Exercise activates the endocannabinoid system
Open accessAbstract
Extensive documentation exists showing that exercise induces analgesia and sedation. Despite decades of research attempting to explicate a neurochemical basis for these phenomena, the mechanism underlying these changes is unknown. Using trained male college students running on a treadmill or cycling on a stationary bike for 50 min at 70-80% of maximum heart rate, we report here the first evidence that exercise of moderate intensity activates the endocannabinoid system, suggesting a new mechanism for exercise-induced analgesia and possibly other physiological and psychological adaptations to exercise.
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Plasma 2AG concentrations show a trend to increase following exercise but do not reach statistical significance.
“In the same study, plasma 2AG concentrations showed a similar trend to increase following exercise, but failed to reach statistical significance (Sparling et al., 2003).”
From Sleep restriction alters plasma endocannabinoids concentrations before but not after exercise in humans (2016) · cites this paper as Sparling et al., 2003
One hour of moderate intensity exercise increases plasma AEA concentrations in young males.
“Finally, a study involving 24 young males demonstrated that 1 h of moderate intensity exercise increased plasma AEA concentrations.”
From Sleep restriction alters plasma endocannabinoids concentrations before but not after exercise in humans (2016) · cites this paper as Sparling et al., 2003
Studies using acute physical exercise as stressor found an increase of plasma AEA but not 2AG.
“Studies utilizing acute physical exercise as stressor have however found different responses, i.e., an increase of plasma concentrations of AEA but not 2AG (Heyman et al., 2012;Raichlen et al., 2013;Sparling et al., 2003).”
From Sleep restriction alters plasma endocannabinoids concentrations before but not after exercise in humans (2016) · cites this paper as Sparling et al., 2003
Cites
1 retracted
Ahluwalia, J., Yaqoob, M., Urbán, L., Bevan, S., & Nagy, I. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01550.x · Cited by 82 · see citing works
RetractedA second endogenous cannabinoid that modulates long-term potentiation
Stella, N., Schweitzer, P., & Piomelli, D. (1997) · Nature · doi:10.1038/42015 · Cited by 1,496 · see citing works
Self-citationControl of pain initiation by endogenous cannabinoids
Calignano, A., Rana, G. L., Giuffrida, A., & Piomelli, D. (1998) · Nature · doi:10.1038/28393 · Cited by 1,055 · see citing works
Self-citationGlass, M., Faull, R. L. M., & Dragunow, M. (1997) · Neuroscience · doi:10.1016/s0306-4522(96)00428-9 · Cited by 1,052 · see citing works
Behavioral Effects of Cannabinoid Agents in Animals
Chaperon, F., & Thiébot, M.-H. (1999) · Critical Reviews in Neurobiology · doi:10.1615/critrevneurobiol.v13.i3.20 · Cited by 311 · see citing works
Quantification of Bioactive Acylethanolamides in Rat Plasma by Electrospray Mass Spectrometry
Giuffrida, A., de Fonseca, F. R., & Piomelli, D. (2000) · Analytical Biochemistry · doi:10.1006/abio.2000.4509 · Cited by 163 · see citing works
Self-citationHohmann, A. G., Tsou, K., & Walker, J. M. (1999) · Journal of Neurophysiology · doi:10.1152/jn.1999.81.2.575 · Cited by 126 · see citing works
Cannabinoids modulate pain by multiple mechanisms of action
Richardson, J. D. (2000) · The Journal of Pain · doi:10.1016/s1526-5900(00)90082-8 · Cited by 109 · see citing works
β-endorphin (1-31) in the plasma of male volunteers undergoing physical exercise
Harbach, H., Hell, K., Gramsch, C., Katz, N., Hempelmann, G., & Teschemacher, H. (2000) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(00)00009-3 · Cited by 48 · cited 1× · see citing works
“INTRODUCTION Physical exercise is known to suppress pain and induce sedation [1], but with the demise of the endorphin hypothesis [2,3], these remarkable changes lack a sound mechanistic explanation.”
BackgroundCook, D., & Koltyn, K. F. (2000) · International journal of sport psychology · Cited by 39 · see citing works
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Physical Activity and Mental Health: Current Concepts
Paluska, S. A., & Schwenk, T. L. (2000) · Sports Medicine · doi:10.2165/00007256-200029030-00003 · Cited by 1,722 · see citing works
Basso, J. C., & Suzuki, W. A. (2016) · Brain Plasticity · doi:10.3233/bpl-160040 · Cited by 911 · see citing works
Exercise and Mental Health: Many Reasons to Move
Deslandes, A., Moraes, H., Ferreira, C., Veiga, H., Silveira, H., Mouta, R., Pompeu, F. A. M. S., Coutinho, E. S. F., & Laks, J. (2009) · Neuropsychobiology · doi:10.1159/000223730 · Cited by 609 · see citing works
The Antidepressive Effects of Exercise: A Meta-Analysis of Randomized Trials
Rethorst, C. D., Wipfli, B. M., & Landers, D. M. (2009) · Sports Medicine · doi:10.2165/00007256-200939060-00004 · Cited by 541 · see citing works
Garland, T., Schutz, H., Chappell, M. A., Keeney, B. K., Meek, T. H., Copes, L. E., Acosta, W., Drenowatz, C., Maciel, R. C., van Dijk, G., et al. (2011) · Journal of Experimental Biology · doi:10.1242/jeb.048397 · Cited by 444 · see citing works
Heyman, E., Gamelin, F.-X., Goekint, M., Piscitelli, F., Roelands, B., Leclair, E., Di Marzo, V., & Meeusen, R. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2011.09.017 · Cited by 427 · see citing works
Dietrich, A., & McDaniel, W. F. (2004) · British Journal of Sports Medicine · doi:10.1136/bjsm.2004.011718 · Cited by 410 · see citing works
Self-citationThe reticular-activating hypofrontality (RAH) model of acute exercise
Dietrich, A., & Audiffren, M. (2011) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2011.02.001 · Cited by 365 · see citing works
Self-citationLessons in exercise neurobiology: the case of endorphins.
