The possible benefits, risks, and what you should know

You may have heard that “magic mushrooms” are making a comeback, but this time, they’re medicinal. Instead of a recreational drug utilized for colorful, otherworldly hallucinations, they’re the latest innovative treatment being used for major depressive disorders. 

Psilocybin, the hallucinogenic chemical found in magic mushrooms, has been effectively criminalized since the 1970s, when it was deemed a Schedule I drug (high potential for misuse with no accepted medical use) by the FDA. However, in 2018 medical researchers began lobbying for a reevaluation and consequently recommended that psilocybin be recategorized to schedule IV, more along the lines of prescription sleep aids. This led to a broader availability for scientific studies, and the results are promising: The majority of trials are finding that psilocybin — in a closely controlled therapeutic setting — could be an effective treatment for people suffering with conditions that are unresponsive to other drugs. Here’s what you should know.

The Descheduling Movement

Derived from several different species of fungi, psilocybin is actually one of the most well-studied psychedelics. It was broadly experimented with in the 1950s and 1960s as a therapeutic aid, most notably by Dr. Timothy Leary. Unfortunately, during that time psilocybin became associated with the countercultural movement and rising opposition to the Vietnam War. In 1970 Congress enacted the Controlled Substances Act, and President Richard Nixon declared drug abuse “public enemy number one.” Over the next five years, the law sorted dozens of substances into a five-tiered list according to their perceived potential for abuse. Drugs in Schedules II through IV could be prescribed by health care providers, but substances in Schedule I were strictly prohibited and said to have no currently accepted medical use, a lack of accepted safety for supervised use and a high potential for abuse. Psilocybin was caught up in the movement, and despite some evidence pointing to the contrary, was swept in along with other Schedule I drugs. 

Thanks to the more recent marijuana legalization movement, psilocybin is getting another chance. Federal lawsuits on rescheduling cannabis opened the door for proponents of psilocybin research, who argue that qualifying evidence is the requirement for establishing “accepted medical use,” not FDA approval. Because several Phase I trials have been successfully completed, and because research has shown psilocybin to not have addictive qualities, more studies are being greenlit than ever before. (This article in Scientific American outlines the arguments.)

How Does Psilocybin Work?

With conventional mental health drugs, there is a typical path most patients follow. After finding the right dose of the right drug, you keep taking it, which creates a new normal for your brain and mind. Psilocybin, on the other hand, is only taken short-term — and only a few times — for potentially long-lasting effects.

Psilocybin binds to several receptors on the neurotransmitter serotonin, particularly the serotonin 2A receptor. When the drug binds to the receptor, the way information is processed across the brain changes, resulting in a “trip” (for lack of a more scientific term) that could provide a spiritual or emotional experience. Christopher Pittenger, M.D., Ph.D., co-director of the Program for Psychedelic Science at Yale School of Medicine, explains it succinctly in this article from Everyday Health: 

“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 a unified understanding of the world around us,” he explains. During this process, new connections are formed in the brain, increasing brain plasticity, and old patterns of thinking (or rigidity in beliefs that make you feel mentally “stuck”) may be broken and rewired.

Who Could Benefit?

Research from 2017 found psilocybin to be beneficial for people with OCD, end-of-life psychological distress and alcohol use disorder, along with supporting smoking cessation. Even more recently, three clinical trials found psilocybin helpful for people suffering from major depressive disorder, anxiety and depression related to terminal cancer.

Several recent Phase II trials treating major depressive disorder with psilocybin have been successful. In a Phase II clinical trial published in The New England Journal of Medicine in November 2022, a single 25-milligram dose of 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. In a separate Phase II trial from September 2023, 104 people with major depressive disorder received a similar therapy and showed significant and sustained reduction in depressive symptoms for 43 days.  

What Should You Expect? 

There are essentially two different approaches to psilocybin therapy, according to 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. It’s kind of a “chicken or the egg” distinction: “Psilocybin-assisted therapy” suggests a form of ongoing therapy that is helped by the occasional use of psilocybin. This would be a psychotherapeutic approach, which would use psilocybin and its effects to garner deeper introspection. On the other hand, there is therapy led by the psychedelic, where psilocybin does more of the heavy lifting:

“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. Hence, it’s the drug that may perform the desired work, and the professionals in the room are not there to provide therapy as much as guidance.

This guidance is just as important as the drug itself, advocates caution. Ensuring that psilocybin is taken in a safe, controlled environment is paramount to preventing a negative experience, which could be detrimental for a patient who is already struggling. Aside from the potential for a “bad trip,” the side effects are minimal, including headache, nausea, dizziness and fatigue.

How Could You Pursue Psilocybin Therapy?

This is the tough part, since psilocybin use has only been decriminalized in Oregon and Colorado as of yet. New York lawmakers are considering approving medical use of psilocybin, with a bill on the docket for the current legislative session. (More information on what the bill entails, here.)

Until the law catches up with the medical community, there are a few ways to seek out psilocybin experiences. You could travel to the states where it is legal, or even cross our northern border: The Journeymen Collective, one alternative wellness company, offers “luxury guided magic mushroom retreats” in the mountains outside of Vancouver. 

Whatever you do, though, do not attempt to undergo psilocybin therapy outside of a legal, clinically approved setting. Recreational use of hallucinogens carries a lot of potential risks and, obviously, is illegal.

Top image by ugurhan from Getty Images Signature, via

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