What Is Psilocybin Therapy? A Detailed Scientific Guide to This Psychedelic Approach for Mental Health

When we discuss psilocybin therapy, we’re not talking about taking “magic mushrooms” to watch the sunrise or “trip” at a music festival, or any other kind of recreational psychedelic pursuit.

Rather, with major academic centers leading the way, research on psilocybin therapy, in the realm of psychedelic therapy, suggests this newer clinical approach — though it’s not federally legal, yet — may be able to help address some of the most difficult-to-treat mental health conditions.

Read on to learn about what psilocybin therapy is, the potential benefits, risks, how to get started, and more.

Definition of Psilocybin Therapy

First, it’s helpful to talk about what psilocybin is. Also called “magic mushrooms” or “shrooms,” psilocybin is a hallucinogenic substance that comes from species of Psilocybe mushrooms, according to the Drug Enforcement Administration (DEA).

In certain doses, the natural substance induces hallucinations, which is when you see, hear, smell, or feel something that seems very real, but it is not, per MedlinePlus. You might hear music, voices, or see lights that don’t exist in the present reality, and some people report increased insightfulness and what is called a “mystical experience,” notes a systematic review. These episodes are also colloquially referred to as having a “trip.”

Aligned with this, another newer term for hallucinogens like psilocybin has been proposed: “Entheogen,” defined as “any substance that, when ingested, catalyzes or generates an altered state of consciousness deemed to have spiritual significance,” per a research article.

Due to expanding research on the possibilities of psychedelic medicine, there has been some enthusiasm surrounding the potential promise of the use of psilocybin in the context of mental health therapy. While the definition is not well defined yet, generally this approach to treatment combines psilocybin with psychological support, according to the mental health care company Compass Pathways, which supports clinical trials on psilocybin.

Archaeological, ethno-historical, and ethnographic evidence has found that hallucinogenic plants and fungi, specifically psilocybin mushrooms, have been used for thousands of years by pre-Columbian Mesoamerican civilizations, including the Olmec, Zapotec, Maya, Mazatec, and Aztec. These psychoactive substances are still used culturally by local shamans and healers in ritual ceremonies, notes a past review.

They were later “discovered” by Western society through contact with a Oaxacan traditional healer in the 1950s, and led to its research and eventually spilling over to public use and subsequent banning by the United States government, per a recent article.

Psilocybin therapy fits under the umbrella of psychedelic-assisted therapy, which is newer in the context of conventional mental health care. In the 1950s, research was emerging on the therapeutic potential of substances like LSD. In 1958, the active ingredient of psilocybin was identified from the Mexican Psilocybe mexicana mushroom by Swiss chemist Albert Hoffman. However, laws enacted by the United States in the 1960s, and later by the United Nations in 1971, ended research, according to one review.

In 1970, psilocybin, along with LSD, were declared schedule 1 drugs. A schedule 1 drug, per the DEA, is one that has “no currently accepted medical use and a high potential for abuse.”

It wasn’t until the 1990s that research started again, with a boom in the 2000s and 2010s, as research on psilocybin found it to possibly be promising for obsessive compulsive disorder (OCD), end-of-life psychological distress, alcohol use disorder, and smoking cessation, notes the review above. In 2016, three clinical trials on psilocybin use in major depressive disorder (MDD) and anxiety and depression in life-threatening cancer were published, which was considered a major turning point in psilocybin therapy research.

There are two differing approaches to psilocybin therapy, says Charles Raison, MD, director of clinical and translational research at Usona Institute in Madison, Wisconsin, a medical research organization that runs clinical trials on psilocybin and 5-MeO-DMT (another psychedelic).

“Psilocybin-assisted therapy suggests that there is some sort of therapy that is helped by the psilocybin. It takes a psychotherapy-first approach, believing that psilocybin facilitates psychotherapy and improves one’s ability to do the work in therapy,” Dr. Raison says.

