Psilocybin therapy: what science has to say

If you’ve heard of magic mushrooms, then you may already know of the mind-altering effects of psilocybin. This substance makes some mushrooms “magical.” In recent years, researchers are heralding this psychoactive substance as an exciting new treatment for mood disorders. 

What does science have to say about psilocybin therapy? Let’s take a look. 

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Psilocybin is a psychoactive substance found in certain mushrooms. Psilocybin-containing mushrooms have been used in mystical or spiritual rituals for centuries in ancient cultures. Today, people continue to use mushrooms as a recreational drug for sensory alterations and a “high” feeling (DEA, 2020). 

These small brown or tan fungi are called “magic mushrooms” or “shrooms,” among many other names.

The “magic” in psilocybin is its hallucinogenic properties, causing significant changes in thought, emotion, and consciousness. Psilocybin activates the serotonin receptors in your prefrontal cortex, the part of your brain that affects your mood, perception, and cognition (Roseman, 2018).

Psilocybin is taken by mouth, often either in tea or a capsule. It has a bitter taste, so many people who take it sweeten it to disguise the bitterness. The strength or quality of psilocybin depends on which mushroom it is, where it is grown, how it is grown, how it is harvested, and finally, if it’s consumed fresh or dried (DEA, 2020). 

When you take psilocybin, the effects happen within the first 30 minutes of taking it and last between four and six hours. For some people, however, these effects can last for days (Brown, 2017).

Psilocybin is absorbed in your gut, and your body converts it into psilocin. The way psilocybin or psilocin impacts you is based on how much psilocybin is in the mushroom, what past experiences you have had with hallucinogenic and other such substances, and even the expectation of what you think you might feel.

A brief history of psilocybin

Psilocybin-containing mushrooms have been used for thousands of years. The pure extraction of psilocybin happened in the late 1950s by a Swiss chemist, Alfred Hoffman. This extraction was quickly synthesized into a medication. Pharmaceutical companies began distributing psychedelic substances, including psilocybin, to treat mental health disorders (Carhart-Harris, 2017). 

There were some studies done in the early 1960s on psilocybin, LSD, and other psychedelic substances. However, due to concerns about the psychedelic power of these substances, psilocybin became a Schedule I controlled substance in the 1970s. This designation meant psilocybin was considered to have no accepted medical purpose and a high potential for substance abuse (Carhart-Harris, 2017).

Once psilocybin became a Schedule I drug, all clinical testing was halted. While people continued to use “magic mushrooms” recreationally, some researchers thought that psilocybin still had therapeutic potential. 

In 2006, Dr. Ronald Griffiths of Johns Hopkins University conducted a clinical trial using psilocybin. This double-blind, randomized, controlled study (neither the researchers nor the participants knew who was getting psilocybin or methylphenidate—the other chemical used in the study) used healthy volunteers. There were definite improvements in psychological well-being for the participants who received psilocybin at the two-month mark. More than half of the participants felt their psilocybin experience to be one of the most profound experiences of their lives (Griffiths, 2006).

This study led to further studies and clinical trials for people with severe depression and anxiety to see how well psilocybin and other psychedelics worked

Psilocybin therapy uses the therapeutic effect of psilocybin, together with psychological support. This combination is a form of what’s called psychedelic therapy. 

The origins of psychedelic therapy arose in the 1950s and early 1960s when the European pharmaceutical company Sandoz began to sell psilocybin to mental health professionals to help them with psychedelic psychotherapy (Reiff, 2020). 

Psilocybin-based psychedelic therapy sessions take place in a supportive environment. Each patient receives psychological preparation to foster emotional openness and trust. The physical environment is typically made to be comfortable and calming with eyeshades, dim lighting, and music. A therapist is present to listen to the patient and provide emotional support as they go through the experience (Roseman, 2018a). 

There are three parts to psychedelic therapy (Reiff, 2020): 

• Preparation—The therapist works together with the person, discussing their history, symptoms, and intentions towards the psychedelic treatment. The therapist also explains what to expect during the psilocybin treatment.

• Medication—The person receives the psilocybin, ideally with two therapists present. 

• Integration—The integration portion happens 6–8 hours after the person takes the psilocybin. The therapist listens to the person and helps them interpret what they saw and felt during their psychedelic experience. They then guide them into meaningful change by identifying visions and insights the person felt during their experience.

According to the researchers, the principle of psychedelic psychotherapy is that a person has a meaningful, profound, and transformative psychological experience. This guided experience is crucial to the effectiveness of the treatment (Roseman, 2018).

Multiple studies on psilocybin show it to be effective at providing quick and lasting relief from depressive symptoms in people with treatment-resistant depression (Carhart-Harris, 2017). A recent study published in JAMA Psychiatry found that 71 percent of people in the study with major depressive disorder (MDD) had substantial improvement with psilocybin therapy combined with psychotherapy. More than half (54%) were in remission a month after treatment (Davis, 2020). 

Other studies have shown significant improvement in obsessive-compulsive disorder (OCD) and alcohol dependence as well (Carhart-Harris, 2017). 

In 2018, the U.S. Food and Drug Administration (FDA) designated psilocybin as a “breakthrough therapy” for treatment-resistant depression. This means that psilocybin has significant therapeutic potential, and its development and review process would be fast-tracked (Compass, 2018). 

In 2019, the FDA granted a second breakthrough therapy approval for treatment-resistant major depressive disorder (MDD) with psilocybin.

There is promising preliminary research on psilocybin’s effect on depressive symptoms and anxiety for people with cancer, migraine and cluster headache relief, and alcohol use disorder. 

