Differential Interactions of Selected Phytocannabinoids with Human CYP2D6 Polymorphisms

Cytochrome P450 2D6 (CYP2D6) is primarily expressed in the liver and central nervous system. It known to be highly polymorphic nature. metabolizes several endogenous substrates such as anandamide (AEA). Concomitantly, it involved phase 1 metabolism of antidepressants, antipsychotics, other drugs. Research field phytocannabinoids (pCBs) has recently accelerated owing their legalization increasing medicinal use for pain inflammation. The primary component cannabis THC, which well-known its psychotropic effects. Since CYP2D6 an important brain inhibited by CBD, we investigated interactions four prevalent polymorphisms with selected (CBD, CBDV, THCV, CBN, CBG, CBC, ?-carophyllene) that are rapidly gaining popularity. We show there differential binding CYP2D6*17 pCBs compared WT CYP2D6. also perform a more detailed comparison *17 CYP2D6, reveals possible regulation AEA CBD. Furthermore, molecular dynamics delineate mechanism this binding, inhibition, regulation. Taken together, have found vary polymorphism specific pCB class.