Can You Take Psychedelics With Antidepressants?

Patrick Smith · May 11th, 2017

Psychedelics are potentially illegal substances, and we do not encourage or condone their use where it is against the law. However, we accept that psychedelics use occurs, and believe that offering responsible harm reduction information is imperative to keeping people safe. For that reason, this guide is designed to ensure the safety of those who decide to use the substance.

This article was updated on Oct. 24, 2021

Moderate doses of psychedelics have been shown to effectively treat depressionanxietyPTSD, and other mental health conditions – and even microdoses have been reported to hold significant benefit. Although we don’t recommend it, many people are turning to psychedelics as a form of self-treatment for mental health conditions. And this brings up the potential problem of antidepressant medication interfering with the effects of psychedelics.

Unfortunately there has been no solid research performed on the interaction between psychedelics and antidepressants. Therefore most of the advice we provide here is based on anecdotal evidence and case reports. We recommend discussing issues with your physician before making any decisions.


The classic psychedelics (including LSDpsilocybin and DMT) work by affecting the serotonin system, and most antidepressants work by targeting serotonin signaling too. Therefore we’d expect for there to be some kind of interaction between the two – unfortunately we just don’t know anything for sure right now.

From anecdotal reports, it looks as if the SSRI class of antidepressants weakens the effects of classic psychedelics – although this absolutely doesn’t mean you should take more of the psychedelic substance to compensate.

Many people advise against taking Lithium or other tricyclics with classic psychedelics, as they have been known to put people into comatose states or induce seizuresAvoid this combination until we know for sure about its safety!

MAOI medications appear to have effects similar to SSRIs when combined with classic psychedelics.

Since we know so little about how classic psychedelics and antidepressants interact, we advise against taking them together. Don’t risk making things worse for yourself. If you are absolutely determined to try a psychedelic, it may be wise to wean yourself off your medication first – but always check with your physician.


Anecdotal reports suggest that taking MDMA while on antidepressants can either numb the effects, completely abolish the effects, or cause a really unpleasant hangover! Since SSRIs mess with your serotonin system, and bind to some of the same targets as MDMA, there is the potential for unpleasant interactions. Dr Ben Sessa, an MDMA researcher, says “The general rule is don’t combine SSRIs with MDMA.”

Taking MDMA while on MAOIs is also potentially dangerous. It’s definitely best to avoid this combination, as it could lead to serotonin syndrome (which can be fatal!).

We don’t know much about what you can combine with mescaline, but as its mode of action is similar to the classic psychedelics, it’s probably best to assume that it won’t combine well with antidepressants.


Ayahuasca is a little more complicated than other psychedelics when it comes to antidepressants, because the psychedelic brew contains MAOIs, which can cause fatal reactions when mixed with other drugs. We advise a total purge from all substances before taking ayahuasca, to avoid the risk of the potentially fatal serotonin syndrome.

Here is a list of all substances you should absolutely avoid if you’re determined to take ayahuasca.


Ibogaine is another natural psychedelic with a potential risk of toxicity. Healthcare professionals recommend weaning off all medication before taking a dose of ibogaine.

Be aware that ibogaine is potentially the most dangerous psychedelic substance out there, as it can cause heart failure in seemingly safe situations. It is usually a last resort for people suffering from severe addiction.


We know nothing about interactions here – although we know that Salvia works on a very different neurotransmitter system than most antidepressants, and we haven’t heard any reports of unpleasant effects resulting from mixing Salvia with antidepressants.


The research and anecdotes in this article provide information to consider if you’re currently taking antidepressants. But the details above in no way replace medical advice. If you’re thinking about taking psychedelics along with antidepressants, it’s critical to speak to your prescribing doctor, psychiatrist, or therapist about the potential risks first. 

Though you might be hesitant to discuss psychedelics with your doctor, remember that the conversation is confidential. Additionally, your doctor is the only person who knows what antidepressants you’re taking, along with the dosage and your medical history.

If your doctor or prescriber doesn’t know how your medication will react with psychedelics, you may want to find someone else to speak with. For example, Third Wave’s psychedelic therapist directory can connect you with a qualified expert. Additionally, the Multidisciplinary Association for Psychedelic Studies has a directory of psychedelic integration professionals who may be able to help.


We’re not medical doctors, and we don’t pretend to be. Unfortunately, the research isn’t in place for anyone to give solid advice about mixing psychedelics with antidepressants. So be safe, be cautious, and always check with your physician before changing your drug-taking habits.

Are you drawn to working with plant medicines on your mental health journey? Third Wave’s Psychedelic Directory offers a vetted list of psychedelic therapists that can guide you through high-dose experiences and microdosing protocols. Check out our video below on microdosing for clinical conditions to gain more insights. We hope you find what you’re looking for.

