Predicting drug–drug interactions between ayahuasca alkaloids and SSRIs using physiologically based pharmacokinetic modeling
Frontiers in Molecular Biosciences – February 18, 2026
Source: OpenAlex
Summary
Ayahuasca may significantly amplify the effects of SSRIs, such as paroxetine and fluoxetine, even with modest increases in DMT exposure. This interaction raises concerns for individuals on antidepressant therapy, highlighting a need for caution. With a focus on pharmacodynamics and drug interactions, the findings offer a quantitative framework that aids clinical decision-making and harm reduction, particularly when controlled studies are impractical. Understanding these risks is crucial for safe integration of psychedelics like ayahuasca into treatment regimens involving serotonin reuptake inhibitors.
Abstract
The findings suggest a clinically relevant interaction between ayahuasca and SSRIs, as even modest increases in DMT exposure may intensify serotonergic effects in individuals receiving antidepressant therapy. This study provides a mechanistic and quantitative framework for assessing interaction risks between ayahuasca alkaloids and SSRIs, supporting clinical decision-making and harm-reduction strategies in contexts where controlled drug-drug interaction studies are not feasible.