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Future Pharmacol., Volume 6, Issue 3 (September 2026) – 2 articles

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7 pages, 301 KB  
Communication
Impact of CYP2D6 Polymorphisms on the Pharmacokinetics of N,N-Dimethyltryptamine and Harmine via PBPK Modeling and Simulation
by Gabriella de Souza Gomes Ribeiro, Pieter Annaert, Frederico Severino Martins and Tania Marcourakis
Future Pharmacol. 2026, 6(3), 34; https://doi.org/10.3390/futurepharmacol6030034 (registering DOI) - 23 Jun 2026
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Abstract
Background/Objectives: In this study, we present an analysis of ayahuasca, a psychedelic preparation containing N,N-dimethyltryptamine (DMT) and β-carbolines, such as harmine (HRM), a reversible monoamine oxidase A (MAO-A) inhibitor that enables the oral bioavailability of DMT. CYP2D6 is a highly polymorphic enzyme associated [...] Read more.
Background/Objectives: In this study, we present an analysis of ayahuasca, a psychedelic preparation containing N,N-dimethyltryptamine (DMT) and β-carbolines, such as harmine (HRM), a reversible monoamine oxidase A (MAO-A) inhibitor that enables the oral bioavailability of DMT. CYP2D6 is a highly polymorphic enzyme associated with interindividual variability in drug exposure, but its influence on the pharmacokinetics of ayahuasca alkaloids remains poorly understood. Methods: Using physiologically based pharmacokinetic (PBPK) modeling, we simulated scenarios for poor (PM), normal (NM), and ultra-rapid (UM) metabolizers by adjusting CYP2D6 enzyme expression for each phenotype. Results: PMs showed increased systemic exposure to DMT (AUC +53.3%; Cmax +40.5%) and HRM (AUC +30.6%; Cmax +22.8%), while UMs exhibited reduced exposure to both compounds. Conclusions: These findings highlight the significant impact of CYP2D6 polymorphisms on the pharmacokinetics of DMT and HRM, reinforcing the value of PBPK modeling for predicting interindividual variability and potential clinical risks. Full article
(This article belongs to the Section Pharmacokinetics, Metabolism and Toxicology)
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Correction
Correction: Khan, M.F.; Khan, M.A. Plant-Derived Metal Nanoparticles (PDMNPs): Synthesis, Characterization, and Oxidative Stress-Mediated Therapeutic Actions. Future Pharmacol. 2023, 3, 252–295
by Mohammad Faheem Khan and Mohd Aamish Khan
Future Pharmacol. 2026, 6(3), 33; https://doi.org/10.3390/futurepharmacol6030033 (registering DOI) - 23 Jun 2026
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Text Correction [...] Full article
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