A recent study published in the American Journal of Obstetrics and Gynecology reviewed cannabis use on reproductive health, pregnancy, and fetal outcomes.
Background
Cannabis, a federally illegal drug, is the most consumed drug in the United States (US). Its consumption is increasing worldwide partly due to legalization in several regions and growing social acceptability and accessibility. Cannabis use has been increasing, particularly among individuals of reproductive age. The elevated consumption of cannabis during the coronavirus disease 2019 (COVID-19) pandemic may partly be attributed to increased stress and anxiety.
The endocannabinoid system mediates the biological effects of cannabis. Endocannabinoid receptor expression has been observed in developing fetuses as early as the fifth gestational week. Cannabinoid receptors have been reported in male/female reproductive tracts, sperms, and placenta, indicating that the endocannabinoid system might regulate reproduction. Delta-9-tetrahydrocannabinol (THC), the principal psychoactive element of cannabis, has been detected in breastmilk and could cross the placenta.
Moreover, evidence about the safety of cannabis use, particularly regarding reproductive health and pregnancy, is limited. As such, nearly 70% of US females believe that consuming cannabis once or twice a week is innocuous. Given the increase in cannabis consumption, it is necessary to study the effects/impact of cannabis on reproductive health and developmental outcomes of offspring.
Cannabinoid pharmacology
Cannabis is a member of the Cannabaceae family and has over 80 bioactive chemical compounds, with THC and cannabidiol being the most commonly known. Cannabinoid receptors (CB1 and CB2) are expressed in the central nervous system and peripheral tissues. Some of the therapeutic properties of cannabinoids include muscle relaxation, analgesia, anti-inflammation, immunosuppression, sedation, mood improvement, anti-emesis, and appetite stimulation, among others. Nonetheless, cannabinoids are not approved for therapeutic use.
Cannabis consumption and legalization
Smoking is the most common way of cannabis administration, followed by edibles. Cannabis use disorder (CUD) occurs in about 10% of regular consumers and 50% chronic users. Therapeutic options for CUD are limited and include psychosocial intervention, motivational enhancement therapy, and cognitive behavioral therapy or a combination. Several American, African, European, and Australian regions have decriminalized the use of cannabis.
The significantly increased consumption of cannabis has been due to the legalization of recreational cannabis. In the US, 18 states legalized recreational cannabis in 2021. These legal changes would likely influence cannabis consumption among adolescents and children. It has been suggested that the puberty and mental health of the pediatric population could be impacted by cannabis use.
Cannabis use by males and paternal impact
The effect of chronic consumption of cannabis among men is inconsistent, with reports of minimal-to-no changes in follicle-stimulating hormone (FSH) levels or poorer semen parameters. Animal studies observed that THC exposure could result in adverse effects on spermatogenesis, decrease in gonadotropins, abnormal sperm morphology, and testicular atrophy.
One recent report demonstrated that cannabis exposure in rats and humans was associated with altered methylation of deoxyribonucleic acid (DNA). The affected genes were implicated in cancers and early development, including neurodevelopment.
Impact of Cannabis on female reproductive health, pregnancy, lactation, and fetal outcomes
Various studies suggest that cannabis affects processes associated with female reproductive health, such as ovulation, secretion of luteinizing hormone (LH) and FSH, and menstrual cyclicity. Studies on mice showed that prolactin, FSH, and LH levels were suppressed upon acute THC administration. Women that use cannabis during pregnancy are often involved in polysubstance use resulting in a synergistic or additive effect.
Moreover, half the women who use cannabis continue it throughout the pregnancy. There are growing concerns about adverse fetal/neonatal outcomes since THC could bind to cannabinoid receptors in the placenta or fetal brain. The risk of miscarriage and stillbirth is also higher but is inconsistent across different studies. Some studies suggested higher odds of admissions to neonatal intensive care unit (NICU), small for gestational age (SGA), placenta abruption, and infant deaths.
Impairment of cytotrophoblast fusion and biochemical differentiation by THC has been observed in vitro. Further, THC inhibits migration of the epithelial layer of amnion, affecting its development during the gestational period and contributing to adverse pregnancy outcomes, including preterm labor. Hyperactivity, impulsivity, abnormal visual and verbal reasoning, and attention deficit have been reported in preschool children born to mothers who used THC during pregnancy.
Lactating mothers are likely to increase cannabis use within two months of childbirth. This raises concerns about the gradual release of THC from lipid-filled tissues in the offspring transferred through breastmilk. Furthermore, chronic usage of cannabis increased THC concentration by more than eight times in breastmilk relative to plasma. Newborns with THC exposure within a month of birth have been observed to have reduced motor development.
Concluding remarks
While the use of cannabis is growing, data on its safety, particularly on reproductive health, are limited. The current literature suggests that its use has significant health implications, and it is gravely concerning that 70% of females believe its consumption is safe during pregnancy. Notably, only half the healthcare providers discouraged perinatal cannabis consumption.
Despite the limited safety information, it is critical to have both individuals and healthcare providers informed about the potential adverse effects of cannabis, particularly before conception, during pregnancy, and during the postpartum period.
