Ayahuasca and SSRIs: what antidepressant users should know

Ayahuasca and SSRIs cannot be taken together. Ayahuasca contains MAO inhibitors, and combining them with an SSRI antidepressant can cause serotonin syndrome, a medical emergency. If you take one, a retreat is only possible after you and the doctor who prescribed it decide, together, that stopping is right for you, and after the medicine has had time to leave your body.

That is the short answer. The longer one matters too, because the weeks before a retreat are where people get hurt: stopping too fast, guessing at a waiting time from a forum, or not telling anyone. This guide explains what is going on in the body, why the waiting time is different for each drug, and how we handle it with you.

Never stop or change an antidepressant on your own. Any change is planned with the doctor who prescribed it. At MexiSol World, medical screening is required before any retreat. Our retreats take place at Finca El Péndulo, in Jalisco.

Why ayahuasca and SSRIs cannot be combined

Ayahuasca is a brew of two plants. The chacruna leaf brings DMT. The vine brings harmala alkaloids such as harmine, which block the enzyme monoamine oxidase (MAO). Without that block, the body breaks DMT down before it can act. As two Australian clinicians wrote in The Conversation, switching off those enzymes also exposes the body to many drug interactions, including with medications for depression.

MAO is also one of the ways your body clears serotonin. SSRIs, such as sertraline (Zoloft), escitalopram (Lexapro), fluoxetine (Prozac) and paroxetine (Paxil), raise serotonin by slowing its reuptake. Put the two together and serotonin has fewer ways out.

The warning is not new. In 1998 James Callaway and Charles Grob published a paper in the Journal of Psychoactive Drugs warning that the MAO-inhibiting alkaloids in ayahuasca, combined with SSRIs, “may induce a serotonin syndrome with potentially grave outcome.”

A 2022 review in Psychopharmacology looked at serotonin toxicity across psychedelics. Its conclusion was clear: true serotonin toxicity typically happens with an overdose, or when a drug that raises serotonin is combined with an MAO inhibitor. Ayahuasca with an SSRI is exactly that second case.

There is also a second layer. A 2026 computer modelling study from the University of São Paulo simulated what fluoxetine and paroxetine do to ayahuasca’s alkaloids. Both raised harmine levels and moderately raised DMT, because they slow the liver enzyme that clears them. It is a simulation built on data from six volunteers, not a trial, but it points the same way.

What serotonin syndrome is

Serotonin syndrome is what happens when serotonin builds up too far in the nervous system. The 2022 review describes it as the most severe end of a spectrum of serotonin toxicity.

The signs that need urgent medical care, according to that review and the US FDA label for Prozac, include:

• Agitation, confusion, hallucinations or, in severe cases, coma
• Muscle jerks and muscle rigidity
• A racing heart and swings in blood pressure
• High fever and heavy sweating
• Seizures

In a 2025 interview with The Microdose, the newsletter of UC Berkeley’s Center for the Science of Psychedelics, Grob described three people in the United States who were on SSRIs when they drank ayahuasca. They became very agitated and confused and sweated heavily. All three returned to baseline afterwards. He suspected serotonin syndrome, and noted that severe cases can involve seizures.

Reported cases are few. That is not the same as safe. It is one of the clearest “never combine” rules in this whole field.

How long off SSRIs before ayahuasca? Why it differs by drug

This is the question people search most, and where online answers disagree. The honest answer is that there is no single number. It depends on the drug, how long you have taken it and your body. Here is why.

Every drug has a half-life: the time it takes for the amount in your blood to fall by half. Some antidepressants leave quickly. Others linger, and some break down into active compounds that linger even longer.

Antidepressant	Half-life, from the US FDA label	What the label says before starting a prescription MAOI
Sertraline (Zoloft)	About 26 hours	At least 14 days after stopping
Fluoxetine (Prozac)	4 to 6 days with regular use; its active metabolite norfluoxetine, 4 to 16 days	At least 5 weeks after stopping

Sources: Prozac label and Zoloft label, DailyMed.

Please read this table for what it is. The label intervals were written for switching to MAOI antidepressants, not for ayahuasca, and they are not a plan for you. They show why fluoxetine needs a much longer gap than sertraline. Grob put it plainly in his interview: SSRIs “can take up to 4 or 5 weeks” to fully leave your system.

The waiting time also starts only after the taper ends, and the taper itself can take far longer than the wait. Your doctor sets both. We then check the plan with you during screening, and we only confirm your place once it is safe.

Your prescriber sets the taper, not the retreat

A retreat center should never tell you how to come off an antidepressant. Not us, not anyone. That decision belongs to you and the doctor who prescribed it, because only they know why you take it, how you have responded and what stopping could mean for you.

Stopping suddenly carries its own risks. Both FDA labels recommend reducing the dose gradually rather than stopping abruptly whenever possible. The NHS says not to stop suddenly or without talking to your doctor, and that a gradual reduction usually takes several weeks or months.

Research supports going slowly. In a 2019 paper in The Lancet Psychiatry, Mark Horowitz and David Taylor found that the short tapers of two to four weeks in many guidelines show minimal benefit over stopping abruptly. Tapers over months, down to much lower doses, did better. Horowitz explains the approach, and how to tell withdrawal from relapse, in a webinar for the University of British Columbia’s Therapeutics Initiative.

For some people, the right answer is not to stop at all. If your doctor thinks coming off is not safe for you now, that matters more than any retreat date.

Ayahuasca while on antidepressants: what the weeks before can feel like

Coming off an antidepressant is not always hard, but it can be. A 2024 meta-analysis in The Lancet Psychiatry pooled 79 studies with 21,002 patients. At least one discontinuation symptom appeared in 31% of people who stopped an antidepressant, against 17% of people who stopped a placebo. After accounting for that, the authors estimate about 15%, one in six or seven people, have symptoms caused by stopping. Severe symptoms were about 3%.

