Cannabinoids and the male reproductive system: Implications of endocannabinoid signaling pathways

The escalating use and legalization of cannabis (marijuana) in the United States reflect shifting societal attitudes and growing awareness of its potential therapeutic benefits. Historically viewed as a harmful psychoactive substance, contemporary research has shown the intricate pharmacology of cannabis, with its diverse array of cannabinoids and their interactions with the endocannabinoid system. Among these cannabinoids, Δ9-tetrahydrocannabinol is the primary psychoactive component, characterized by its activation of cannabinoid receptors. The discovery of endocannabinoids, including anandamide and 2-arachidonoylglycerol, illuminated the body's innate cannabinoid signaling pathways and their involvement in several physiological processes. Endocannabinoids exert both positive and negative effects on the male reproductive system. They facilitate erectile function by modulating neurotransmission and vasodilation, offering potential therapeutic avenues for conditions like erectile dysfunction and prostatitis. However, chronic exogenous cannabinoid use, mainly of tetrahydrocannabinol, poses risks to male reproductive health by disrupting spermatogenesis, causing hormonal imbalances, and potentially influencing cancer cell proliferation. Understanding endocannabinoid signaling in the male reproductive system is essential to fully comprehend both the therapeutic benefits and potential drawbacks of cannabis use. Further research is required on these mechanisms, to provide insights that can guide clinical practice and policy-making regarding cannabis use. In this narrative review, we highlight the need for additional research into how cannabinoids affect male reproductive health, particularly with prolonged use. Investigating cannabinoids' impacts on spermatogenesis, hormonal balance, and cancer cell proliferation can provide valuable insights for healthcare professionals.