Microdosing for Clinical Conditions

Reader Interactions


  1. Avatarmatc2017 says

    > it may be wise to wean yourself off your medication first – but always check with your physician.

    The physician will insist you continue consuming your pills for years.

    Instead watch videos/conferences of Irving Kirsh about SSRI’s.
    Also watch some by Robert Whitaker.

    Then you’ll know more than the physician and can take a decision on your own health.

    • AvatarDave Evans says

      Psilocybin is a naturally-occurring substance so Big Pharma can’t patent it. You must stay on SSRIs. Big Meat recommends eating lots of meat. Who is the we in “we don’t recommend..”?

    • AvatarJACLEEN says

      I take a low dose of amitriptyline for sleep. Do not notice any effect regarding improving depression. I have skipped taking my anti-depressant at least a night or two in a row because if I do not take it at a certain time it does not help me sleep. How long do you think I would need to refrain from taking amitriptyline before using mushroom tea? I have use mushroom tea in the past and enjoyed it very much. I do not believe I was taking amitriptyline at that time however. Very curious to fine This out because based on my current situation with life in general, I believe I benefit greatly from it greatly from a nice mellow mushroom tea experience. I am 50 years old and help me. I do not take any other medications.

      • AvatarBritt at The Third Wave says

        Hi Jacleen,

        Thank you for reaching out! Since we are not medical professionals, it would be advised that you seek guidance from your doctor regarding how long it takes for the medication to get out of your system, and to make sure that it is safe for you to refrain from the medication for that time.

        Best of luck to you! Let me know if I can answer any additional questions and I’ll do my best to help out.

        – Britt at The Third Wave

        • AvatarPatrick Dieter says

          So, in other words, you have to make a disclaimer like that to CYA, even though you know damned well that no sane person is EVER going to go to their doctor and say “Doc, I want to trip on psychedelics. What do you think about me stopping my meds?” Cue men in white coats.

          • AvatarBob says

            That’s not true–especially among younger docs. All my docs know and I use that conversation as an opportunity to educate THEM. Their response is a kind of litmus test. If they clutch their pearls, I find a different doctor.

    • AvatarDylan says

      Can I take acid or shrooms while on Lexapo? I’m currently on 20 mgs and my physician advised against the combination since others have died while doing so , but I don’t know if that is actual research since he didn’t know that it was for sure because of the mixture.

      • AvatarLorraine says

        I micro-dosed LSD for 30 days in 10 doses every three days as recommended by Dr. Faldiman. I am on Lexapro 20 mgs, Wellbutrin 300 mg, and Delpin (to help the previous two meds to be better absorbed). I didn’t read any material on whether I should or shouldn’t microdose. I was on vacation in a tropical area for two weeks when I began. I completed the last two weeks at home.

        This is what happened: I became more calm, my anxiety dissipated, and I felt spiritually refreshed and connected. I was more connected to my feelings and found myself journaling profound insights. I felt peace, gratefulness and a love for others.

        I’m glad I didn’t read the negatives of combining LSD with anti-depressants. If you decide to micro-dose, it’s recommended that you state three of four intentions for this 30 day experience. I became very clear about my intentions early on. Now I am implementing them as new goals in my life. Last, you have to believe and trust the process. This means letting go of fear.

      • AvatarShelbi says

        I took mushrooms while on Lexapro without realizing mixing antidepressants with psychedelics could be dangerous. I didn’t notice any “cool” effects and about three hours in I had a nervous breakdown. That could have just been me though.

      • AvatarPatrick Dieter says

        Nope. Just typical doctor BS – “Tell ’em anything to keep them from doing anything that actually works.” Plus most doctors still believe that LSD is a psychotomimetic that causes brain damage, addiction, and permanent psychosis. None of those things are true, of course, but the government has made such claims repeatedly. Since the substances are illegal, it’s all but impossible to refute because no legitimate study can occur.

  2. AvatarNoEffect says

    I’m on two SSRIs (Lexapro and Abilify) as well as Xanax, and LSD has absolutely no effect on me after multiple attempts including those in which I’ve waited several days to a week w/out taking the Xanax and not taking the SSRIs for a few days. And you’re right: Increasing the dosage of LSD doesn’t help me feel its effects.

    • AvatarDr.Dao says

      Abilfy is neither an SSRI or an anti-depressant. It is anti-psychotic, prescribed as an add-on when SSRI’s alone are not working. Also called “Major tranquilizers” the antipsychotics are strongly sedating. It’s not the least bit surprising that you experience NoEffect from psycheldelics on those two, plus Lexapro. They are effectively “blocking” the effect.

