Combination of cannabinoids, Δ9- tetrahydrocannabinol (THC) and cannabidiol (CBD), mitigate experimental autoimmune encephalomyelitis (EAE) by altering the gut microbiome.
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Abstract<p>Multiple Sclerosis (MS), is a common autoimmune disease that affects the central nervous system. Currently, there is no cure for MS, and most treatments involve the use of immunosuppressive drugs that can have adverse effects or increased toxicity. Cannabis, commonly known as marijuana, is a product of the Cannabis sativa, and for several centuries has been used as an alternative medicine in many cultures. Cannabis sativa produces over 421 chemical compounds, including about 80 terpenophenols named phytocannabinoids, and include both psychotropic THC and non-psychoactive CBD. In the currently study, we show that a combination therapy using THC and CBD results in amelioration of EAE, an animal model of MS, by reducing hind limb paralysis, decreasing immune cellular infiltration into the brain, and mitigating the presence of inflammatory biomarkers, including gram negative bacteria-associated lipopolysaccharide (LPS). Interestingly, the gut microbiome plays an important role in immune function and studies have shown that it is altered significantly in MS patients. Inasmuch, we performed 16S rRNA sequencing on experimental groups to investigate the gut microbiome composition after using a combination of THC and CBD compared to disease controls. Interestingly, we found that EAE mice showed increase in the mucin degrading bacterial species, Akkermansia municiphila, which was significantly reduced in disease mice treated with THC+CBD. Collectively, our data suggests that THC+CBD can ameliorate EAE by preventing accumulation of mucin-degrading bacteria that would lead to increased gut microbial dysbiosis.</p>
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