Pharmacokinetic Effects of Combined Exposure to Nicotine and THC via E-Cigarettes in Pregnant Rats

Abstract

Nicotine and cannabis are two of the most commonly consumed licit and illicit drugs during pregnancy, often consumed together via e-cigarettes. Vaping is assumed to be a safer alternative than traditional routes of consumption, yet the potential consequences of prenatal e-cigarette exposure are largely unknown, particularly when these two drugs are co-consumed. In a novel co-exposure model, pregnant Sprague-Dawley rats received nicotine (36 mg/mL), THC (100 mg/mL), the combination, or the vehicle via e-cigarettes daily from gestational days 5-20, mimicking the first and second human trimesters. Maternal blood samples were collected throughout pregnancy to measure drug and metabolite levels, and core body temperatures before and after exposure were also measured. Pregnant dams exposed to combined nicotine and THC had lower plasma nicotine and cotinine levels than those exposed to nicotine alone; similarly, the combined exposure group also had lower plasma THC and THC metabolite (THC-OH and THC-COOH) levels than those exposed to THC alone. Prenatal nicotine exposure gradually decreased basal core body temperatures each day, with chronic exposure, whereas exposure to THC alone decreased temperatures during the individual sessions. Despite these physiological effects, no changes were observed in food or water intake, weight gain, or basic litter outcomes. These data suggest that combined exposure to nicotine and THC elicits both separate and interactive physiological effects of nicotine and THC on pregnant dams. These data and use of this model can help improve education for pregnant mothers about prenatal e-cigarette use and has important implications for public policy.HIGHLIGHTSRepeated prenatal nicotine exposure via e-cigarettes gradually decreased temperaturesPrenatal THC exposure via e-cigarettes decreased temperatures during intoxicationCombined prenatal exposure via e-cigarettes altered plasma drug and metabolite levelsThis co-exposure model elicits separate and interactive effects of nicotine and THC

Cannabis for morning sickness: areas for intervention to decrease cannabis consumption during pregnancy

“…THC is commonly consumed in combination with other widely available drugs such as nicotine, CBD, and alcohol (Forray et al 2015 ). Murine research shows that fetal exposure to THC in combination with nicotine impacts THC metabolism (Breit et al 2021 ), THC in combination with CBD altered offspring behavior and physiology (Maciel et al n.d ), (Kanyo et al 2021 ), and craniofacial development (Fish et al 2019 ). While the research investigating CBD exposure along during pregnancy is a new point of interest, the findings are moving (Ochiai et al 2021 ), (Pandelides et al 2020 ).…”