by Kent Bassett

Will psychedelic-assisted therapy be able to help people with neuroplastic pain and other symptoms?

High-quality research on this question has been prevented by government prohibition on research since the 1970s and 80s, so we don’t have clear answers from the scientific literature. Three prominent researchers at the intersection of pain and psychedelics are working to change that.

Note: I do not provide support for or advocate the use of psychedelics. This information is being provided for educational purposes.

What is Psychedelic Assisted Therapy with MDMA?

MDMA-assisted therapy involves a 6- or 7-hour dosing session where a patient listens to music with headphones on and wears an eye-shade mask to allow themselves to go inward and explore. MDMA stands for 3,4-Methyl​enedioxy​methamphetamine, which was banned in 1985 after being used by therapists for years to facilitate healing. To learn the background of MDMA-assisted therapy, I can recommend the Rachel Nuwer’s book I Feel Love and Michael Pollan’s Netflix documentary, How To Change Your Mind.

Prior to the dosing session, patients and therapists have “prep sessions” where they discuss what issues, stressors, traumas, or fears they want to face and transform. Before the session, which usually starts in the morning, they set an intention to heal their traumas or symptoms.

According to the MAPS protocol: “The MDMA-assisted session consists of periods of inner focus during which the participant attends to her/his intrapsychic experience without talking, alternating with periods of interaction with the therapists. The ratio of inner focus to interaction is typically approximately 50:50, but varies considerably from session to session.”

Compared to classic psychedelics like LSD and psilocybin, MDMA is a much more social drug, typically. Many people become quite chatty, and want to connect with their therapist or facilitator. They can feel trust in a deeper way than they’ve felt in years, which allows them to jump-start the therapy process, or get more from the therapy. This trust allows them to open up and face things that were previously inaccessible.

Safety profile: there are several dangers of MDMA that can be mitigated by proper use. It’s important to test MDMA it to make sure it’s pure and doesn’t contain fentanyl or methamphetamine, and making sure not to take don’t take more than about 120-180 milligrams. Sometimes people accidentally take high doses, which can be fatal. Other risks including mixing MDMA with other drugs like alcohol, or cocaine, which can be very dangerous. Sometimes people do not drink enough water, or they take in too much water, which can lead to water toxification, which can be fatal. Dancing for hours in hot environments is also dangerous with MDMA because it can cause “hyperthermia,” which can be fatal or lead to neurotoxic brain damage. For a full accounting of risks of MDMA you can check out https://dancesafe.org or Rachel Nuwer’s book. She notes that MDMA is a relatively safe drug once people learn about its risks and take measures to mitigate them. Much research has been done on the neurotoxicity of MDMA, and the conclusion Nuwer reaches after surveying the research is that when used properly, MDMA is not neurotoxic, and its benefits for so many people with deep psychological suffering out-weigh its risks.

Because of successful phase three trials, the FDA is likely to approve MDMA as a medication for PTSD in the next 12 months. When this happens, MDMA will be prescribed off-label for chronic pain conditions just like SSRI antidepressant drugs are used off-label for chronic pain, and it will be legal to do so.

What is Psychedelic-Assisted Therapy with Psilocybin?

Psilocybin-assisted therapy has some key differences with MDMA, though both have shown promise in helping people with chronic pain. Each individual experiences the two drugs differently, but generally speaking, psilocybin sessions are shorter, about four hours instead of six, and many people spend the whole time listening to music with headphones on and wearing an eye-shade. In that sense they tend to be less social, compared to in an MDMA session a person may spend half the time talking to a facilitator. Psilocybin journeys are much more likely to involving seeing visions and hallucinations, sometimes including visits with other beings, spiritual figures, or loved ones.

Does MDMA-Assisted Therapy Work for Chronic Pain?

We have some compelling anecdotes from people whose chronic pain conditions have been eliminated after MDMA-Assisted Therapy. In Rachel Nuwer’s book, I Feel Love: MDMA and the Quest for Connection in a Fractured World, she opens with the story of Callie, a woman whose mother was a heroin addict.

To the outside world, Callie projected success. But privately she was experiencing an array of distressing symptoms. She stopped cleaning her house and kept her possessions in "huge, unorganized piles on the floor which I would just sort of walk over to get anywhere." She developed chronic pain in her lower back and neck, and carpal tunnel in her wrists.

Callie started with talk therapy, but she wanted to go deeper. So in 2016 she sought out an underground therapist willing to give her MDMA, the illegal drug also known as Ecstasy or Molly. On the morning of her appointment she swallowed a capsule and lay back on a futon in a sunlit library-like room, her therapist stationed nearby. She quietly closed her eyes for the first thirty minutes or so, but soon she was up on her feet, pacing, speaking, and asking her therapist to hold her hand.

Under MDMA's influence and her therapist's guidance, Callie regressed into a childlike state that ultimately allowed her to uncover a long-buried memory from when she was around seven years old. Her mother was having another psychotic episode and had become convinced that aliens were on their way to Earth, and as soon as they arrived, they were going to eat everyone-including Callie and her sister. The only recourse they had, her mother told them, was to commit suicide by alcohol to poison the aliens.

Callie's mom began forcing the girls to drink, but Callie was crying and gagging too much to finish what she had been given. Distraught, her mother dragged the girls out onto the street to prepare for the aliens' arrival. "This was sheer desperation— an animal instinct gone awry," Callie said. "I thought she was taking us somewhere to kill us."

