Cannabis is the most frequently used illicit drug among pregnant women, yet the potential consequences of prenatal cannabis exposure on development are not well understood. Electronic cigarettes have become an increasingly popular route of administration among pregnant women, in part to user's perception that e-cigarettes are a safer route for consuming cannabis products. Importantly, half of pregnant women who consume cannabis also report consuming alcohol, but research investigating co-consumption of these drugs is limited, particularly with current routes of administration. The purpose of this study was to establish a co-exposure vapor inhalation model of alcohol and THC in pregnant rats, to ultimately determine the effects on fetal development. Pregnant Sprague-Dawley rats were exposed to moderate doses of THC via e-cigarettes, alcohol, the combination, or vehicle daily from gestational days 5–20. Importantly, pharmacokinetic interactions of alcohol and THC were observed during pregnancy. Combined exposure consistently increased blood alcohol concentrations, indicating that THC alters alcohol metabolism. In addition, THC levels also increased over the course of pregnancy and THC metabolism was altered by alcohol. Alcohol, but not THC, exposure during pregnancy reduced maternal weight gain, despite no group differences in food intake. Neither prenatal alcohol nor THC exposure altered gestational length, litter size, sex ratio or birth weight. However, prenatal alcohol exposure delayed eye opening, and prenatal THC exposure decreased body weights during adolescence among offspring. These individual and synergistic effects suggest that this novel co-exposure vapor inhalation paradigm can effectively be used to expose pregnant dams, exerting some effects on fetal development, while avoiding nutritional confounds, birth complications, or changes in litter size. With this model, we have demonstrated that combining THC and alcohol alters drug metabolism, which could have important consequences on prenatal development.

大麻是孕妇最常用的非法药物，但产前接触大麻对发育的潜在影响尚不清楚。电子烟已成为孕妇中越来越流行的给药途径，部分原因是用户认为电子烟是消费大麻产品的更安全途径。重要的是，一半服用大麻的孕妇也报告饮酒，但调查这些药物的共同消费的研究是有限的，特别是在目前的给药途径下。本研究的目的是建立妊娠大鼠酒精和四氢大麻酚共暴露蒸气吸入模型，最终确定对胎儿发育的影响。怀孕的 Sprague-Dawley 大鼠通过电子烟、酒精、从妊娠 5-20 天起，每天使用组合或车辆。重要的是，在怀孕期间观察到酒精和 THC 的药代动力学相互作用。联合暴露持续增加血液酒精浓度，表明 THC 改变了酒精代谢。此外，THC 水平在怀孕期间也会增加，并且 THC 代谢会因酒精而改变。尽管食物摄入量没有组别差异，但怀孕期间接触酒精而不是 THC 会减少母亲的体重增加。产前饮酒和四氢大麻酚暴露都不会改变胎龄、产仔数、性别比或出生体重。然而，产前接触酒精会延迟睁眼，产前接触四氢大麻酚会降低后代青春期的体重。这些个体和协同效应表明，这种新的共同暴露蒸汽吸入模式可以有效地用于暴露怀孕的水坝，对胎儿发育产生一些影响，同时避免营养混淆、分娩并发症或产仔数的变化。通过这个模型，我们已经证明，将 THC 和酒精结合可以改变药物代谢，这可能对产前发育产生重要影响。