A runner's high depends on cannabinoid receptors in mice
Open accessAbstract
Exercise is rewarding, and long-distance runners have described a runner's high as a sudden pleasant feeling of euphoria, anxiolysis, sedation, and analgesia. A popular belief has been that endogenous endorphins mediate these beneficial effects. However, running exercise increases blood levels of both β-endorphin (an opioid) and anandamide (an endocannabinoid). Using a combination of pharmacologic, molecular genetic, and behavioral studies in mice, we demonstrate that cannabinoid receptors mediate acute anxiolysis and analgesia after running. We show that anxiolysis depends on intact cannabinoid receptor 1 (CB1) receptors on forebrain GABAergic neurons and pain reduction on activation of peripheral CB1 and CB2 receptors. We thus demonstrate that the endocannabinoid system is crucial for two main aspects of a runner's high. Sedation, in contrast, was not influenced by cannabinoid or opioid receptor blockage, and euphoria cannot be studied in mouse models.
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Exercise-induced elevations of endocannabinoid levels have been proposed to account partially for anxiolytic, anti-nociceptive and neuroprotective properties of exercise.
“Exerciseinduced elevations of endocannabinoid levels have been proposed to account partially for anxiolytic (Tantimonaco et al., 2014;Fuss et al., 2015), anti-nociceptive (Galdino et al., 2014) and neuroprotective (Hill et al., 2010a) properties of exercise, which are all responses that instead are affected in a negative direction by sleep loss (e.g.Roy-Byrne et al., 1986;Schuh-Hofer et al., 2013;”
From Sleep restriction alters plasma endocannabinoids concentrations before but not after exercise in humans (2016) · cites this paper as Fuss et al., 2015
In mice, central and peripheral CB1 and CB2 receptors are necessary for inducing anxiolysis and analgesia after running.
“Indeed, recent research suggests that at least in mice, central and peripheral CB1 and CB2 receptors are necessary for inducing anxiolysis and analgesia after running (Fuss et al., 2015).”
From Sleep restriction alters plasma endocannabinoids concentrations before but not after exercise in humans (2016) · cites this paper as Fuss et al., 2015
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Running increases cell proliferation and neurogenesis in the adult mouse dentate gyrus
van Praag, H., Kempermann, G., & Gage, F. H. (1999) · Nature Neuroscience · doi:10.1038/6368 · Cited by 3,880 · see citing works
The Neuroendocrinology of Stress: A Never Ending Story
Lightman, S. L. (2008) · Journal of Neuroendocrinology · doi:10.1111/j.1365-2826.2008.01711.x · Cited by 3,570 · see citing works
Running enhances neurogenesis, learning, and long-term potentiation in mice
van Praag, H., Christie, B. R., Sejnowski, T. J., & Gage, F. H. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.23.13427 · Cited by 2,904 · see citing works
Adult hippocampal neurogenesis buffers stress responses and depressive behaviour
Snyder, J. S., Soumier, A., Brewer, M., Pickel, J., & Cameron, H. A. (2011) · Nature · doi:10.1038/nature10287 · Cited by 1,473 · see citing works
The Endocannabinoid System Controls Key Epileptogenic Circuits in the Hippocampus
Monory, K., Massa, F., Egertová, M., Eder, M., Blaudzun, H., Westenbroek, R., Kelsch, W., Jacob, W., Marsch, R., Ekker, M., et al. (2006) · Neuron · doi:10.1016/j.neuron.2006.07.006 · Cited by 706 · see citing works
Self-citationThe Runner's High: Opioidergic Mechanisms in the Human Brain
Boecker, H., Sprenger, T., Spilker, M. E., Henriksen, G., Koppenhoefer, M., Wagner, K. J., Valet, M., Berthele, A., & Tolle, T. R. (2008) · Cerebral Cortex · doi:10.1093/cercor/bhn013 · Cited by 527 · see citing works
Carr, D. B., Bullen, B. A., Skrinar, G. S., Arnold, M. A., Rosenblatt, M., Beitins, I. Z., Martin, J. B., & McArthur, J. W. (1981) · New England Journal of Medicine · doi:10.1056/nejm198109033051006 · Cited by 372 · see citing works
Exercise activates the endocannabinoid system
Sparling, P. B., Giuffrida, A., Piomelli, D., Rosskopf, L., & Dietrich, A. (2003) · Neuroreport · doi:10.1097/00001756-200312020-00015 · Cited by 313 · see citing works
Raichlen, D. A., Foster, A. D., Gerdeman, G. L., Seillier, A., & Giuffrida, A. (2012) · Journal of Experimental Biology · doi:10.1242/jeb.063677 · Cited by 269 · see citing works
Gatley, S. J., Gifford, A. N., Volkow, N. D., Lan, R., & Makriyannis, A. (1996) · European Journal of Pharmacology · doi:10.1016/0014-2999(96)00279-8 · Cited by 252 · see citing works
Fuss, J., Ben Abdallah, N. M. ‐., Vogt, M. A., Touma, C., Pacifici, P. G., Palme, R., Witzemann, V., Hellweg, R., & Gass, P. (2010) · Hippocampus · doi:10.1002/hipo.20634 · Cited by 240 · see citing works
Self-citationCluny, N. L., Vemuri, K. V., Chambers, A., Limebeer, C. L., Bedard, H., Wood, J., Lutz, B., Zimmer, A., Parker, L., Makriyannis, A., et al. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2010.00908.x · Cited by 194 · see citing works
