Can Psilocybin Mushrooms Be Effective Antidepressants?

Eden Loi · August 28th, 2017

Depression is a global epidemic, affecting hundreds of millions worldwide.[1] It is one of the most commonly diagnosed mental disorders in the United States, and compared to the other mental disorders, is responsible for the most disabilities.[2]

Unfortunately, rates of depression continue to rise. Researchers found that, even after controlling for changing attitudes surrounding mental health, our modern lifestyles are leading to rising depression rates.[3] Global revenues from antidepressant sales are expected to reach over $13 billion by 2018.[4] The rise of depression around the world is gaining momentum, and treating it requires a new approach.

Could psilocybin mushrooms, the ancient psychedelic fungi, be the answer to solving our mental health epidemic?


Selling more of the same antidepressants is unsustainable—research has shown that antidepressants are hardly more effective than placebos,[5] and a comprehensive review of existing studies on antidepressants concluded that “there seems to be little reason to prescribe antidepressant medication to any but the most severely depressed patients.”[6] Despite the millions of prescriptions filled (and billions of dollars made), depression persists.

Could psychedelics be used as an alternative antidepressant? Therapists and psychologists have considered this possibility since the early 20th century, but the War on Drugs made it nearly impossible to conduct clinical research. However, that resistance seems to be receding. In recent years, a few studies examining the effects of psychedelics have trickled through and delivered promising findings.

Are you curious about journeying with psilocybin to heal from mental illness? Visit Third Wave’s Psychedelic Directory to find a psilocybin mushrooms retreat center.


Neuroscientists have coined a term for the areas of our brain associated with our sense of self, our memories, and our “inner voice”: they call it the default mode network, or the DMN. This network of brain activity defines and keeps us who we are.

The DMN provides us with a consistent autobiography and experience. While such a default brain state is necessary and beneficial, it may also lead to problems. The DMN isn’t something we can consciously control; if you happen to be unhappy or uncomfortable in a default state, then you are out of luck. A DMN is great as long as it is healthy, but abnormal activity may cause problems, which seems to be the case for people with depression.

Researchers took brain scans of people experiencing major depressive disorder and found that they had an overactive DMN. For most people, the DMN shuts down when they fall into deep focus and engagement, or experience a “flow” state. But an overactive DMN makes this much more challenging, sometimes nearly impossible.


People who have tried psilocybin mushrooms talk about losing their ego during their trip, an experience termed ego-death or ego-dissolution. When you undergo a loss of ego, anxiety and fear often disappear as well. Ego-death is the reason why, after using psychedelics, many people report feeling connected with friends, strangers, the whole universe.

It might be easy to dismiss these reports as banal, woo-woo psychedelic hype, but recent brain scans revealed a stunning explanation for how psilocybin affects the ego. Researchers from Imperial College London administered psilocybin to a group of volunteers, and then scanned their brains to see how their brain activity changed. The scans showed that the ego-death associated with psilocybin was verifiable — our DMN takes a break when we ingest psilocybin.

Subsequent research showed that in patients with depression, psilocybin mushrooms shut down the DMN, acting as a ‘reset’ for the brain’s overworked self-critical systems. The results of this study show that the resetting of the DMN is directly linked to patients’ improvements in depression scores, contributing to evidence that the DMN is directly involved in depression, and that psilocybin mushrooms can successfully address this.

If you want to find out more about “How mushrooms tap into our subconscious” check out our podcast interview with Bett Williams where we talk about Psilocybin, Private Rituals, and Personal Journeys or Click here to read the transcript


In a literal and metaphorical way, psilocybin mushrooms break down walls. The everyday, default brain network confining our thoughts is torn down, and brain activity rushes to new areas. At an experiential level, these brain changes manifest in profound ways—changed perspectives, unexpected insights, and feelings of purpose and engagement that may have long been dormant. People who have successfully used psilocybin mushrooms for personal growth know the feeling when their entire outlook changes, yet they still retain a sense of clarity and certainty. No longer steeped in a network of stale beliefs, they are often able to confront and address past traumas, anxieties, and fears.