On the other hand, another belief and approach is that it’s the psilocybin that’s doing most of the work. “In doses studied for trials in FDA approval, psilocybin [may facilitate] a powerful hallucinogenic experience, one in which people tend to be inward-focused,” he says. You may have two therapists or “guides” in the room monitoring you while you’re having a psilocybin experience, but there is not a lot of talking. In other words, it’s the drug that may perform the work, and the professionals in the room are not there to provide therapy (as we typically understand it), but to make it a safe and comfortable experience.

Right now, the answer to whether it’s the drug or the drug-psychotherapy interaction is: “we don’t know,” says Christopher Pittenger, MD, PhD, co-director of the Program for Psychedelic Science at Yale School of Medicine in New Haven, Connecticut. “This is a really active question with lots of really strong opinions on both sides,” he says.

The way that psychedelics, including psilocybin, work in the brain, however, is more clear, in that they’re seemingly different from conventional medications in mental health. With conventional mental health drugs, “after finding the right dose, you keep taking it, which creates a new normal for your brain and mind. When it works — and sometimes it doesn’t — it shifts the balance of your environment so that your brain functions in a beneficial way,” explains Dr. Pittenger. Psilocybin, on the other hand, differs in that you only take it in the short-term for potentially long-lasting effects.

Why? Psilocybin binds to several receptors on the neurotransmitter serotonin. The most important of which appears to be the serotonin 2A receptor. When the drug binds to the receptor, the way information is processed across the brain changes, says Pittenger.

In addition, the “trip” may also provide a spiritual and emotional experience that also changes the brain in some way, for some patients. “If you look at where in the brain that receptor is expressed, it’s in the area that’s most relevant to how we pull different aspects of the world together to form an unified understanding of the world around us,” he explains. Keep in mind that during this process, not only are new brain connections formed — called brain plasticity — but old patterns of thinking (or rigidity in beliefs that make you feel mentally “stuck”) may also be broken and rewired. Though, more research is needed to better understand and substantiate this.

Other potential factors that could support the effects of psychedelic therapy with psilocybin include the "set and setting" that includes for example: client and practitioner expectations and beliefs, features of the practitioner and relationship dynamics with the client, the environment of the therapy (e.g. the actual space where one sits or lays, eye coverings, music), and cultural receptivity, per a review.

There is also some evidence that participants in clinical studies on psilocybin therapy who report having a greater “mystical experience” (e.g. a state of increased insightfulness, awe, transcendence, and sacredness) may have improved symptoms reduction and clinical outcomes, per the aforementioned systematic review.

Research is still early and we may not have uncovered psilocybin’s full potential. “It is early days. [Some people, including myself] and others in this space, [as well as some] skeptical outsiders, are impressed by what we’ve seen,” says Pittenger. With that in mind, here are some potential benefits of using psilocybin in a therapeutic setting to address certain health concerns:

May Help Treat Major Depression

“Major depression is the leading indication at this point for psilocybin. If [clinical trials] continue to go well, this is likely the first indication it will be approved for,” says Raison.

In a phase 2 clinical trial, published in November 2022 in The New England Journal of Medicine (NEJM), a single 25 milligram (mg) dose of a synthetic psilocybin, along with psychological support, reduced depression scores over three weeks better than a 10 mg or control (1 mg) dose for people who had treatment-resistant depression. The participants in the study had tried two to four other treatments for their depression before psilocybin, to no success.

And in another new phase 2 clinical trial, published in September 2023 in JAMA, included 104 people who were diagnosed with major depressive disorder for at least 60 days’ duration and moderate or greater symptom severity. Participants were randomized into a psilocybin group (who received a 25 mg synthetic dose and psychological support) and a control group (who received 100 mg of a niacin placebo with psychological support). The authors found that those in the psilocybin group showed a clinically significant and sustained reduction in depressive symptoms and functional disability at 43 days, compared with the control group, and concluded that psilocybin in conjunction with psychotherapy may be a potential novel treatment for MDD.

