The balance between pro-aging and counteracting homeostatic mechanisms largely determines the progression of aging. The endocannabinoid system is thought to be part of the latter system because it modulates the physiological processes underlying aging. Its activity declines during aging and CB1 receptor expression and G protein coupling are reduced in the brain tissues of older animals. However, a direct link between endocannabinoid tone and aging symptoms has not been demonstrated. Here the authors show that a low dose of Δ9-tetrahydrocannabinol (THC) reversed the age-related decline in cognitive performance of mice aged 12 and 18 months. This behavioral effect was accompanied by enhanced expression of synaptic marker proteins and increased hippocampal spine density. THC treatment restored hippocampal gene transcription patterns in 12 month old mice to levels closely resembling those of THC-free animals aged 2 months. The transcriptional effects were dependent on glutamatergic CB1 receptors and histone acetylation, as their inhibition blocked the beneficial effects of THC. The authors suggest that restoration of CB1 signaling in old individuals could be an effective strategy to treat age-related cognitive impairments. By contrast, THC was not effective in young animals and actually impaired their performance. “It seems that the young brain becomes old and the old brain becomes young”, when the results from the different age groups were compared.
Bilkei-Gorzo A, Albayram O, Draffehn A, Michel K, Piyanova A, Oppenheimer H, Dvir-Ginzberg M, Rácz I, Ulas T, Imbeault S, Bab I, Schultze JL, Zimmer A: A chronic low dose of Δ9-tetrahydrocannabinol (THC) restores cognitive function in old mice. Nature Medicine [May 8, 2017; Epub ahead of print]; doi: 10.1038/nm.4311.