Impact of cannabinoids on pregnancy, reproductive health, and offspring outcomes

Abstract

Cannabis is the most commonly used federally illegal drug in the United States and the world, especially among people of reproductive age. In addition, the potency of cannabis products has increased significantly in the past decade. This is concerning because the available evidence suggests an adverse effect of cannabis exposure on male and female reproductive health. Exposure to cannabinoids may have differential impacts on female reproductive health across a woman's lifespan, from preconception to pregnancy, throughout lactation, and during menopause. Moreover, cannabis use has been associated with adverse effects on fetal outcomes and longer-term offspring health and developmental trajectories. Despite the prevalence of cannabis use, there is limited available evidence regarding its safety, especially in regard to reproductive health, pregnancy, and lactation. The biological effects of cannabis are mediated by the endocannabinoid system, and studies have reported the presence of cannabinoid receptors in the male and female reproductive tract, on sperm and the placenta, suggesting that the endocannabinoid system plays a role in regulating reproduction. Cannabis use can affect male and female fertility and has been associated with altered reproductive hormones, menstrual cyclicity, and semen parameters. Use of cannabis in male patients has also been associated with erectile dysfunction, abnormal spermatogenesis, and testicular atrophy. In female patients, cannabis use has been associated with infertility and abnormal embryo implantation and development. The main psychoactive component of cannabis, the delta-9-tetrahydrocannabinol, can also cross the placenta and has been detected in breast milk. Maternal cannabis use during pregnancy and lactation has been associated with adverse effects, including small-for-gestational-age infants, preterm birth, fetal neurodevelopmental consequences, and impaired offspring sociobehavioral and cognitive development. The prevalence of cannabis use for alleviating menopausal symptoms has also increased despite the limited information on its benefits and safety. Given that cannabis use is on the rise, it is critical to understand its impact on reproductive health and offspring developmental outcomes. This is an understudied but timely subject requiring much further information to guide healthcare providers and those interested in conceiving or who are pregnant and lactating, and those at the end of their reproductive time span.

Keywords: cannabinoids; cannabis; cannabis use disorder; delta-9-tetrahydrocannabinol; fertility; low birthweight; marijuana; maternal cannabis use; menopause; preterm birth; reproductive health; small for gestational age; substance use.

Figure 1.. Past year cannabis use among females aged 12 or older: 2010–2020.^,

Prevalence of past year cannabis use has increased most rapidly in females aged 26 years or older.

Figure 2.. Human endocannabinoid system.

Consists of cannabinoid receptors and endocannbinoids. The two most common cannabinoid receptors are CB1 and CB2. CB1 receptors are predominantly located in the brain and central nervous system, but can also be found in other tissues. CB2 receptors are largely found in peripheral organs, especially cells associated with the immune system.

Figure 3.. Adverse effects of cannabis consumption on the placenta, fetus and offspring.

FGR: fetal growth restriction, SGA: small for gestational age, PTB: preterm birth, ASD: autism spectrum disorder, PLE: psychotic-like experience.