One of the interesting ways psilocybin may assist in pulling you out of depression is that it may help break through what experts call “cognitive rigidity,” or a tendency to get stuck in self-defeating thoughts, behavioral patterns, ruminations, or intrusive thoughts that get in the way of your relationships or happiness, says Pittenger. “Addressing cognitive rigidity can help across a broad variety of things. Some people talk about developing acceptance or self-compassion or not judging themselves for their failures,” he explains.

May Help Treat Alcohol Use Disorder

In a double-blind randomized trial of 93 people published in August 2022 in JAMA Psychiatry found that when taken in combination with psychotherapy (including motivational enhancement therapy and cognitive behavioral therapy), the psilocybin group had a significantly lower percentage of heavy drinking days in the roughly eight months after treatment, compared with a therapy group who took a placebo. Participants in the psilocybin group reported drinking heavily on 10 percent of days, whereas the control group said they drank heavily on 24 percent of days. Those in the psilocybin group also consumed less alcohol on the days they did drink, on average.

May Help With Smoking Cessation

Quitting tobacco is known to be notoriously tough. In a small uncontrolled pilot study by scientists at Johns Hopkins University, published in January 2017 in The American Journal of Drug and Alcohol Abuse, two to three moderate-to-high doses of psilocybin alongside cognitive behavioral therapy (CBT) helped 10 of the 15 participants quit smoking for 12 months, and were abstinent by laboratory confirmation at the 12-month follow-up.

Later research by Johns Hopkins uncovered a potential reason why: The psychedelic experience may help “reshape” a smoker’s identity so that they see themselves as a nonsmoker, making it potentially easier to stick with the newfound change.

Interestingly, of participants in the 2017 study above, 13 rated their psilocybin experiences among the five most personally meaningful and spiritually significant of their lives, suggesting also a potential role of the mystical experience in how psilocybin therapy may work.

May Treat Anorexia

Anorexia nervosa is an incredibly difficult disorder to treat, says Raison. “There is data emerging that psilocybin may help treat people who have anorexia,” he says.

One pilot study published as a poster supplement in May 2022 in Biological Psychiatry on adults with anorexia who took a single 25 mg dose of psilocybin with psychotherapy, four of the five had “clinically significant” reductions in their scores on an eating disorder questionnaire; two also reported a decrease in anxiety, verified by a validated anxiety measure. More research is needed moving forward with more patients, but these findings may suggest a potential benefit of psilocybin for patients struggling with anorexia.

May Soothe End-of-Life Anxiety

Facing a terminal diagnosis like cancer can be incredibly scary and confusing for many people, and, as a result, 40 percent of cancer patients develop depression or anxiety, notes a meta-analysis.

Psilocybin, however, may have the ability to change one’s thoughts, perceptions, and emotions, per research. In this study on patients with life-threatening cancer diagnosis and anxiety and or depression, psilocybin therapy at a 22 mg or 30 mg per 70 kilograms (of body weight) dose, along with facilitated support, improved patient and clinician measures of depression and anxiety, and improved quality of life, life meaning, and optimism, compared with a very low placebo-like dose of the drug. What’s more, people reported less anxiety surrounding death. For 80 percent of people, these changes stuck around for six months.

When used in a safe therapeutic setting, “psilocybin is medically rarely a problem,” says Pittenger. However, there is a good reason for seeking out a clinic that is providing psilocybin therapy legally, rather than trying it on your own. “Using psychedelics recreationally increases the chance of having a negative experience. In my mind, it’s clearly important that there be an environment of safety in which the psychedelic is delivered,” he says.

In addition, research trials have not included people who have schizophrenia or psychosis, as there is reasonable concern that psilocybin (or other psychedelics) in this population could cause worsened hallucinations and harm.

Another thing to keep in mind — and exactly why you should only seek therapy from a licensed clinic and not try to use psychedelics on your own — is that the recent NEJM study on psilocybin for treatment-resistant depression points out the side effects of psilocybin treatment included headache, nausea, dizziness, and fatigue. Concerning, also, was that a small number of treatment-resistant study participants also experienced increased suicidal ideation or self-injurious behavior. (Note that suicidal ideations were often present in the study participants when evaluated at baseline before starting the study.)

