What to Know About Using Psilocybin for Depression

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Psilocybin is a substance found in many species of mushrooms (often referred to as “magic mushrooms”) that produces psychedelic effects. When this substance is ingested, it produces feelings of euphoria and sensory hallucinations that last for several hours.

Some research suggests that when combined with psychotherapy, psilocybin may be an effective treatment for some mental health conditions, particularly depression.

Depression is one of the most common forms of mental illness. The National Institute of Mental Health reports that an estimated 7.1% of all adults in the U.S. experienced at least one episode of depression during the previous year.

Fortunately, standard treatments such as antidepressants and psychotherapy can be effective. However, a recent resurgence of interest in the use of psychedelics to treat mental illness has revealed that substances such as psilocybin may be another effective tool in the treatment of depression.

Psychedelic-Assisted Therapy

So how does a psychedelic-assisted therapy session work? In a safe and comforting environment, an individual will take a low dose of psilocybin under the supervision of a professional.

Afterwards, the therapist will work with the individual to help them integrate their psychedelic session. The goal is to help the person process and find meaning in what they have just experienced.

It is important to recognize that psychotherapy is a critical component in this process. Working with a therapist helps the individual process and make sense of their psychedelic experience in a way that may produce lasting mental health benefits.


While there has been a recent uptick in interest and research on the therapeutic uses for psilocybin and other psychedelics, their use for medicinal and spiritual purposes is nothing new.

Various cultures and religious traditions have long utilized psychedelic substances as part of traditional medicine and spiritual rituals. 

It was the discovery of LSD in the 1940s that led to a great deal of research on the possible mental health uses of psychedelic compounds. 

From the 1940s through the 1960s, thousands of studies on the use of LSD and psilocybin were conducted, but this line of research was largely halted by the 1970 passage of the Controlled Substances Act (CSA).

The CSA classified psilocybin as a Schedule I drug, meaning that it had "significant potential for abuse and dependence" and "no recognized medicinal value.” This made the drug illegal for any use.

In 2006, researchers gained approval to investigate the potential of psilocybin as a treatment. This research concluded that psilocybin is generally safe and could have a positive impact on well-being.

The National Survey on Drug Use and Health (NSDUH) reported that between 2009 and 2015, approximately 8.5% of respondents stated that they had tried psilocybin at some point during their lives. 


Psilocybin has effects that are similar to those of LSD. People may experience feelings of relaxation and euphoria. The substance works by acting on pathways in the brain that involve the use of the neurotransmitter serotonin. This action results in changes in perception and altered consciousness.

After taking psilocybin, people may experience effects such as:

  • Distorted perceptions, including an altered sense of time or place
  • Euphoria
  • Hallucinations
  • Highly spiritual or introspective experiences

Hallucinations are often a common experience after taking psilocybin. Research suggests that this is due to an increase in communication across different networks in the brain.

Some researchers speculate that this may play a role in psilocybin's beneficial impact on depression. By changing brain connections and forming new ones, it may help people get out of depressive patterns. 


While research on the use of psilocybin-assisted therapy for depression is ongoing, the results of clinical trials have yielded promising results.

A 2016 study indicated that psilocybin therapy was linked to a significant reduction in symptoms of anxiety and depression in people who were going through cancer treatment.

In addition to these effects, the treatment was also linked to a number of other benefits as well. Those treated with psilocybin reported experiencing increased optimism and better quality of life.

A follow-up study suggested that these effects were also enduring. Participants maintained significant reductions in depressive symptoms five years after treatment. The researchers also noted that between 71 and 100% of the participants described psilocybin-assisted therapy as among the "most personally meaningful and spiritually significant experiences of their lives."

One 2020 study published in JAMA Psychiatry and led by researchers from John Hopkins Medicine found that two doses of psilocybin and supportive psychotherapy resulted in rapid, significant antidepressant effects. Around 67% of participants experienced a 50% reduction in symptoms. These effects also appear to be lasting. By four weeks after treatment, 54% of the participants who had psilocybin treatment were no longer depressed.

Researchers are also exploring the potential for psilocybin to treat other conditions including addictions and anxiety.


