Decades of citizen science are finally translating into clinical trials for psychedelic pain treatments.
Here’s another strange and under-studied prospect of psychedelics: a world without severe chronic pain.
For Court Wing, a former martial artist and CrossFit trainer, the most surprising thing about participating in a 2020 clinical trial at NYU for psilocybin and major depressive disorder wasn’t that his depression — which had resisted treatment for over five years — disappeared. It was that his long-standing chronic pain, something unrelated to the trial’s focus, also disappeared. “Shockingly, I was in complete remission,” he told Vox.
And if you start poking around the internet or psychedelic conferences, a whole subterranean trove of similar stories opens up. An estimated 51 million Americans suffer from chronic pain — excruciating conditions like migraines, phantom limb pains, or fibromyalgia — and often go without effective treatments. But psychedelics like psilocybin mushrooms and LSD seem to offer serious relief.
At least, to people who have access. The Drug Enforcement Administration still considers these psychedelics as illegal Schedule I substances, which means federal law prohibits them from being prescribed as medicines (though states can move ahead anyway, as they have with marijuana).
Most clinical trials in today’s psychedelic “hype bubble” prioritize mental health conditions, which will likely lead to MDMA being approved by the FDA later this year for PTSD treatment. The downside of that singular focus, however, is that those suffering from chronic pain have been left to turn to the psychedelic underground for support.
Still, the rising awareness around psychedelics as potential treatments for mental health has raised their profile across the board, helping to finally generate some traction around other uses too, like pain. A major milestone in that journey is the National Institutes of Health’s announcement last month of a nearly $22 million grant for clinical trials on psychedelic-assisted therapy and chronic pain relief.
The road from funding more trials to doctors being able to legally prescribe psychedelics for chronic pain will likely take years, however. That’s time a lot of people don’t have; the depth of pain in these communities is nearly impossible to imagine. “People in the general public have no reference for this type of pain,” said Wing, who recently co-founded the Psychedelics and Pain Association (PPA). “Not unless they work in the profession, or have someone close to them that has this type of chronic pain, will they get the kind of desperation that’s involved.”
When a novel and relatively safe treatment like low- to moderate-dose psychedelics can alleviate that kind of desperation, it’s difficult to not want the regulatory process to move quicker. But none of the necessary steps — getting funding, clinical trials, DEA rescheduling, and designing the care infrastructure — are exactly known for being swift.
“We do want to be careful. We don’t want people trying this randomly at home. But if we get this right, we could relieve the suffering of millions,” said Wing, who emphasized the value of harm reduction practices and professional guidance. “For some people, it’s the difference between a life worth living or not.”
One condition that’s pulling a ton of attention toward psychedelic treatments for chronic pain is cluster headaches — also known as “suicide headaches.”
They’re among the most painful conditions known to humankind. The title of a real study on survey responses from 493 people with cluster headaches begins: “You will eat shoe polish if you think it would help.”
Most people end up going about five years before receiving a proper diagnosis. Even then, the treatment options are slim. The first FDA-approved treatment, Emgality, came in 2019, and clinical trials found that it roughly cut the number of attacks in half for 71 percent of patients. No known treatment had ever straight-up ended a cluster headache.
But back in 1998, someone posted on an internet forum that LSD seemed to have negated his cluster headaches. A community of “Clusterbusters” then began to coalesce around the illicitly tinged knowledge that an effective psychedelic treatment exists, even if most doctors don’t know about it, and certainly can’t prescribe it.
Today’s revival of psychedelic research is often traced to the late Roland Griffiths’s 2006 study on psilocybin and mystical experiences. But that same year, Yale psychiatrist R. Andrew Sewell also published a paper that reviewed 53 cluster headache patients who’d self-medicated with either psilocybin or LSD. Seventeen of 19 users who took psilocybin during an episode reported that it ended their attacks. More broadly, 25 of 48 psilocybin users and 7 of 8 LSD users reported that the psychedelics put an end to their cluster periods altogether.