Common symptoms listed by the NHS and the Zoloft label include:

• Dizziness, nausea and headaches
• Trouble sleeping
• Anxiety, irritability and low mood
• Electric shock sensations, often called “brain zaps”

The NHS notes that these usually start within a few days and last a few weeks, but can last longer for some people, especially after long use or high doses. Some symptoms can feel like your depression or anxiety coming back. Horowitz and Taylor point out that withdrawal can be mistaken for relapse, which is one more reason to stay in close touch with your doctor.

NPR reported in 2025 that the longer people take these drugs, the more likely they are to have problems coming off them, and that doctors advise going slowly, never cold turkey.

None of this is meant to scare you. It is meant to help you plan. Leave more time than you think you need, keep your doctor close, tell the people around you, and let us know how you are doing. If the taper is harder than expected, moving your retreat to a later date is always a better choice than rushing.

How we review antidepressants on the intake call

At MexiSol World, nothing is confirmed until we have reviewed your health. Our medical screening has three parts:

1. Your medications, and any taper, which is always done with your prescribing doctor.
2. Why you are coming, so we understand what you hope for.
3. Your commitment to the process, before, during and after the week.

When you register, we ask about every medication, supplement and herb you take. If you take an SSRI or another antidepressant, we talk it through on a call. We will tell you plainly whether the retreat could be possible with a plan made with your doctor, or whether it is better to wait. Before you arrive, we confirm that the plan was followed and that you are safe to take part.

Please tell us everything, even what seems minor. St. John’s wort, 5-HTP, tramadol and some cough syrups also act on serotonin. The full list is in which medications are unsafe with ayahuasca and on our medical information page.

Other options if stopping is not right for you now

With ayahuasca and SSRIs, sometimes the honest answer is “not yet.” That is not a failure. Some paths people take:

• Waiting. Staying on your medication and coming in a later season, when you and your doctor feel ready.
• Choosing a later date so the taper is not rushed. We hold retreats through the year, so there is no need to squeeze a taper into a deadline.
• Asking about psilocybin, carefully. Our psilocybin retreat also includes one Satori ceremony, and Satori contains an MAO inhibitor, so the same medication review applies. It is not a way around this question. More in ayahuasca or psilocybin.

If you are still deciding whether this is the right time, is ayahuasca right for me? is a good place to start.

Frequently asked questions

How long do I need to be off SSRIs before ayahuasca? There is no single number. It depends on the drug, how long you took it and your health. Fluoxetine stays in the body much longer than sertraline, so its gap is longer. Your prescribing doctor plans the taper, and we review the timing with you before anything is confirmed.

Can I take ayahuasca and Zoloft together? No. Sertraline is an SSRI, and ayahuasca contains MAO inhibitors. Together they carry a risk of serotonin syndrome. Any change to your Zoloft is a decision for you and your doctor.

Is microdosing or a small cup of ayahuasca safe on an SSRI? We do not offer ayahuasca to anyone still taking an SSRI, at any amount. The interaction comes from the MAO inhibitors in the brew, not only from how strong the experience is.

What if my doctor says I should not stop my antidepressant? Then please follow your doctor’s advice. Your long-term health comes first. We are happy to talk about timing, or about whether another moment would suit you better.

Do I have to tell you about my antidepressant? Yes. Our screening asks about every medication, supplement and herb. Hiding a medication puts you in danger in ceremony, and we cannot keep you safe without knowing.

Talk to us before you book

If you take an antidepressant and are thinking about a retreat, start the conversation early, with your doctor and with us. Book a discovery call, have your list of medications and supplements at hand, and we will go over your situation together. Nothing is confirmed or charged until we have talked.

This article is general information, not medical advice.

Sources

• Callaway, J. C. and Grob, C. S. (1998). Ayahuasca preparations and serotonin reuptake inhibitors: a potential combination for severe adverse interactions. Journal of Psychoactive Drugs.
• Malcolm, B. and Thomas, K. (2022). Serotonin toxicity of serotonergic psychedelics. Psychopharmacology.
• Ribeiro, G. S. G. et al. (2026). Predicting drug-drug interactions between ayahuasca alkaloids and SSRIs using physiologically based pharmacokinetic modeling. Frontiers in Molecular Biosciences.
• Horowitz, M. A. and Taylor, D. (2019). Tapering of SSRI treatment to mitigate withdrawal symptoms. The Lancet Psychiatry.
• Henssler, J. et al. (2024). Incidence of antidepressant discontinuation symptoms: a systematic review and meta-analysis. The Lancet Psychiatry.
• US Food and Drug Administration (2026). Prozac (fluoxetine) prescribing information. DailyMed, US National Library of Medicine.
• US Food and Drug Administration (2025). Zoloft (sertraline) prescribing information. DailyMed, US National Library of Medicine.
• NHS (2025). Stopping or coming off antidepressants. NHS.
• Corwin, E. (2025). People say they’ve faced withdrawals from SSRIs. They want recognition and research. NPR.
• Bright, S. and Caldicott, D. (2017). Weekly Dose: ayahuasca, a cautionary tale for tourists eager to try this shamanic brew. The Conversation.
• Hu, J. C. (2025). The risks of mixing ayahuasca and SSRIs: 5 Questions for UCLA psychiatry professor Charles Grob. The Microdose, UC Berkeley Center for the Science of Psychedelics.
• Therapeutics Initiative (2024). Dr. Mark Horowitz: Antidepressant withdrawal effects and how to safely stop them. YouTube.