If properly used, the substance could significantly improve the effectiveness of psychotherapy. Talking about one’s mental state is difficult already, even when free from depression. Too many therapists deal with the frustrating experience of trying to communicate through a brick wall with patients who are unable to open up because of their pain or fear. If psilocybin could be combined with therapy to loosen up patients, a groundbreaking new treatment for depression could emerge.

Using psilocybin mushrooms and other psychedelics for therapy was briefly explored during the mid 20th century, but the War on Drugs halted further research until a few years ago, when researchers conducted a promising pilot study on psilocybin for therapy treatment.

In a study from NYU, and another similar study from Johns Hopkins University, patients with anxiety and depression linked to terminal illness were administered psilocybin as a tool for therapy treatment. The results of both studies showed a significant reduction in patient anxiety and depression, which remained more than six months after their therapy sessions ended. There were no significant dangers involved, and besides a few cases of nausea, no negative side effects, during or after, were reported.

The results are not exclusive to terminal-related depression. Another study gave psilocybin to people with treatment-resistant depression, and was similarly successful in producing long term, lasting treatment for depression after only two sessions.


Psilocybin is currently a Schedule I controlled substance. According to this classification, it poses a high risk for addiction and offers no known medical benefit. However, the recent research into psilocybin strongly suggests the opposite. Psilocybin mushrooms show great promise in treating depression and anxiety, and not only is it not addictive, but may even help with treating addiction.

While public opinion and private interests may want to keep psilocybin criminalized, the research findings are leading to progress. The FDA recently approved a phase 3 clinical trial studying psilocybin, which could result in reclassification. If reclassified, psilocybin-assisted therapy and psilocybin antidepressants may not be too far away.

For now, though, psilocybin is illegal in most countries. People with treatment resistant depression, or who do not want to use antidepressants, have few options. Self-administering poses risks, and cannot be guaranteed work as successfully as the preliminary research. If you plan to use psilocybin mushrooms, take the proper time and care to prepare for the experience.

If you live in a place where you can legally obtain psilocybin mushrooms or truffles, try our Microdosing Course. It’s a safe way to delve into the world of psychedelic wellness on a much less intense level than a full macrodose journey. You can microdose by yourself (no guide needed!) and may start seeing improvements in your emotional health and personal goals in as little as a week.

Reader Interactions


  1. AvatarSean says

    From many many experiences through out my teens, i agree full heartedly with this research as it pulled me out of a life long depressive mindstate. Noticing in my 20s that my depression is again occurring, along with addiction problems, i am very excited to try micro dosing. Thanks for this article

  2. AvatarClaudia Colarusso says

    I think the article was informative for people just learning about micro-dosing. I have been up on it for a while, along with other medicinal plants, Ayahuasca and Kratin, With Kratin, you also have to self administer and ‘tweek’ your own dosage also, as you would with psilocybin mushrooms. Which brings me to the point of prescribing. Because is say “take 1 three times a day” on a prescription bottle,that is a blanket prescription for every person that is diagnosed with lets say; sinus infections. “Who is the one to say, 3 antibiotics (poison) is correct dose for every person? It is stated as law by the FDA. With that being said; as in any holistic supplements, it can read take one to three pills if needed per day. In microdosing; it should be understood and recommended, to start with a low dose, and graduate to a higher dose, until you have reached your plateau of what you are seeking as a benefit to what you are taking them for. NOW anyone can take more as said, as to the same as with prescribed medicine, from a ‘physician’ I myself, had to tweek all my meds I was taking, some still taking, due to the paradoxical effects some of them gave me and with strong adverse drug reactions. Antidepressants. Some made me more depressed, others not making me sleep for DAYS….I did it myself, I know my body and the way my brain works….Doctors where shocked that they worked on such a low dosage. WELL, we are NOT all the SAME, and don’t have the same chemical make up in our minds, body, and soul..

