Research press release


Nature Medicine

Cannabinoid might improve learning and memory in old mice



Andreas Zimmerたちは、若齢(2か月齢)、成熟(12か月齢)、老齢(18か月齢)マウスで、THCの低用量長期投与の効果を調べた。すると、若齢マウスでは投与により学習・記憶課題の処理能力が損なわれたが、成熟マウスと老齢マウスでは、同じ投与で学習・記憶が実際に改善されることが分かった。成熟、老齢マウスのこのような行動変化に伴って、海馬全域の遺伝子発現パターンが、若齢マウスで観察されたのと似た状態に回復していた。


The effects of chronic, low-dose administration of the cannabinoid THC - the main psychoactive ingredient in marijuana - on neurocognitive behavior and gene expression patterns in young and old mice are reported online in Nature Medicine this week. These preclinical findings suggest that, at least in mice, THC treatment can ameliorate age-related learning and memory deficits. However, it is too premature to determine whether these effects might also apply to other species, including humans.

Psychoactive compounds found in marijuana, such as the cannabinoids Δ9-tetrahydrocannabinol (THC) or cannabidiol, exert their actions on the nervous system by interacting with endogenous cannabinoid (endocannabinoid) receptors. The potential use of cannabinoids to treat human neurological conditions such as epilepsy or pain remains an active, yet controversial, area of research. Although cannabinoid use is generally thought to elicit acute cognitive impairments and might carry a high potential for abuse, its effects on the aged brain are not well characterized. Previous work has found that the brain endocannabinoid system is downregulated during the course of normal aging.

Andreas Zimmer and colleagues examined the effects of chronic, low-dose THC administration in young (two months old), mature (12 months old) and old (18 months old) rodents. They find that although treatment impaired behavioral performance on learning and memory tasks in young mice, similar treatment actually improved learning and memory in mature and old mice. These changes in behavior in older animals were associated with a restoration of global hippocampal gene expression patterns back to a state similar to that observed in young animals.

Essential next steps include additional preclinical investigation to more thoroughly document the time course and persistence of these effects, as well as to determine their mechanistic basis. Furthermore, it remains to be determined whether similar age-dependent effects would be observed in other animal models that exhibit age-related cognitive decline more similar to that observed in humans (such as in nonhuman primates).

doi: 10.1038/nm.4311

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