CYP2D6 is a member of the cytochrome P450 family, liver enzymes that handle many medicines. For psilocybin, a 2025 systematic review lists CYP2D6 and CYP3A4 as the main enzymes that metabolize psilocin, with a smaller role for monoamine oxidase A (Meshkat et al., 2025).
It also links two toad-associated compounds. A 2022 review reports that CYP2D6 removes the methyl from 5-MeO-DMT’s methoxy group to make bufotenine, an active metabolite that binds 5-HT2A more strongly than its parent (Reckweg et al., 2022).
For DMT, P450 enzymes play a smaller part than MAO-A. In a 2015 urine study, more DMT was handled by a less efficient P450-dependent route after it was smoked than after it was swallowed (Riba et al., 2015). Whether genetic differences in enzymes like this one explain why people respond differently to psilocybin is uncertain; a 2026 review says the evidence so far is mostly preclinical (Hampsey et al., 2026). Questions about medicines that affect the enzyme belong with a pharmacist. This is not medical advice.
Sources
- Meshkat et al., 2025, Pharmaceutics
- Reckweg et al., 2022, Journal of Neurochemistry
- Riba et al., 2015, Drug Testing and Analysis
- Hampsey et al., 2026: pooled psilocybin and LSD pharmacokinetics (PMC)
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