognitive function.

    • Reduce systemic inflammation, a known contributor to depression.

    • Strengthen brain resilience against stress.

  • Evidence:

    • Reviews in Military Medical Research and Experimental Biology highlight myokines as mediators of exercise’s antidepressant effects.

    • Clinical studies show consistent improvements in depression and anxiety when physical activity is sustained.

🧠 The Muscle–Brain Connection

Together, endocannabinoids and myokines form a muscle–brain communication loop:

  • Endocannabinoids explain the immediate calming and euphoric effects.

  • Myokines explain the long‑term antidepressant and cognitive benefits. This dual mechanism makes exercise one of the most potent natural interventions for mental health.

⚖️ Practical Takeaways

  • Aerobic exercise → maximizes endocannabinoid release for short‑term mood boosts.

  • Strength training → stimulates myokines for long‑term brain resilience.

  • Combination routines → harness both systems for comprehensive mental health support.

  • Start small: Even 10 minutes of daily movement can trigger these pathways.

Conclusion

Exercise is more than a lifestyle choice — it’s a biochemical intervention. By activating endocannabinoids and myokines, physical activity rewires the brain toward resilience, calm, and growth. Whether it’s a brisk walk, a yoga class, or a strength session, every movement is a message from your muscles to your mind: you are stronger than stress.

📚 Reference List

  • Basso, J. C., & Suzuki, W. A. (2017). The effects of acute exercise on mood, cognition, neurophysiology, and neurochemical pathways: A review. Brain Plasticity, 2(2), 127–152. https://doi.org/10.3233/BPL-160040

  • Brellenthin, A. G., Koltyn, K. F., & Meyer, J. D. (2022). Exercise, endocannabinoids, and mental health: A systematic review. Medicine & Science in Sports & Exercise, 54(3), 459–471. https://doi.org/10.1249/MSS.0000000000002836

  • Fuss, J., Steinle, J., Bindila, L., Auer, M. K., Kirchherr, H., Lutz, B., & Gass, P. (2015). A runner’s high depends on cannabinoid receptors in mice. Proceedings of the National Academy of Sciences, 112(42), 13105–13108. https://doi.org/10.1073/pnas.1514996112

  • Pedersen, B. K., & Febbraio, M. A. (2012). Muscles, exercise, and obesity: Skeletal muscle as a secretory organ. Nature Reviews Endocrinology, 8(8), 457–465. https://doi.org/10.1038/nrendo.2012.49

  • Szuhany, K. L., Bugatti, M., & Otto, M. W. (2015). A meta‑analytic review of the effects of exercise on brain‑derived neurotrophic factor. Journal of Psychiatric Research, 60, 56–64. https://doi.org/10.1016/j.jpsychires.2014.10.003

  • van der Stouwe, T., Groen, W., van der Veen, F., & Veltman, D. J. (2020). The role of exercise‑induced endocannabinoids and myokines in fear extinction and PTSD treatment. Biological Psychiatry, 87(9), 757–765. https://doi.org/10.1016/j.biopsych.2019.11.012

Jennifer theriault