Encyclopedia of Sexuality and Gender

Living Edition
| Editors: Amy D. Lykins


Living reference work entry
DOI: https://doi.org/10.1007/978-3-319-59531-3_53-1



Endocannabinoids (eCBs) are lipid messengers, synthesized from membrane phospholipids, that act as retrograde messengers in the nervous system. The endocannabinoid system is composed by two Gi/o-coupled cannabinoid receptors (CB1 and CB2), their endogenous ligands, and the enzymes involved in their synthesis and degradation. CB receptors are expressed throughout the body; however, CB1 receptors are predominantly expressed in the central and peripheral nervous systems, while the CB2 receptor is mainly found in peripheral and brain immune cells, although recent evidence suggests its expression also in neuronal and glial cells (Xi et al., 2011). In the brain, CB1 receptors are located mainly on presynaptic GABAergic and glutamatergic terminals, where its activation decreases neurotransmitter release, while CB2 receptors are expressed at pre- and postsynaptic sites. Anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are the...

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  1. Alger, B. E., & Kim, J. (2011). Supply and demand for endocannabinoids. Trends in Neurosciences, 34, 304–315.  https://doi.org/10.1016/j.tins.2011.03.003CrossRefPubMedPubMedCentralGoogle Scholar
  2. Balon, R. (2017). Cannabis and sexuality. Current Sexual Health Reports, 9, 99–103.  https://doi.org/10.1007/s11930-017-0112-7CrossRefGoogle Scholar
  3. Canseco-Alba, A., & Rodríguez-Manzo, G. (2014). Low anandamide doses facilitate male rat sexual behaviour through the activation of CB1 receptors. Psychopharmacology, 231, 4071–4080.  https://doi.org/10.1007/s00213-014-3547-9CrossRefPubMedGoogle Scholar
  4. Canseco-Alba, A., & Rodríguez-Manzo, G. (2016). Intra-VTA anandamide infusion produces dose-based biphasic effects on male rat sexual behavior expression. Pharmacology, Biochemistry and Behavior, 150–151, 182–189.  https://doi.org/10.1016/j.pbb.2016.11.004CrossRefPubMedGoogle Scholar
  5. Canseco-Alba, A., & Rodríguez-Manzo, G. (2019a). Sexual interaction is essential for the transformation of non-copulating rats into sexually active animals by the endocannabinoid anandamide. Behavioural Brain Research, 359, 418–427.  https://doi.org/10.1016/j.bbr.2018.11.015CrossRefPubMedGoogle Scholar
  6. Canseco-Alba, A., & Rodríguez-Manzo, G. (2019b). Endocannabinoids interact with the dopaminergic system to increase sexual motivation: Lessons from the sexual satiety phenomenon. Frontiers in Behavioral Neuroscience, 13, 184.  https://doi.org/10.3389/fnbeh.2019.00184CrossRefPubMedPubMedCentralGoogle Scholar
  7. Fiorino, D. F., Coury, A., & Phillips, A. G. (1997). Dynamic changes in nucleus accumbens dopamine efflux during the Coolidge effect in male rats. The Journal of Neuroscience, 17, 4849–4855.  https://doi.org/10.1523/JNEUROSCI.17-12-04849.1997CrossRefPubMedPubMedCentralGoogle Scholar
  8. Fuss, J., Bindila, L., Wiedemann, K., Auer, M. K., Briken, P., & Biedermann, S. V. (2017). Masturbation to orgasm stimulates the release of the endocannabinoid 2-arachidonoylglycerol in humans. The Journal of Sexual Medicine, 14, 1372–1379.  https://doi.org/10.1016/j.jsxm.2017.09.016CrossRefPubMedGoogle Scholar
  9. Gardner, E. L. (2005). Endocannabinoid signaling system and brain reward: Emphasis on dopamine. Pharmacology, Biochemistry, and Behavior, 81, 263–284.  https://doi.org/10.1016/j.pbb.2005.01.032CrossRefPubMedGoogle Scholar
  10. Gorzalka, B. B., Hill, M. N., & Chang, S. C. H. (2010). Male–female differences in the effects of cannabinoids on sexual behavior and gonadal hormone function. Hormones and Behavior, 58, 91–99.  https://doi.org/10.1016/j.yhbeh.2009.08.009CrossRefPubMedGoogle Scholar
  11. Gorzalka, B. B., Morrish, A. C., & Hill, M. N. (2008). Endocannabinoid modulation of male rat sexual behavior. Psychopharmacology, 198, 479–486.  https://doi.org/10.1007/s00213-007-0901-1CrossRefPubMedGoogle Scholar
