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.
Combining the sigma1 receptor antagonist CM304 with delta9-tetrahydrocannabinol (THC) enhances pain relief without worsening THC's side effects. In mice, CM304 increased the pain-blocking effect of THC and caused greater body temperature drops when combined. A high dose of CM304 alone reduced movement. In rats, CM304 made THC's pain relief more potent. CM304 did not produce THC-like effects in rats trained to recognize THC, nor did it amplify THC's subjective effects. The findings suggest sigma1 receptor antagonists could be safer adjuncts to cannabinoid-based pain treatments, offering pain relief without increasing adverse effects like sedation or abuse potential.
Cannabis and its psychoactive component Δ9-tetrahydrocannabinol (THC) can improve working memory in aged rats, depending on sex and route of administration. Acute cannabis smoke enhanced working memory accuracy in aged male rats but impaired it in aged females, with no effect on young adults. Chronic oral THC improved working memory in aged rats of both sexes, again with no effect on young adults. Neither cannabis smoke nor oral THC affected hippocampus-dependent memory tasks in any age group. The findings suggest that cannabis may attenuate some age-related working memory deficits without worsening other cognitive impairments, though effects vary by sex and administration route.