As we progress technologically, so do the lifestyle-oriented diseases we see as a human race. Our so-called modern lifestyle is packed with perennial stress, which is further worsened by unhealthy diet and drug addiction or abusing habits. Because of these factors, men across the globe are gradually losing their fertility potential. Alarmingly, 7% of men are suffering with infertility problems. Most of the conventional treatments, including hormone replacement therapy, cannot provide guaranteed positive treatment outcomes.
It has been a long held belief by many that cannabis use may cook your manhood and render you impotent. Even some research studies have warned that marijuana use may double the risk of lowering a male’s fertility.
Over the years, we have seen several conflicting studies on cannabis-induced male infertility. One such study, published in 2015, concluded that cannabis use was linked to a 28% reduction in sperm count. The same study noted that cannabis may have a disruptive effective on men’s fertility, even in men without any clinical history of impaired spermatogenesis.
To counter these findings, a recent experimental study has suggested that cannabis activation of CB2 receptors could actually treat male infertility.
Some studies have reported evidence of chromosomal changes and altered sperm morphology in cannabinoid-exposed experimental animals. However, cytogenetic studies have contradicted these findings and no adverse events on meiotic spermatocytes were observed.
Most of these studies have investigated the effects of the synthetic version (HU-210) of 9-tetrahydrocannabinol and concluded that marijuana can cause male infertility. By now, we are well aware of the differences between the synthetic and natural forms of cannabinoids.
Because of these kinds of conflicting studies, cannabis has ended up in a politico-legal tangle.
We need to fully understand that male infertility is a multi-factorial problem that can occur as a result of chromosomal mutations, endocrine problems, stress, obesity, metabolic syndrome, psychological disorders and the use of certain medications.
Spermatogenesis at a Glance
Sperm production, also called spermatogenesis, is a highly-coordinated physiological process of the male reproductive system that involves various phases of sperm production, maturation and differentiation. The three main phases of spermatogenesis — the mitotic, meiotic and differentiative haploid phases — are associated with development of spermatogonia, spermatocytes and spermatids, respectively.
The early phase of spermatogenesis occurs in the basal compartment of seminiferous epithelium from the spermatogonial stem cells, which undergo a series of cell division processes to form primary spermatocytes. This is followed by meiosis and genetic exchange processes that result in the formation of spermatids, followed by the formation of functional sperm cells.
The ECS and Male Reproductive System Physiology
Since its discovery, the endocannabinoid system (ECS) has been shown to be implicated in several fundamental physiological functions as well as in several disease processes. Studies have demonstrated the modulation of the ECS during the cell cycle process by altered expression of CB1 and CB2 receptors and enzymes such as anandamide and 2-arachidonoylglycerol.
The key role of CB1 receptors (present in Leydig cells) in testosterone production via the regulation of pituitary-gonadal axis has been demonstrated by research evidence. The regulation of testosterone production may be controlled by feedback inhibition in response to CB1 receptors. Hyperactivation of these receptors may impair testosterone production in the Leydig cells. Targeting CB1 receptors and activation may cause adverse effects in men’s fertility.
One study confirmed the role of CB1 receptors in early stage spermatozoa. The same study has found increased CB1 expression in the testicular cells during various stages of spermatogenesis. These findings suggest that CB1 receptors have an influential and regulatory role in sperm production. Similarly, the regulatory role of CB2 receptors in spermatogenesis has been recently proposed.
Based on the available evidence, we can see that the ECS is modulated during spermatogenesis via autocrine endocannabinoid signaling and the pivotal role cannabinoid receptors in sperm production.
Cannabis as a Treatment for Male Infertility
Recently, a team of scientists conducted an experimental study to see if cannabis could treat male infertility.
In the pre-clinical study, the researchers administered a CB2 receptor agonist, antagonist and an inert placebo, which served as the control. The experimental animals were monitored up to 21 days, and an increased rate of spermatogenesis was observed in the CB2 activator group. Although it was a chemical mimetic of naturally-occurring cannabinoids, the receptor stimulation induced spermatogenesis in the experimental animals. However, suppressed or inhibited spermatogenesis was observed in the CB2 inhibitor group, which might be due to delayed germ cell differentiation. No effects were found in the placebo group.
The results of this study could confirm the notion that CB2 receptors are associated with sperm production and its activation could possibly treat male infertility.
That’s not all. The same study warned that prolonged CB2 activation may also suppress testosterone production, a sex hormone that is vital for male fertility. Hence, the hypostimulation and hyperstimulation could have significant, but disruptive, effects in spermatogenesis.
This means weed is definitely good for men’s health — if used appropriately. But there is no doubt that prolonged, heavy users may potentially suffer infertility problems.
Too much of anything is good for nothing!
Targeting CB2 Receptors with Cannabinoids to Correct Male Infertility
As of now, there is no cure or reliable medical management available to treat certain types of male infertility. Instead of considering synthetic chemicals to influence or interfere with spermatogenesis processes, modulating the important spermatogenesis regulators, such as the endocannabinoid system (ECS) by phytocannabinoids, could be useful.
Studies have hypothesized that ∆9-tetrahydrocannabinol has the potential to regulate acrosome formation, sperm motility and survival.
The experimental study showed us that the activation of CB2 receptors by cannabinoid-like molecules activates the MAP-kinase pathway by increasing Erk1/2 phosphorylation reaction. This particular pathway has remarkable pro-differentiative effects on sperm production, particularly by increasing the mRNA expression of c-kit and also the meiotic nuclei fraction at all prophase stages of spermatocytes. These physiological functions are important for normal sperm production, maturation and survival in male reproductive organs.
Other studies have confirmed the pro-differentiative effects of CB2 receptors in germ cells (spermatogonia and spermatids) by up-regulating certain genes, including Stra8 genes and Dmc1 genes, that are responsible for meiotic prophase maintenance and progression. These findings confirmed the involvement of CB2 receptors in mitotic and meiotic phases of sperm production by means of autocrine endocannabinoid signaling mechanisms.
Hence, we can see that the activation of CB2 receptors might be useful to improve spermatogenesis in men suffering with infertility issues.
Although the experimental study mentioned above warned that cannabinoid activation of CB2 receptors may suppress testosterone production, we should note that the cannabinoid employed in this study is a THC-like synthetic molecule and NOT a naturally-occurring form of THC.
Taken together, the pivotal role of the ECS in the regulation of male infertility has been proven. Until we see safer benefits after administration of naturally-occurring THC, we should consider that persistent or prolonged activation of the ECS may disrupt the physiology of spermatogenesis, possibly lower testosterone production and impair sperm production to some extent in male reproductive organs.
Despite these cons, some studies have contended that there is no evidence to demonstrate that cannabis can adversely affect male fertility.
This recent study provides some degree of nascent evidence that cannabis could interfere with CB2 receptors and therefore treat male infertility. This particular property of cannabis could be exploited as a therapeutic strategy for treatment of male infertility.
The role of the endocannabinoid system (ECS) in the regulation of spermatogenesis, sperm functions and sex hormone synthesis is well documented. So, we have several good reasons to believe that the activation of the ECS by phytocannabinoids can potentially treat, or possibly cure, male infertility by modulating the underlying pathological factor(s).
Maybe in the future cannabis could be employed as a complementary therapy, along with lifestyle and dietary modifications, to treat male infertility, particularly in men with impaired sperm production.