Influence of solvent, sex, and age on pharmacokinetic and acute behavioral effects of vaporized cannabis extract in mice
Sara R Westbrook, Allison L Jensen, Vanessa Copeland-Solorzano, Jacob Buursma, Gillian Freeby, Taytum Von Melville, Tyler Edwards, K. Hayashi, Ryan J Mclaughlin, Kristen M Delevich
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study |
|---|---|
| Population | Adolescent and adult mice of both sexes |
| Intervention | Vaporized cannabis extract |
| Dose | 0 mg/ml, 150 mg/ml, or 300 mg/ml vaporized cannabis extract |
| Duration | Immediately after exposure up to 60 min post-exposure |
| Topics | Cannabis |
| Key findings | Vaporized cannabis extract dissolved in PEG produced higher plasma THC levels and stronger behavioral effects than when dissolved in PG/VG; adolescents were less sensitive to locomotor suppression, and females metabolized THC more slowly than males. |
Abstract
Abstract The legalization of cannabis in several states across the US has increased the need to better understand its effects on the body, brain, and behavior, particularly in different populations. Rodent models are particularly valuable in this respect because they provide precise control over external variables. Previous rodent studies have found age and sex differences in response to injected Δ 9 -tetrahydrocannabinol (THC), the major psychoactive component of cannabis. However, this route of administration does not mimic the most common way humans consume cannabis, i.e. through inhalation. Here, we sought to address this gap by investigating age and sex differences in pharmacokinetics and the acute behavioral effects of vaporized cannabis extract in mice. Adolescent (postnatal day [P] 35-50) and adult (≥ P70) mice of both sexes received noncontingent exposure to 0 mg/ml, 150 mg/ml, or 300 mg/ml vaporized cannabis extract diluted in either 80% propylene glycol/20% vegetable glycerol (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 and its metabolites were analyzed. Measured THC levels were higher in both the plasma of vapor-exposed mice and the cannabis extract solutions themselves when PEG was the solvent compared to PG/VG. Vaporized cannabis (dissolved in 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 the plasma THC levels achieved. Although we found no significant sex differences in the acute behavioral effects of vaporized cannabis, there were significant sex differences in plasma THC metabolites indicating that female mice may metabolize vaporized cannabis more slowly than male mice. Taken together, the current findings add to a growing number of studies implementing vaporized cannabinoid delivery approaches by revealing PEG as the superior solvent for studies involving cannabis extract.
Comparable studies
Other preclinical and animal studies on cannabis, most cited first.
Citations in the library
Cites 7
- Are adolescents more vulnerable to the harmful effects of cannabis than adults? A placebo-controlled study in human males Translational Psychiatry November 29, 2016
- Pharmacokinetics and central accumulation of delta-9-tetrahydrocannabinol (THC) and its bioactive metabolites are influenced by route of administration and sex in rats. Scientific Reports December 14, 2021
- Pharmacokinetic and pharmacodynamic properties of aerosolized ("vaped") THC in adolescent male and female rats. Psychopharmacology December 2021
- Lasting effects of repeated ∆9 -tetrahydrocannabinol vapour inhalation during adolescence in male and female rats. British Journal of Pharmacology 2020
- Effects of Δ9-THC and cannabidiol vapor inhalation in male and female rats. Psychopharmacology September 2018
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