Review of cannabis use on reproductive health, pregnancy and fetal outcomes

A recent study published in American Journal of Obstetrics and Gynecology examined cannabis use on reproductive health, pregnancy and fetal outcomes.

Study: Impact of cannabinoids on pregnancy, reproductive health and offspring outcomes. Image Credit: Yarygin / Shutterstock

Background

Cannabis, a federally illegal drug, is the most widely used drug in the United States (USA). Its consumption is on the rise worldwide in part due to legalization in different regions and increasing social acceptability and accessibility. Cannabis use is on the rise, particularly among individuals of reproductive age. The high consumption of cannabis during the 2019 coronavirus (COVID-19) pandemic can be partly 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, sperm and placenta, indicating that the endocannabinoid system may regulate reproduction. Delta-9-tetrahydrocannabinol (THC), the main psychoactive element in cannabis, has been detected in breast milk and may cross the placenta.

Additionally, there is limited evidence on the safety of cannabis use, particularly with regards to reproductive health and pregnancy. As such, nearly 70% of US women believe that consuming cannabis once or twice a week is harmless. Given the increase in cannabis use, it is necessary to study the effects / impact of cannabis on reproductive health and developmental outcomes of the offspring.

Cannabinoid Pharmacology

Cannabis is a member of the Cannabaceae family and contains 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-inflammatory, immunosuppression, sedation, mood enhancement, anti-emesis, and appetite stimulation, among others. However, cannabinoids are not approved for therapeutic use.

Cannabis use and legalization

Smoking is the most common way of administering cannabis, followed by edibles. Cannabis use disorder (CUD) occurs in approximately 10% of regular users and 50% of chronic users. Treatment options for CUD are limited and include psychosocial intervention, motivational enhancement therapy, and cognitive-behavioral therapy or a combination. Several regions in America, Africa, Europe and Australia have decriminalized the use of cannabis.

The significant increase in cannabis use is due to the legalization of recreational cannabis. In the United States, 18 states legalized recreational cannabis in 2021. These legal changes would likely affect the use of cannabis among teens and children. It has been suggested that puberty and the mental health of the pediatric population could be affected by cannabis use.

Male cannabis use and paternal impact

The effect of chronic cannabis use among men is inconsistent, with reports of little or no changes in follicle-stimulating hormone (FSH) levels or poorer sperm parameters. Animal studies have observed that THC exposure could cause adverse effects on spermatogenesis, decreased gonadotropins, abnormal sperm morphology and testicular atrophy.

A recent report showed that cannabis exposure in rats and humans was associated with impaired deoxyribonucleic acid (DNA) methylation. Affected genes were implicated in tumors 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, luteinizing hormone (LH) and FSH secretion, and menstrual cyclicality. Studies in mice showed that prolactin, FSH and LH levels were suppressed upon acute THC administration. Women who use cannabis during pregnancy are often involved in the use of polysubstances resulting in a synergistic or additive effect.

Furthermore, half of all women who use cannabis continue it throughout their pregnancy. There are growing concerns about adverse fetal / neonatal outcomes as THC may 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 have suggested greater chances of admission to neonatal intensive care units (NICUs), small-for-gestational age (SGA), placental abruption, and infant deaths.

Impaired cytotrophoblast fusion and biochemical differentiation by THC was observed in vitro. Furthermore, THC inhibits the migration of the epithelial layer of the amnion, influencing 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.

Breastfeeding mothers are likely to increase cannabis use within two months of giving birth. This raises concerns about the gradual release of THC from the lipid-filled tissues in the offspring transferred through breast milk. Additionally, chronic cannabis use increased THC concentration more than eight times in breast milk compared to plasma. Infants with THC exposure within one month of birth have been observed to have reduced motor development.

Concluding remarks

While cannabis use is on the rise, data on its safety, particularly reproductive health, are limited. Current literature suggests that its use has significant health implications and it is of grave concern that 70% of women believe its consumption is safe during pregnancy. Notably, only half of healthcare workers discouraged perinatal cannabis use.

Despite limited safety information, it is imperative that both individuals and healthcare professionals are informed about the potential adverse effects of cannabis, particularly before conception, during pregnancy and during the postpartum period.

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