  3. AvatarAnonymous says

    I’d also recommend you watch Dr. Jordan B. Peterson speak about SSRIs, Depression, etc. before you decide to take yourself off your SSRIs. I tried once. It was hellish.

  4. AvatarTena says

    I began micro-dosing this year and the outcome for me has been monumental. I take Lexapro 10 mg BUT I cut into 4 pieces so I’m barely on SSRI … I’m attempting to stop anti-depressants altogether because they have not worked during most periods of my life. I live in Ohio and in winter my SAD is unbearable. Suicidal, can’t function UNTIL I tried micro-dosing. Completely different human being. My biggest concern is continued sourcing. I’m a 47-year-old woman that by chance found a connection that will not be permanent. I also must share I was on Suboxone for 11 years from Heroin abuse and getting off of Suboxone was a breeze during micro-dosing. I made hundreds of attempts lost careers and almost my life during my failed attempts. There are so many benefits we don’t know about with Psychedelics, truly the difference between life and death. Thanks for a wonderful article.

  5. Avatarvicki says

    I am on 4mg. of suboxone, also 90mg. cr of Prozac. will it alter any of my meds? I am very interested in trying the shrooms. what does anybody have to offer to help me!!!!

  6. AvatarMatt says

    You can purchase a growing kit legally for about 150.00 US Dollars, and you can purchase the spores legally for about 40 US dollars and grow your own if you have a bit of a green thumb.

  7. AvatarAdrienne Stover says

    I have bee n wondering why after eating 35 fresh picked shrooms…….it didnt even phase me…….ive been on methadone for 15 years and 40mg of p[rozac for 30 yrs. .sadly i know the harm all this crap has done to me and i am tryuing to deal with itnow……frustrated and angry……..

  8. AvatarJoe says

    I have been on 0.5 mg of Clonazepam for 15 years for PNE seizures in deep sleep. My PTSD was due to being kept in a closet for the first 2 1/2 years after being artificially induced 3 weeks early. I was not touched except when I was fed, diapered and given enemas. I have read that benzos alter the GABA receptor sites. Given that I have a gut feeling that psilocybin will work. Am I crazy too?

    • AvatarChris says

      I take 1 MG of Clonazepam twice a day and have taken two large doses of mushrooms and have microdosed a few times. While the large doses cause the expected effects, there was no problem regarding any kind of drug interaction.

  9. AvatarCautiousandcurious says

    What about SAM-e? I take 600mg of SAM-e daily; I don’t take any other medications.
    Will that affect microdosing or should I wean myself off of it?
    I plan to try microdosing with Psilocybin.

  10. Avatarrosemary says

    can anyone help me!! i took antidepressant fluoxamine around 3 months eventhough the total month of my depression is 10 i think i want to stop taking antidepressant as it does not help! and start microdosing..hmm idk either can or not and if i said to my dr of course she will never allow me to microdose the ‘ “”””illegal drug”””‘. i want a guidance or it was too late??

    • AvatarHaya says

      Hello, you are definitely not alone in your reasons for wanting to microdose.
      Also, there are many doctors who are now comfortable to talk to their patients about psychedelics, especially after the release of Michael Pollan’s “How to Change Your Mind: What the New Science of Psychedelics Teaches Us About Consciousness, Dying, Addiction, Depression, and Transcendence”

      The Multidisciplinary Association for Psychedelic Studies offers a list of integrative therapists, medical and mental health practitioners that are comfortable talking to their patients about psychedelics:

      I hope you find this information helpful!

  11. AvatarJennifer says

    Hello! I would like to try a psilocybin retreat but I’ve been on bupropion for years. Could I safely stop taking it, temporarily, to try psilocybin?

    • AvatarHaya says

      As always consult your primary healthcare provider, especially with regards weaning yourself off medications, however, there is no known reason why bupropion would interact negatively with psilocybin.

      It would probably be safer to remain on your current schedule of medication and take psilocybin in addition.

      Although again, check all this with a healthcare professional before making any decisions.