In addition to these more common side effects listed above, others include elevated blood pressure and heart rate, and anxiety and confusion. Less commonly reported adverse events also include migraine, physical discomfort, strong or extreme fear, paranoia, psychosis, and psychological discomfort. Yet many of these are short term and are believed to be related to the therapeutic and emotional processing in the session. Data from clinical trials, in which proper screening is completed and psilocybin use is monitored, report no serious adverse events, per a research review.

If you have depression, anorexia, alcohol use disorder, or are looking to quit smoking or are faced with a terminal diagnosis, then you may opt to look into psilocybin therapy, depending on the legalities in your area. Right now, since psilocybin is federally illegal, and only legal in certain states, it is difficult to access in a safe, therapeutic way.

However, if you have a history (or family history) of schizophrenia or psychosis, hallucinogenic psychedelics, including psilocybin, could worsen your symptoms. Additional contraindications include bipolar disorder, and borderline personality disorder, per the aforementioned research review.

There are a couple of potential ways you may find psilocybin therapy in the United States, but it’s overall not very accessible at this time:

• You could possibly look for a clinical trial at ClinicalTrials.gov and search to see if there are any that are actively recruiting in your area where you fit the criteria.
• You may find it in clinics in Oregon or Colorado (the only two states where psilocybin has been decriminalized) and, if necessary, put your name on a waiting list.

What’s critical is looking for an option that operates legally — underground psilocybin services put you at risk, as these operate with a lack of regulatory framework and oversight that can be dangerous and put you in harms way, says Sara Gael, a licensed professional counselor and harm reduction officer at the Multidisciplinary Association for Psychedelic Studies (MAPS) in San Jose, California. “Although I’m not saying it’s not possible to have a safe, productive, and healing experience doing psilocybin in a community or social context — or what others would call ‘recreational’ — support and guidance with a therapist is helpful. I highly recommend not taking it by yourself.” she says.

A good clinic will provide psilocybin in a therapeutic capacity, meaning you will work with a therapist or guide professional, says Gael. Don’t be afraid to interview your potential therapist, she says. Here are some questions you may want to ask them, per Gael:

• What is your training?
• Who are your mentors?
• How long have you been working with psilocybin?
• What is your therapeutic approach?
• How does psilocybin work?
• What type of mental health issues do you specialize in?
• What are the ethical guidelines in your practice?

Next, it’s time for you to be honest and upfront with your therapist. Be sure they ask you, and you tell them:

• Why you are seeking treatment
• What mental health challenges and traumas you are hoping to work through with psilocybin therapy
• What your medical history contains, in entirety
• What mental health and other medical concerns run in your family

It’s also important, says Gael, to find a therapist in this space who specializes in your mental health issue, whether it be depression, OCD, or trauma, for instance. “A red flag to me is when [a psychedelic-oriented therapist] says ‘I work with anybody’, because this is a really specialized field and there are a lot of [therapists] who come in and say they are generalists,” she says. One organization, Psilocybin Assisted Therapy Association (PATA), is a nonprofit that promotes therapy alongside psilocybin and offers online training for therapists.

In addition, be sure to thoroughly disclose your mental health history, as well as your personal and family medical history, especially if there is schizophrenia or psychosis in your background.

If you are actively seeing a mental health provider, it’s good to discuss with them if you are pursuing psilocybin therapy, and you can also ask your psilocybin team if they are open to keeping your usual provider updated.

If you do move forward, discuss dosage and protocol with the psilocybin therapist so you have a clear understanding of what will take place. For the safest approach, especially if you’ve never taken psilocybin before, Gael recommends starting at a lower dose and increasing slowly. “Get to know what psilocybin feels like before you move into higher doses,” she says.

“Psilocybin can be a very intensive therapeutic experience in a short period of time, but when it works [for some people], it [may have] a long-lasting effect,” says Pittenger.

