Regulations Should Be Eased for Cannabis and Psilocybin

By Dr. Kevin Boehnke  

The U.S. Drug Enforcement Agency announced in late April 2024 that it plans to ease federal restrictions on cannabis, reclassifying it from a Schedule I drug to the less restricted Schedule III, which includes drugs such as Tylenol with codeine, testosterone and other anabolic steroids. This historic shift signals an acknowledgment of the promising medicinal value of cannabis.

The move comes in tandem with growing interest in the use of psilocybin, the active component in magic mushrooms, for treatment of depression, chronic pain and other conditions. In 2018 and 2019, the U.S. Food and Drug Administration granted a breakthrough therapy designation to psilocybin, meant to expedite drug development given that preliminary studies suggest it may have substantial therapeutic value over currently available therapies for treatment-resistant depression and major depressive disorder.

Both of these developments represent a dramatic change from long-standing federal policy around these substances that has historically criminalized their use and blocked or delayed research efforts into their therapeutic potential.

As an assistant professor of anesthesiology and a pain researcher, I study alternative pain management options, including cannabis and psychedelics.

I also have a personal stake in improving chronic pain treatment: In early 2009 I was diagnosed with fibromyalgia, a condition characterized by widespread pain throughout the body, sleep disturbances and generalized sensory sensitivity.

I have seen and experienced firsthand the ways that clinicians and patients talk about chronic pain medications, and find them to generally be disempowering to the patient, clinician, and drugs themselves. My goal in this article is to help provide a new and more useful lens to think about medications, especially given the poor treatment outcomes for people with chronic pain, the frustration providers express about treating these ‘challenging patients,’ and the ongoing opioid overdose crisis.

I see cannabis and psilocybin as promising therapies that can contribute to bridging that need. Given that an estimated 50 million Americans have chronic pain – meaning pain that persists for three months or more – I want to help understand how to effectively use cannabis and psilocybin as potential tools for pain management.

Cannabis History

Cannabis, also known as marijuana, is an ancient medicinal plant. Cannabis-based medicines have been used for at least 5,000 years for applications such as arthritis and pain control during and after surgery.

This use extended through antiquity to modern times, with contemporary cannabis-based medications for treating certain seizure disorders, promoting weight gain for HIV/AIDS-related anorexia and treating nausea during chemotherapy.

As with anything you put in your body, cannabis does have health risks: Driving while high may increase risk of accidents. Some people develop cyclical vomiting, while others develop motivation or dependence problems, especially with heavy use at younger ages.

That said, lethal overdoses from cannabis are almost unheard of. This is remarkable considering that nearly 50 million Americans use it each year.

In contrast, opioids, which are often prescribed for chronic pain, have contributed to hundreds of thousands of overdose deaths over the past few decades. Even common pain medications like nonsteroidal anti-inflammatory drugs, such as ibuprofen, cause tens of thousands of hospitalizations and thousands of deaths each year from gastrointestinal damage.

Furthermore, both opioids and nonopioid pain medications have limited effectiveness for treating chronic pain. Medications used for chronic pain can provide small to moderate pain relief in some people, but many ultimately cause side effects that outweigh any gains.

These safety issues and limited benefit have led many people with chronic pain to try cannabis as a chronic pain treatment alternative. Indeed, in survey studies, my colleagues and I show that people substituted cannabis for pain medications often because cannabis had fewer negative side effects.

However, more rigorous research on cannabis for chronic pain is needed. So far, clinical trials – considered the gold standard – have been short in length and focused on small numbers of people. What’s more, my colleagues and I have shown that these studies employ medications and dosing regimes that are far different from how consumers actually use products from state-licensed cannabis dispensaries. Cannabis also causes recognizable effects such as euphoria, altered perceptions and thinking differently, so it is difficult to conduct double-blind studies.

Despite these challenges, a group of cannabis and pain specialists published a proposed guideline for clinical practice in early 2024 to synthesize existing evidence and help guide clinical practice. This guideline recommended that cannabis products be used when pain is coupled with sleep problems, muscle spasticity and anxiety. These multiple benefits mean that cannabis could potentially help people avoid taking a separate medication for each symptom.

