Is it safe to use psilocybin mushrooms while on antidepressants?

May 29, 2022

Written by: Edan Armas and the Mushroom Tao team
Readers: Dr. Sa'ed Al-Olimat, Sarah Gorban, Dr. Emily Kulpa
Editor: Tara Ruttenberg

Eddie's story

Trigger warning: this article contains references to suicidal ideation and accounts of one person’s unpleasant encounters with psychiatrists. Please note that this is one person’s story, and many people have positive experiences with their doctors.

When he was 15 years old, Eddie* was taken to a psychiatrist to help him process his parents’ divorce.

During this first appointment, the doctor prescribed Zoloft® (fluoxetine), a common antidepressant. But after reading about its severe side effects, Eddie refused to take it. He played goalie for the varsity hockey team and didn’t want to risk slowing his reflexes, which he had read was one of the potential side effects. 

At his next appointment, the psychiatrist brushed off Eddie’s concerns and placed a blue pill in his hand. Eddie remembers this experience well. 

“After I refused to take the medication at home, he coerced me into taking the first dose of Zoloft® in his office. That pill began a 26-year nightmare of illness, ever-changing cocktails of prescription medications, and countless misguided psychiatrists – the combination of which beat me to within a millimeter of my life. 

Shortly after starting Zoloft®, I reported multiple distressing side effects, including lethargy, slowed reflexes as a goalie, and even suicidal ideation. After hearing this, the psychiatrist prescribed Ritalin to boost my energy and agility before hockey games and practices. Following his directions, I suffered from vomiting, a racing heart, agitation, and many sleepless nights. 

When I first reported to my doctor that I was having suicidal thoughts (a known side effect of selective serotonin reuptake inhibitors [SSRIs] especially in adolescents and teens), he cut me off and started rambling about something else because he didn’t want to hear about them. He ended our session early and rushed me out the door. He made it clear that my suicidal thoughts were not welcome in his space.

He would brag when a pharmaceutical company sales rep took him out to Morton’s for a steak dinner. Ironically, he was a vegetarian. So, he sold out my health for less than the price of a steak dinner.”

It’s difficult to imagine what Eddie has been through.   

He shared that he was often taking 5-8 different medications simultaneously during the last seven years of his ordeal. Organizing and taking pills consumed his time and mental energy. When traveling, half of his carry-on would be filled with bottles of different medications.

“It was twisted because the severe withdrawal symptoms made it impossible for me to come off the highly addictive medications that were unknowingly causing my most serious problems.”

This is a plight common to those undergoing pharmaceutical treatment for depression. The side effects of antidepressants, which might include insomnia, weight gain, suicidal ideation, and sexual dysfunction, can often exacerbate the original condition. While these medications can sometimes help people get out of bed in the morning, they are notorious for sucking the magic out of life.

But if you’re reading this article, this is probably not news to you. You might be tired of the never-ending labyrinth of pharmaceutical treatment, and aware that psilocybin has helped others in similar situations.

Such was the case for Eddie, who out of frustration and desperation, finally sought out alternative treatment. Fortunately, he discovered psilocybin mushrooms in early 2020. He connected with an underground guide who gave him some microdose capsules, and he also experimented with growing his own mushrooms.

He started taking small amounts of psilocybin several times a week, a practice known as microdosing. The medicinal effects were subtle, but they gave Eddie a glimmer of hope. 

He wanted to experiment with a greater dose, but was scared of the potential interactions with his other medications. One doctor took the risk and told Eddie to go for it, curious himself about the potential for psilocybin to treat his patient’s long-term depression. This gave Eddie the confidence to take a 3.5-gram dose, considered a medium-to-high dose. Although potentially blunted by his medication, the mild positive effects he experienced were significant enough to give him even more faith in psilocybin as a treatment option.

At first, his psychiatrist was skeptical about Eddie’s enthusiasm about psilocybin. But after witnessing the positive shifts Eddie experienced following his second psilocybin macrodose journey, he expressed interest in trying it himself. During Eddie’s 27 years of experience as a psych patient, he had never witnessed a doctor express similar interest in any prescription medication.

Still, even after his initial positive experiences with psilocybin, Eddie struggled with the tapering process. During his first two attempts to completely taper off medications, he followed advice from his doctor and therapist and returned to the original levels of medications to avoid severe withdrawal symptoms. 

