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Reversing Brain Ageing with THC!

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Review of “A chronic low dose of Δ9-tetrahydrocannabinol (THC) restores cognitive function in old mice” from Nature Medicine by Stuart P. Atkinson

The search for tonics, tinctures, potions, and poultices that may, or may not, vanquish the signs of aging has recently stumbled across a somewhat unexpected champion in Δ9-tetrahydrocannabinol (THC), the principal psychoactive component in Cannabis sativa! Or perhaps not so unexpected; a little research uncovers several studies linking the age-related decline in the endocannabinoid system (ECS) in the brain [1-4], and this motivated researchers from the laboratory of Andreas Zimmer (University of Bonn, Germany) to thoroughly assess this relationship in the search for a means to reverse aging in the human brain.

Now, in their new Nature Medicine study, Bilkei-Gorzo et al. demonstrate that chronic low dose treatment of aging animals with THC may represent an effective means to reverse any decline in cognitive performance [5].

Initial comparisons of young (2 months), mature (12 months), and old (18 months) demonstrated the expected age-related decline in behaviors linked to aging in the brain. However, low dose THC treatment over 28 days (employing an implanted osmotic minipump) led to a long-lasting improvement in the cognitive performance of mature and old mice, but a reduction in performance in young mice.

Improvements correlated with the heightened expression of synaptic marker proteins, increased hippocampal spine density, and the reversion of hippocampal gene expression profiles in mature and old mice to a profile more similar to young untreated mice. The transcriptional changes associated with these profiles required the activity of glutamatergic CB1 receptors and increased levels of histone acetylation at the regulatory regions of critical genes such as Klotho (Kl) and brain-derived neurotrophic factor (Bdnf).

The authors note that THC administration to older individuals displays an excellent safety profile with no adverse side effects and, therefore, treatment strategies that provide chronic low doses of THC may represent a suitable means to reverse aging in the normal human brain.

Keep your eyes glued to the Stem Cells Portal to discover more on the remarkable effects of THC on the aging brain!

References

  1. Wang L, Liu J, Harvey-White J, et al. Endocannabinoid signaling via cannabinoid receptor 1 is involved in ethanol preference and its age-dependent decline in mice. Proc Natl Acad Sci U S A 2003;100:1393-1398.
  2. Berrendero F, Romero J, Garcia-Gil L, et al. Changes in cannabinoid receptor binding and mRNA levels in several brain regions of aged rats. Biochim Biophys Acta 1998;1407:205-214.
  3. Romero J, Berrendero F, Garcia-Gil L, et al. Loss of cannabinoid receptor binding and messenger RNA levels and cannabinoid agonist-stimulated [35S]guanylyl-5'O-(thio)-triphosphate binding in the basal ganglia of aged rats. Neuroscience 1998;84:1075-1083.
  4. Piyanova A, Lomazzo E, Bindila L, et al. Age-related changes in the endocannabinoid system in the mouse hippocampus. Mech Ageing Dev 2015;150:55-64.
  5. Bilkei-Gorzo A, Albayram O, Draffehn A, et al. A chronic low dose of Delta9-tetrahydrocannabinol (THC) restores cognitive function in old mice. Nat Med 2017;23:782-787.