Cannabis Improved Working Memory in Aged Rats But Not Young Ones, With Sex Differences in Smoke Exposure

Acute cannabis smoke enhanced working memory in aged male rats but impaired it in aged females, with no effects in young adults of either sex. Chronic oral THC enhanced working memory in aged rats of both sexes without affecting young adults. Neither route of administration affected hippocampus-dependent spatial memory in any group. Minimal age differences were found in THC pharmacokinetics.

Two experiments in young adult and aged rats of both sexes. Experiment 1: acute cannabis smoke exposure with working memory (prefrontal cortex-dependent) and spatial memory (hippocampus-dependent) tests. Experiment 2: chronic oral THC consumption with the same cognitive assessments. THC pharmacokinetics measured for both routes.

The fastest-growing demographic of cannabis users is older adults, yet almost all cannabis-cognition research uses young subjects. This study flips the script: instead of asking whether cannabis harms young brains, it asks whether cannabis helps aging brains, and finds evidence that it can.

The endocannabinoid system declines with age, and this decline is linked to cognitive deterioration. These findings suggest exogenous cannabinoids may compensate for this age-related endocannabinoid deficit, potentially explaining why cannabis affects older and younger brains so differently. This has significant implications for medical cannabis use in aging populations.

Animal study using rats, which have shorter lifespans and different endocannabinoid system dynamics than humans. Cognitive tasks in rats approximate but do not replicate human working memory. The sex difference with smoke but not oral administration suggests route-specific effects that complicate interpretation.