“In April 2021, I committed to the tapering process once again after experiencing a guided 6.5-gram psilocybin journey. It was a difficult eight-month taper, and this was only possible after I had experienced some of the wonderful benefits of psilocybin. By the end of December, for the first time in 27 years, I was completely off all prescription medications. The relief I feel now is indescribable. I feel healthier, happier, more cerebral, more lucid and more sober than I’ve ever felt in my adult life.”  

“Now, I microdose regularly with the support of my psychedelic integration coach, who has been vital in my healing journey. She helps me process and incorporate the positive changes facilitated by the mushrooms. I still feel withdrawal symptoms regularly, but am able to manage them.” 

He has a renewed relationship with life. He’s less “healed” than he is full — full of gratitude, love, and compassion for himself and the world. He has since reconnected with friends he had lost touch with and re-engaged with the parts of life he had lost decades ago. Hiking, spending time at the beach, and enjoying the fresh air are some of his favorite activities, providing him time to reflect on the past and dream about possibilities. And for the first time since high school, he bought a new pair of hockey skates and started playing on the frozen lake behind his house. “I’m picking up right where I left off,” he jokes.

Experiencing this fullness of life is possible for you, too. But is it safe to take psilocybin simultaneously with antidepressants? What does it mean to taper, and how do you do it?

In this guide, we’ll discuss how mushrooms work, how they interact with various medications, and how you might be able to start incorporating psilocybin into your life. 

*Name has been changed to protect patient privacy.

What are psilocybin mushrooms and how do they work?

Psilocybin mushrooms are naturally occurring and found in many places around the world. They are considered entheogens or psychedelics, and have been ingested as part of ceremonial and healing rituals for thousands of years in various cultures. They can occasion mystical experiences and have a popular reputation for alleviating symptoms of depression, anxiety, and other mental health challenges.

Unlike the conventional approach of antidepressants, which seeks to “fix” mental illness by covering up painful emotions, mushrooms can empower you to reconnect with and express your feelings as a basis for treating the root causes of depression. 

This is an important distinction. Although psilocybin is gaining a reputation in the Western world for exhibiting powerful antidepressant effects, the gift of the mushroom is more than the elimination of a mental disorder. 

Psilocybin mushrooms offer an invitation; a simple yet revolutionary opening into the intelligence, love, and compassion of the natural order of the Universe.

From a neuroscience perspective, this “opening” is reflected by the way psilocybin affects the brain’s Default Mode Network (DMN)

The DMN is a neural network responsible for filtering the countless pieces of information your brain processes each moment into that which is most necessary for survival. The DMN creates our ego, or consistent sense of self. Like a conductor, the DMN tells the rest of the brain, or orchestra, how to play the song of “you.”

A strong ego is an excellent tool for understanding threats to your survival. However, when the DMN is overactive, this sense of self can become rigid and resistant to change. The hypercritical self-talk and negative beliefs that torment many people are difficult to overcome, because at a neurological level the brain considers them to be essential components of self and, by extension, survival.

On psilocybin, the mind enters into a “pivotal mental state,” a dynamic and flexible mode of psychological functioning. In this highly sensitive state, in which thought processes, perception, and behavior styles are less stable, the floodgates of information open, generating more processing power than normal. Being in this state allows for shifts in fundamental belief systems, habits, and perspectives of the self. For a more nuanced discussion, consider reading this article.

In effect, the mushrooms can give you the opportunity to remember and trust your consciousness and intuition. You are presented with an opening, neurologically and spiritually, to know yourself anew.

What’s the connection between psilocybin mushrooms and antidepressants?

A key concept in psychedelic healing is contraindication. Put simply, contraindications are any conditions or medications that could cause harm if combined with a psychedelic substance.

For decades, antidepressant use has been thought to be contraindicated with psilocybin because both substances act on serotonin receptors. Serotonin is a neurotransmitter that stabilizes mood and supports happiness and general well-being, the imbalance of which plays an active role in a variety of mental health conditions, including major depressive disorder (MDD), generalized anxiety disorder (GAD), obsessive-compulsive disorder (OCD), and post-traumatic stress disorder (PTSD).

