Magic mushrooms and antidepressants: what is known about mixing them

People who take an antidepressant often wonder what happens if they also use magic mushrooms. The honest answer is that science has only partial, patchy answers. Most of the data come from studies of pure, measured psilocybin in clinics, from online surveys, and from a handful of case reports. Very little of it is about the mushrooms people actually find or buy, and no study can tell any one person what would happen to them.

This guide sets out what the published literature reports, how strong each finding is, and what is unknown. It does not tell anyone what to take, when, or how to change a prescription. For that, the person to ask is your prescriber or pharmacist.

Is it safe to mix magic mushrooms and antidepressants?

No study can answer that for you. A 2025 scoping review pulled together 18 studies on antidepressants taken alongside classic psychedelics and concluded that the combination was generally safe and tolerable in those studies, with no increased risk of serotonin syndrome, particularly for psilocybin. Its authors also say some studies saw weaker acute effects while others did not, that the evidence comes largely from case reports, qualitative studies, surveys and open-label studies, and that randomized, placebo-controlled trials are needed (Tap et al., 2025). That is a finding about the studies reviewed, mostly pure or measured psilocybin and many in research settings. It is not a statement that mixing antidepressants with mushrooms you find or buy is safe. Evidence: preliminary.

That reassurance has limits. A 2024 systematic review of drug interactions with classic psychedelics (52 studies, 10 of them on psilocybin) found attenuated effects, potentiated effects and cases where nothing changed. It found no serious adverse drug events apart from a few case reports. It also warned that many included studies gave limited information about outcomes or methods and that case reports can be biased (Halman et al., 2024). And the review of psilocybin’s interactions with psychiatric medicines counted only one randomized trial combining psilocybin with an SSRI, in 23 healthy volunteers (Sarparast et al., 2022).

Health Canada’s page on magic mushrooms says using them with other substances such as cannabis, amphetamines or alcohol raises the risk of serious side effects and adverse events. The page does not name antidepressants or other prescription medicines, so it gives no medicine-by-medicine guidance (Health Canada, magic mushrooms; page modified 20 October 2026).

What kinds of evidence exist, and how much can they tell us?

• A controlled lab trial. One double-blind, placebo-controlled crossover trial gave healthy volunteers measured psilocybin after two weeks of escitalopram or placebo (Becker et al., 2022). Strongest design here, but small, and healthy people are not patients on long-term treatment.
• Surveys and forum analyses. People report their own past experiences online, or posts are read for patterns (Gukasyan et al., 2023; Sakai et al., 2024). These can show a pattern worth testing. They cannot prove cause, and nobody checked what was taken or how much.
• Clinical-trial safety data. A small open-label trial kept participants on an SSRI (Goodwin et al., 2023). It has no comparison group.
• Case reports. One patient’s story (Barnett et al., 2025; Frye et al., 2024). Vivid, and sometimes the first warning of a risk, but a single case cannot tell how common anything is.

Do SSRIs and SNRIs weaken the effects of magic mushrooms?

Some studies say yes; the one controlled trial found something different. Evidence: preliminary and mixed.

In a 2023 online survey, researchers collected 611 reports of people taking psilocybin mushrooms with an antidepressant. The estimated probability of weaker-than-expected effects was 0.47 for SSRIs, 0.55 for SNRIs and 0.29 for bupropion, which is not a serotonin-targeting antidepressant. The authors concluded that SSRIs and SNRIs appear to weaken the effects compared with a non-serotonergic antidepressant (Gukasyan et al., 2023). A 2024 analysis of 443 Reddit posts found a similar split: 54% described weaker effects and 39% no change (Sakai et al., 2024).

The controlled trial pointed another way. Healthy volunteers took escitalopram or placebo for two weeks, then measured psilocybin. Escitalopram had no relevant effect on the positive mood effects, and it did not change blood levels of psilocin, the active form. Ratings of bad drug effects, anxiety and some physical effects, such as cardiovascular ones, were lower after escitalopram. The authors say longer antidepressant pretreatment and studies in patients are still needed (Becker et al., 2022). Reading “fewer bad effects” as a benefit would be a mistake: it is one small result in one setting.

Why might the studies differ? We cannot say. They differ in design, products, doses, people and length of antidepressant use, and the surveys rest on memory and self-report. What the studies agree on is that the question is open.

What about the weeks after an antidepressant is stopped?

In the same 2023 survey, 1,542 reports involved taking mushrooms after stopping an SSRI or SNRI. The probability of weakened effects was about 0.3 and did not differ significantly from the earliest post-discontinuation timepoint (within one week) through three to six months. The authors say the dampening may last as long as about three months after discontinuation (Gukasyan et al., 2023). Evidence: preliminary, self-reported and retrospective.

Clinical trials often ask people to stop serotonergic antidepressants first. A 2024 exploratory analysis of one trial found that people who had stopped an SSRI or SNRI to join did less well on the trial’s measures than people who were not taking one. The authors stress that they cannot infer cause, that the analysis is hypothesis-generating, and that a controlled trial of stopping versus continuing is “urgently required” (Erritzoe et al., 2024). This is research, not guidance: it does not show that stopping, continuing or timing anything is right for any individual.