It is also important to recognize that while psilocybin is generally described as safe, it can also produce unwanted effects such as:

  • Delusions
  • Drowsiness
  • Headaches
  • Nausea
  • Nervousness
  • Panic
  • Paranoia
  • Psychosis

The psychedelic experiences that psilocybin induces can also sometimes result in what is referred to as a “bad trip.” During this experience, a person may experience intense feelings of anxiety and fear. It can also lead to frightening experiences of paranoia, delusions, and hallucinations.

While it isn't possible to stop a bad trip, being in a comforting environment with a supportive person can be helpful, which is why it is important to only try psilocybin for depression under the supervision of a mental health professional.

Psilocybin also has the potential to pose risks to people who have experienced episodes of mania or psychosis. For this reason, people with certain mental health conditions such as bipolar disorder or schizophrenia should not try psilocybin-assisted therapy.

Potential of Psilocybin in Therapy

Despite interest in the therapeutic potential of psilocybin, it remains a Schedule I substance and illegal for use.

However, research suggests that there is a low risk for physical dependence and abuse. In one study, researchers recommended scheduling the substance no more restrictively than a Schedule IV.

The Schedule IV category is defined as substances that have a low risk of dependence and low potential for abuse. This category includes drugs such as Ambien and Xanax.

In 2019, the FDA granted what is known as breakthrough therapy status to psilocybin-assisted therapy. This is intended to hasten the research and development process for drugs that have shown preliminary results in clinical trials in the treatment of serious illnesses.

While it isn’t likely that people will be able to pick up a prescription for the substance at their local pharmacy, there may be a time in the future when people are able to visit a doctor or mental health professional in order to receive psilocybin-assisted treatment for their depression.

Press Play for Advice On Treating Emotional Pain

Hosted by Editor-in-Chief and therapist Amy Morin, LCSW, this episode of The Verywell Mind Podcast, featuring psychologist Brian Pilecki, shares how psychedelics can be used to treat emotional pain. Click below to listen now.

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9 Sources
Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read our editorial process to learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.
  1. National Institute of Mental Health. Major depression.

  2. Griffiths RR, Richards WA, McCann U, Jesse R. Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significancePsychopharmacology (Berl). 2006 Aug;187(3):268-83;284-92. doi: 10.1007/s00213-006-0457-5

  3. Johnson MW, Griffiths RR, Hendricks PS, Henningfield JE. The abuse potential of medical psilocybin according to the 8 factors of the Controlled Substances ActNeuropharmacology. 2018;142:143-166. doi:10.1016/j.neuropharm.2018.05.012

  4. Petri G, Expert P, Turkheimer F, et al. Homological scaffolds of brain functional networks. J R Soc Interface. 2014;11(101):20140873. doi:10.1098/rsif.2014.0873

  5. Carhart-Harris RL, Erritzoe D, Williams T, Stone JM, Reed LJ, Colasanti A, Tyacke RJ, Leech R, Malizia AL, Murphy K, Hobden P, Evans J, Feilding A, Wise RG, Nutt DJ. Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin. Proc Natl Acad Sci U S A. 2012;109(6):2138-43. doi: 10.1073/pnas.1119598109

  6. Ross S, Bossis A, Guss J, Agin-Liebes G, Malone T, Cohen B, Mennenga SE, Belser A, Kalliontzi K, Babb J, Su Z, Corby P, Schmidt BL. Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial. J Psychopharmacol. 2016;30(12):1165-1180. doi: 10.1177/0269881116675512

  7. Agin-Liebes GI, Malone T, Yalch MM, Mennenga SE, Ponté KL, Guss J, Bossis AP, Grigsby J, Fischer S, Ross S. Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer. J Psychopharmacol. 2020;34(2):155-166. doi: 10.1177/0269881119897615

  8. Davis, Alan et al. Effects of psilocybin-assisted therapy on major depressive disorder: A randomized clinical trial. JAMA Psychiatry. 2020, Nov. doi: 10.1001/jamapsychiatry.2020.3285

  9. U.S. Food and Drug Administration. Breakthrough therapy.

By Kendra Cherry, MSEd
Kendra Cherry, MS, is a psychosocial rehabilitation specialist, psychology educator, and author of the "Everything Psychology Book."