Dishman, R. K., & O'Connor, P. J. (2009) · Mental health and physical activity · doi:10.1016/j.mhpa.2009.01.002 · Cited by 243 · see citing works
A runner's high depends on cannabinoid receptors in mice
Fuss, J., Steinle, J., Bindila, L., Auer, M. K., Kirchherr, H., Lutz, B., & Gass, P. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1514996112 · Cited by 229 · see citing works
Exercise-induced endocannabinoid signaling is modulated by intensity
Raichlen, D. A., Foster, A. D., Seillier, A., Giuffrida, A., & Gerdeman, G. L. (2013) · European Journal of Applied Physiology · doi:10.1007/s00421-012-2495-5 · Cited by 181 · see citing works
Self-citationMotion Sickness, Stress and the Endocannabinoid System
Choukèr, A., Kaufmann, I., Kreth, S., Hauer, D., Feuerecker, M., Thieme, D., Vogeser, M., Thiel, M., & Schelling, G. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010752 · Cited by 140 · see citing works
Davis, M. L., Powers, M. B., Handelsman, P., Medina, J. L., Zvolensky, M., & Smits, J. A. J. (2015) · Evaluation & the Health Professions · doi:10.1177/0163278714529970 · Cited by 114 · see citing works
Physical activity and the endocannabinoid system: an overview
Tantimonaco, M., Ceci, R., Sabatini, S., Catani, M. V., Rossi, A., Gasperi, V., & Maccarrone, M. (2014) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-014-1575-6 · Cited by 112 · see citing works
Ota, K. T., & Duman, R. S. (2013) · Neurobiology of Disease · doi:10.1016/j.nbd.2012.05.022 · Cited by 94 · see citing works
Galdino, G., Romero, T., Pinho da Silva, J. F., Aguiar, D., de Paula, A. M., Cruz, J., Parrella, C., Piscitelli, F., Duarte, I., Di Marzo, V., et al. (2014) · Anesthesia & Analgesia · doi:10.1213/ane.0000000000000340 · Cited by 72 · see citing works
Wood, J. T., Williams, J. S., Pandarinathan, L., Courville, A., Keplinger, M. R., Janero, D. R., Vouros, P., Makriyannis, A., & Lammi-Keefe, C. J. (2008) · Clinical Chemistry and Laboratory Medicine · doi:10.1515/cclm.2008.242 · Cited by 71 · see citing works
Aggarwal, S. K. (2013) · The Clinical Journal of Pain · doi:10.1097/ajp.0b013e31824c5e4c · Cited by 62 · see citing works
Cedernaes, J., Fanelli, F., Fazzini, A., Pagotto, U., Broman, J.-E., Vogel, H., Dickson, S. L., Schiöth, H. B., & Benedict, C. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.09.014 · Cited by 59 · see citing works
Do Endocannabinoids Cause the Runner’s High? Evidence and Open Questions
Siebers, M., Biedermann, S. V., & Fuss, J. (2023) · The Neuroscientist · doi:10.1177/10738584211069981 · Cited by 46 · see citing works
- Authors
- Sparling, P. B., Giuffrida, A., Piomelli, D., Rosskopf, L., & Dietrich, A.
- Affiliations
- Georgia Institute of Technology (US)
- Venue
- Neuroreport
- Published
- 2003-12
- Volume
- 14
- Issue
- 17
- Pages
- 2209-2211
- ISSN
- 0959-4965 (ISSN-L)
- OpenAlex
- W1979315934
- Cited by
- 313
- References
- 10
- Citations by year
- 2026: 12 · 2025: 18 · 2024: 12 · 2023: 20 · 2022: 19 · 2021: 22 · 2020: 19 · 2019: 22 · 2018: 14 · 2017: 16 · 2016: 17 · 2015: 14 · 2014: 17 · 2013: 13 · 2012: 12
- FWCI
- 1.93
- Type
- journal article
- Language
- en
- Open access
- green
- escholarship.org
- Licence
- cc-by
- Locations
- Neuroreport (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
- Keywords
- endocannabinoid system, physical activity, exercise-induced analgesia, sedation, moderate-intensity exercise, treadmill running, stationary cycling, exercise adaptation, neurochemical mechanisms
- MeSH terms
- Adolescent, Adult, Analysis of Variance, Arachidonic Acids, Exercise Test, Humans, Male, Exercise, Polyunsaturated Alkamides, Cannabinoid Receptor Modulators, Endocannabinoids
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