Cannabis sativa extract and fertility: Preclinical evaluation in male and female Wistar rats

Currently, there are reservations regarding the medicinal use of Cannabis sativa extract and its potential to impact fertility. Certain cannabinoids, such as Δ⁹-tetrahydrocanabinol (THC), can modulate both male and female sex hormones, potentially leading to alterations in fertilization viability. This study aims to evaluate the effects of standardized Cannabis sativa extract (CSE) and its respective placebos on fertility and early embryonic development in Wistar rats, including both male and female subjects. The animals were divided into 7 groups, each consisting of 20 animals, and different doses of a Cannabis sativa extract (160.32 mg/mL) were administered to assess fertility outcomes. Male and female fertility assessments were conducted according to the guidelines outlined in the "Guide for the Conduct of Non-Clinical Toxicology and Pharmacological Safety Studies Required for Drug Development," including clinical exams, biochemical analyses, macroscopic evaluations, relative organ weight measurements, sperm production, and morphology assessments, as well as morphometric and histopathological analyses of the testes. The results indicated that none of the tested doses (0.28, 2.8, 28, or 56 mg/kg/bw) significantly affected sex hormone levels in either male or female rats. Additionally, no alterations were observed in male organ morphology and sperm characteristics. In female rats, fertility was unaffected, and blastocyst implantation was not impaired across all doses, even up to 7 days post-pregnancy confirmation. No direct toxic effects on the embryo were observed. In conclusion, treatment with Cannabis sativa extract did not result in any significant changes in fertility or pregnancy feasibility in either male or female rats.