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Effects of cannabis smoke exposure in young and aged mice

Emely Gazarov
University of Florida

Co-Authors: Sabrina Zequeira1, Alexandria S Senetra1, Bailey McCracken1, John Howard1, Abhisheak Sharma1, Christopher R McCurdy1, Jada Lewis1, Jennifer L Bizon1, Barry Setlow1
1University of Florida

With the rise in cannabis use among older adults, as well as increasing cases of Alzheimer’s disease (AD), there is an urgent need to investigate the impacts of cannabis use on the aging brain and AD pathology. As a first step in this process, we evaluated the pharmacokinetics of Δ9THC and two of its metabolites following acute exposure to smoke from burning cannabis cigarettes in mice of different ages and strains.

To determine the time course of Δ9THC and its two major metabolites (11-OH-THC and 11-COOH-THC), young-adult C57BL/6J mice (n = 72, half female) were exposed to smoke generated from burning 5 cannabis cigarettes sequentially over one hour. Trunk blood and brain were collected at 6 time points (10, 20, 40, 60, 120 & 240 min following smoke exposure). Plasma and brain homogenates were analyzed for Δ9THC and metabolites using a validated UPLC-MS/MS method. To assess the effects of age and strain on Δ9THC pharmacokinetics, male and female B6, FVB, SW, and 129 mice (n = 89, 4-24 months old) followed the same smoke regimen, with samples collected 10 and 40 min following smoke exposure. To determine the effect of dose on Δ9THC and its metabolites, mice (n = 20) were exposed to smoke from either 3 or 5 cannabis cigarettes and samples were collected 40 min post-smoke exposure.

The results revealed that plasma Δ9THC concentrations peaked at 10 and 40 minutes for males and females, respectively, while brain Δ9THC concentrations peaked at 20 and 40 minutes for males and females, respectively. Females had significantly greater plasma 11-COOH-THC concentrations than males. There were no age or strain differences in plasma Δ9THC concentrations at 10 or 40 min; however, 129 mice had significantly higher brain Δ9THC concentrations than FVB mice. Additionally, a 3-cigarette dose produced significantly lower 11-COOH-THC plasma concentrations compared to a 5-cigarette dose. This effect was not evident in plasma or brain concentrations of Δ9THC and 11-OH-THC. Ongoing studies are determining the effects of chronic cannabis smoke exposure on markers of inflammation in young-adult and aged mice, and on AD-like tau pathology in rTg4510 mutant tau transgenic mice.

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