Some believe that combining antidepressants and psilocybin could cause serotonin syndrome, also known as serotonin toxicity, which can cause a range of clinical symptoms from mild to life-threatening. This condition occurs when excess serotonin accumulates in the body and can manifest as agitation, diarrhea, fever, and increased blood pressure, dilated pupils, shivering, and confusion. In severe cases, serotonin syndrome may manifest as high fever, tremors, seizures, irregular heartbeat, unconsciousness, or even death in rare instances.

However, despite the fact that many psilocybin studies and retreats do not accept participants who are using antidepressants, there is little evidence that serotonin syndrome is likely to occur when combining mushrooms with most antidepressant medications. 

In fact, combining two or more antidepressant medications may be more likely to cause serotonin syndrome than combining psilocybin and an antidepressant. Kayse Gehret, a microdosing coach in LA, contends that most restrictions are “driven by liability.”

“It’s very unlikely with psilocybin, even with journey dose experiences, that serotonin syndrome will be an issue. With microdosing, the risk is far less,” Gehret notes. 

As research into psychedelics begins to flourish, a stream of recently published scientific studies  explore the combination effects of antidepressants and psilocybin.

For example, one study from the University of Basel in Switzerland found that escitalopram, commonly known as Lexapro®, had no negative effects on participants treated with psilocybin. 

One limitation of this study is that SSRI therapy has a “lag effect,” which means it can take weeks or months to experience an effect from the medication. Since participants in this study took the SSRI for only two weeks, the neural shifts that occur with prolonged SSRI use were unlikely to be present. Therefore, it is difficult to rely on the data from this study to conclude that psilocybin will work without blunted effects in a patient currently using an SSRI. Also, since this study was sponsored by MindMed, a corporation with vested interest in obtaining positive results, it is wise to evaluate these results with a critical eye.  

However, while research is still in its early stages, a review published by pharmacists Kelan Thomas and Benjamin Malcolm of Spirit Pharmacist supported the safety of combining psilocybin and most antidepressants. Seeking advice from several experienced medical and mental health practitioners can be helpful in your decision-making process.

How do I taper off antidepressants before using psilocybin mushrooms?

Tapering off antidepressants involves taking incrementally lower dosages over a set period of time, which can range anywhere from two weeks to several months. 

There are many factors involved in determining the duration of the tapering process. These factors include how long you’ve been on antidepressants, the specific antidepressant(s) and the dose you are taking, as well as overall health and lifestyle. 

Certain antidepressants, such as Effexor®, have been known to be especially hard to taper off. In some cases, the tapering process can take years, and may result in severe withdrawal symptoms if not done slowly enough. 

As mentioned, since the risk of serotonin syndrome is relatively low when combining psilocybin and most antidepressants, the main reason for caution here is related to minimizing and managing the withdrawal symptoms of the medications, which can include brain zaps, fatigue, constipation, insomnia, dizziness, irritability, and gastrointestinal issues. 

Many journeyers report that antidepressants can blunt the effects of psilocybin. Pharmacist Kevin Lanzo, co-founder of the Psychedelic Pharmacists Association, explains: “an SSRI works kind of like a blanket that insulates specific parts of your brain from things like the negative feelings that appear in a person struggling with depression. That 'blanket' effect can also insulate the brain from some effects of psychedelic molecules like psilocybin too.” 

Some people taper before high-dose journeys so they can remove this “blanket” and gain the most benefit from psilocybin.

There is a growing trend of people choosing to microdose while they taper. However, please note that some journeyers tapering off antidepressants while microdosing still report having difficult withdrawal symptoms. So it’s important to evaluate expectations based on personal circumstances.

The golden rule with microdosing is to “start low and go slow.” Microdosing coach Gehret generally suggests that people tapering off antidepressants take double a normal microdose to account for the blunting effects of the medication. This means that instead of taking a microdose of 0.1 grams, you may find it helpful to take 0.2 grams to start. 

From there, you can evaluate how you respond, and increase or decrease your dosage accordingly. With microdosing, you are looking to find the lowest effective dose that provides the most therapeutic benefits. Many people microdose psilocybin mushrooms on a schedule of four days on and three days off, or five days on and two days off. The off-days allow for the natural tolerance that builds up to fade away.

