Cannabinoids and Cytochrome P450 Interactions

Abstract

Biotransformation via a hydrolytic pathway is the major route of endocannabinoid metabolism and the deactivation of substrates is characteristic, in contrast to the minor oxidative pathway via CYP involved in the bioactivation reactions. Phytocannabinoids are extensively metabolized by CYPs. The enzymes CYP2C9, CYP2C19, and CYP3A4 catalyze most of their hydroxylations. Similarly, CYP represents a major metabolic pathway for both synthetic cannabinoids used therapeutically and drugs that are abused. In vitro experiments document the mostly CYP inhibitory activity of the major phytocannabinoids, with cannabidiol as the most potent inhibitor of many CYPs. The drug-drug interactions between cannabinoids and various drugs at the CYP level are reported, but their clinical relevance remains unclear. The direct activation/inhibition of nuclear receptors in the liver cells by cannabinoids may result in a change of CYP expression and activity. Finally, we hypothesize the interplay of central cannabinoid receptors with numerous nervous systems, resulting in a hormone-mediated signal towards nuclear receptors in hepatocytes.

Differences in sociodemographic characteristics, clinical features and serum liver function tests of male cannabis and synthetic cannabinoid users

“…11,22 Among cytochrome P450 (CYP) enzymes, CYP3A4 was found to be the major CYP enzyme responsible for the oxidative metabolism of SCs; and CYP2C9, CYP2C19 and CYP1A2 seem to have contributions. [31][32][33] Besides, SCs and their basic molecules were shown to be capable of inhibiting CYP1A. 34 Research of Borini et al 14 on C use revealed that serum AST, ALT and AP levels were increased without any correlation with the amount or duration of marijuana consumption.…”

Cannabinoids for epilepsy: What do we know and where do we go?

“…13 There are a range of other possible targets for CBD, which may be relevant to its antiseizure and other pharmacologic effects. 17 There are likely to be active metabolites with both molecules. Both, however, have similar effects on rodent seizure models.…”

Cannabinoids in child neurology

“…Kannabinoidy są metabolizowane przez wątrobę za pomocą cytochromu p450 [50]. Zarówno CBD, jak i THC hamują szlak cytochromu P450, szczególnie izoenzymy CYP3A4, CYP2C.…”

“…Zarówno CBD, jak i THC hamują szlak cytochromu P450, szczególnie izoenzymy CYP3A4, CYP2C. CBD dodatkowo ma wpływ hamujący na działanie innych izoenzymów jak 2D6, 1A2, 2B6 [50]. Powszechnie wiadomo, że CYP3A4, CYP2C są pobudzane przez karbamazepinę, topiramat, fenytoinę i kwas walproinowy.…”