Despite the lack of attention by medical professionals, there’s a surprisingly long history of studying psychedelics for pain relief. The PPA maintains a database of research showing studies reaching all the way back to 1930, covering painful conditions from fibromyalgia to phantom limb syndrome and cancer pain.
One reason that research hasn’t turned more heads is the lack of randomization or placebo controls, something that the NIH grant could help remedy (though there’s an ongoing debate as to whether randomized placebo-controlled trials are the best methods to study psychedelics in general — how do you go about “blinding” someone to whether or not they’re tripping on acid?).
Research on psychedelics and pain, today, is at a tipping point. According to the PPA’s database, after the 1930 study, research dropped off until the ’60s, with a few more studies coming out per decade until the early 2020s. In 2022, that number shot up to 16, and another 10 in 2023. Now, with the NIH grant, more are poised to follow.
“I cannot tell you how hard we’ve had to push in the last four years to get this into the discussion,” said Wing, who cofounded the PPA alongside Psychedelics Today CEO Joe Moore and Bob Wold, the founder of Clusterbusters.
A January 2023 review of the literature by anesthesiologist Selina van der Wal and colleagues surveyed a series of potential mechanisms of action. They ranged from activating the brain’s serotonin receptors (which are known to be involved in pain processing), altering how brain regions communicate with each other and process pain perception, to the anti-inflammatory properties of psychedelics.
Wing is especially interested in how psychedelics could update our understanding of how chronic pain works. Most chronic pain lasts long after the underlying tissue damage is already healed. At that point, pain may no longer be a signal stemming from damage in the body, but a stubborn prediction that the mind has learned to make about the body. In this view, chronic pain is like a haunting memory that the mind recasts into the present. This is also why psychotherapy is among the best tools we have to treat chronic pain, and may be a powerful pairing with psychedelics.
“People think pain is an input, that it’s a sensation traveling from the body to the brain and signaling damage,” he explained over the phone from the Horizons psychedelic conference in New York. “But that’s just not the case. Pain is actually an output of the central nervous system. It’s a perception that’s part of this whole idea of predictive processing.”
In August of last year, National Cancer Institute oncologist Farah Zia and colleagues published a review of where future research should focus. It outlines a few areas: digging into the potential mechanisms of action, whether micro- or macro-doses are more effective, whether complementary therapies should be included, expanding the search for conditions that may benefit, and the logistical thicket of treatment protocols.
Though Wing emphasized the importance of best practices for risk reduction and the value of being in communication with health care providers (though not many will walk you through a psychedelic dosing protocol), he often says that we don’t need more research to prove that psychedelics can be effective treatments for chronic pain. Instead, “we have to establish that this has already been proven.”
For some conditions, like cluster headaches, studies, including van der Wal’s review, are already recommending that Phase 3 trials get underway in order to win FDA approval as fast as possible. But again, that will take a lot of time. And other conditions that lag behind cluster headaches will take even longer, leaving people to suffer in the interim.
“There has to be a middle way,” said Wing. “In the meantime, how do we help the people suffering on the ground?”
One option is to recognize that, as sociologist Joanna Kempner put it to me, “the cat’s out of the bag, so far as psychedelics are concerned … and given how much unmet need there is in pain populations, people are going to use them.”
State decriminalization efforts, along with investments in harm reduction and public education, can reduce the risks around criminalizing people seeking psychedelic treatments while the FDA approval process churns along. “The debate around medicine versus decriminalization is a false binary,” said Kempner.
Her forthcoming book — Psychedelic Outlaws — chronicles the journey of the Clusterbusters’ citizen-science network, which continues to fill a critical void of knowledge and support in the absence of professional guidance. She explained that among people she interviewed, “Clusterbusters’ patient network might have saved their lives, but they wanted to be able to ask their doctors for advice. Regulation would help make it easier and safer for them to obtain a standard-sized dose of their treatment. And, most importantly, they hoped that good scientific research would help others find relief, too.”
“As I often witnessed,” Kempner added, “psychedelics really did save many people’s lives.”
A version of this story originally appeared in the Future Perfect newsletter. Sign up here!
