We have all heard of the benefits of cannabidiol (CBD) such as chronic pain relief, anxiety reduction, and reduction of seizures in children with epilepsy. Most physicians will recommend the use of CBD instead of marijuana, because it lacks the psychoactive component tetrahydrocannabinol (THC). But what if there were some benefits to THC, particularly in elderly individuals? Bilkei-Gorzo et al. (2017) demonstrated that chronic use of a low dose of Δ9 -tetrahydrocannabinol (THC) not only improved the cognitive function in mature and old mice, but it also reversed age-related cognitive decline. Does this mean that THC could be used as an effective treatment to reverse age-related cognitive function? To answer that question, we must first explore how THC affects the brain, particularly in an elderly brain.
THC binds to CB1 and CB2 cannabinoid receptors which are G-protein coupled receptors that trigger a cascade of physiological and psychological effects in the brain such as changes in blood pressure, heart rate, reaction time, memory impairments, and suppression of motor skills (Matsuda et al, 1990 and Munro et al. 1993). THC is considered an exogenous cannabinoids (eCBs), and eCBs can change synaptic plasticity at excitatory synapses through the neurotransmitter GABA and at inhibitory synapses through the neurotransmitter glutamate (Zhu and Lovinger, 2007). As we have learned in human physiology, the effects of THC are directly dependent on the type of receptors they bind to and those receptors’ secondary messenger systems. Research has shown that CB1 receptors on excitatory GABAergic neurons in the hippocampus may provide some protection against age-dependent cognitive decline (Albayram et al., 2011). In the study done by Bilkei et al. (2017), they found the genes that encode for CB1 and other cognitive protective genes were upregulated after the administration of THC and genes related to aging effects were downregulated. Interestingly, they found that young mice treated with THC had gene expression and synaptic changes similar to the control mature and old mice (Bilkei et at., 2017). THC appears to have an opposite effect on young mice inducing cognitive decline. This begs the question, what are the differences between elderly and young brains that are responsible for such changes in cognitive function while using THC?
Unfortunately, that is a topic for another day, but new studies are starting to look more closely at gene expression and epigenetic factors in aging which may yield some interesting results. Although there is still much further research to be done before clinical trials on human beings can be begin, chronic low doses of THC is a promising treatment option for reducing the effects of aging on cognitive functioning. That being said, it is probably too early to be experimenting with getting grandma high; however, the future we may see THC replace DHEA for cognitive enhancement in the elderly.
References
Albayram, O., Alferink, J., Pitsch, J., Piyanova, A., Neitzert, K., Poppensieker, K., Mauer, D., Michel, K, Legler, A., Becker, A., Monory, K., Lutz, B., Zimmer, A., & Bilkei-Gorzo, A. (2011). Role of CB1 cannabinoid receptors on GABAergic neurons in brain aging. Proceedings of the National Academy of Sciences, 108(27), 11256-11261. https://doi.org/10.1073/pnas.1016442108
Bilkei-Gorzo, A., Albayram, O., Draffehn, A., Michel, K., Piyanova, A., Oppenheimer, H., Dvir-Ginzber, M., Rácz, I., Ulas, T., Imbeault, S., Bab, I., Schultze, J., & Zimmer, A. (2017). A chronic low dose of Δ 9-tetrahydrocannabinol (THC) restores cognitive function in old mice. Nature Medicine, 23(6), 782.
Matsuda, L. A., Lolait, S. J., Brownstein, M. J., Young, A. C., & Bonner, T. I. (1990). Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature. 346(6284), 561–564.
Munro, S., Thomas, K. L., & Abu-Shaar, M. (1993). Molecular characterization of a peripheral receptor for cannabinoids. Nature, 365(6441), 61.
Zhu, P. J., & Lovinger, D. M. (2007). Persistent synaptic activity produces long-lasting enhancement of endocannabinoid modulation and alters long-term synaptic plasticity. Journal of neurophysiology, 97(6), 4386-4389. doi:10.1152/jn.01228.2006
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