Cannabis smoke and oral Δ9THC enhance working memory in aged but not young adult subjects
Sabrina Zequeira, Emely A. Gazarov, Alara A. Güvenli, Erin C. Berthold, Alexandria S. Senetra, Marcelo Febo, Takato Hiranita, Lance Richard McMahon, Abhisheak Sharma, Christopher R. McCurdy, Barry Setlow, Jennifer L. Bizon
bioRxiv (Cold Spring Harbor Laboratory) September 29, 2024 preprint DOI: 10.1101/2024.09.26.615028 via OpenAlex
Summary
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.
Study at a glance
| Characteristics | Experimental study |
|---|---|
| Population | Young adult and aged rats of both sexes |
| Intervention | Cannabis smoke |
| Topics | Cannabis |
| Keywords | Smoke Working memory Developmental psychology Medicine |
| Key finding | Acute cannabis smoke enhanced prefrontal cortex-dependent working memory in aged male rats but impaired it in aged females, while chronic oral Δ9THC enhanced working memory in aged rats of both sexes, with no effects on hippocampus-dependent tasks. |
Abstract
With increased legalization of recreational and medical cannabis, use of this drug is growing rapidly among older adults. As cannabis use can impair cognition in young adults, it is critically important to understand how consumption interacts with the cognitive profile of aged individuals, 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. Acute exposure to 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 exposure regimen had minimal effects on a hippocampus-dependent trial-unique non-matching to location mnemonic task, irrespective of age or sex. In a second set of experiments, chronic oral consumption of Δ9-tetrahydrocannabinol (Δ9THC) enhanced working memory in aged rats of both sexes, while having no effects in young adults. In contrast, the same oral 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. Together, these 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.