When tapering off antidepressants and experimenting with psychedelics, it’s important to conduct your own research and consider consulting not only your doctor or licensed medical professional, but also an experienced psychedelic facilitator or integration specialist

Specifically, you may want to consider the offerings of Spirit Pharmacist, Dr. Emily Kulpa, or The Holistic Apothec, who are pharmacists specialized in working with those who wish to taper.

It is also important to consult with a medical professional on how to restart previous antidepressant medications if that is the course of treatment chosen following one or more psilocybin experiences. 

For further research and support in your tapering process, please consider consulting this guide from Harvard Medical School or exploring the Surviving Antidepressants forum.

As always, we are happy to support your process at any stage in the psilocybin journey, so please reach out to us at Mushroom Tao and we’ll do our best to be of service

In the next section, we examine some common antidepressant medications to offer a more detailed look into their distinct safety profiles.

Overview of common antidepressant medications

Can I take psilocybin mushrooms and SSRIs?

Selective serotonin reuptake inhibitors, or SSRIs, are the most frequently prescribed type of antidepressant. Basically, SSRIs increase the levels of serotonin, often referred to as the “feel good hormone,” in the brain by preventing neurons from clearing out excess serotonin in the synapses, the connective gaps between cells. 

This causes the serotonin to remain in the synapses longer than usual and to stimulate neuron receptors more frequently. In the long run, these receptors become artificially overstimulated, which ultimately leads certain brain cells to decrease the quantity of serotonin receptors produced. 

This can cause the “numb” or “robotic” feeling that some people report as an effect of chronic antidepressant use. Simply, chronic SSRI use can cause an individual to be unable or less able to feel true joy. 

Some common SSRIs include:

  • Citalopram (Celexa®, Cipramil®)
  • Fluvoxamine (Faverin®, Luvox®)
  • Escitalopram (Lexapro®)
  • Paroxetine (Paxil®, Seroxat®)
  • Fluoxetine (Prozac®, Sarafem®)
  • Sertraline (Zoloft®)

As discussed above, there is no strong scientific evidence to support the claim that combining SSRIs and psilocybin causes serotonin syndrome. In fact, very little scientific research has been done regarding this issue. 

In our experience, many of those who take psychedelics while on SSRIs report that the SSRI either dulls or negates the psychedelic experience. A few report that the SSRI did not affect the journey at all. 

Lola SH, host of the psychedelic education Zamin Podcast (in Farsi), shared an anecdote of her experience tapering off Prozac® and other medications, including Xanax®, while microdosing psilocybin for ten weeks. She contended that “if somebody is determined to taper down or quit SSRIs, I don’t see any interference between them and psilocybin. I didn’t see any interference at all in my case.”

Can I take psilocybin mushrooms and SNRIs?

Serotonin-norepinephrine reuptake inhibitors (SNRIs) are another commonly prescribed class of antidepressants. They work similarly to SSRIs, except SNRIs also increase levels of norepinephrine, another neurotransmitter.

Some common SNRIs include:

  • Duloxetine (Cymbalta®)
  • Venlafaxine (Effexor®)
  • Levomilnacipran (Fetzima®)
  • Desvenlafaxine (Khedezla®, Pristiq®)
  • Milnacipran (Savella®)

There have been no scientific reports of severe negative effects of combining SRNIs and psilocybin. Because they work so similarly to SSRIs, their risk profile is essentially the same. 

Can I take psilocybin mushrooms and SMSs or SARIs?

Serotonin modulators and stimulators (SMSs) and serotonin antagonists and reuptake inhibitors (SARIs) are two other classes of antidepressants that function similarly to SSRIs.

SMSs and SARIs are unique in that they turn on or off a number of additional serotonin receptors, in addition to boosting serotonin levels in the brain.

Some common SMSs/SARIs include:

  • Vilazodone (Viibryd®)
  • Trazodone (Desyrel®)
  • Vortioxetine (Trintellix®)

There is no strong evidence that SMSs/SARIs pose a risk for serotonin syndrome. However, several anecdotes (one, two, three) point to blunted psychedelic effects when taking one of these medications, so we suggest tapering off these medications before taking psilocybin.

