Acute cannabis smoke enhanced working memory accuracy in aged male rats but impaired it in aged females, with no effects in young adults of either sex. The same smoke had minimal effects on a hippocampus-dependent memory task regardless of age or sex. Chronic oral Δ9-tetrahydrocannabinol (Δ9THC) enhanced working memory in aged rats of both sexes while not affecting young adults, and did not affect spatial learning or memory in either age group. Minimal age differences in Δ9THC pharmacokinetics were observed. Cannabis and Δ9THC can attenuate working memory impairments that emerge in aging without exacerbating age-associated hippocampus-dependent cognitive decline.
Delta-8-THC, a cannabinoid growing in popularity for its reported therapeutic effects, was studied in male rats to understand its pharmacokinetics. After a single oral dose of 7.5 mg/kg, the compound showed very low oral bioavailability of 3.0%, with a peak plasma concentration of 13.4 ng/mL reached in 0.5 hours. Intravenous dosing at 1.25 mg/kg revealed a clearance rate higher than rat liver blood flow, suggesting elimination occurs partly outside the liver, and a large volume of distribution, indicating extensive movement into tissues. The elimination half-life was 13.9 hours. These findings suggest that oral Delta-8-THC is poorly absorbed, while its distribution and clearance patterns resemble those of other cannabinoids.