Can Psilocybin or "Magic Mushrooms" be Used to Treat Depression?

Recently, psychedelic substances have received more and more attention for their potential to treat mental illness, including depression. One of the most frequently mentioned of these substances is psilocybin – the active ingredient in magic mushrooms or “shrooms”.

So why do some people, including researchers, think this substance – often viewed as a recreational drug – might be suitable for treating depression? Although the process is not fully understood, scientists believe that psilocybin binds to specific serotonin receptors. Serotonin is a neurotransmitter, which is a chemical that transmits messages between nerve cells in our body and brain. One of serotonin’s functions is to regulate mood. Most antidepressants work by increasing the amount of serotonin produced in our brains. Because psilocybin also acts on serotonin, some hope it may have similar antidepressant effects. ⁽¹⁾

Psilocybin and other Hallucinogenic Drugs

Hallucinogens, often referred to as “psychedelic drugs”, are psychoactive substances that, when ingested, typically cause changes in sensory perception (sight, hearing, taste, touch, and smell) and other significant changes in mood, thought, and consciousness. When taken at high doses, they may cause a person to perceive things that aren’t really there, otherwise known as hallucinations.

Hallucinogens can be found in nature or synthesized in a lab, and the specific effects of different hallucinogenic substances can vary widely. Some common hallucinogens include LSD, mescaline, DMT, and psilocybin.

Common psychological/cognitive effects experienced acutely during psilocybin use include distortions in the perception of the passage of time (especially the feeling that time has slowed), feelings of joy and euphoria, unusual and introspective thinking, and profound mystical or spiritual experiences. In addition, psilocybin can cause a variety of physical side effects, including headaches, drowsiness, increased heart rate, pupil dilation, and lack of coordination.

What are the risks: Negative Effects,“Bad Trips”, and HPPD

Magic mushrooms are often taken with the aim of experiencing the above psychological/cognitive effects, but can cause additional unpleasant effects, colloquially referred to as a “bad trip”. These effects may include:

Anxiety
Paranoia
Frightening thoughts

It is essential to be fully aware of the risks and potential harms associated with psilocybin use in order to make an informed decision about whether to consider incorporating it into your treatment and how to do so safely.

In a 2016 survey of nearly two thousand people who reported previously experiencing negative effects when taking psilocybin, 2.6% of those surveyed said they acted aggressively or violently, and 2.7% said they sought medical help.⁽²⁾ Five of the participants with self-reported pre-existing anxiety, depression or suicidal thoughts attempted suicide while on the drug during their worst bad trip.

The use of hallucinogens is also associated with a condition called Hallucinogen Persisting Perception Disorder (HPPD). Although considered rare (it occurs in roughly 4.0% to 4.5% of people with a history of hallucinogen use), HPPD can cause people to experience ongoing changes in perception (sometimes referred to as “flashbacks”) for weeks or months after taking psilocybin.⁽³⁾

Given the risks, if you are considering using psilocybin, it’s important to do so in a safe environment and under supportive conditions, like under the supervision of a trained mental health professional, especially for those who are already struggling with their mental health.

What the Research Says About Psilocybin and Depression

Research on the potential therapeutic effects of psilocybin is limited but growing. While there was some research interest on the topic in the 1950s, this abruptly stopped when hallucinogens were outlawed in the 1960s, and interest has only recently begun to resurge.

A 2021 randomized clinical trial study of 24 participants with major depressive disorder found that participants who received psilocybin-assisted therapy showed improvement in both self-reported and clinician-rated depression scores at a 1-month follow-up. ⁽⁴⁾
In addition, a 2020 meta-analysis that included four studies found some support for psilocybin’s usefulness in treating depression and anxiety.⁽⁵⁾

Although these preliminary studies seem promising, they were limited by very small sample sizes and lack of long-term follow up. Furthermore, psilocybin has been used in research only under very specific conditions, so we do not know how it affects people outside of these circumstances.

Given these limitations, further careful study is required before any definitive conclusions can be drawn or recommendations given regarding psilocybin’s use in treating depression.

What we currently know about psilocybin and depression only applies in cases where:

1. Psilocybin use is paired with psychological intervention

In all current research, psilocybin has been used together with psychotherapy. Taking psilocybin alone without the assistance of a trained medical or mental health professional has not been researched or found to be an effective depression treatment.
Discussions of psychedelics often refer to the importance of “set” and “setting”. Set refers to an individual’s current mindset, and setting refers to the physical and social atmosphere where the experience takes place. Set and setting play a tremendous role in shaping the experience of taking psychedelics, and a negative mindset or unsafe setting can increase the odds of having an unpleasant experience or “bad trip”.
This is a major reason why psilocybin taken to treat depression should only be used under the supervision of a trained medical or mental health professional. It is highly unadvisable to consume psychedelics alone due to the unpredictable nature of their effects and the potential for accidental injury if unsupervised.⁽⁶⁾

2. Only for treatment resistant depression and coping with terminal illness

The majority of early research on psilocybin and depression has been conducted in people coping with terminal illness and treatment resistant depression. Treatment resistant depression means that participants have already tried well established, research supported methods for treating depression, such as psychotherapy and antidepressant medication, without success. Thus, psilocybin is a last resort option, not a first-line depression treatment.
Research on the effect of psilocybin on depressed individuals without a concurrent health issue and/ or treatment resistant depression is very limited at this time.

