BY BEN THOMAS | Original illustration for Ember by Adam Higton
The debate over psilocybin legalization is heating up. Following Oregon’s legalization of “magic mushrooms” in 2020, Washington may be the next to decriminalize psychoactive fungi—while California’s senate has approved a landmark bill that would legalize possession of mushrooms as well as LSD, MDMA, and DMT.
But even as scientific evidence for mushrooms’ mental-health benefits continues to mount, the federal government still fights tooth-and-nail to prevent legalization—sparking a lawsuit from one doctor who says the U.S. Drug Enforcement Administration (DEA) has no right to deny his patients the therapeutic relief of psilocybin.
What does psilocybin actually do in the brain and body? Can mushrooms really cure depression and anxiety—and if so, are they likely to get legalized any time soon? Let’s take a deeper look at the world’s most controversial fungi, and assemble a clearer picture of what we know for sure.
When psilocybin enters the bloodstream, the body quickly converts it into its active form, psilocin—a close relative of the neurotransmitter chemical serotonin. And since neurons throughout many different brain areas respond to serotonin in a wide variety of ways, psilocin (a serotonin mimic) produces a whole kaleidoscope of effects as it travels through the brain and plugs into various types of serotonin receptors.
For example, in the frontal lobes, psilocin’s serotonergic activity can generate visual hallucinations, like shifting colors and geometric patterns. Psilocin’s interactions with other brain areas aren’t as thoroughly researched yet—but at some point the chemical triggers a release of dopamine, leading to a flood of euphoric alertness, while kickstarting a feedback loop in which neurons pump out even more dopamine and serotonin.
But while most psilocybin research has focused on psilocin’s serotonergic properties, more recent findings hint that its neurological effects may be more complex than we realized. A 2019 study led by Felix Blei, a pharmaceutical microbiologist at Friedrich Schiller University, found that four species of psychoactive mushrooms contain monoamine oxidase inhibitors (MAOIs)—a class of chemicals widely prescribed to treat depression.
In fact, the latest scientific research shows that psilocybin holds significant therapeutic promise not only for depression, but also for a wide range of other mental health issues—including anxiety, obsessive-compulsive disorder (OCD), and even alcohol and tobacco addiction.
A 2015 study led by Peter Hendricks, a public health professor at the University of Alabama at Birmingham, found that people who suffer from depression experience much lower rates of suicidal thinking after taking psilocybin. A 2011 study led by Charles Grob, a psychiatrist at Harbor-UCLA Medical Center, reported that psilocybin significantly reduces anxiety in advanced-stage cancer patients.
A 2006 study led by Francisco Moreno, a psychiatrist at the University of Arizona, Tucson, found that psilocybin relieves many symptoms of OCD. And a 2021 study reports that the “oceanic boundlessness” of a psilocybin experience leads to positive psychological breakthroughs in a strikingly high 59 percent of people who suffer from treatment-resistant depression (compared to a 19-percent breakthrough rate among people who participate in cannabis therapy).
What’s more, research shows that psilocybin is not only non-addictive—it can actually help treat addiction, by reducing dependence on harmful substances. For example, a 2015 study led by Michael Bogenschutz, a psychiatrist at the University of New Mexico Health Sciences Center, found that a combination of psilocybin-induced therapy and motivational therapy significantly reduces alcohol cravings, resulting in much lower rates of relapse among people with chronic alcoholism.
And in a 2014 study, a team led by Matthew Johnson, a behavioral psychiatrist at Johns Hopkins University School of Medicine, found that psilocybin significantly improves smokers’ likelihood of successfully kicking the habit. While this was only a small pilot study, its results are striking: among participants who received psilocybin, 80 percent were still tobacco-free a full six months down the road—even if all their previous quit attempts had been unsuccessful.
Even The New York Times recently examined psilocybin and MDMA's increasing acceptance as therapeutic treatments in psychiatry, reporting that despite the need for more studies, researchers have concluded that "psilocybin, DMT, and other psychoactive chemicals can help people feel more tolerance, understanding, and empathy. They also induce neuroplasticity, the brain’s ability to change and reorganize thought patterns, enabling people with psychological disorders to find new ways to process anxiety, depression, or deeply embedded trauma."
A growing number of doctors believe prescription-based psilocybin programs could bring relief to patients who suffer from all these issues—as well as other mental health conditions, such as post-traumatic stress disorder (PTSD). But even as a few states push for full legalization, the federal government remains strongly resistant even to clinical adoption.
Seattle physician Sunil Aggarwal, who specializes in end-of-life care, is currently suing the DEA for denying his patients the right to receive psilocybin as a clinical therapy. And while this case might be the first of its kind in the U.S., it does have a legal precedent: Canada has granted clinicians the right to administer psilocybin to terminally ill patients—potentially paving the way for broader medical legalization.
But some states may beat these exceptions to the punch. Oregon, for example, fully legalized psilocybin in 2020, and cities like Oakland, Santa Cruz, and Denver have decriminalized possession at the local level. California may soon follow suit: the state’s senate has approved a bill to legalize possession of a wide range of psychedelics, including psilocybin, LSD and DMT. Legalization also looks imminent in Washington—while polls indicate that 54 percent of Colorado voters will support legal psilocybin if activists can get it onto state ballots in 2022.
In many ways, the path toward psilocybin legalization clearly echoes the past decade’s legal battles around cannabis. Oregon and California, which were among the first states to allow doctors to prescribe medical marijuana, are now spearheading the decriminalization of psilocybin. Meanwhile, researchers are developing non-hallucinogenic psilocybin variants, which may streamline legality in swing states, just as non-psychoactive CBD did for cannabis. In fact, a number of canna companies have already launched psilocybin startups, anticipating a sizable U.S. market as legalization gains momentum.
That market’s immediate future depends largely on what California and Washington decide. If both states opt for full legalization, others may follow their lead—but that’s far from guaranteed due to American political stigma against psychedelics and the ongoing negative impact of the War on Drugs. One thing, however, is certain: the debate around legal psilocybin is fully underway, and it’s unlikely to quiet down any time soon, especially with such an abundance of therapeutic promise.
Ben Thomas is a journalist and novelist who's lived in 40+ countries. He specializes in telling stories from the frontiers of science, history, culture and the cosmos—and the points where all these fields intersect.