Phytocannabinoids, the Endocannabinoid System and Male Reproduction

Jinhwan Lim; Erica Squire; Kwang-Mook Jung

doi:10.5534/wjmh.220132

Phytocannabinoids, the Endocannabinoid System and Male Reproduction

World J Mens Health. 2023 Jan;41(1):1-10. doi: 10.5534/wjmh.220132.

Authors

Jinhwan Lim¹, Erica Squire², Kwang-Mook Jung³

Affiliations

¹ Department of Environmental and Occupational Health, University of California Irvine, Irvine, CA, USA.
² Department of Anatomy and Neurobiology, University of California Irvine, Irvine, CA, USA.
³ Department of Anatomy and Neurobiology, University of California Irvine, Irvine, CA, USA. kmjung@uci.edu.

Abstract

The endocannabinoid system (ECS) is comprised of a set of lipid-derived messengers (the endocannabinoids, ECBs), proteins that control their production and degradation, and cell-surface cannabinoid (CB) receptors that transduce their actions. ECB molecules such as 2-arachidonoyl-sn-glycerol (2-AG) and anandamide (arachidonoyl ethanolamide) are produced on demand and deactivated through enzymatic actions tightly regulated both temporally and spatially, serving homeostatic roles in order to respond to various challenges to the body. Key components of the ECS are present in the hypothalamus-pituitary-gonadal (HPG) axis, which plays critical roles in the development and regulation of the reproductive system in both males and females. ECB signaling controls the action at each stage of the HPG axis through CB receptors expressed in the hypothalamus, pituitary, and reproductive organs such as the testis and ovary. It regulates the secretion of hypothalamic gonadotropin-releasing hormone (GnRH), pituitary follicle-stimulating hormone (FSH) and luteinizing hormone (LH), estrogen, testosterone, and affects spermatogenesis in males. Δ⁹-tetrahydrocannabinol (THC) and other phytocannabinoids from Cannabis sativa affect a variety of physiological processes by altering, or under certain conditions hijacking, the ECB system. Therefore, phytocannabinoids, in particular THC, may modify the homeostasis of the HPG axis by altering CB receptor signaling and cause deficits in reproductive function. While the ability of phytocannabinoids, THC and/or cannabidiol (CBD), to reduce pain and inflammation provides promising opportunities for therapeutic intervention for genitourinary and degenerative disorders, important questions remain regarding their unwanted long-term effects. It is nevertheless clear that the therapeutic potential of modulating the ECS calls for further scientific and clinical investigation.

Keywords: Cannabinoids; Endocannabinoids; Male; Reproduction; Spermatogenesis; Therapeutics.

Publication types

Review

Grants and funding

GW210033/USA Department of the Army/United States of America