Effects of cannabis smoke and oral Δ9THC on cognition in young adult and aged rats
S. Zequeira, E. Gazarov, A. A. Güvenli, Erin C. Berthold, Alexandria S. Senetra, Marcelo Febo, Takato Hiranita, Lance R. McMahon, Abhisheak Sharma, C. R. McCurdy, Barry Setlow, Jennifer L. Bizon
Psychopharmacology February 7, 2025 DOI: 10.1007/s00213-025-06754-6 via Semantic Scholar
Summary
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.
Study at a glance
| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Population | Young adult and aged rats of both sexes |
| Interventions | cannabis smoke oral Δ9-tetrahydrocannabinol |
| Keywords | Medicine |
| Key finding | Acute cannabis smoke enhanced working memory in aged male rats but impaired it in aged females, while chronic oral THC enhanced working memory in aged rats of both sexes, with no effects on young adults or on hippocampus-dependent memory tasks. |
Abstract
With increasing legalization of recreational and medical cannabis, use of this drug is growing rapidly among older adults. As cannabis can impair cognition in young adults, it is critically important to understand how its consumption interacts with the cognitive profile of aged subjects, who are already at increased risk of decline. The current study was designed to determine how cannabis influences multiple forms of cognition in young adult and aged rats of both sexes when delivered via two translationally-relevant routes of administration. Rats were exposed acutely to cannabis smoke or chronically to oral Δ9-tetrahydrocannabinol (Δ9THC), followed by cognitive testing. Acute cannabis smoke enhanced prefrontal cortex-dependent working memory accuracy in aged males, but impaired accuracy in aged females, while having no effects in young adults of either sex. In contrast, the same cannabis smoke regimen had minimal effects on a hippocampus-dependent trial-unique non-matching to location mnemonic task, irrespective of age or sex. Chronic oral consumption of Δ9THC enhanced working memory in aged rats of both sexes, while having no effects in young adults. In contrast, the same Δ9THC regimen did not affect spatial learning and memory in either age group. Minimal age differences were observed in Δ9THC pharmacokinetics with either route of administration. The results show that cannabis and Δ9THC can attenuate working memory impairments that emerge in aging. While these enhancing effects do not extend to hippocampus-dependent cognition, cannabis does not appear to exacerbate age-associated impairments in this cognitive domain.