Influence of prenatal cannabinoid exposure on early development and beyond

Abstract

Public perception surrounding whether cannabis use is harmful during pregnancy often diverges greatly from the recommendations of doctors and healthcare providers. In contrast to the medical guidance of abstinence before, during, and after pregnancy, many women of reproductive age believe cannabis use during pregnancy is associated with little potential harm. Legalization and social cues support public perceptions that cannabis use during pregnancy is safe. Moreover, pregnant women may consider cannabis to be a safe alternative for treating pregnancy related ailments, including morning sickness. Compounding the problem is a lack of medical and federal guidance on safe, low, or high-risk levels of cannabis use. These issues mirror the continuing debate surrounding alcohol use and health, in particular, whether there are safe or lower risk levels of alcohol consumption during pregnancy. Clinical studies to date suffer from several limitations. First, most human studies are correlative in nature, meaning that causal associations cannot be made between in utero cannabis exposure and health and behavioral outcomes later in life. Due to obvious ethical constraints, it is not possible to randomly assign pregnant mothers to cannabis or other drug exposure conditions—a requirement needed to establish causality. In addition, clinical studies often lack quantitative information on maternal exposure (i.e., dose, frequency, and duration), include a small number of individuals, lack replication of outcome measures across cohorts, rely on self-report to establish maternal drug use, and suffer from unmeasured or residual confounding factors. Causal associations between maternal cannabis exposure and offspring outcomes are possible in preclinical cohorts but there is a large amount of heterogeneity across study designs and developmental differences between rodents and humans may limit translatability. In this review, we summarize research from human and preclinical models to provide insight into potential risks associated with prenatal cannabinoid exposure (PCE). Finally, we highlight gaps in knowledge likely to contribute to the growing divide between medical guidance and public attitudes regarding cannabis use during pregnancy.

Dynamic Overrepresentation of Accumbal Cues in Food- and Opioid-Seeking Rats after Prenatal THC Exposure

“…Additionally, no significant effects of sex were found (Supplementary Figure 1 ). Altogether, these results align with clinical findings suggesting a link between PCE and a propensity to manifest enhanced motivation later in life 11 . These findings highlight the utility of our rat model to study this clinically-relevant phenotype while circumventing residual confounding factors inherent to clinical studies.…”

“…Much like seen in human cohorts 11 , the risk for augmented drug reinforcement was higher for males relative to females. Of note, sex-dependent behavioral effects of PCE paralleled its neurobiological signatures.…”

“…In terms of Berridge and Robinson's (2016) 62 framework of addiction 63 , these observations support the hypothesis of a hypersensitized 'wanting' system, in contrast to reward valuation ('liking') or learning alterations, which we (and others 17 ) demonstrate are not implicated in the motivational phenotype of PCE. A specific increase in incentive salience provides a satisfactory explanation for this and prior rodent studies reporting enhanced effortful motivation and psychomotor activation 64 in response to heroin 65,66 , food 17 , THC 14 and alcohol 67 (reviewed in 11 ). Preclinical and clinical evidence have established a causative role for enhanced mesostriatal dopamine function in the attribution of incentive salience and, ultimately, the pathogenesis of addiction 68,69 .…”

“…Impulsivity deficits are one of the outcomes most consistently associated with PCE [51][52][53][54][55] and are hypothesized to underlie increased risk of substance use observed after PCE 11 . Thus, a failure in inhibitory control required to interrupt or suppress highly-automatized reward-seeking behaviors could contribute to the PCE hypermotivational phenotype 56 .…”

The impact of prenatal alcohol and synthetic cannabinoid exposure on behavioral adaptations in adolescent offspring and alcohol self-administration in adulthood

“…Children and adolescents with prenatal alcohol or cannabinoid exposure display anxiety-like behavior and hyperarousal (Jutras-Aswad, DiNieri, Harkany, & Hurd, 2009; Mulligan & Hamre, 2023; Nashed, Hardy, & Laviolette, 2021; Weile et al, 2020; Weiss, Jonn - Seed, & Harris - Muchell, 2007). In the current study, males treated with PAE + PCE showed an increase in locomotor behavior in the open field test relative to males exposed to PCE alone; however there was no evidence of hyperactivity when compared to the vehicle control group.…”