Cannabis use during pregnancy: Pharmacokinetics and effects on child development

Abstract

The broad-based legalization of cannabis use has created a strong need to understand its impact on human health and behavior. The risks that may be associated with cannabis use, particularly for sensitive subgroups such as pregnant women, are difficult to define because of a paucity of dose-response data and the recent increase in cannabis potency. Although there is a large body of evidence detailing the mode of action of Δ⁹-tetrahydrocannabinol (THC) in adults, little work has focused on understanding how cannabis use during pregnancy may impact the development of the fetal nervous system and whether additional plant-derived cannabinoids might participate. This manuscript presents an overview of the historical and contemporary literature focused on the mode of action of THC in the developing brain, comparative pharmacokinetics in both pregnant and nonpregnant model systems and neurodevelopmental outcomes in exposed offspring. Despite growing public health significance, pharmacokinetic studies of THC have focused on nonpregnant adult subjects and there are few published reports on disposition parameters during pregnancy. Data from preclinical species show that THC readily crosses the placenta although fetal exposures appear lower than maternal exposures. The neurodevelopmental data in humans and animals suggest that prenatal exposure to THC may lead to subtle, persistent changes in targeted aspects of higher-level cognition and psychological well-being. There is an urgent need for well-controlled studies in humans and preclinical models on THC as a developmental neurotoxicant. Until more information is available, pregnant women should not assume that using cannabis during pregnancy is safe.

Keywords: Cannabis; Child development; Exposure; Pharmacokinetics; Pregnancy.

Figure 1:

Endogenous signaling system is used by multiple cell types in brain and periphery. It encompasses cannabinoid receptors CB₁ and CB₂ (primarily expressed by neurons and immune cells microglia, respectively), the two endocannabinoids anandamide (arachidonolyl ethanolamine, AEA) and 2-AG (2-arachidonoyl glycerol) and the enzymes that produce them (not shown) and inactivate them, namely fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MGL), α/β-hydrolase domain 6 (ABHD6) and cyclooxygenase 2 (COX2, not shown). Additional molecular components are GPR55 that is modulated by cannabidiol (CBD).

Figure 2:

Simplified metabolic pathway of ∆⁹-tetrahydrocannabinol (THC), or ∆¹-tetrahydrocannabinol, under the monoterpenoid naming system, in humans. Both 11-hydroxy- ∆⁹-tetrahydrocannabinol (11-OH-THC), or 7-hydroxy- ∆¹-tetrahydrocannabinol, and 8-hydroxy- ∆⁹-tetrahydrocannabinol (8-OH-THC), or 6-hydroxy- ∆¹-tetrahydrocannabinol, are active metabolites.