Fortunately, Callie's father dropped by unexpectedly, and he quickly put a stop to the situation. But while Callie wasn't physically harmed, in recovering the memory of that horrific day she realized she'd been living "with this fear that my mom would kill me, and the fear had been so terrifying and unacceptable that I hadn't allowed myself to know about it."

This epiphany marked a turning point in Callie's life. She has not raged out or broken anything for years, and her chronic pain went away and has not returned.

Clinical Trials and Articles About Psychedelic-Assisted Therapy for Chronic Pain and Other Somatic Symptoms

For a layperson’s guide the state of research on psychedelics to chronic pain, I would point you to Clare Watson‘s article in Nature, “The psychedelic remedy for chronic pain.” Since Nature keeps her article behind a paywall, I will provide a summary of some of what Watson discussed and the scientists she identified as leaders in this emerging field.

Peter Hendricks, Ph.D. is a clinical psychologist and professor at the University of Alabama at Birmingham. He’s currently conducting a double-blinded, controlled trial to assess psychedelic-assisted therapy with psilocybin for people with fibromyalgia, which is a form of widespread neuroplastic pain. Psilocybin is the active ingredient in psilocybe cubensis psychedelic mushrooms (a.k.a. magic mushrooms). The results are not published yet.

Dr. Hendricks has also co-authored an article published in Expert Review Of Neurotherapeutics, “Adapting psychedelic medicine for headache and chronic pain disorders.” After reviewing studies of psychedelic therapy for headaches and migraines, they conclude that “psychedelic interventions for headache and chronic pain disorders hold promise.” Data from another small migraine and psilocybin study of ten people “suggests there is an enduring therapeutic effect in migraine headache after a single administration of psilocybin.”

Another prominent researcher at the intersection of chronic pain and psychedelics is Joel Castellanos.

“Chronic pain as an emergent property of a complex system and the potential roles of psychedelic therapies,” by Maya Armstrong, Joel Castellanos, Devon Christie, published in the journal Frontiers in Pain Research, 19 April 2024

This article is an excellent, albeit dense, survey of the current neuroscience of chronic pain that discusses its complex biopsychosocial causes, which do not typically resolve in the face of standard biomedical approaches. They note how predictive coding and prior beliefs are key factors in driving and maintaining chronic pain states. This is another way of saying that the fear of pain, and the fear of damage in the body can drive ongoing symptoms in the absence of actual tissue damage, or far beyond what could be explained by tissue damage.

And the authors conclude that psychedelic-assisted therapy, as a complex treatment, might be capabable of treating this complex biopsychosocial problem—chronic pain—it “could lead to meaningful improvements for millions of people who suffer with chronic pain.”

In another study co-authored by Dr. Castellanos, Microdosing psilocybin for chronic pain: a case series, published in the journal PAIN, he writes

“Through self-administration of psilocybin, these patients have achieved robust pain relief with decreased reliance on traditional analgesic medications. Despite varying preparations and uncertain potencies, the analgesic effects for all 3 patients occurred at doses without a psychedelic experience and with minimal cognitive or somatic adverse effects. Furthermore, the efficacy of pain relief and, in some cases, the duration of the effect were magnified when coupled with functional exercise. In addition, in 1 case, repeated dosing seemed to produce increased relief, suggesting a possible long-term plasticity-mediated effect. These commonalities highlight psilocybin's therapeutic potential in the treatment of chronic pain that warrants further investigation.”

Another prominent pain and psychedelics researcher is James Close, who works at the Centre for Psychedelic Research, Division of Brain Sciences, Imperial College London, London, United Kingdom. In an article he co-authored,“Self-Medication for Chronic Pain Using Classic Psychedelics: A Qualitative Investigation to Inform Future Research,” was published in Frontiers in Psychiatry:

“Across a range of psychedelic substances and doses, reported pain scores improved substantially during and after psychedelic experiences.”

“Analysis suggested two possible processes at play during psychedelic self-medication for chronic pain: (1) Positive Reframing of contributors' relationships with their chronic pain toward perspectives of hope, empowerment, and optimism. (2) Somatic Presence fostered increased embodiment and was associated with lasting analgesia. Psychedelics were not used in isolation and were regularly combined with various other modalities including meditation, breathwork, and movement, which contributors felt impacted the success of their self-medication.”

It is interesting to note that people who successfully self-treated their pain with psychedelics used two common tools that are taught in Pain/Neural Reprocessing Therapy (PRT): positive reframing, and mindfulness. And those two factors were noted in a study that was not about PRT.

Further Resources For
Psychedelic-Assisted Therapy

MAPS: A Manual for MDMA-Assisted Psychotherapy in the Treatment of Posttraumatic Stress Disorder

Documentary: Netflix Series With Michael Pollan: How To Change Your Mind, Ep 3 - The MDMA Episode

Psychedelic Medicine Podcast: MDMA-Assisted Therapy For Alcohol Use Disorder Podcast with Ben Sassa, MD

Tim Ferris Podcast: Interview with Neuroscientist Gul Dolen, PhD, on using “Critical Periods for Learning” with Psychedelics

Note: I do not provide support for or advocate the use of psychedelics. This information is being provided for educational purposes.