A case report illustrates why stopping a medication is a medical decision. A 31-year-old man with depression, anxiety and alcohol use disorder had been treated with escitalopram and naltrexone and had been sober for three months. The escitalopram was stopped a week before an unregulated psilocybin “ceremony” he chose after web-based research. He had a heavy relapse to drinking within two weeks after the psilocybin and three weeks after stopping the escitalopram. The authors wrote that it is possible the discontinuation was associated with a return of depression and anxiety symptoms that directly contributed to the relapse (Frye et al., 2024). That is the authors’ hypothesis about one person, not a finding. It cannot show how often this happens.

Can combining them cause serotonin syndrome?

Serotonin syndrome, also called serotonin toxicity, is a drug-induced “toxidrome” in which serotonin levels between nerve cells rise as a result of drug interactions. Mild cases bring tremor and diarrhea. Severe cases can bring delirium, neuromuscular rigidity, seizures, coma and hyperthermia (very high body temperature) (Tap et al., 2025).

On paper, the risk looks lower for psilocybin than for many drugs. A systematic review notes that psilocybin and psilocin lack clinically significant activity at the serotonin reuptake pumps, so they do not substantially raise serotonin levels between nerve cells. The authors reasoned that serotonin toxicity from psilocybin is therefore unlikely (Sarparast et al., 2022). The 2025 scoping review found no increased risk of serotonin syndrome in its included studies (Tap et al., 2025).

Real-world reports are less tidy. Among the 443 Reddit posts, 8% described negative physical or psychological effects. Thirteen reports may reflect serotonin toxicity, and one raised concern about a psychotic or manic episode. The authors say the interactions are likely complex and call for prospective studies (Sakai et al., 2024). Posts cannot be checked, so these are signals, not diagnoses. Evidence: unresolved.

A small open-label trial of a synthetic psilocybin product, taken with an SSRI by 19 adults with treatment-resistant depression, reported adverse events in 12 participants. Most were mild and resolved the day they began, and there were no serious adverse events. Follow-up lasted three weeks. The authors say larger, comparator-controlled trials are necessary (Goodwin et al., 2023). A clinic-run trial with monitoring and support is a very different situation from using mushrooms alone.

What about MAOIs and magic mushrooms?

Monoamine oxidase inhibitors (MAOIs) are a class of antidepressant that block an enzyme which breaks down serotonin and other chemicals. We found no controlled human study of psilocybin with an MAOI. The 2024 systematic review’s MAOI findings come from studies of LSD and DMT, not psilocybin. In its discussion of the MAOIs found in ayahuasca, the review cites earlier work saying that combining MAOIs with each other or with SSRIs or SNRIs “has been thought to carry the greatest risk of serotonin toxicity”. That is a general pharmacology expectation, not a result for psilocybin (Halman et al., 2024). Evidence: unresolved.

What exists for psilocybin mushrooms is a case report. A 42-year-old man with treatment-resistant depression, prescribed the MAOI tranylcypromine and an amphetamine-containing medicine, among others, took Psilocybe cubensis mushrooms. About half an hour later he developed severe hypertension with chest pain, palpitations and headache. His ECG showed ST elevation and he was diagnosed with a heart attack, but cardiac catheterization found no significant abnormalities, and he went home after an overnight stay without lasting physical harm (Barnett et al., 2025).

The authors say this may be the first published report of a hypertensive emergency after psilocybin mushrooms and an MAOI. They note that earlier studies suggest classic psychedelics, including synthetic psilocybin, should not cause one with an MAOI. They write that they “suspect” phenylethylamine, a compound found in P. cubensis and other psilocybin mushrooms, interacted with the MAOI and the amphetamine. They did not test this. They advise warning people prescribed MAOIs about the potential for hypertensive emergency with psilocybin mushrooms, particularly with norepinephrine-releasing medicines such as amphetamines (Barnett et al., 2025). This is one case and the mechanism is a suspicion, not a finding. Evidence: unresolved, from a single case report.

There is a further wrinkle. Researchers have found β-carbolines, a group that includes harmine and harmane and that blocks monoamine oxidase, in four Psilocybe species, and noted that these compounds interfere with psilocybin breakdown (Blei et al., 2020). We did not find a study showing whether this matters for people taking prescribed MAOIs.

What about lithium, and why do seizures come up?

Lithium is a mood stabilizer, not an antidepressant, but it comes up in questions from people who also take antidepressants. A 2021 study read online accounts of classic psychedelics taken with mood stabilizers from Erowid, Shroomery and Reddit. Of 62 reports of lithium with a psychedelic, 47% involved seizures and another 18% resulted in bad trips, while 39% involved medical attention. None of 34 reports with lamotrigine, another mood stabilizer, involved seizures. The authors provisionally concluded that psychedelic use may pose a significant seizure risk for patients on lithium, and said further research is needed (Nayak et al., 2021).

