The Impact of Early Life Exposure to Cannabis: The Role of the Endocannabinoid System

Abstract

Cannabis use during pregnancy has continued to rise, particularly in developed countries, as a result of the trend towards legalization and lack of consistent, evidence-based knowledge on the matter. While there is conflicting data regarding whether cannabis use during pregnancy leads to adverse outcomes such as stillbirth, preterm birth, low birthweight, or increased admission to neonatal intensive care units, investigations into long-term effects on the offspring’s health are limited. Historically, studies have focused on the neurobehavioral effects of prenatal cannabis exposure on the offspring. The effects of cannabis on other physiological aspects of the developing fetus have received less attention. Importantly, our knowledge about cannabinoid signaling in the placenta is also limited. The endocannabinoid system (ECS) is present at early stages of development and represents a potential target for exogenous cannabinoids in utero. The ECS is expressed in a broad range of tissues and influences a spectrum of cellular functions. The aim of this review is to explore the current evidence surrounding the effects of prenatal exposure to cannabinoids and the role of the ECS in the placenta and the developing fetus.

The Effects of Cannabis Use during Pregnancy on Low Birth Weight and Preterm Birth: A Systematic Review and Meta-analysis

“…No language restriction was applied. The search was restricted to studies published after 2000, because of the increase in THC potency in the last decades 22 . The mesh terms "marijuana use", "marijuana abuse", "cannabis" and "cannabinoids" were 5…”

“…The search was restricted to studies published after 2000 because of the increase in THC potency in the last decades. 22 The mesh terms "marijuana use", "marijuana abuse", "cannabis," and "cannabinoids" were used to define the search expression, being adapted according to the different datasets. The search was followed by reference tracking, examining the references of the selected publications based on full-text assessment.…”

Major Phytocannabinoids and Their Related Compounds: Should We Only Search for Drugs That Act on Cannabinoid Receptors?

“…The first ones isolated in 1975 (examples: dehydrocannabifuran DCBF-C5, cannabifuran CBF-C5) [23] The discovery of these compounds led to the identification of cannabinoid receptors (CB1 and CB2) and endogenous ligands of the endocannabinoid system. There is evidence that this system plays an essential role in many normal physiological processes, such as memory, cognition, learning, motor control, anxiety, appetite, sleep, lipogenesis, fertility, formation of insulin and muscle fibers, vasomotricity, intestinal and bronchial motility, and immune modulation, but also in pathological-like pain, inflammation, and cancer [24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42].…”

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

“…In addition to the physical health effects, preclinical studies have shown severe brain developmental consequences associated with prenatal synthetic cannabinoid exposure in chickens (Psychoyos, Hungund, Cooper, & Finnell, 2008), mice (Gilbert et al, 2016) and rats (Mereu et al, 2003). While examining later life behavior, prenatal cannabis use has also been found to have long-term effects on diminished verbal and memory skills (Day et al, 1994), increased impulsivity and hyperactivity (Richardson, Ryan, Willford, Day, & Goldschmidt, 2002) and decreased attention and concentration during childhood and adolescence (Fried & Smith, 2001; Martínez-Peña et al, 2021). Consequences of use also affect adult functioning including substance use, memory deficits and cognition, motivation and behavioral regulation (De Genna, Willford, & Richardson, 2022; Zamberletti & Rubino, 2022), as well as altered neural functioning during visuospatial working memory (Smith, Fried, Hogan, & Cameron, 2006).…”