Can I take psilocybin mushrooms and TCAs?

Tricyclic antidepressants (TCAs) and Tetracyclic Antidepressants (TeCAs) boost the levels of serotonin and norepinephrine in the brain, similar to how SNRIs work. They also function by triggering the muscarinic M1, histamine H1, and alpha-adrenergic receptors, and obstructing specific ion channels in the brain. 

Some common TCAs include:

  • Doxepin (Adapin®, Sinequan®)
  • Noxiptiline (Agedal®, Elronon®, Nogedal®)
  • Amitriptylinoxide (Ambivalon®, Amioxid®, Equilibrin®)
  • Clomipramine (Anafranil®)
  • Amoxapine (Asendin®)
  • Nortriptyline (Aventyl®, Pamelor®)
  • Pipofezine (Azafen®/Azaphen®)
  • Tianeptine (Coaxil®, Stablon®)
  • Melitracen (Dixeran®, Melixeran®, Trausabun®)
  • Amitriptyline (Elavil®, Endep®)
  • Lofepramine (Gamanil®, Lomont®)
  • Opipramol (Insidon®)
  • Dimetacrine (Istonil®)
  • Maprotiline (Ludiomil®)
  • Amineptine (Maneon®, Survector®)
  • Desipramine (Norpramin®, Pertofrane®)
  • Dibenzepin (Noveril®, Victoril®)
  • Dosulepin (Prothiaden®)
  • Mirtazapine (Remeron®)
  • Nitroxazepine (Sintamil®)
  • Trimipramine (Surmontil®)
  • Setiptiline (Tecipul®)
  • Imipramine (Tofranil®)
  • Mianserin (Tolvon®)
  • Protriptyline (Vivactil®)

These medications were some of the first drugs developed for depression, but because they are known for their serious side effects, they are currently only prescribed when other medications have proven unsuccessful.

The FDA requires all tricyclic antidepressant products to be labled with a warning that side effects may include suicide and/or suicidal thoughts. 

When combined with psilocybin, these medications pose little risk for serotonin syndrome, but it is likely that they will blunt the effects of the mushroom. However, because of these medications’ serious side effects, we recommend caution and a more in-depth consultation with psychedelic professionals before combining them with psilocybin. 

Can I take psilocybin mushrooms and MAOIs?

Monoamine oxidase inhibitors (MAOIs) are a class of drugs that boost the levels of serotonin, dopamine, and norepinephrine in the brain by preventing the breakdown of these neurotransmitters by the monoamine oxidase enzyme.

Some common MAOIs include:

  • Bifemelane (Alnert®, Celeport®)
  • Moclobemide (Aurorix®, Manerix®)
  • Selegiline (Eldepryl®, Emsam®, Zelapar®)
  • Toloxatone (Humoryl®)
  • Metralindole (Inkazan®)
  • Isocarboxazid (Marplan®)
  • Phenelzine (Nardil®)
  • Tranylcypromine (Parnate®)
  • Pirlindole (Pirazidol®)
  • Caroxazone (Surodil®, Timostenil®)

Like TCAs, MAOIs were some of the first antidepressants created. They can have severe side effects and are only used when other treatments have been unsuccessful.

There is no scientific evidence demonstrating risk of serotonin syndrome when MAOIs are combined with psilocybin. However, the combination of magic mushrooms and certain MAOIs such as syrian rue or Banisteriopsis caapi can create a psilohuasca experience, which can be longer lasting and more intense than a pure psilocybin experience. If you are thinking about combining MAOIs and mushrooms, please do in-depth research so you know what to expect. 

Can I take psilocybin mushrooms and NRIs/NDRIs?

Norepinephrine reuptake inhibitors (NRIs) and norepinephrine-dopamine reuptake inhibitors (NDRIs) are two classes of drugs that increase the amount of norepinephrine (and dopamine, in the case of NDRIs) in the brain.

Some common NRIs/NDRIs include:

  • Methylphenidate (Concerta®, Ritalin®)
  • Reboxetine (Edronax®)
  • Teniloxazine (Lucelan®, Metatone®)
  • Atomoxetine (Strattera®)
  • Viloxazine (Vivalan®)
  • Bupropion (Wellbutrin®)

Unlike the other medications described, NRIs and NDRIs do not affect serotonin levels and are not frequently prescribed antidepressants.