      • AvatarMaggie says

        Haya, You present your information and replies very carefully and this boosts my confidence in this organization.
        Ive been a mental health prescriber for many years and I think that the challenge will ultimately be to discern approximately how long it will take for serotonin receptors to wash out after discontinuation in order to safeguard the initiation of psychededlic treatment. Currently, the official position of Neuro-psychopharmacologists is that we just dont know exactly how these meds really work and what we teach our patients is mostly conjecture. In addition, different SSRI’s and NSRI’s and different psychedelic substances have different half-lives and washout times. Drugs like psilocybin have very short half-lives, as do venlafaxine and Lexapro and Paxil. To complicate matters, it would not be clinically advisable for a patient who has a history of psychotic or suicidal
        depressions, even if the clinician personally feels that the patient might benefit, unless that patient is under close supervision, like the currently open study at Johns Hopkins is providing.
        I am personally exploring the option of micro-dosing due to a life-threatening illness, and I also take anti-depressants, and so this is my personal quest for answers. Happily, most of the good prescribers, MD’s and NP’s are very open to helping their patients find the best ways to restore themselves. No clinician is satisfied to see a patient suffer….

  12. AvatarJust an avid enthusiest says

    So I’m taking 20 mg of Prozac daily and have plans to take mushrooms this weekend. Ive

    done them in the past and had a good experience but I was not on Prozac at the time. Ive

    done some research and it says that it should only dampen the effect of the mushrooms

    and I was wondering if there was any real risk of seratonin syndrome occuring (I’ll only be

    taking 2 grams of mushrooms) Anybody have any articles or first hand experiences that

    could help me make a good decision?

  13. AvatarO. Felix Culpa says

    In my youth, 1960s and 70s, I enjoyed most of the major psychedelics. So, I am very familiar with their effects. For the past several years I been taking 60 mg of the SSRI Cymbalta. I wanted to have the psychedelic experience again in my senior years. So, I grew my own mushrooms, weighed the dosage and ate them. I was amazed that I experienced no effect at all. It was only then that I realized the Cymbalta could negate the effects of psilocybin. It just didn’t occur to me. Now I have to figure out if I want to try to wean myself off the Cymbalta. I would have thought Paul Stamets or Michael Pollan might have mentioned this interaction!

    • AvatarJoe says

      Did you eat the mushrooms fresh, without drying them? To properly dose you must dry them out, when they are fresh it adds far too much variance in weight. 3 grams of fresh mushrooms is not equal to 3 dried. You have to eat alot of cubensis to equate to a psychadelic 3g of dried. So it is likely you are not eating enough.

  14. AvatarBob says

    Went to Amsterdam. Tried to smoke 1g of indica – no effect whatsoever. Only got my clothes soaked in awful weed scent. Ate 10gr of tampanese truffles – no effect (a very slight nausea for 15 min). All bought from popular shops.. I am on 10mg Cipralex and 25mg melitor.

  15. Avatarstorm mcadams says

    Okay so this is going to be a little difficult I microdose pretty much as much as I can. However kind of got the feeling I was doing it too much and now that I’m not doing it my depression has returned and my doctor wants me to go on Lexapro but I’ve never taken an antidepressant before and I’m not going to stop taking shrooms. I guess I just don’t know what to do.

  16. AvatarMike Brinn says

    I am on cymbalta for neuropathic pain. I took 45 grams of fresh picked shrooms yesterday with absolutely no effect. It was to be my first trip in 50+ years. Very disappointing. Weaning myself off Cymbalta, willing to bear the pain for the sake of the experience. Anyone know how long it takes for the blocking effect to subside? I figure a month, analogous to waiting a month between trips, but if anyone has experience with this I’d love to hear.

    • AvatarHe dd a says

      Im on cymbalta, antidepressive medication. When I took mushrooms had a complete blackout of the experience afterwards, so I don’t recommend takings mushrooms on cymbalta, but the interesting thing is that it does not occur any blackout when I have been taking LSD (150 mic).

  17. AvatarCharlie says

    Started microdosing the beginning of this month without checking about the reactions with Desvenlafaxine, which I’ve been on for about two years after decades on Prozac. I am 64 and this is my first experience with these substances.

    No noticeable effects on 0.5 gm P. cubensis (dried) nor on doses up to 2 gms.

    It seems Desvenlafaxine (Pristiq) blocks the effects, as might be expected.

  18. AvatarRhonda Barron says

    I am 66 years old and take 60 my of cymbalta daily which helps me greatly with pain and 300 mg of seroquel nightly which helps me sleep.
    After reading much about psilocybin my 36 year old daughter tried microdosing with 1/3 gm every three days and has had profound improvements with her anxiety and more. She also has taken a 2 1/2 gram dose recently which also provided dramatic effects. She described it as one of the most difficult but necessary experiences of her life.

    I also tried the same 2 1/2 gram dose after stopping my seroquel for two nites but had no noticeable effects. I would love to experience a lessening of anxiety and symptoms of ptsd. Any advise or recommendations would be greatly appreciated.

