Prenatal Cannabinoid Exposure: Emerging Evidence of Physiological and Neuropsychiatric Abnormalities

Abstract

Clinical reports of cannabis use prevalence during pregnancy vary widely from 3% to upwards of 35% in North America; this disparity likely owing to underestimates from self-reporting in many cases. The rise in cannabis use is mirrored by increasing global legalization and the overall perceptions of safety, even during pregnancy. These trends are further compounded by a lack of evidence-based policy and guidelines for prenatal cannabis use, which has led to inconsistent messaging by healthcare providers and medically licensed cannabis dispensaries regarding prenatal cannabis use for treatment of symptoms, such as nausea. Additionally, the use of cannabis to self-medicate depression and anxiety during pregnancy is a growing medical concern. This review aims to summarize recent findings of clinical and preclinical data on neonatal outcomes, as well as long-term physiological and neurodevelopmental outcomes of prenatal cannabis exposure. Although many of the outcomes under investigation have produced mixed results, we consider these data in light of the unique challenges facing cannabis research. In particular, the limited longitudinal clinical studies available have not previously accounted for the exponential increase in (-)-Δ9– tetrahydrocannabinol (Δ9–THC; the psychoactive compound in cannabis) concentrations found in cannabis over the past two decades. Polydrug use and the long-term effects of individual cannabis constituents [Δ9–THC vs. cannabidiol (CBD)] are also understudied, along with sex-dependent outcomes. Despite these limitations, prenatal cannabis exposure has been linked to low birth weight, and emerging evidence suggests that prenatal exposure to Δ9–THC, which crosses the placenta and impacts placental development, may have wide-ranging physiological and neurodevelopmental consequences. The long-term effects of these changes require more rigorous investigation, though early reports suggest Δ9–THC increases the risk of cognitive impairment and neuropsychiatric disease, including psychosis, depression, anxiety, and sleep disorders. In light of the current trends in the perception and use of cannabis during pregnancy, we emphasize the social and medical imperative for more rigorous investigation of the long-term effects of prenatal cannabis exposure.

Role of Brain Modulators in Neurodevelopment: Focus on Autism Spectrum Disorder and Associated Comorbidities

“…It was previously reported that neurons mostly express CBDRs1, and CBDRs2 are predominately found in immune cells including microglia and mast cells [ 183 , 184 ]. Importantly, in utero exposure to exogenous cannabinoids was found to produce deficits in maturation of the foetal brain which are strongly associated with SCH [ 185 , 186 ]. Do these deficits indicate a role of eCB signalling in neurodevelopment since exogenous cannabinoids are able to bind to some other “off-target” receptors?…”

Quality of Life and a Surveillant Endocannabinoid System

“…Of note, although many benefits of phytocannabinoids have been discussed in the context of neurodegenerative diseases and stress relief, the use of Cannabis during critical periods of development such as gestation and lactation as well as during adolescence may be harmful. Prenatal Cannabis exposure predicts fetal growth restriction, preterm delivery, and neonatal intensive care (Nashed et al, 2020). In human term placenta, THC increases AEA levels, which might be detrimental for the balance of trophoblast cells turnover leading to alterations in normal placentation and fetal growth (Maia et al, 2019).…”

Impact of Acute and Chronic Cannabis Use on Stress Response Regulation: Challenging the Belief That Cannabis Is an Effective Method for Coping

“…This sex difference may be driven by sex-specific effects of cannabis. Animal studies found that THC was metabolized to its highly potent compounds in female rats while it was metabolized to various compounds in male rats (Narimatsu et al, 1991). Female adult rats, but not male adult rats, showed symptoms analogous to depression when chronically treated with THC during adolescence (Rubino et al, 2008).…”