Maternal‐fetal transmission of delta‐9‐tetrahydrocannabinol (THC) and its metabolites following inhalation and injection exposure during pregnancy in rats

Abstract

Cannabis use during pregnancy has increased over the past few decades, with recent data indicating that, in youth and young adults especially, up to 22% of people report using cannabis during pregnancy. Animal models provide the ability to study prenatal cannabis exposure (PCE) with control over timing and dosage; however, these studies utilize both injection and inhalation approaches. While it is known that Δ9‐tetrahydrocannabinol (THC; primary psychoactive component of cannabis) can cross the placenta, examination of the transmission and concentration of THC and its metabolites from maternal blood into the placenta and fetal brain remains relatively unknown, and the influence of route of administration has never been examined. Pregnant female rats were exposed to either vaporized THC‐dominant cannabis extract for pulmonary consumption or subcutaneous injection of THC repeatedly during the gestational period. Maternal blood, placenta, and fetal brains were collected following the final administration of THC for analysis of THC and its metabolites, as well as endocannabinoid concentrations, through mass spectrometry. Both routes of administration resulted in the transmission of THC and its metabolites in placenta and fetal brain. Repeated exposure to inhaled THC vapor resulted in fetal brain THC concentrations that were about 30% of those seen in maternal blood, whereas repeated injections resulted in roughly equivalent concentrations of THC in maternal blood and fetal brain. Neither inhalation nor injection of THC during pregnancy altered fetal brain endocannabinoid concentrations. Our data provide the first characterization of maternal‐fetal transmission of THC and its metabolites following both vaporized delivery and injection routes of administration. These data are important to establish the maternal‐fetal transmission in preclinical injection and inhalation models of PCE and may provide insight into predicting fetal exposure in human studies.

Impact of prenatal cannabis exposure on functional connectivity of the salience network in children

“…Therefore, administration of exogenous cannabinoids, such as THC and/or cannabidiol, may disrupt the developing eCB system and impact postnatal outcomes. Indeed, a recent preclinical study in a cannabis inhalation model demonstrated that up to 30% of THC in circulating maternal blood reaches the fetal brain (Baglot et al, 2022). In sum, our findings add to the growing body of evidence suggesting that PCE, particularly during early gestation, can have detrimental effects on offspring neurodevelopment.…”

Influence of prenatal cannabinoid exposure on early development and beyond

“…The precise impact of potency and patterns of maternal cannabis use on the developing fetus remains unclear. Regardless of the method of consumption, it is clear from human and preclinical studies that the major psychoactive component of cannabis, THC, crosses the placenta into fetal tissues where it has the potential to interfere with development [for review see (16) and (17)(18)(19)(20)(21)(22)(23)(24)(25)].…”

Characterising ‘the munchies’; effects of delta-9-tetrahydrocannabinol (THC) vapour inhalation on feeding patterns, satiety, and macronutrient-specific food preference in male and female rats

“…A validated vapour inhalation system (La Jolla Alcohol Research Inc., California, USA) was used as previously described [35, 38]. Rats were subjected to inhalation of vapour from a THC-dominant cannabis extract containing 89.7% THC, 0.3% CBD, 1.7% CBG, 1.4% CBN and 0.6% CBC (Aphria Inc., Ontario, Canada) diluted to 10% THC in polyethylene glycol vehicle.…”

“…Plasma and hypothalami samples were run through tandem mass spectrometry (LC-MS/MS) at the University of Calgary Southern Alberta Mass Spectrometry facility to measure THC, CBD, and THC metabolite concentrations (11-OH-THC and THC-COOH), as previously described [35, 38]. In short, 250 μl thawed plasma and homogenised whole hypothalami were added to a 20:1 solution of acetonitrile and deuterated analyte standards for THC, CBD, 11-OH-THC and THC-COOH (at a known concentration of 10 ng/ml in 1:1 methanol and water; Cerilliant, Round Rock, TX, USA).…”