Psilocybin Is Going Mainstream, but Research and Regulation Lag

(Editor’s Note: President Trump has signed an executive order directing his administration to speed up the review of psychedelic drugs. Although the order focuses on treating mental health conditions, psychedelics such as psilocybin mushrooms have shown promise as treatments for chronic pain.)

By Hollis Karoly and Kent Hutchison

Amid a renaissance in the science of psychedelics, public interest in psilocybin – or magic mushrooms, as they’ve long been known – is surging.

One study found that rates of psilocybin use increased 44% among adults ages 18-29 from 2019 to 2023, and 188% among those over age 30. This amounts to more than 5 million adults using psilocybin in 2023 alone. And those numbers are rising: A study published in early 2026 found that about 11 million adults in the United States used psilocybin in the previous year.

In many ways, the growing scientific and public interest in psilocybin mirrors the early days of recreational cannabis legalization in the U.S. Much like how cannabis commercialization quickly outpaced the development of regulations necessary to protect public health, the expanding psilocybin market and surging public interest are moving faster than the science and regulations needed to ensure it is used safely.

We are substance use researchers who have spent more than a decade studying the many new, high-THC cannabis products that have flooded the legal-market.

Now, we similarly aim to bridge the gap between public enthusiasm for psilocybin and the limited scientific evidence available about its potential benefits and risks. Currently, this type of real-world data on the effects of psilocybin mushrooms is almost nonexistent.

How Do Psilocybin Mushrooms Work?

Psilocybin is a prodrug, which means that it has very low activity until the body converts it into psilocin. Psilocin is the compound primarily responsible for the psychoactive effects of psilocybin mushrooms.

Psilocin resembles the chemical messenger serotonin, which is involved in regulating a range of physiological and psychological functions, including mood, appetite, cognition and sensory perception. As a result, when psilocin binds to serotonin receptors, it alters how people think, feel and experience the world.

Importantly, research suggests that psilocin also alters the brain’s ability to strengthen or weaken neural connections, referred to as synaptic plasticity. This process likely underlies the profound and sometimes long-lasting effects psilocybin mushrooms can have on thoughts, emotions and perception.

Psilocybin mushrooms contain numerous other compounds, together known as tryptamines, such as baeocystin, norbaeocystin and aeruginascin. Research on rodents shows that mushrooms containing these compounds may elicit stronger and longer-lasting effects than psilocybin alone.

But very little is known about how these other tryptamines affect humans. This is because federal regulations require researchers to use an isolated, synthetic version of psilocybin in clinical studies rather than the entire mushroom.

Thus, the many ongoing clinical trials testing psilocybin as a treatment for various mental health conditions use synthetic psilocybin that does not contain these other tryptamines.

A Legal Gray Area

Psilocybin is more accessible than ever before.

In 2019, Denver, Colorado, became the first American city to decriminalize psilocybin mushrooms. This means that possession becomes the lowest law enforcement priority and criminal penalties are reduced or eliminated, but it does not fully legalize them.

Over the next two years, several other U.S. cities including Oakland and Santa Cruz, California; Seattle, Washington; and Detroit, Michigan, followed suit. In 2020, Oregon legalized psilocybin for supervised use in licensed settings, and Colorado did the same in 2022. These legal, supervised-use programs allow access to psilocybin mushrooms in regulated environments without a prescription.

Even for people living outside those states and cities, the barriers to accessing psilocybin mushrooms are low. With a quick Google search and around US$35, anyone can legally purchase kits containing the materials needed to grow psilocybin-containing mushrooms.

These kits are legal to buy and sell because they contain only mushroom spores, which are tiny reproductive cells from which mushrooms grow. Once these spores begin growing into mushrooms, they can produce psilocybin, making the mushrooms a federal Schedule 1 substance.

Because psilocybin mushrooms exist in this legal gray area and are governed by different rules across states, psilocybin mushrooms are essentially unregulated across most of the U.S.

As a result, consumers lack reliable information about what their mushrooms contain, how much they should take and how to use them safely.

Psilocybin Potency Is Increasing

Much like the cannabis industry, which has seen a steady increase in product variety and product strength since legalization, the psilocybin mushroom market is experiencing rapid growth.

For instance, psilocybin edibles are now available and increasingly popular.

In addition, selective cultivation practices are being used by individual and commercial growers to systematically increase the amount of psilocybin contained in their mushroom strains. For example, the Oakland Hyphae Cup, a community contest intended to identify the best mushroom strains, has shown wide variability in psilocybin content across samples.

Researchers are identifying a similar pattern of widely variable psilocybin content in scientific studies of psychedelic mushrooms from around the world.

Potential Harms of Psilocybin

Despite psilocybin’s therapeutic promise, it also carries risks. Psilocybin can cause headaches, nausea, dizziness and changes in blood pressure.

