Scientists have shown that an active ingredient of cannabis significantly upregulates autophagy, extending both lifespan and healthspan in C. elegans nematode worms and demonstrating benefits to mouse neurons.
Two of the most well-known components of marijuana are tetrahydrocannabinol, or THC, and cannabidiol, or CBD. They have the same atomic composition, but differ in structure. THC provides the high that is often associated with marijuana use. CBD, on the other hand, is considered benign and seems to possess antipsychotic, pro-cognitive, anti-inflammatory, anti-seizure, and antioxidant properties. In June 2018, the FDA approved Epidiolex, the first CBD-based prescription medication, for rare forms of epilepsy, and later for the treatment of some seizures. However, the research into both compounds is still in its infancy.
In this new study, scientists dived deeper into the workings of CBD using C. elegans nematode worms, which is considered a good model for initial studies, including in geroscience.
Previous research has shown that CBD can increase lifespan in C. elegans and zebrafish, but the mechanism had remained unknown. Another study found that CBD induces autophagy in cultured neuronal cells. In this new study, the researchers attempted to investigate the relationship between these two effects.
Autophagy is the process of clearing away various cellular debris, such as misfolded proteins and dysfunctional organelles. Unsurprisingly, this maintenance system appears to be very important for health and longevity in numerous model organisms and in humans.
The CBD treatment greatly increased autophagic activity in several tissues and cell types, most drastically by 78% in neurons. The researchers then validated those findings in vitro on several types of cells, including mouse primary hippocampal neurons. Importantly, impaired autophagy in the brain is considered a major cause of Alzheimer’s disease.
Worms on CBD lived significantly longer than controls. The researchers also measured the worms’ healthspan. Many interventions that prolong lifespan in C. elegans often lead to functional impairment, such as decreased motility. Three popular health metrics in C. elegans that decline with age are pharyngeal pumping rate, reproductive capacity, and locomotion, and all three were significantly restored, rather than impaired, by CBD treatment.
The gene SIRT1 has been a popular object of study in geroscience. One of its roles is a mediator of autophagy. By knocking out SIRT1 in mouse neurons, researchers were able to obliterate many of the benefits of CBD, pointing at a crucial role of SIRT1 in mediating CBD-induced effects.
CBD is an intriguing compound that might have numerous beneficial qualities. This study expands our understanding of CBD's effects, linking them to autophagy, an important process that keeps popping up on geroscientists' radars.
It is encouraging that CBD demonstrates the strongest pro-autophagy effect in neurons, making it a potential anti-Alzheimer’s drug. Obviously, the fact that CBD increases autophagy in worms does not mean that using marijuana makes humans healthier, and we’ll need to see human trials on CBD and other compounds.
SOURCES AND FURTHER READING
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Cannabidiol induces autophagy and improves neuronal health associated with SIRT1 mediated longevity - https://pubmed.ncbi.nlm.nih.gov/35445360/
Effect of Cannabidiol on the Long-Term Toxicity and Lifespan in the Preclinical Model Caenorhabditis elegans - https://pubmed.ncbi.nlm.nih.gov/33998871/
Developmental exposure to cannabidiol (CBD) alters longevity and health span of zebrafish (Danio rerio) - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7205952/
Cannabidiol induces autophagy via ERK1/2 activation in neural cells - https://www.nature.com/articles/s41598-021-84879-2
EPIDIOLEX® (cannabidiol) - https://youtu.be/zepKBzlKzdY
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