Influence of Carrier Oil, Sex, and Age on Pharmacokinetic and Acute Behavioral Effects of Vaporized Cannabis Extract in Mice.

Abstract

The legalization of cannabis in several states across the United States has increased the need to better understand its effects on the body, brain, and behavior, particularly in different populations. Previous rodent studies have revealed age and sex differences in response to injected Δ⁹-tetrahydrocannabinol (THC). However, the pharmacokinetic and pharmacodynamic properties of THC administered through more translationally relevant routes of administration are less well known. Here, we addressed this gap by investigating age and sex differences in pharmacokinetics and the acute behavioral effects of vaporized cannabis e-liquid in mice. Adolescent (postnatal day [P] 35-50) and adult (≥P70) mice of both sexes received noncontingent exposure to vehicle vapor, 150 mg/mL (CAN150), or 300 mg/mL (CAN300) vaporized cannabis extract diluted in either 80% propylene glycol/20% vegetable glycerin (PG/VG) or 100% polyethylene glycol 400 (PEG). Immediately after exposure, body temperature, hot plate withdrawal latency, and locomotion were assessed. Blood was collected at 0, 30, and 60 min after vapor exposure, and plasma THC, 11-hydroxy-THC, and 11-nor-9-carboxy-THC were analyzed. THC concentrations were higher in both the plasma of vapor-exposed mice and the cannabis extract solutions when PEG was the carrier oil compared with PG/VG. Vaporized cannabis (mixed with PEG) at the highest dose tested induced hypothermic, antinociceptive, and locomotor-suppressing effects in all groups of mice. We found a dose-dependent age difference in locomotion, indicating that adolescents were less sensitive to the locomotor-suppressing effects of vaporized cannabis, which may be related to differences in circulating THC levels. Although we found no sex differences in the acute behavioral effects of vaporized cannabis, there were sex differences in plasma THC metabolites, suggesting that female mice may metabolize vaporized cannabis more slowly than male mice. Taken together, these findings add to a growing literature implementing vaporized cannabinoid delivery approaches by revealing PEG as a more effective carrier oil than PG/VG for studies involving cannabis extract.