Less commonly, some people experience psychotic symptoms, suicidal thoughts, anxiety, paranoia, confusion or emotional distress.

Another serious potential side effect of psychedelic drugs is what’s known as hallucinogen persisting perception disorder. It involves ongoing perceptual distortions similar to those experienced while directly under the influence of psilocybin, which can persist for weeks, months or years, even once the psilocybin has left the body.

Harms are more likely when people take high doses.

As mushroom potency increases without market regulation, consumers may inadvertently ingest more psilocybin than intended, increasing the risk of harm. Without sufficient research on modern psilocybin products, consumers have little guidance on how to reduce potential harms.

Next Steps in Research and Regulation

Studying psilocybin in the real world requires creative research approaches.

Our team hopes to work within federal restrictions to study people using their own psilocybin mushroom products at home, while providing real-time data to our research team using app-based surveys.

Independent laboratories using state-of-the-art measurement techniques can aid researchers like us by providing information about the potency of the mushroom products that people are using.

While ongoing clinical trials provide important data about the effects of psilocybin under tightly controlled conditions, real-world data is needed to understand how modern psilocybin mushrooms are used and experienced by consumers.

These insights matter not only for scientists and policymakers but for the growing number of people trying psilocybin mushrooms for relief, self-improvement or out of curiosity. In a largely unregulated market, and with few clear guidelines on safe use, consumers are left to simply figure it out on their own.

Hollis Karoly, PhD, is a clinical psychologist, neuroscientist and Associate Professor of Psychiatry at the University of Colorado Anschutz Medical Campus. Her research is funded by the National Institutes of Health.

Kent Hutchison, PhD, is a Professor of Psychology and Neuroscience at the University of Colorado in Boulder and the Founder of the Center for Research and Education Addressing Cannabis and Health. His research is also funded by the National Institutes of Health.

This article originally appeared in The Conversation and is republished with permission.

Magic Mushrooms May Relieve Chronic Pain and Depression

By Crystal Lindell

A new study shows that psilocybin, the active ingredient in what’s colloquially called magic mushrooms, could help relieve chronic pain and depression by targeting specific parts of the brain — at least in mice.

Psilocybin is a naturally occurring alkaloid with psychoactive properties that’s been used for pain relief for thousands of years. In the United States, however, it is classified as an illegal Schedule One controlled substance. 

Researchers at the Perelman School of Medicine at the University of Pennsylvania tested psilocybin on laboratory mice with chronic nerve injury and inflammatory pain.

They found that a single dose reduced both pain, anxiety and depression in the mice, judging by their behavior. The benefits lasted almost two weeks.

Unlike many pharmaceuticals, researchers say psilocybin gently activates specific nerves in the brain, called serotonin receptors.

“Unlike other drugs that fully turn these signals on or off, psilocybin acts more like a dimmer switch, turning it to just the right level,” lead author Joseph Cichon, MD, an assistant professor of Anesthesiology and Critical Care at Penn, said in a press release.

”This new study offers hope. These findings open the door to developing new, non-opioid, non-addictive therapies as psilocybin and related psychedelics are not considered addictive.”

To pinpoint where the effects originated, researchers injected psilocin — the active metabolite that the body rapidly converts from psilocybin — into different parts of the mice’s central nervous system. The team then used advanced fluorescent microscopy, a technique that uses glowing dyes to detect nerve activity, to see which neurons are activated and firing.

When psilocin was injected directly into the prefrontal cortex of the brains of the mice, it provided the same pain relief and mood improvements as when psilocybin was given to the whole body. But when researchers injected psilocin into the spinal cords of the mice, they found that it didn’t have the same calming effect.

“Psilocybin may offer meaningful relief for patients by bypassing the site of injury altogether and instead modulating brain circuits that process pain, while lifting the ones that help you feel better, giving you relief from both pain and low mood at the same time,” said Cichon.

Researchers hope their findings, published in the journal Nature Neuroscience, could help spur advancements in treatments for other conditions, such as addiction or post-traumatic stress disorder.

Cichon says more research is needed to determine the effectiveness of psilocybin.

“In my anesthesiology practice, I often see that both pain and mood symptoms can worsen following surgery due to the physiological and psychological stress imposed by the procedure,” he said. “While psilocybin shows promise as a treatment for both pain and depression, it remains uncertain whether such therapies would be safe, effective, or feasible in the context of surgery and anesthesia.”

The Penn team plans further studies to investigate dosing strategies, long-term effects, and the ability of the brain to re-wire itself through the use of psilocybin.

“While these findings are encouraging, we don’t know how long-lived psilocybin’s effects are or how multiple doses might be needed to adjust brain pathways involved in chronic pain for a longer lasting solution,” said co-author Stephen Wisser, a PhD student in Cichon’s lab.