Self-citationMcLaughlin, P. J., Winston, K. M., Swezey, L. A., Wisniecki, A., Aberman, J., Tardif, D. J., Betz, A. J., Ishiwari, K., Makriyannis, A., & Salamone, J. D. (2003) · Behavioural Pharmacology · doi:10.1097/00008877-200312000-00002 · Cited by 164 · see citing works
Lomazzo, E., Bîndilă, L., Remmers, F., Lerner, R., Schwitter, C., Hoheisel, U., & Lutz, B. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.198 · Cited by 141 · see citing works
Self-citationHill, M. N., Titterness, A. K., Morrish, A. C., Carrier, E. J., Lee, T. T. ‐., Gil‐Mohapel, J., Gorzalka, B. B., Hillard, C. J., & Christie, B. R. (2009) · Hippocampus · doi:10.1002/hipo.20647 · Cited by 129 · see citing works
Alterations in the Hippocampal Endocannabinoid System in Diet-Induced Obese Mice
Massa, F., Mancini, G., Schmidt, H., Steindel, F., Mackie, K., Angioni, C., Oliet, S. H. R., Geißlinger, G., & Lutz, B. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.2648-09.2010 · Cited by 105 · see citing works
Self-citationComparison of Potency and Duration of Action of Nalmefene and Naloxone
Glass, P. S. A., Jhaveri, R., & Smith, L. (1994) · Anesthesia & Analgesia · doi:10.1213/00000539-199403000-00021 · Cited by 96 · see citing works
Ventral Tegmental Area Cannabinoid Type-1 Receptors Control Voluntary Exercise Performance
Dubreucq, S., Durand, A., Matias, I., Bénard, G., Richard, É. M., Gómez, E. S., Glangetas, C., Groc, L., Wadleigh, A., Massa, F., et al. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.10.025 · Cited by 95 · see citing works
The endocannabinoid system mediates aerobic exercise-induced antinociception in rats
Galdino, G. S., Romero, T. R. L., Silva, J. F. P., de Aguiar, D. C., de Paula, A. M., Cruz, J. S., Parrella, C., Piscitelli, F., Duarte, I. D. G., Marzo, V. D., et al. (2013) · Neuropharmacology · doi:10.1016/j.neuropharm.2013.09.022 · Cited by 88 · see citing works
Fuß, J., & Gass, P. (2010) · Experimental Neurology · doi:10.1016/j.expneurol.2010.03.016 · Cited by 46 · see citing works
Self-citationFuß, J., Vogt, M. A., Weber, K.-J., Burke, T. F., Gass, P., & Hensler, J. G. (2013) · Synapse · doi:10.1002/syn.21666 · Cited by 28 · see citing works
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Kandola, A., Ashdown-Franks, G., Hendrikse, J., Sabiston, C. M., & Stubbs, B. (2019) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.09.040 · Cited by 1,309 · see citing works
Mikkelsen, K., Stojanovska, L., Polenakovic, M., Bosevski, M., & Apostolopoulos, V. (2017) · Maturitas · doi:10.1016/j.maturitas.2017.09.003 · Cited by 1,072 · see citing works
Mandolesi, L., Polverino, A., Montuori, S., Foti, F., Ferraioli, G., Sorrentino, P., & Sorrentino, G. (2018) · Frontiers in Psychology · doi:10.3389/fpsyg.2018.00509 · Cited by 1,038 · see citing works
Basso, J. C., & Suzuki, W. A. (2016) · Brain Plasticity · doi:10.3233/bpl-160040 · Cited by 911 · see citing works
Nakagawa, T., Koan, I., Chen, C., Matsubara, T., Hagiwara, K., Lei, H., Hirotsu, M., Yamagata, H., & Nakagawa, S. (2020) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph17020614 · Cited by 124 · see citing works
Yu, Q., Wong, K.-K., Lei, O.-K., Nie, J., Shi, Q., Zou, L., & Kong, Z. (2022) · Sports Medicine - Open · doi:10.1186/s40798-022-00529-5 · Cited by 80 · 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
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- Authors
- Fuss, J., Steinle, J., Bindila, L., Auer, M. K., Kirchherr, H., Lutz, B., & Gass, P.
- Affiliations
- Heidelberg University (DE)
- Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, 55099 Mainz, Germany;
- Max Planck Institute of Psychiatry (DE)
- Medizinisches Labor Bremen, 28357 Bremen, Germany
- University Medical Center of the Johannes Gutenberg University Mainz (DE)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2015-10-05
- Volume
- 112
- Issue
- 42
- Pages
- 13105-13108
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4620874
- OpenAlex
- W2122443470
- Cited by
- 229
- References
- 21
- Citations by year
- 2026: 23 · 2025: 17 · 2024: 29 · 2023: 16 · 2022: 20 · 2021: 25 · 2020: 23 · 2019: 23 · 2018: 15 · 2017: 19 · 2016: 19
- FWCI
- 12.70
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Deutsche Forschungsgemeinschaft (SFB636, FOR926)
- Topics
- Health Sciences › Medicine › Pharmacology › Cannabis and Cannabinoid Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- runner's high, cannabinoid receptors, endocannabinoid system, anxiolysis, analgesia, CB1 receptor, CB2 receptor, GABAergic neurons, forebrain, anandamide, beta-endorphin, opioid receptors, sedation, euphoria
- MeSH terms
- Animals, Behavior, Animal, Male, Mice, Inbred C57BL, Physical Conditioning, Animal, Running, Receptor, Cannabinoid, CB1, Receptor, Cannabinoid, CB2, Mice
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