    I would love to participate in one of your studies Paul. I am always that 1 percent, when it comes to adverse drug reactions. For example: 1 percent of the population in the antibiotic world, experiences depression when on Levaquin. After researching what was new in my regimen of supplements daily, Finding this out after I was crying for no reason at my desk at work. I found another colleague of mine, sobbing, then finding out he was on Levaquin for a sinus infection. He was so thankful, he thought he was losing his mind, crying over nothing. Where as everyone else on it, was ‘normal’going about their daily work routine. (I worked in a department of 98 people)
    The blanket effect of anything doesn’t work. Individualization, per treatment is necessary to what the patient thinks is beneficial for them. Now if you get a person that just wants to trip all day and take bountiful amounts, disclosure must read. If taken without using caution; may be harmful…..Like cigarettes do…they ‘may’ cause cancer. That word in the English language goes a long way. May.


  3. AvatarJimmy says

    I think this is absolutely amazing. However, correct me if I’m wrong as I did only skim the article, but microdosing psilocybin can be very very hard, unfortunately, due to the varying levels of psilocybin in each mushroom, whereas with LSD, you can accurately dose with relative ease with the proper scales and equipment, and because mushrooms have such a varied response from dose to dose, I’ve found that a dose that was just enough to cross the threshold on another day, for whatever reason, maybe due to stomach content, I’m really not sure, but that same dose will cause visual disturbances and euphoria and actually cause a weak trip. I believe (and this is just my opinion here on out), the only way to semi-accurately microdose would be to powder the mushrooms in a food processor or blender, and then weigh portions into capsules). For me, as I’ve been doing this with some B+ and psilocybe cubensis powder for the last couple of weeks, my ideal dose with the medications I take is .2g or 1/5th of a gram, every three days or so. I’m extremely interested in this subject and I’m excited to continue to learn and, hopefully, finally find a solution for my depression that ISNT some form of SSRI medication.

  4. Avatardrayce says

    I know for an experiential fact that that taking moderate doses or microdoses of Psylocybe mushrooms helps w/depression, anxiety and general well-being. About 13 weeks ago I made the leap off two drugs: Buspirone (anxiolytic) and Sertraline (SSRI antidepressant). I consumed 0.5 grams in increments on the first day until I should have been ‘tripping balls’ at about 35 grams FRESH mushroom material- with little or no effect except increase in SSRI-like side-effects. I waited 3 days and tried again, this time w/dried material. Same thing. It took a full 2 weeks to get the ‘meds’ out of my system- and on THAT day- Wow- I had a mild ‘trip’ similar to what I recalled from my youth (I’m 48 now.), with only 1.7 gms. dried material. I am continuing my experiment or therapy with about 1.0 gram dried every 4 days. This is a little over the ‘microdose’ and the ‘threshold’ of a ‘psychedelic’ experience, but seems effective for me and does not impair my judgement or ability EXCEPT the 2 hours when I can ‘feel’ them working. I time the doses so I’m comfortable, safe and quiet at home, usually late at night or in the afternoon at a time when I usually meditated- and which i do now. The results are fantastic! Not only do I not need the meds I was taking for ~6 years- I have realized many of the benefits listed in this very article.

    The only problem, for me, was my inability to procure the material previously due to obvious reasons.
    I thank everybody that is involved in ‘search’, research and spreading information about these magical fruits.
    Real, factual, scientific information has been repressed way too long. Keep up the good work.
    Thank You

  5. AvatarHunter Van Meter says

    This was a great piece, I used high doses of LSD during my depression and it really turned things around, I have been curious about whether or no psilocybin had the same capabilities, this quite efficiently answered my questions

  6. AvatarJohn says

    Nice, thorough article. While psilocybin-specific, I think it touches on the nature of how psychedelics may work in cases of depression, how it can help break the tenacious depressive cycle. I’ve had direct experience with this.

    I’ve had recurrent depression for 20 years (many of them being quite severe). I am currently undergoing ketamine-assisted psychotherapy, and can attest to the psychedelic state producing insights that were otherwise unavailable in my ordinary conscious state. And those insights have stuck, slowly changing the way I perceive myself, change my behavior, change how I see my part in the world – and in that way has lifted my depression (for now) .