There is no evidence that NRIs and NDRIs react with psilocybin. However, to be safe and to experience the full benefits of the mushrooms, we suggest tapering off NDRIs and NRIs before taking psilocybin. 

Can I take psilocybin mushrooms and lithium?

Lithium is a mood-stabilizing drug that is more frequently used for bipolar disorder than major depression and is not categorized as a conventional antidepressant.

However, if you are taking lithium, it is NOT recommended that you ingest psilocybin. An analysis of online trip reports showed that seizure is a significant possibility when lithium is combined with various psychedelics.

What if my doctor or psychiatrist is not knowledgeable about psilocybin?

With the rapid expansion of psychedelic science, more and more health professionals are tuning into how psilocybin works and how to use it safely.

However, if your doctor or psychiatrist is not knowledgeable about magic mushrooms or is against using them, here are a few resources available to you.

You can apply to be part of a clinical trial. Please note that since many people are vying to be part of these studies, there are no guarantees that you will be selected; and if you are selected, there is a possibility you will receive a placebo instead of psilocybin.  

The Multidisciplinary Association for Psychedelic Studies (MAPS) has an excellent directory of integration specialists

Psychedelic Support is a psychedelic therapy resource that provides lists of licensed practitioners who can help with preparation and integration, and community groups where you can connect with likeminded beings. 

Tripsitters offers a comprehensive list of retreats, practitioners, local groups, and reading material for further study.

If you have specific questions about antidepressants, interactions, and/or tapering, you may want to consider the offerings of Spirit Pharmacist or Dr. Emily Kulpa.

If you have any questions or want to discuss your personal situation, feel free to reach out to us directly. If we don’t have the answers to your questions, we can refer you to other professionals in the psychedelic community who might be able to better assist you.

Are there other options available?

If you don’t feel comfortable mixing antidepressants and psilocybin, and don’t want to go through a tapering process, there are other healing modalities you might consider pursuing.

Ketamine clinics

Ketamine operates on a completely different set of receptors than any of the antidepressants discussed here, and is therefore generally regarded as a safe medicine to use in combination.

While not known for the mystical or transpersonal experiences typically associated with classical psychedelics like psilocybin mushrooms, LSD, and ayahuasca, ketamine is a fast-acting medicine used against depression and acute suicidality. For some, it can be an effective tool to break through the negative beliefs and stories that contribute to the causes of depression.

Compassionate preparation and integration before and after a journey are necessary components of psychedelic healing. When searching for a ketamine clinic, you’ll want to look for locations offering adequate support. 

You may want to explore this guide on how to find a supportive ketamine clinic near you. Websites like this can help you explore your options.  


While there are many styles of breathwork, the style most commonly compared to the healing effects of psychedelics is Holotropic Breathwork, designed by Stanislov Grof.

Holotropic Breathwork involves lying down and breathing rapidly in a synchronized rhythm, usually to the accompaniment of evocative music. People can experience profound somatic and emotional releases as well as altered states of consciousness.

Although breathwork is relatively simple, this doesn’t mean you should take it lightly or do it without the support of an experienced practitioner. You might approach a breathwork session like a psilocybin ceremony, with adequate preparation before, an energetically supportive space during, and thorough integration after the experience.

The bottom line

We recommend approaching psilocybin respectfully, with intention, and with the support of the growing psychedelic community.

Generally, there is no strong evidence that consuming psilocybin mushrooms while taking most antidepressants is dangerous. Some journeyers decide to do what Eddie did -- to experiment with psilocybin while they are still on one or more antidepressant medications. 

However, to be safe and to experience the full benefits of the mushrooms, it may be beneficial to completely taper off antidepressants before taking psilocybin. In any case, we advise consulting with as many experienced professionals as possible before making any decisions regarding this process. 

Wishing you all the best on your journeys. If you feel we may be able to support your process by answering questions or providing a consultation, we are happy to hear from you. 

Read More

Dive into another in-depth article.

Back to Blog Home

Start at Home

Start working with psilocybin in the comfort of your own home.

Explore Microdosing

Private Retreat

Do transformational inner work with experienced guides.

Explore Retreat
Back to top