Decreasing sperm quality in mice subjected to chronic cannabidiol exposure: New insights of cannabidiol-mediated male reproductive toxicity.

Cannabidiol (CBD) is a natural cannabinoid present in the Cannabis sativa plant, widely prescribed as an anticonvulsant drug, especially for pediatric use. However, its effects on male reproduction are still little investigated. Therefore, the present study assessed the effects of CBD on the spermatogenesis and sperm quality. For this, twenty-one-day-old Swiss mice received CBD for 34 consecutive days by gavage at doses of either 15 or 30 mg/kg. Chronic exposure to CBD decreased the frequency of stages VII-VIII and XII of spermatogenesis and an increase in the frequency of stage IX were noted. Furthermore, the seminiferous epithelium height reduced at stage IX and increased at stage XII in both CBD-treated groups. There was a significant rise of sperm DNA damage, while no genotoxic effects were observed in leukocytes. The activities of superoxide dismutase and catalase decreased, while malondialdehyde levels increased in the sperm of mice treated with a higher dose of CBD. Mice exposed to 30 mg/kg of CBD showed a reduction in the mobile spermatozoa percentage and in curvilinear velocity, while straight line and average path velocity decreased in both treated groups. The number of acrosome-intact spermatozoa declined in the CBD 30 group, and the number of abnormal acrosomes raised in both CBD groups. On the other hand, the weight of reproductive organs, sperm count, and hormone levels were not affected by CBD treatment. These findings show that dysregulation of the endocannabinoid system by CBD can reduce sperm quality. The mechanisms responsible may be associated with disorders during spermatogenesis, especially during the final stages of nuclear remodelling and assembly of acrosome. However, changes in mitochondrial function, as well as the reduction on the antioxidant enzyme activities during epididymal transit, at least partly, may also be involved.

Chronic cannabidiol exposure promotes functional impairment in sexual behavior and fertility of male mice.

Cannabidiol (CBD) is a potent substance extracted from Cannabis sativa. As it has been suggested that marijuana can affect the reproductive system, we decided to assess the effects of chronic CBD exposure on the male reproductive system in an animal model. 21-day old male Swiss mice received CBD for 34 consecutive days at doses (p.o.) of either 15 or 30 mg/kg, and a control group received sunflower oil. Body weight gain and circulating progesterone concentration did not significantly change in CBD-treated animals. In the sexual behavior analysis, the CBD 15 group presented a delay in performing the first mount and intromission, and a reduced number of mounts and ejaculations. The CBD 30 group showed a 30% reduction in fertility rate and a 23% reduction in the number of litters. Our results indicate that chronic CBD exposure promotes functional impairment of the reproductive system of male Swiss mice.

Chronic exposure to cannabidiol induces reproductive toxicity in male Swiss mice.

Children and adults with frequent and severe episodes of epilepsy that do not respond to standard treatments (such as carbamazepine, phenytoin and valproate) have long been prescribed cannabidiol (CBD) as an anticonvulsant drug. However, the safety of its chronic use in relation to reproduction has not been fully examined. This study aimed to assess the effects of chronic CBD exposure on the male reproductive system. CBD was orally administered to 21-day-old male Swiss mice at doses of 15 and 30 mg kg-1 daily (CBD 15 and 30 groups, respectively), with a control group receiving sunflower oil, for 34 consecutive days. After a 35 day recovery period, the following parameters were evaluated: weight of reproductive organs, testosterone concentration, spermatogenesis, histomorphometry, daily sperm production and its morphology. The CBD 30 group had a 76% decrease in total circulating testosterone, but it remained within the physiological normal range (240-1100 ng dl-1 ). CBD treatment induced a significant increase in the frequency of stages I-IV and V-VI of spermatogenesis, and a decrease in the frequency of stages VII-VIII and XII. A significant decrease in the number of Sertoli cells was observed only in the CBD 30 group. In both CBD groups the number of spermatozoa in the epididymis tail was reduced by 38%, sperm had head abnormalities, and cytoplasmic droplets were observed in the medial region of flagellum. These results indicated that chronic CBD exposure was associated with changes in the male reproductive system, suggesting its reproductive toxicity.