Since the Controlled Substance Act was passed in 1970, the federal government has designated cannabis as a Schedule I substance, along with other drugs such as heroin and LSD. Possession of these drugs is criminalized, and under the federal definition they have “no currently accepted medical use, with a high potential for abuse.” Because of this designation and the limits placed on drug manufacturing, cannabis is very difficult to study.

State and federal regulatory barriers also delay or prevent studies from being approved and conducted. For example, I can purchase cannabis from state-licensed dispensaries in my hometown of Ann Arbor, Michigan. As a scientist, however, it is very challenging to legally test whether these products help pain.

Reclassifying cannabis as a Schedule III drug has the potential to substantially open up this research landscape and help overcome these barriers.

Emerging Role of Psychedelics

Psychedelics, such as psilocybin-containing mushrooms, occupy an eerily similar scientific and political landscape as cannabis. Used for thousands of years for ceremonial and healing purposes, psilocybin is also classified as a Schedule I drug. It can cause substantial changes in sensory perception, mood and sense of self that can lead to therapeutic benefits. And, like cannabis, psilocybin has minimal risk of lethal overdose.

Clinical trials combining psilocybin with psychotherapy in the weeks before and after taking the drug report substantial improvements in symptoms of psychiatric conditions such as treatment-resistant depression and alcohol use disorder.

Risks are typically psychological. A small number of people report suicidal thoughts or self-harm behaviors after taking psilocybin. Some also experience heightened openness and vulnerability, which can be exploited by therapists and lead to abuse.

There are few published clinical trials of psilocybin therapy for chronic pain, although many are ongoing, including a pilot study for fibromyalgia conducted by our team at the University of Michigan. This treatment may help people develop a healthier relationship with their pain by eliciting greater acceptance of it and decreasing rumination often related to negative thoughts and feelings around pain.

As with cannabis, some states, such as Colorado and Oregon, have decriminalized psilocybin and are building infrastructure to increase accessibility to psilocybin-assisted therapy. One recent analysis suggests that if psychedelics follow a similar legalization pattern to cannabis, the majority of states will legalize psychedelics between 2034 and 2037.

Challenges Ahead

These ancient yet relatively “new” treatments offer a unique glimpse into the messy intersection of drugs, medicine and society. The justifiable excitement about cannabis and psilocybin has led to state policies that have increased access for some people, yet federal criminalization and substantial barriers to scientific investigation remain. In the years ahead, I hope to contribute toward pragmatic studies that work within these difficult parameters.

For example, our team developed a coaching intervention to help veterans use commercially available cannabis products to more effectively treat their pain. Coaches emphasize how judicious use can minimize side effects while maximizing benefits. Should our approach work, health care providers and cannabis dispensaries everywhere could use this treatment to help clients in chronic pain.

Approaches like these can supplement more traditional clinical trials to help researchers determine whether these drug classes offer benefit and whether they have comparable or less harm than current treatments. As our society connects to the rich history of healing using these ancient drugs, these proposed changes may offer safer and substantive options for the 50 million Americans living with chronic pain.

Kevin F. Boehnke, PhD, is an Assistant Professor in the Department of Anesthesiology and the Chronic Pain and Fatigue Research Center at the University of Michigan.  He receives funding from the National Institutes of Health, the State of Michigan Veteran Marijuana Research Program, and has received grants from Tryp Therapeutics and Journey Biosciences.

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

Can Psychedelics Be Used to Treat Fibromyalgia?

By Pat Anson, PNN Editor

A startup pharmaceutical company has announced plans for a clinical trial to see if a psychedelic compound may be useful in treating fibromyalgia.

California-based Tryp Therapeutics is partnering with scientists at the Chronic Pain & Fatigue Research Center at University of Michigan Medical School for the Phase 2a study, which would be the first to evaluate the effictiveness of psilocybin – the psychoactive compound in “magic mushrooms” -- in treating fibromyalgia.

"We are thrilled to collaborate with such forward-looking clinicians and scientists to develop additional treatment options for fibromyalgia," Jim Gilligan, PhD, Tryp’s President and Chief Science Officer said in a statement.

"The Chronic Pain & Fatigue Research Center at the University of Michigan brings incomparable experience with evaluating treatments for fibromyalgia and other chronic pain indications, and there is nothing more important to our collective team than creating therapies that will address the daily distress of these patients."