While the DEA considers psilocybin an illegal substance with no accepted medical use, Oregon and Colorado have legalized it for supervised therapeutic use. Several cities in California, Michigan, Minnesota, Washington and Maine have also decriminalized it. And efforts are underway to change psilocybin’s federal status. 

The Food and Drug Administration has granted a breakthrough therapy designation to psilocybin to expedite research and drug development. Over 60 scientific studies have shown the ability of psilocybin and other psychedelics to reduce pain from fibromyalgia, cluster headache, complex regional pain syndrome (CRPS) and other conditions.

Can ‘Magic Mushrooms’ Help Dying Patients?

By JoNel Aleccia, Kaiser Health News

Back in March, just as anxiety over COVID-19 began spreading across the U.S., Erinn Baldeschwiler of La Conner, Washington, found herself facing her own private dread.

Just 48 and the mother of two teenagers, Baldeschwiler was diagnosed with stage 4 metastatic breast cancer after discovering a small lump on her chest, no bigger than a pea.

Within weeks, it was the size of a golf ball, angry and red. Doctors gave her two years to live.

“It’s heartbreaking,” she said. “Frankly, I was terrified.”

But instead of retreating into her illness, Baldeschwiler is pouring energy into a new effort to help dying patients gain legal access to psilocybin — the mind-altering compound found in so-called magic mushrooms — to ease their physical and psychic pain.

“I have personally struggled with depression, anxiety, anger,” Baldeschwiler said. “This therapy is designed to really dive in and release these negative fears and shadows.”

Erinn Baldeschwiler

Dr. Sunil Aggarwal, a Seattle palliative care physician, and Kathryn Tucker, a lawyer who advocates on behalf of terminally ill patients and chairs a psychedelic practice group at Emerge Law Group, are championing a novel strategy that would make psilocybin available using state and federal “right-to-try” laws that allow terminally ill patients access to investigational drugs.

They contend that psilocybin — whether found in psychedelic mushrooms or synthetic copies — meets the criteria for use laid out by more than 40 states and the 2017 Right to Try Act approved by the Trump administration.

“Can you look at the statute and see by its terms that it applies to psilocybin?” Tucker said. “I think the answer is yes.”

Currently, psilocybin use is illegal under federal law, classified as a Schedule 1 drug under the U.S. Controlled Substances Act, which applies to chemicals and substances with no accepted medical use and a high potential for abuse, such as heroin and LSD.

Recently, however, several U.S. cities and states have voted to decriminalize possession of small amounts of psilocybin. This month, Oregon became the first state to legalize psilocybin for regulated use in treating intractable mental health problems. The first patients will have access beginning in January 2023.

It’s part of a wider movement to rekindle acceptance of psilocybin, which was among psychedelic drugs vilified — and ultimately banned — after the legendary counterculture excesses of the 1960s and 1970s.

“I think a lot of those demons, those fears, have been metabolized in the 50 years since then,” Aggarwal said. “Not completely, but we’ve moved it along so that it’s safe to try again.”

He points to a growing body of evidence that finds that psilocybin can have significant and lasting effects on psychological distress. The Johns Hopkins Center for Psychedelic and Consciousness Research, launched this year, has published dozens of peer-reviewed studies confirming that psilocybin helped patients grappling with major depressive disorder and suicidal thoughts.

Researchers are also looking at psilocybin as a treatment for post-traumatic stress disorder (PTSD), Lyme disease syndrome, cluster headaches and migraines. A small placebo-controlled study by Yale researchers found that migraine sufferers experienced a significant decrease in weekly migraine days after only one dose of psilocybin. 

“Psilocybin was well-tolerated; there were no unexpected or serious adverse events or withdrawals due to adverse events. This exploratory study suggests there is an enduring therapeutic effect in migraine headache after a single administration of psilocybin,” researchers found. 

Psilocybin Shifts Perception

Psilocybin therapy appears to work by chemically altering brain function in a way that temporarily affects a person’s ego, or sense of self. In essence, it plays on the out-of-body experiences made famous in portrayals of America’s psychedelic ’60s.

“What psychedelics do is foster a frame shift from feeling helpless and hopeless and that life is not worth living to seeing that we are connected to other people and we are connected to a universe that has inherent connection,” said Dr. Ira Byock, a palliative care specialist and medical officer for the Institute for Human Caring at Providence St. Joseph Health.

“Along with that shift in perspective, there is very commonly a notable dissolution of the fear of dying, of nonexistence and of loss, and that’s just remarkable.”