  19. AvatarChelsie says

    Ive eaten up to 3.5 grams of dried mushrooms while on 40 mg citalapram. I noticed the “experience” was lessened and also I felt a little weird sick on the come down but that could just be the come down alone. But hey, I’m not dead. Don’t suddenly stop your meds! Thats not safe! 😊

  20. AvatarBob Shaman says

    Effexor has a short half life so you could reduce the dose. Day before by 50% and then skip the day of dosing with shrooms. SSRI’s seem to reduce the effect. I suspect for most folks the whole serotonin syndrome is a bit urban legend- there are NO STUDIES only a case reports, most of which involve other drugs in combinations and are second hand. I have not seen lab data and vitals signs- just “anectodal reports’- so basically hearse. . I have been on SSRI and taken Ayahuasca as well as mushrooms and the effect is less- no serotonin syndrome issues at 75 Effexor. It could be I am just a fast metabolizer. I have notice that low dose sequel seems to reallly block psychedelic effects- so “anti-psychotics “ like Abilify as well seem to block the effects of psychedelics. Of course I don’t recommend you go off your medications. If it has a short half life like Seroquel- it’s out of your system (say a low dose like 50 mg) in about 2 days.

    If you are not mentally stable then do not take psychedelics. If you have been stable on your medications for some time, you could wean down over a few days if your drug (that is an SSRI) has a short half life. Antipsychotics will likely block all effects. However those on antidepressants ( as long as not Prozac- long half life) you could cautiously experiment if on low to moderate dosages ( at your own risk of course). Medical science really doesn’t know shit about this- they haven’t done any research and likely won’t anytime soon. I have a pharmacy background- however I still advise use caution.

  21. AvatarMatt Christian says

    I am on 5mg Paxil once a day, and the last 3 times I have taken shrooms I felt nothing more than a slight euphoria and found myself being content with starring at nothing. This is after taking 3 grams of golden teacher extracted psilocybin crystal the last time. The 1st 2 times was dried penis envy @ 2grams. With this his being said, I had absolutely No negative effects.

  22. AvatarAbra says

    I have been taking antidepressants for the last seventeen years because of a trauma that I experienced at that time that was too big for me to process.
    I am taking 225mg of effexor, 300mg of wellbutrin, and 1/4 of a .5mg clonazepam in the morning. I was taking 125mg of seroquel at bedtime but I’ve been reducing that amount, currently lm taking 50mg and hope to be off of it in the next couple of weeks. My doctor is very supportive and is helping me to reduce the wellbutrin next, then effexor.
    I want to begin microdosing mushrooms so that the withdrawal effects of coming off these prescription medicines is lessened…and so that my body learns to feel well in a more natural way.
    Any advice is appreciated!

    • AvatarMarian says

      Abra, with so many drugs already in your system, and with a supporting doctor, I’d strongly recommend approaching him and asking if he can help first. only after that start scouring the internet for answers. Best of luck!

  23. AvatarAnne-Marié says

    Hi I’ve been on the antidepressant Serdep (100mg) for most of my adult life (am 47 yrs old) and am struggling to wean myself off it. I went cold turkey a few months ago and it was hell, so I went back on Serdep. Shrooms is illegal in South Africa but I have a contact now who gave me 100mg capsules of shrooms as I want to use microdosing to wean myself of Serdep – I would rather use shrooms for the rest of my life than chemical products. I am supposed to take 1x serdep a day – must I use the shrooms together with the serdep and then slowly start to skip the serdep, or what would you advice? I cant speak to my doctor as it is illegal to use and I’ll definitely not get any support. Any suggestion would be highly appreciated.

  24. AvatarTrevor says

    From personal experience ssri, snri meds like cymbalta, effexxor, welbutrin, paxil, prozac, all greatly diminishtge full psychedelic Experience. I can consume 10 plus grams of strong psilocybin mushrooms with minimal effect. And dmt has very little effect on me. If you want to nit waste your time and money, you need to completely stop all ssri type meds for at least four weeks to completely rebuild the natural pathways and transmitter sites needed for the tryptamine to stick to. Taking antidepressant drugs restrict the amount of available spots the drug can attach to therefore you dont get the intended effect or benafit. I am 44 and have been using psychedelics like lsd, psilocybin, ketamine (only 1 time at 20) dmt, salvia extract and marijuana. There is so much to be learned through the magical ethnobotanical plants mother earth shares with us. Everything we need is provided by nature, and i believe that if you want to know the truth, you need to investigate for yourself and you will discover the answers that you seek. Life is a mystery for each of us to discover and enjoy as we share this planet with each other. Psychedelics teach us about how life is supposed to be lived, in coordination with all. Peace and love to all my brothers and sisters of pacha mama.

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