Cannabinoid signalling and effects of cannabis on the male reproductive system

Marijuana is the most widely consumed recreational drug worldwide, which raises concerns for its potential effects on fertility. Many aspects of human male reproduction can be modulated by cannabis-derived extracts (cannabinoids) and their endogenous counterparts, known as endocannabinoids (eCBs). These latter molecules act as critical signals in a variety of physiological processes through receptors, enzymes and transporters collectively termed the endocannabinoid system (ECS). Increasing evidence suggests a role for eCBs, as well as cannabinoids, in various aspects of male sexual and reproductive health. Although preclinical studies have clearly shown that ECS is involved in negative modulation of testosterone secretion by acting both at central and testicular levels in animal models, the effect of in vivo exposure to cannabinoids on spermatogenesis remains a matter of debate. Furthermore, inconclusive clinical evidence does not seem to support the notion that plant-derived cannabinoids have harmful effects on human sexual and reproductive health. An improved understanding of the complex crosstalk between cannabinoids and eCBs is required before targeting of ECS for modulation of human fertility becomes a reality. Many aspects of human male reproduction can be modulated by cannabinoids and endocannabinoids (eCBs). Preclinical studies have shown that the endocannabinoid system (ECS) is involved in negative modulation of testosterone secretion, but the effect of in vivo exposure to cannabinoids on spermatogenesis remains a matter of debate. An improved understanding of the complex crosstalk between cannabinoids and eCBs might enable targeting of the ECS for modulation of human fertility. Key points Marijuana has the highest consumption rate of any recreational drug in the Western world. Endocannabinoids and their receptors, enzymes and transporters, which together form the endocannabinoid system (ECS), are present in various components of the male reproductive tract, including male genital glands, testis and sperm. Preclinical studies have shown that the ECS is involved in negative modulation of testosterone secretion by acting at both central and testicular levels. As yet, clinical data are insufficient to conclude that cannabinoids have a harmful effect on human male sexual function and fertility. Although cannabinoid receptors are present in the testes and sperm, the effects of cannabinoid exposure on spermatogenesis largely remain to be clarified. The