Other · 2026
Computer models predict higher ayahuasca alkaloid levels when combined with SSRIs
- Original title
- Predicting drug-drug interactions between ayahuasca alkaloids and SSRIs using physiologically based pharmacokinetic modeling.
- Authors
- Ribeiro GSG, Paranhos BAPB, Dörr F, et al.
- Journal
- Frontiers in molecular biosciences, 2026
- Molecules
- Ayahuasca, DMT
- Conditions
- Other
- Participants
- 6
- Evidence grade
- Very low
- Source
- Read the original paper
The question
What happens to blood levels of the two main ayahuasca compounds if someone is also taking a common antidepressant? The researchers used computer modelling to estimate the size of that interaction.
What they did
Ayahuasca contains DMT, a psychedelic compound, and harmine, which blocks an enzyme (monoamine oxidase A) so that DMT survives being swallowed. The team built physiologically based pharmacokinetic (PBPK) models — computer simulations of how a drug moves through the body — for DMT and harmine, using blood measurements from a controlled clinical study in which six volunteers drank ayahuasca. They built similar models for the antidepressants fluoxetine and paroxetine (and fluoxetine’s breakdown product, norfluoxetine) from published clinical data, then simulated taking them together, both as a single dose and as ongoing daily use.
What they found
In the simulations, both fluoxetine and paroxetine raised exposure to harmine and produced moderate increases in DMT blood concentrations. The authors link this to blocking of the liver enzyme CYP2D6, which normally helps clear these compounds, plus stronger blockade of monoamine oxidase A. The altered profiles appeared under both single-dose and ongoing antidepressant dosing. The abstract gives no numerical values for the size of these increases.
The fine print
These are predictions from computer models, not measurements in people who actually combined the two. The underlying ayahuasca data came from just six volunteers, and the abstract reports no percentages, ratios or confidence intervals. No clinical outcomes or adverse events were measured, so the real-world consequences remain unquantified. This summary is based on the abstract only.
What it means
Modelling suggests that common SSRI antidepressants could meaningfully raise blood levels of ayahuasca’s active compounds, which is a reason for caution and for further study, but the prediction has not yet been confirmed in people.
Evidence grade: Very low. This is a computer simulation study built on plasma data from only six volunteers, not a trial that actually gave ayahuasca and SSRIs together to people.
This summary is based on the study’s published abstract.