Though exactly how each session is run and the number of sessions needed depends on your individual concerns and goals, as well as the clinic or clinical trial, this is how it’s done at Usona research, says Raison (shared for illustrative purposes, protocols differ depending on site and client needs):

• Before: Preparation session(s) takes place for one to six hours. You’ll meet with a session facilitator (or guide) to talk about your concerns, why you’re there, and what you hope to get out of the treatment. This builds rapport between you and the facilitator, which helps provide that safe environment that’s so important to make the most out of the session.
• During: A dosing session with psilocybin can take anywhere from five to eight hours, says Raison. You’ll lie down on a bed in a comfortable room, put on an eye mask and then listen to a specific playlist, according to Compass Pathway. Your therapist-guide will be with you the entire time.
• After: Integration sessions provide an opportunity to talk to your therapist about the experience, which will help you make sense of what just happened. This can take place over a couple meetings for a few hours in total.

For more information on the process of psilocybin-assisted therapy, one care model supported by PATA, includes stages — education, preparation, set and setting, the experience, and integration — all with a licensed mental health professional trained in this type of therapeutic approach, or with psychedelic practitioners.

What Does Psilocybin Therapy Cost?

Psilocybin is not federally legal, and that includes psilocybin therapy. There are states that have decriminalized the psychedelic, including Oregon and Colorado. Because this is in the beginning and clinics are just beginning to receive their licenses to operate in places like Oregon, it’s still not clear how much psilocybin therapy will cost.

On X (formerly known as Twitter), one journalist pulled the cost for the “first legal, licensed psilocybin clinic in the United States,” and noted that the cost of one session ranges from $300 for a low-dose group session to $3,500 for a high-dose six-hour individual session. Currently, there are a lot of questions regarding access to these clinics, including the barriers to access that a high-cost therapy like this creates. At this time, medical insurance does not cover psilocybin sessions. And remember: The use, sale, and possession of psilocybin in the United States is illegal under federal law.

Summary

Psilocybin is a hallucinogenic substance from Psilocybe mushrooms with ancient roots in Mesoamerican civilizations. There has been emerging clinical research in psilocybin-assisted therapy for mental health treatment for conditions like depression, end-of-life anxiety, substance use disorders, tobacco dependence, and anorexia. Though it is currently federally illegal in the United States, there are efforts to decriminalize it in certain states, like Oregon and Colorado, which may make it more available to be used as a mental health treatment.

Under the guidance of a professional therapist, psilocybin treatment may be safe and potentially effective for some patient groups, though precautions are still needed.

Best Organizations

Multidisciplinary Association for Psychedelic Studies (MAPS)

Though the nonprofit organization is focused more on MDMA, this is a go-to resource for learning more about psychedelic research. In June 2023, MAPS also hosted Psychedelic Science, the largest psychedelic research conference featuring the biggest names in the psychedelic space.

Best Companies

Compass Pathways

The mental health care company is focused on psilocybin clinical trials for people with treatment-resistant depression. Beyond publishing clinical studies, one of their many values is to promote accessible and affordable psilocybin therapy so it can be available to those who need it, in future.

Usona Institute

The medical research organization employs scientists, clinicians, researchers to evaluate the safety and efficacy of psilocybin and 5-MeO-DMT. On their website, you can learn about their current psilocybin trials.

Best for Clinical Trials

ClinicalTrials.gov

Given psilocybin use is illegal in most of the United States, one option to access it is through a clinical trial. Your ability to be accepted into a clinical trial depends on what’s in your area and whether or not your health background fits the study criteria. However, it is worth a look if you’re interested in psilocybin therapy.

Best Book

How to Change Your Mind: What the New Science of Psychedelics Teaches Us About Consciousness, Dying, Addiction, Depression, and Transcendence

This book — and the Netflix series it inspired — is worth a read as Michael Pollan unpacks the history of psychedelics and travels the world as he dives into LSD and psilocybin use as a medical treatment. What makes it particularly engaging is how much this is a personal journey for him, too.