Dados do Trabalho

Title

THE EFFECT OF CANNABIS USE ON FEMALE FERTILITY

Objective

To gather and understand the impact of marijuana/Cannabis consumption on female reproductive health and the outcomes of neonatal complications.

Methods

From a bibliographic review, data were collected from several articles related to the proposed subject, published between 1979 and 2022. The articles were selected after conducting a search in the literature, through the platforms Google Scholar (Google acadêmico) and PubMed. Studies were included after a thorough reading of the abstracts and after the complete articles, with a English and Portuguese language, including papers with both basic and clinical approach.

Results

After the search strategy, 61 articles were selected. Two of those were excluded due to lack of access to the full article. Therefore, related articles were included in the proposed review. Cannabis/marijuana is one of the oldest known psychotropic drugs and a champion of consumption especially among people of reproductive age. The best studied components in cannabis are the cannabinoids named cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), which is the main psychoactive ingredient. Cannabinoid-like compounds have been identified in vivo, collectively referred to as endocannabinoids (ECB). The endocannabinoid system (ECS) is a multifunctional homeostatic system involved in diverse physiological and pathological conditions. The biological effects of cannabis are mediated through this system, and studies report the presence of cannabinoid receptors in the female reproductive tract, suggesting that the endocannabinoid system plays a role in regulating reproductive physiology. ECS ligands are ECB, whose actions are mimicked by exogenous cannabinoids such as THC and CBD. Responses to ECS ligands are mediated by numerous receptors such as CB1 (cannabinoid receptor 1) and CB2 (cannabinoid receptor 2), both of which are present in the female reproductive system. Thus, we observed that exposure to cannabinoids can have differential impacts on female reproductive health throughout a woman's life, from preconception to pregnancy, either naturally or through assisted reproduction techniques, and during lactation. Many studies have shown that follicular development is negatively affected as the presence of exogenous cannabinoids reduces the release of hormones from the hypothalamic-pituitary-ovarian axis including sex hormones such as LH (luteinizing hormone) and FSH (follicle stimulating hormone). Furthermore, user’s ovaries were shown to be anovulatory, leading to primary infertility, in addition to the shortening of the luteal phase in women with chronic use of the substance. Pregnant women using either natural or synthetic derivatives were associated with gestational disorders, such as abnormal embryo development, tubal pregnancy, implantation failure, premature delivery, intrauterine growth restriction, low birth weight and increased risk of spontaneous miscarriages. Although little is known about its effects on lactation, it is known that THC easily crosses the placental membrane and, being liposoluble, is transferred through breast milk. Several results indicate that appropriate and regulated endocannabinoid signaling, both in the blastocyst and in the uterus, is necessary for the establishment of uterine receptivity and blastocyst implantation competence, reducing the chance of pregnancy failures. However, it is necessary to better understand the doses and physiological mechanisms that involve the cannabinoid system so that there is an established threshold between benefits and risks.

Conclusion

The data indicate a negative effect of cannabis use on female fertility during many stages of female reproductive life, even in hormone and gamete production, or during pregnancy. However, the literature still lacks concrete, controlled and sufficient data to actually ensure that there is damage, since it is still not well understood how the endocannabinoid system acts in reproductive and fertilization processes.

Keywords

Cannabinoids, endocannabinoid system, miscarriage, implantation failure, infertility.