Effects of cannabis smoke and oral Δ9THC on cognition in young adult and aged rats

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Abstract
Rationale 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. Objectives 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. Methods Rats were exposed acutely to cannabis smoke or chronically to oral Δ9-tetrahydrocannabinol (Δ9THC), followed by cognitive testing. Results 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. Conclusions 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.
Funding Information
  • National Institute on Aging (R01AG072714)
  • Florida Department of Health (21A11)
  • National Institute of Neurological Disorders and Stroke (T32AG061832)
  • Evelyn F. McKnight Brain Research Foundation (Evelyn F. McKnight Brain Research Foundation)

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