The numbers for psilocybin alone are small, and we are reporting them second-hand. We could not open the full text of the original study (the publisher’s site blocked automated access), so the psilocybin-only figures below come from a later systematic review, not from the original paper. That review says 2 of 6 reports of lithium with psilocybin resulted in seizures, and none of 10 reports of lamotrigine with psilocybin did. It also describes the evidence as low quality because of lack of standardization, selection bias and lack of clinical verification (Sarparast et al., 2022). The 2024 systematic review likewise cites “several reported instances of lithium causing seizures when used concurrently with LSD or psilocybin” (Halman et al., 2024). Evidence: preliminary. This is a possible harm signal from self-selected online reports. It is not a measured rate.

How strong is the evidence for each interaction?

The last row is not an antidepressant. It is there because many people take more than one medicine. The source describes it as reductions in effects on pupil size and visual changes (chlorpromazine) and visual changes (buspirone) (Sarparast et al., 2022). Other combinations are not covered here, and a pharmacist is better placed to check your own list.

Why can’t these studies say what happens with real mushrooms?

• Mushrooms are not pure psilocybin. The controlled trial used a measured psilocybin dose in a lab. Mushrooms contain other compounds, such as the one the authors of the MAOI case report suspected (an untested suspicion) (Barnett et al., 2025) and the β-carbolines found in some species (Blei et al., 2020).
• Content varies. Laboratory measurements of psilocybin content differ widely, and a name is not a guide to strength; see our article on what laboratory studies of mushroom potency show.
• Online reports are self-selected. People who post tend to be those with something to say, and nobody confirms the product, the amount or the medicine.
• Healthy volunteers are not patients. The one controlled trial studied healthy volunteers over a short pretreatment, and its authors call for longer pretreatment and patient studies (Becker et al., 2022).
• Medicines differ within a class. Reports often group SSRIs together, though doses, drugs and how long someone has taken them vary. Fluoxetine has an especially long half-life, so Gukasyan and colleagues re-ran one analysis without it (Gukasyan et al., 2023).

What should I do if I take an antidepressant and I am curious or already using mushrooms?

Speak to your prescriber or pharmacist. A pharmacist can check your whole list of medicines, including over-the-counter drugs and supplements, which this article cannot. Health Canada says to tell your doctor and pharmacist about all the health products you take (Health Canada, antidepressant drugs). CAMH says to always talk with a prescriber or pharmacist before using any substances to understand potential interactions (CAMH).

Do not stop or change your medication on your own. Health Canada and CAMH both say so, and the case report above is one example of a relapse after a medication was stopped. If a prescriber decides a change is right, they can plan it with you. This article gives no instructions on tapering, timing or combining, and none of the studies above provide them for individuals.

Medication changes can also affect mood. A scoping review notes that stopping an antidepressant can bring a significant burden and could worsen depression and increase suicidal ideation (Tap et al., 2025). If you or someone you know is thinking about suicide, the Government of Canada says to call or text 9-8-8 at any time. For immediate danger or urgent medical support, call 9-1-1 (Government of Canada, mental health: get help).

Our safety page covers everyday risks, and our guide to whether magic mushrooms are safe puts them in a wider frame.

When does it become an emergency?

If someone has taken mushrooms and is on medication and develops severe symptoms such as seizures, delirium or confusion, a very high temperature, rigid muscles, chest pain or a severe headache, treat it as an emergency and call 9-1-1. These are the kinds of signs described in the sources above: seizures with lithium reports, serotonin syndrome signs, and chest pain with severe hypertension in the MAOI case (Tap et al., 2025; Nayak et al., 2021; Barnett et al., 2025). Health Canada’s page lists convulsions, high body temperature and increased heart rate and blood pressure among the short-term physical effects of magic mushrooms themselves (Health Canada, magic mushrooms).

For a suspected poisoning in Ontario, the Ontario Poison Centre says it is available by phone 24 hours a day, every day of the year, on 1-800-268-9017 (toll-free), and helps with poison emergencies and questions about poisoning (Ontario Poison Centre). More numbers are on our safety page.

What we still don’t know

• Whether SSRIs or SNRIs reliably weaken the effects of mushrooms. Surveys and one trial disagree (preliminary).
• How long any dampening lasts after stopping, and whether it differs between drugs. The only estimate is from a retrospective survey (preliminary).
• How often serotonin toxicity happens with SSRIs and psilocybin mushrooms, if at all. Reviews report none, but forum posts raise concern (unresolved).
• What happens with MAOIs and psilocybin mushrooms, beyond one case report and an untested suspicion about phenylethylamine (unresolved).
• How common seizures are with lithium and psilocybin. The figures come from self-selected online reports and are not rates (preliminary).
• Whether any of this applies to a given person. These studies describe groups, and medicines, doses and health conditions differ (unresolved).

Before relying on anything here, check the date on this page, because research moves quickly. Related reading: psilocybin for depression: what the trials found and what psilocybin is.

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