Harnessing Pharmacogenomics in Clinical Research on Psychedelic-Assisted Therapy
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CYP2D6 PMs show higher ibogaine exposure and lower noribogaine; halving dose recommended for PMs. CYP2D6 genotyping advised for ibogaine clinical trials.
Dosing: Standard ibogaine dosing discussed in context of CYP2D6-dependent metabolism; PMs recommended ~50% dose reduction; 20 mg single dose used in referenced Glue et al. 2015 PK study (oral)
Contraindications: CYP2D6 poor metaboliser status (dose reduction to ~50% recommended for ibogaine), CYP2D6 ultrarapid metaboliser status (may require higher dose or may not be suitable candidates), Concurrent use of CYP2D6 inhibitors (e.g., paroxetine — causes phenoconversion to PM-like state), Concurrent use of CYP3A4 inhibitors (e.g., grapefruit juice — potent intestinal CYP3A4 inhibition), Liver transplant recipients (donor liver genotype controls recipient CYP2D6 phenotype), Comorbidities affecting hepatic function (cancer, liver disease — can cause phenoconversion)