The study will evaluate the safety and efficacy of TRYP-8802, an oral formulation of synthetic psilocybin developed by Tryp. The treatment, which will also include psychotherapy, is designed to target pain through neuroplasticity, which alters and reorganizes neural networks in the brain.

Fibromyalgia is a poorly understood disorder characterized by widespread body pain, fatigue, poor sleep, anxiety and depression. Standard treatments for fibromyalgia, such as non-steroidal anti-inflammatory drugs (NSAIDs) and gabapentinoids (Lyrica, Neurontin), often prove to be ineffective or have unwelcome side effects.

"Existing treatment options for fibromyalgia are often ineffective and show significant side effects," said Daniel Clauw, MD, Director of the Chronic Pain & Fatigue Research Center.

Tryp plans to submit an Investigational New Drug application to the FDA for the Phase 2 trial in September. Phase 2 studies typically involve a few hundred people with a disease or condition, and are designed to test the safety and efficacy of a treatment.  A much larger Phase 3 study is usually required before the FDA will even consider approval.

Interest in using psychedelics to treat medical conditions has been growing in recent years, primarily as a way to treat depression, anxiety and other mental health issues. Preliminary research suggests that microdoses of LSD, psilocybin and other psychedelics may also be effective in treating pain.

Another pharmaceutical startup – Mind Medicine (MindMed) – recently announced plans to  investigate LSD as a treatment for cluster headache and an unnamed “common, often debilitating, chronic pain syndrome.”

Tryp Therapeutics is focused on developing psilocybin-based compounds for the treatment of diseases with unmet medical needs. The company recently announced a partnership with the University of Michigan to study synthetic psilocybin as a treatment for neuropsychiatric disorders. Tryp is also working with the University of Florida to investigate psilocybin as a treatment for eating disorders.

LSD, psilocybin and other psychedelics are classified as Schedule I controlled substances, meaning they have a high potential for abuse and currently have no accepted medical use in the United States.

MindMed Investigating Use of Psychedelics to Treat Chronic Pain

By Pat Anson, PNN Editor

A startup pharmaceutical company has announced plans to investigate the use of LSD and other psychedelics to treat chronic pain.

New York-based Mind Medicine (MindMed) is exploring the use of psychedelics to treat two pain conditions, which it is calling “Project Angie.” The company is already investigating the use of psychedelics to treat addiction, anxiety and attention deficit hyperactivity disorder (ADHD).

"With the launch of Project Angie, we seek to align closely with MindMed's core mission to improve mental health and combat substance use for the many patients in need. If we can help to develop a new paradigm to treat pain, it may have the potential to greatly reduce the use of addictive medicines such as opioids currently ravaging society and its mental health," MindMed CEO & Co-Founder J.R. Rahn said in a statement.

MindMed did not disclose what pain conditions it was developing treatments for, but it is working with researchers in Switzerland who have a Phase 2 clinical trial underway on the use of LSD to treat cluster headache. The company said it is also evaluating a second indication for a “common, often debilitating, chronic pain syndrome.”

Interest in using psychedelics to treat medical conditions has been growing in recent years. Preliminary research suggests that microdoses of LSD, psilocybin (magic mushrooms) and other psychedelics may offer a new way to treat pain. The exact mechanism in which psychedelics have an analgesic effect is not fully understood, but early research indicates that LSD can modulate serotonin receptors that help regulate pain and inflammation.

"Evidence dating back to the 1950s suggests that LSD and other psychedelics may have analgesic effects, but this treatment area remains largely untapped by companies studying psychedelics, with the majority of research focusing solely on psychiatric indications," said Rob Barrow, MindMed’s Chief Development Officer. 

The company is planning to submit a Pre-Investigational New Drug (IND) application to the Food and Drug Administration for a Phase 2a proof of concept study of LSD (lysergic acid diethylamide) in the second half of 2021.

MindMed will have to clear some high regulatory hurdles. LSD, psilocybin, MDMA (Ecstasy) and other psychedelics are classified as Schedule I controlled substances, meaning they have a high potential for abuse and currently have no accepted medical use in the United States.

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

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.