Recreational use of marijuana during pregnancy and negative gestational and fetal outcomes: An experimental study in mice

Abstract

The prevalence of marijuana use among pregnant women is high. However, the effects on gestation and fetal development are not well known. Epidemiological and experimental studies present conflicting results because of the route of administration, dose, time of exposure, species used, and how Cannabis toxicity is tested (prepared extracts, specific components, or by pyrolysis). In this study, we experimentally investigated the effects of maternal inhalation of Cannabis sativa smoke representing as nearly as possible real world conditions of human marijuana use. Pregnant mice (n=20) were exposed (nose-only) daily for 5min to marijuana smoke (0.2g of Cannabis) from gestational day (GD) 5.5 to GD17.5 or filtered air. Food intake and maternal weight gain were recorded. Ultrasound biomicroscopy was performed on 10.5 and 16.5dpc.On GD18.5, half of the dams were euthanized for the evaluation of term fetus, placenta, and resorptions. Gestation length, parturition, and neonatal outcomes were evaluated in the other half. Five minutes of daily (low dose) exposure during pregnancy resulted in reduced birthweight, and litter size was not altered; however, the number of male pups per litter was higher. Besides, placental wet weight was increased and fetal to placental weight ratio was decreased in male fetuses, showing a sex-specific effect. At the end of gestation, females from the Cannabis group presented reduced maternal net body weight gain, despite a slight increase in their daily food intake compared to the control group. In conclusion, our results indicate that smoking marijuana during pregnancy even at low doses can be embryotoxic and fetotoxic.

Tobacco, alcohol and illicit drugs during pregnancy and risk of neuroblastoma: systematic review

“…As far as biological plausibility models are concerned, the active ingredient of marijuana, Δ-9-tetrahydrocannabinol (THC) and its metabolites, appears to play a role in carcinogenesis as it crosses the placenta, accumulates in the developing embryo and may result in adverse gestational and fetal outcomes such as reduced birth weight, as demonstrated in animal models 37. Furthermore, marijuana tar was found to induce higher levels of the carcinogen-metabolising enzyme cytochrome P4501A1 (CYP1A1) messenger RNA (mRNA) 38.…”

Cannabis use during pregnancy: Pharmacokinetics and effects on child development

“…While there were significant increases in offspring mortality at both doses, broad-based behavioral testing (including the rest-activity cycle, latency to attach to a nipple and ontogeny of locomotor activity) did not reveal adverse effects of early THC exposure ( Brake et al, 1987; Hutchings et al, 1987, 1989, 1991a, 1991b). In a recent inhalation mouse study, a dose of ~ 0.5 mg/kg/day THC smoke from GD 5.5–17.5 produced deficits in fetal growth and reduced birthweights in cannabis-exposed offspring (Benevenuto et al, 2017). Pups with a history of gestational THC exposure showed a surprising 9.9% drop in birthweight and significant decrements in the weight of lungs, brain, thymus, and liver.…”

Effects of prenatal marijuana exposure on neuropsychological outcomes in children aged 1‐11 years: A systematic review

“…The use of marijuana during pregnancy could have implications for foetal brain development . Marijuana is lipid soluble and able to cross the placenta and blood‐brain barrier to accumulate in foetal tissues including brain tissues .…”

“…The strongest evidence of adverse effects of prenatal marijuana exposure comes from animal studies . These studies demonstrated that even low doses of marijuana during pregnancy can result in adverse cognitive and developmental effects in offspring . In human studies, there are variations in the effect's direction, degree and duration .…”