Prenatal cannabinoid exposure: why expecting individuals should take a pregnancy pause from using cannabinoid products

Abstract

Cannabinoid use in all populations is increasing as legalization across the United States continues. Concerningly, there is a lack of caution provided by medical providers to pregnant individuals as to the impact the use of cannabinoids could have on the developing fetus. Research continues in both the preclinical and clinical areas, and is severely needed, as the potency of delta-9-tetrahydrocannabinol (THC), the primary psychoactive component of cannabis, has increased dramatically since the initial studies were completed. Thus far, clinical studies raise compelling evidence for short term memory deficits, impulse control issues, and attention deficiencies following prenatal cannabinoid exposure (PCE). These changes may be mediated through epigenetic modifications that not only impact the current offspring but could carry forward to future generations. While additional studies are needed, a pregnancy pause from cannabinoid products should be strongly recommended by providers to ensure the optimal health and well-being of our future generations.

Keywords: intrauterine exposure; neurodevelopmental outcome; prenatal cannabinoid exposure; prenatal cannabis exposure; prenatal marijuana exposure.

Figure 1

Summary of the broad impact prenatal cannabinoid exposure can have on fetal development. Multiple fetal systems can be impacted by prenatal cannabinoid exposure, including but not limited to abdominal wall, uronephrological, epigenetic, neurological, and cardiac. Figure created with BioRender.com.

Figure 2

The pro-homeostatic function of the endocannabinoidome. The ubiquitous expanded endocannabinoid system (eCB, i.e., the endocannabinoidome, eCBome), which consists of many eCB-like lipid mediators, and their metabolic enzymes and molecular targets, is an overarching neuromodulatory system that plays crucial roles in neurodevelopment and neuroplasticity, in several physiological and cognitive processes, and responds to endogenous and exogenous perturbations [modified from Sun and Dey (11), Orsolini et al. (12), Di Marzo (13)].

Figure 3

Multidimensional interactions between the genome, epigenome, and exposome determine the phenome. The multidimensional interactions between the genome (DNA), epigenome (i.e., the sum of all epigenetic marks/chromatin scars throughout the genome), and exposome (lifestyle/environmental exposures) determine the phenome (health status). Epigenetic alterations induced by cumulative lifestyle and environmental exposures (e.g., perinatal drug exposure, diet, drugs, stressors, and toxins), leading to alterations in the germline of the exposed individual, can be transmitted to the subsequent generations. The interaction between lifestyle and environmental exposures is represented by the exposome (alters the epigenome via DNA methylation (methylome), histone remodeling and post-translational modification (PTM), and gene expression regulators (small RNAs)), which, in turn, alters the genome, without altering the DNA sequence, and modulates gene expression, which, as a result, alters the phenome, which represents all phenotypic traits [modified from Paoloni-Giacobino (50)].

Figure 4

Natural and synthetic cannabinoids can target pregnancy events. Both natural and synthetic cannabinoids target multiple stages of pregnancy. Perinatal use of natural and synthetic cannabinoids disturbs several events in pregnancy including preimplantation embryo development, embryo development, oviductal embryo transport, implantation, placentation, and perhaps, decidualization and parturition [modified from Sun and Dey (11)].