  12. Hull, E. M., & Rodríguez-Manzo, G. (2017). Male sexual behavior. In D. W. Pfaff & M. Joëls (Eds.), Hormones, brain, and behavior (3rd ed., pp. 1–57). Oxford, UK: Academic/Elsevier. ISBN 978-0-12-803592-4.  https://doi.org/10.1016/B978-0-12-803592-4.00001-8CrossRefGoogle Scholar
  13. Klein, C., Hill, M. N., Chang, S. C., Hillard, C. J., & Gorzalka, B. B. (2012). Circulating endocannabinoid concentrations and sexual arousal in women. The Journal of Sexual Medicine, 9, 1588–1601.  https://doi.org/10.1111/j.1743-6109.2012.02708.xCrossRefPubMedGoogle Scholar
  14. López, H. H. (2010). Cannabinoid–hormone interactions in the regulation of motivational processes. Hormones and Behavior, 58, 100–110.  https://doi.org/10.1016/j.yhbeh.2009.10.005CrossRefPubMedGoogle Scholar
  15. Mani, S., Mitchell, A., & O'Malley, B. (2001). Progesterone receptor and dopamine receptors are required in delta9-tetrahydrocannabinol modulation of sexual receptivity in female rats. Proceedings of the National Academy of Science U.S.A., 98, 1249–1254.  https://doi.org/10.1073/pnas.98.3.1249CrossRefGoogle Scholar
  16. Merari, A., Barak, A., & Plaves, M. (1973). Effects of 1(2)-tetrahydrocannabinol on copulation in the male rat. Psychopharmacologia, 28, 243–246.  https://doi.org/10.1007/BF00429304CrossRefPubMedGoogle Scholar
  17. Mondino, A., Fernández, S., Garcia-Carnelli, C., Castro, M. J., Umpierrez, E., Torterolo, P., et al. (2019). Vaporized Cannabis differentially modulates sexual behavior of female rats according to the dose. Pharmacology Biochemistry and Behavior, 187, 172814.  https://doi.org/10.1016/j.pbb.2019.172814CrossRefGoogle Scholar
  18. Mycevych, P. E., & Meisel, R. L. (2017). Integrating neural circuits controlling female sexual behavior. Frontiers in Systems Neuroscience, 11, 42.  https://doi.org/10.3389/fnsys.2017.00042CrossRefGoogle Scholar
  19. Rodríguez-Manzo, G., & Canseco-Alba, A. (2015a). Biphasic effects of anandamide on behavioural responses: Emphasis on copulatory behavior. Behavioural Pharmacology, 26, 607–615.  https://doi.org/10.1097/FBP.0000000000000154CrossRefPubMedGoogle Scholar
  20. Rodríguez-Manzo, G., & Canseco-Alba, A. (2015b). Anandamide reduces the ejaculatory threshold of sexually sluggish male rats: Possible relevance for human lifelong delayed ejaculation disorder. The Journal of Sexual Medicine, 12, 1128–1135.  https://doi.org/10.1111/jsm.12866CrossRefPubMedGoogle Scholar
  21. Rodríguez-Manzo, G., & González-Morales, E. (2020). Endocannabinoids mediate long-lasting behavioural and physiological changes in male rats induced by the repeated activation of the mesolimbic system by copulation to satiety. Behavioural Brain Research, 383, 112510.  https://doi.org/10.1016/j.bbr.2020.112510CrossRefPubMedGoogle Scholar
  22. Scimeca, G., Chisari, C., Muscatello, M. R. A., Cedro, C., Pandolfo, G., Zoccali, R., et al. (2017). Cannabis and sexual behavior. In V. R. Preedy (Ed.), Handbook of cannabis and related pathologies (pp. 180–187). London: Academic/Elsevier.  https://doi.org/10.1016/B978-0-12-800756-3.00021-1. Chap. 19.CrossRefGoogle Scholar
  23. Succu, S., Mascia, M. S., Sanna, F., Melis, T., Argiolas, A., & Melis, M. R. (2006). The cannabinoid CB1 receptor antagonist SR 141716A induces penile erection by increasing extra-cellular glutamic acid in the paraventricular nucleus of male rats. Behavioural Brain Research, 169, 274–281.  https://doi.org/10.1016/j.bbr.2006.01.017CrossRefPubMedGoogle Scholar
  24. Wiebe, E. W., & Just, A. (2019). How cannabis alters sexual experience: A survey of men and women. The Journal of Sexual Medicine, 16, 1758–1762.  https://doi.org/10.1016/j.jsxm.2019.07.023CrossRefPubMedGoogle Scholar
  25. Xi, Z. X., Peng, X. Q., Li, X., Song, R., Zhang, H. Y., Liu, Q. R., et al. (2011). Brain cannabinoid CB2 receptors modulate cocaine's actions in mice. Nature Neuroscience, 14, 1160–1166.  https://doi.org/10.1038/nn.2874CrossRefPubMedPubMedCentralGoogle Scholar

Authors and Affiliations

  1. 1.Departamento de FarmacobiologíaCinvestav-Sede SurMexico CityMexico
  2. 2.Dirección de Investigación, Instituto Nacional de Neurología y NeurocirugíaMexico CityMexico