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Metabolism of Endocannabinoids by CYP2D6, the primary brain cytochrome P450

Cytochrome P450 2D6 (CYP2D6) is highly expressed in the brain.  It is responsible for the metabolism of pharmaceutical drugs.  The enzyme is highly polymorphic and differ from ethnicities resulting in variable metabolisms. Brain CYP2D6 has been linked to neurological diseases and inflammation.  The endocannabinoid system is a group of endogenous cannabinoid receptors capable of modulating pain, memory, inflammation, etc. These receptors can be found in the brain and have been a potential drug target for neurological disease. The omega 3 endocannabinoids(eCB), docosahexaenoyl ethanolamide (DHEA) and eicosapentaenoyl ethanolamide (EPEA), have been shown to express anti-inflammatory properties. The main goal for our investigation was to elucidate how CYP2D6 can metabolize omega 3 endocannabinoids. Our study revealed that omega 3 eCB are endogenous substrates of CYP2D6 and metabolize them into anti-inflammatory epoxides.  The anti-inflammatory epoxides have been shown to reduce the levels of interleukin 6 (pro-inflammatory IL) by increasing the levels of interleukin 10(anti-inflammatory IL). The study of these metabolites can help in the development of new pharmaceuticals to treat neuroinflammation, one of the main causes for neurodegeneration.

Author: 
Hector Rosa Lopez
School: 
Universidad del Este
Department: 
Neuroscience
Research Advisor: 
Dr. Aditi Das
Department of Research Advisor: 
Comparative Biosciences
Year of Publication: 
2017