The key is to offer the drugs under controlled conditions, in a quiet room supervised by a trained guide, Byock said. “It turned out they are exceedingly safe when used in a carefully screened, carefully guided situation with trained therapists,” he said. “Almost the opposite is true when used in an unprepared, unscreened population.”

The FDA has granted “breakthrough therapy” status to psilocybin for use in U.S. clinical trials conducted by Compass Pathways, a psychedelic research group in Britain, and by the Usona Institute, a nonprofit medical research group in Wisconsin. More than three dozen trials are recruiting participants or completed, federal records show.

But access to the drug remains a hurdle. Though psychedelic mushrooms grow wild in the Pacific Northwest and underground sources of the drug are available, finding a legal supply is nearly impossible.

End of Life Washington, a group focused on helping terminally ill patients use the state’s Death With Dignity Act, recently published a policy that supports psilocybin therapy as a form of palliative care. Other treatments for anxiety and depression, such as medication and counseling, may simply not be practical or effective at that point, said Judith Gordon, a psychologist and member of the group’s board of directors.

“When people are dying, they don’t have the time or the energy to do a lot of psychotherapy,” she said.

Baldeschwiler agrees. With perhaps less than two years to live, she wants access to any tool that can ease her pain. Immunotherapy has helped with the physical symptoms, dramatically shrinking the size of the tumor on her chest. Harder to treat has been the gnawing anxiety that she won’t see her 16-year-old daughter, Shea McGinnis, and 13-year-old son, Gibson McGinnis, become adults.

“They are beautiful children, good spirits,” she said. “To know I might not be around for them sucks. It’s really hard.”

Kaiser Health News (KHN) is a national health policy news service. It is an editorially independent program of the Henry J. Kaiser Family Foundation which is not affiliated with Kaiser Permanente.

Magic Mushrooms, Psychedelics and Chronic Pain

By Roger Chriss, PNN Columnist

The recent news that Denver has decriminalized “magic” mushrooms is the latest sign of growing interest in the use of psychedelics. Whether it’s microdosing mushrooms to stimulate the mind or using them to treat depression and chronic pain, psychedelic drugs are having a moment.

Magic mushrooms are any of roughly 200 different types of fungi that produce psilocybin, a hallucinogenic substance. Other psychedelics include LSD, DMT, ayahuasca and ibogaine. For reasons of chemistry and cultural baggage, DMT is generally avoided, LSD is used with extra caution and psilocybin is getting the most attention in clinical studies.

Preliminary research has found positive outcomes for psychedelic therapy in smoking cessation,  anxiety, post-traumatic stress disorder and refractory depression. And there are promising findings on psychedelics for cluster headaches and phantom limb pain.

A 2015 review in the Journal of Psychoactive Drugs reported that for patients with cluster headaches, psilocybin and other hallucinogens “were comparable to or more efficacious than most conventional medications.”  

In a 2006 Neurology review, researchers interviewed 53 cluster headache patients who used LSD or psilocybin. Most reported success in stopping cluster attacks and extending periods of remission.

And a 2018 Neurocase report described positive results for one patient with intractable phantom pain who combined psilocybin with mirror visual-feedback.

Obviously, these studies are very preliminary. Patient self-reports on drug use outside of clinical settings have limited value as evidence of efficacy. And case reports are by definition too small-scale to generalize from.

Fortunately, more clinical trials are underway for psilocybin and LSD. Last year the FDA approved a “landmark” psilocybin trial for treatment-resistant depression. And the Multidisciplinary Association for Psychedelic Studies is also working to promote robust clinical research.

Of course, psychedelics are not without risks. As described in detail in the book DMT: The Spirit Molecule, patients need to be screened and monitored before, during and after psychedelic therapy.

Michael Pollan, author of “How to Change Your Mind”, told The New York Times that psilocybin has risks “both practical and psychological, and these can be serious.”

There are also risks of conflating the pop culture phenomenon of microdosing to clinical benefits obtained under medical supervision.

The “betterment of healthy people” through microdosing is enthusiastically endorsed in books like “A Really Good Day” by Ayelet Waldman. But a 2018 placebo-controlled study on LSD microdosing found no “robust changes” in perception, mental acitivty or concentration.

The microdosing trend could stymie serious research and bias public opinion about psychedelics — just as it did in the 1960’s.

The potential for psychedelic therapy in the management of chronic pain disorders is two-fold. First, psychedelics may represent a safe and effective way to manage otherwise intractable disorders like cluster headaches and phantom limb pain. Second, psychedelics may help address the depression, PTSD and anxiety that often contribute to or accompany such disorders.

It is to be hoped that more research on psychedelics comes quickly.

Roger Chriss lives with Ehlers Danlos syndrome and is a proud member of the Ehlers-Danlos Society. Roger is a technical consultant in Washington state, where he specializes in mathematics and research.

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.