3. Only in certain doses

Little research has been done to determine the ideal therapeutic dosage of psilocybin. A 2021 meta-analysis looking at dose effect suggested that “the optimal dose of psilocybin may be 30-35mg for a person who weighs 70kg (154 lbs); [but] future clinical trials are warranted for further evaluation on its effect” due to the small number of studies available on the topic and the variation in quality of those studies. ⁽⁷⁾ As with any drug, determining the correct dose is of the utmost importance in ensuring that you experience the desired therapeutic effect. Because researchers are still determining the ideal therapeutic dose for psilocybin, it is imperative to only take psilocybin under the direction and supervision of a health professional trained and experienced in its use.
Another topic that is often brought up in discussions of psychedelic use is “microdosing”. Microdosing is the practice of consuming a very low dose of a hallucinogen, such as psilocybin, which results in a much weaker, sub-hallucinogenic experience. The studies referred to throughout this article examined full dose usage of psilocybin, and current research on the effects of microdosing is limited.⁽⁸⁾

Is it Legal to Use?

In the U.S.:

Psilocybin is federally classified as a Schedule 1 controlled substance and is effectively illegal to use outside of research.
In the late 2010s, there was a push for decriminalization of psilocybin in a number of jurisdictions. As of December 2021, psilocybin is decriminalized in the cities of Denver, CO; Washington, DC; Somerville and Cambridge, MA; and Oakland and Santa Cruz, CA.
In addition, psilocybin is both decriminalized and legalized for therapeutic use across the entire state of Oregon.
Despite state and county laws, psilocybin’s sale, possession, and use are still illegal under federal law.

In Canada:

As of December 2021, psilocybin is illegal to sell, possess, or transport, but “magic mushroom” spores and growing kits are legal as they do not contain psilocybin.
Recently, legislation expanding the legality of psilocybin has been passed, but only in very particular circumstances: In 2020, eleven end-of-life patients received permission to pursue psilocybin-assisted psychotherapy to help ease anxiety and depression. That same year, sixteen health professionals received permission from the Ministry of Health to use psilocybin themselves to help develop therapies for future use.

In the U.K.:

Psilocybin is considered a Schedule 1 drug within the Misuse of Drugs Act, along with other hallucinogens such as LSD and DMT. Schedule 1 drugs cannot be possessed or prescribed legally and a Home Office licence is required for use in research.
However, as recently as October 2021, Prime Minister Boris Johnson has stated that he plans to examine the latest advice on the legalisation of psilocybin.⁽⁹⁾

Outside of a few specific cities and regions, consuming psilocybin to treat depression without the supervision of a trained professional is not legal, has not been researched, and is not recommended due to associated risks and the potential for harm.

The Bottom Line

All in all, the preliminary research that exists on the usefulness of psilocybin for treating depression seems promising, but is very limited.

Given the limits to current research, it is important to remain focused on the facts instead of getting swept up in media sensationalism. Until further evidence emerges on the topic, it is best to proceed with caution before trying psilocybin to treat depression.

If you are currently struggling with depression, talk therapy and traditional antidepressant medication are the first line of treatment you should seek. Their effectiveness has been supported by vast amounts of research, and their use is much less risky.

In addition to professional support, there are a number of self-care strategies you can use to help manage your depression, such as staying physically active and learning to effectively manage stress. See our Practical Tips page to learn about additional healthy coping strategies.

References:

Madsen, M.K., Fisher, P.M., Burmester, D. et al. Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels.Neuropsychopharmacol. 44, 1328–1334 (2019). https://doi.org/10.1038/s41386-019-0324-9
Carbonaro, T. M., Bradstreet, M. P., Barrett, F. S., MacLean, K. A., Jesse, R., Johnson, M. W., & Griffiths, R. R. (2016). Survey study of challenging experiences after ingesting psilocybin mushrooms: Acute and enduring positive and negative consequences. Journal of psychopharmacology (Oxford, England), 30(12), 1268–1278. https://doi.org/10.1177/0269881116662634
Kurtom M, Henning A, Espiridion E D (2019) Hallucinogen-persisting Perception Disorder in a 21-year-old Man. Cureus 11(2). doi:10.7759/cureus.4077
Davis, A. K., Barrett, F. S., May, D. G., Cosimano, M. P., Sepeda, N. D., Johnson, M. W., Finan, P. H., & Griffiths, R. R. (2021). Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial. JAMA psychiatry, 78(5), 481–489. https://doi.org/10.1001/jamapsychiatry.2020.3285
Goldberg, S. B., Pace, B. T., Nicholas, C. R., Raison, C. L., & Hutson, P. R. (2020). The experimental effects of psilocybin on symptoms of anxiety and depression: A meta-analysis. The Experimental Effects of Psilocybin on Symptoms of Anxiety and Depression: A Meta-Analysis, 284. https://doi.org/10.1016/j.psychres.2020.112749
Jarrett, C. (2021, December 10). How to have a safe psychedelic trip. Psyche. Retrieved November 2021, from https://psyche.co/guides/how-to-have-a-safe-psychedelic-trip
Li, N., Hu, Y., Chen, W., & Zhang, B. (2022). Dose effect of psilocybin on primary and secondary depression: a preliminary systematic review and meta-analysis. Journal of Affective Disorders, 296, 26-34. https://doi.org/10.1016/j.jad.2021.09.041.
Anderson, T., Petranker, R., Christopher, A., Rosenbaum, D., Weissman, C., Dinh-Williams, L. A., Hui, K., & Hapke, E. (2019). Psychedelic microdosing benefits and challenges: an empirical codebook. Harm Reduction Journal, 16(1). https://doi.org/10.1186/s12954-019-0308-4
McSorley, B. C. (2021, October 20). Boris Johnson to consider calls to legalise magic mushroom drug psilocybin. BBC News. Retrieved November 2021, from https://www.bbc.com/news/uk-politics-58980382

Psilocybin for Treating Depression: Understanding Its Use and Risks