    The psychedelic state has opened up a door to self-knowledge that in my case, breaks the repetitive, well-honed pattern of thinking that helps initiate and allow depression to build on itself, further disabling me. The “sense of self” and the thoughts that accompany it in my depressed state have been broken down in the last 3 months – the insights are changing my perception of self, changing my awareness and reactions to a deeply rooted unhealthy sense of self, and those changes are propelling a new way of relating to “self” – and if you are familiar with brain plasticity, possibly healthier neural pathway are opening up that can be reinforced over time.

    While my experience is with ketamine, I can totally see the same function with Psilocybin (and am likely try it sometime).

  7. AvatarRobert Iddon says

    Echoing a lot of what I’ve already read but great article none the less. I’ve not experienced psilocybin properly apart from trying magic truffles earlier this year – was hardly ground breaking but I did have a mostly positive experience. I’d love to volunteer for treatment as I’ve been a long time sufferer of anxiety, depression as well as addiction and so far nothing really works long-term. Fingers crossed the law changes soon!

  8. AvatarRay Harrilla says

    I think that we are on the right track – But not all ‘trips’ need an outside help. For some it may be necessary – but not for all. Most of my private ‘vacations’ were done on my own and in the woods at my own set times and locations. I haven’t had a ‘vacation’ in about 20 or so years. I’m now 79 yrs old but miss my vacations.
    Most of my own trips were on or near full moons, in the woods or away from others.
    Wish you all good luck on your adventure…

  9. Avatarjeanne hollman says

    Self criticism fosters depression. For me, grass in the 60’s & 70’s stopped the criticism and gave me joy. Now, I won’t inhale and in IL. can’t get eatable grass even if have handicaps, which I don’t. Would love to try mushroom but I live in Chicago.

  10. AvatarAdam Bayliss says

    I liked this article the effects of flow states on the default mode network was very interesting

  11. AvatarÅdne Aschehoug Aadnesen says

    I have been using mushrooms for many years.And their antidepressant effect lasts for months.When their effect is over,i return to my depression,and start reading and thinking about mushrooms again.
    So they offer a space between the hardships of life,a room to breathe and heal,before the curtain falls again.

  12. AvatarCarole Anne Rogers says

    There are several 4-substituted tryptamines that can be used as well as psilocybin, like 4-HO-MET etc., as well as DET (orally active with a 2-3 hour duration, ideal for psychotherapeutic applications). Frankly, the sooner we are free of puritanical legislators (and a media that thrives on & profits from stories of ‘drug addicts’ & ‘tragic consequences’, as well as a misinformed, terrified/judgmental public) and able to continue the work of Dr Albert Hoffman, Dr Alexander Shulgin, Dr David Earl Nichols et al, the better.

  13. AvatarShaman GeeGee says

    Aye Mushrooms and LSD are not for everyone just like the side effects of mental health drugs that include suicide or suicidal thoughts. Mushrooms can do the same thing. I’m tired of reading all these post trying to hint that there some miracle drug that’s going to make you a billionaire or fix all your mental health problems hallucinogenic don’t work that.

  14. AvatarShaman GeeGee says

    There definitely not for everyone with depression or mental health issues. I’m not saying the drugs they give are any better.
    You just need to really look at why a person is having those problems to begin with. For some people it could help find those answers, If the person is in the mind set to search within there self for those answers and they have the ability to reflect on ones self. For some it will make it a lot worse.

  15. AvatarJonathan Heuschen says

    It’s an introspective drug, it is neither good or bad. But everything is about set and settings, if you use it wisely with the right mindset and objectives, it can brings you huge benefits and eventually rewire your way to see the world in a more positive way. As for an “antidepressant” per say… meh… MDMA is a better antidepressant, imo.

  16. Avatarkasia says

    definitelyI agree;) mushroms are great to heal depression especially that they go into deep root of suffering that cause all the problem.;)peace to all users and nonusers;)

  17. AvatarLance says

    Is it not morally wrong to adhere to the law if you know it to be unjustified? Should we really bow to a figure of supposed authority?
    As far as I know, I am a free and sentient being whom may partake in anything I wish, as long as I don’t infringe upon others right to do the same.
    This society is not civilised or advanced in any way.
    I have and will continue to use magic mushrooms and any other sychoactive substance that take my fancy.
    That is my birth right.
    Death to statism