Starting in 2019, certain cities in the U.S. decriminalized personal possession of psilocybin-containing mushrooms, including Denver, Oakland, Santa Cruz, Washington DC, Somerville, and Cambridge, Massachusetts. In November of 2020, the state of Oregon decriminalized psilocybin use for people over 21 with diagnosed depression, anxiety, or post-traumatic stress disorder (PTSD). This does not mean that it is possible to get a psilocybin prescription in these locations (Mason, 2020).

The U.S. federal government still considers psilocybin mushrooms to be illegal. Currently, psilocybin therapy is available only in clinical studies and not in standard medical practice. It is considered illegal in most of the world (Mason, 2020).

There are a number of potential benefits of psilocybin therapy. 

Relief lasts a long time 

The research from these studies shows that even a single dose can help depressive symptoms in cancer patients for up to five weeks after two doses. In contrast, people who take antidepressants like selective serotonin reuptake inhibitors (SSRIs) need to take their medicine every day around the same time, long-term (Reiff, 2020).

It works quickly

Psilocybin usually works within one week of taking it, compared to typical antidepressant therapy, which usually takes between six to eight weeks to show any effects. If you have severe symptoms of depression, this may be too long to wait. If you have any suicidal thoughts, please seek immediate medical attention (Carhart-Harris, 2017).

It reboots the brain

The Imperial College London study did functional MRI (fMRI) brain scans on people who received two doses of psilocybin. The people in the study reported immediate relief from their depressive symptoms, which was confirmed by the brain scans. The scans showed a reduction in blood flow to the emotional response area of the brain that handles stress and fear. These studies suggest that psilocybin works by “resetting”  or “rebooting” activity in the brain (Carhart-Harris, 2017a).

It fosters an emotional connection with oneself

Antidepressants reduce negative or low moods, but they can also dull positive emotions. For some people, the overall effect can be a  dampened, flattened, or numb feeling. In contrast, psilocybin appears to increase emotional responses. In a small study, people who took psilocybin showed stronger emotional reactions to faces after receiving the two doses (Roseman, 2018).

It has fewer side effects

Many antidepressants commonly cause dry mouth, drowsiness or insomnia, dizziness, constipation or diarrhea, and sexual side effects. Some of these side effects may subside, but others can stay for as long as you take the medication. However, psilocybin is used short-term, and its side effects are not as lengthy and long-lasting as other medications used to treat depression (DEA, 2020).

You might be thinking psilocybin therapy sounds like a miracle cure, but it’s not without its downsides. The two main issues with psilocybin therapy are: 

It isn’t easy to get 

Psilocybin-containing mushrooms are illegal in the U.S. This means that psilocybin capsules are only available in clinical trials. If you have depression and want to try psilocybin treatment, you won’t be able to without enrolling in a clinical trial. Access to clinical trials is growing but still very limited. 

It can cause a “bad trip” 

Some people may have an emotionally painful experience when taking psilocybin. The benefits people have reported in the studies may reflect the psychotherapeutic care and the control and structure of the study. All doses are calibrated to the person’s weight, and the participants get full support throughout the study process (DEA, 2020). 

Though there are “magic mushrooms” available legally in some countries or as an illicit drug, it is impossible to vouch for the quality of those options. Some people who self-medicate with mushrooms may have what some people call a “bad trip.” 

These experiences can include (DEA, 2020):

• Paranoia

• Frightening hallucinations

• Confusion 

• Derealization

• Depersonalization

In the majority of clinical trials, no study participants were left alone when taking the psilocybin. A psychotherapist and sometimes even two were typically present to help guide and integrate the experience, ensuring safety and reducing the likelihood of a bad trip (Reiff, 2020). 

The side effects of psilocybin are similar to other psychoactive substances like LSD (lysergic acid diethylamide) and MDMA (ecstasy). People may have a transformed and heightened mood with an altered perception of time and space. However, the effects of psilocybin depend on several factors: strength and quality of the psilocybin, environment, mental state, and personality of the person using it (Jo, 2014).

Some people report these feelings during a psilocybin session (Carhart-Harris, 2017):

• Tranquility

• Euphoria

• Derealization or the feeling your environment isn’t real

• Depersonalization or an out-of-body feeling

• Spiritual awareness and awakening

• Seeing vivid colors or bright lights

Side effects of psilocybin may include (Carhart-Harris, 2017):

• Psychological distress

• Dizziness

• Drowsiness

• Unable to concentrate

• Nausea and vomiting

• Muscle weakness

• Paranoia

• High blood pressure

• Tachycardia (rapid heart rate)

People who feel anxious about trying psychedelic drugs or have mental health conditions like schizophrenia may risk having a poor experience with psilocybin mushrooms. 

Psilocybin mushrooms are considered low-toxic (Jo, 2014). Psilocybin is not chemically addictive. There are no withdrawal symptoms when stopping psilocybin (Nichols, 2016).

Not everyone can participate in a clinical trial. For example, the Imperial College London trial accepted people with proven treatment-resistant depression, with an average of 18 years with depressive symptoms. If you want to be in a psilocybin trial, you will be screened carefully. You may not be able to use psilocybin if you or your family have a history of psychotic conditions like schizophrenia. 

While you can't get psilocybin from your healthcare provider yet, studies are testing the psilocybin's effectiveness. You may want to speak to your healthcare provider to see if psilocybin might help you.

You can check the Psychedelic Clinical Trials Database to see if you are a candidate.

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Current version

July 21, 2021

Written by

Tobi Ash, MBA, RN, BSN

Fact checked by

Steve Silvestro, MD

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About the medical reviewer

Steve Silvestro, MD, Ro

Dr. Steve Silvestro is a board-certified pediatrician and Associate Director, Clinical Content & Education at Ro.