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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 Δ(9)-tetrahydrocannabinol (THC) restores cognitive function in old mice. Nat Med. 2017 Jun;23(6):782-787. Epub 2017 May 8 PubMed.
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University of New South Wales
This is a fascinating study which demonstrates that THC, the psychoactive ingredient of cannabis, restores cognitive function in older mice. The authors also showed that this was mediated by stimulation of cell plasticity and signalling mechanisms in older animals. The cannabinoid receptor 1 (CB1) appears to be important, and the authors suggest that the regular administration of low-dose THC normalized the weak cannabinoid signalling that occurs with aging. The authors also present data to suggest that this reverses age-related epigenetic changes, possibly through the activation of histone acetylase.
These findings are consistent with previous knowledge. The cannabinoid system, targeted by cannabis, is a complex network of receptors and molecules that have many functions in the brain, and help reduce neuronal damage and promote repair. Previous studies have shown that THC and cannabidiol (CBD), another alkaloid found in cannabis, reduce Alzheimer’s-type pathology in mouse models of Alzheimer’s disease. It is also known that sirtuin 1 (SIRT1), which removes acetyl groups from many histones, interacts with the cannabinoid receptor. Cannabis is therefore of interest in aging.
However, there are many unanswered questions. Importantly, this study showed that THC had the opposite effects in young mice, worsening memory and evoking the molecular profile of older mice. There is good evidence that cannabis worsens cognition in humans, particularly young adults who abuse it over a period of time. The reasons for discrepant effects in young and old mice are not known. Are they related to an optimal level of stimulation of CB1 and CB2? If yes, how does one achieve this optimal level and at what age does the transition from deleterious to beneficial effects occur? Is the effect the same in humans? Replication of the findings in mice, and the studies of cannabinoid system in aging humans are necessary before one can consider translating any such findings to intervention studies.
There has been some work in animal models of Alzheimer’s disease to see if cannabis could slow the progression of the pathology. The results have not been consistent. Understanding the changes in the cannabinoid system with aging may help to clarify the mechanisms. Many other questions remain. What is a low dose? The dose of 3 mg/Kg, when translated into human terms, is not necessarily a low dose. The psychoactive effects of THC may be unacceptable, and long-term effects of such interventions are unclear. It is not known if the same results can be achieved with CBD, which does not have psychoactive properties.
In short, this report should prompt further work on the cannabinoid system with aging, and its implications for human health, both in normal aging and in age-related diseases. It is too early to regard THC, or cannabis in general, as an elixir of youth.
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