Post Tag: Research

In part 2 of the article, “Surprising Results: Psilocybin Trial for Depression Alleviates Chronic Pain,” the disappearance of Court’s chronic pain leads to a new understanding of cortical remapping, mirror box therapy, and how science can treat phantom limb pain.

Immediate Changes Post-Dosing

I had years of experience in cold water training from my Aikido career, but as my depression had increasingly grown worse, I developed a severe cold intolerance. It had become painful to stand under the shower, with my scalp almost spasming in contraction, when I used to be able to stand in late winter melt-water waterfalls and rivers with ease. But post-dosing, my cold tolerance came roaring back; allowing me to stand under a cold shower for minutes at a time with no numbness and no pain – it was almost like it was happening to someone else or there was a micro-force field on the surface of my skin. I found myself having to leave the shower because I just had other things to do. Cold water tolerance is a gold-standard for measuring pain response in clinical trials, and in fact, later that year, the Department of Psychopharmacology at Maastricht University, sponsored by the Beckley Foundation, conducted the first LSD and pain study in nearly 50 years, showing that low-dose LSD significantly increased cold water tolerance without interfering with day-to-day activities.

I had been known for my mobility and flexibility throughout my career and my ability to train others to achieve the same results, but mine had been compromised for a good while at this point. But the day after my session, I was able to resume positions that I hadn’t been able to comfortably acquire in months, if not years. Movement now felt smooth and effortless once again, and I swear there was even improvement in the tissue quality in areas that had become “crunchy.”

There was also a significant change in my inflammatory baseline. Depression is seen as a disorder that also includes fairly significant neurological inflammation and is often bi-directional with chronic pain, but many of the same receptors that psilocybin operates on are also contained within the gastrointestinal tract, and mine had altered sensation for a month afterward. I believe my systemic inflammation significantly improved during that period because within three months of my dosing, I reacquired personal training records that had become elusive, and by summer, I passed those PRs and set new ones. I also felt incredibly less “puffy.” Accidentally banging into something didn’t hurt anymore and persistent joint aches and lack of motor activation disappeared. There were additional improvements in neurological issues that will be described in a future case study, but that was just as immediate and impactful.

Lockdown Leads to the Lowdown on the First Psychedelic Pain Studies

Within the training and recovery world, patients and trainees can loosely be categorized as super, normal, non, and negative responders. I had stopped being responsive to both training and rehabilitation efforts at the peak of my depression, and was entering negative-responder territory, which was severely distressing. Fascinatingly, I now seem to be trending somewhere between a normal and high responder. I began proclaiming to the researchers at NYU that psychedelics were going to completely change chronic pain treatment within five years. And I also had a secret; the day after my dosing session, I had what’s referred to as a huge download: I realized that if you could consider things like depression, PTSD, and severe anxiety to be nociplastic outputs of the Central Nervous System (CNS) that causes iterative rumination (a.k.a. looping maladaptive outputs), that was no different from the looping maladaptive outputs that characterize chronic pain – the neurology of which I had been studying for years at that point. Due to the extreme visual qualities of the psychedelic experience and the rapidity of my own remission, I saw, in a flash, that since psilocybin was an impact booster for neuroplasticity, it would enhance the impact of mirror box therapy for phantom limb pain or likely any other neuromodulation.

“Remapping” is the term describing the tactic of using visual or other sensory receptor inputs to modify and change nociplastic or noxious/painful outputs of the brain. As this is part of the Z-Health process, I had been introduced to the concept of mirror box therapy years earlier as part of my certifications, but I thought I had come up with a whole new approach and kept it to myself, barely hinting at what I believed I had uncovered. But, since NYC was locked down and I was unable to work, I had nothing to do but go online and research what had happened to me.

Within two weeks or so, I found an old photocopied English abstract from a 1962 study in Japan, by Kuromaru, et al., using low-dose LSD to treat phantom-limb pain with 50% of its participants going into instant remission by the end of their session, and the authors pointedly declaring that stacking the LSD with movement had a far stronger impact on resolving both phantom limb pain and phantom limb syndrome. Stacking inputs is a common practice within the neuromodulation world for pain treatment, often coupling a weaker input with a stronger one, and I realized that this was what had clearly happened to me while I was in my post-dosing neuroplastic window. It finally felt like I was getting traction again; that drills and exercises were once again effective, and crucially, maintaining their own momentum. I didn’t have to be hypervigilant anymore in my daily routine for these drills to become “sticky.” I also realized that the Kuromaru study had, in fact, been released earlier than the Kast study from 1964 investigating the analgesic properties of LSD for terminal cancer and other painful conditions, which is frequently and incorrectly cited as the first psychedelic pain study. I became aware of other previous psychedelic pain studies, as well as recent ones like Dr. Charles Nichols’ work on the anti-inflammatory properties of psychedelics, and studies involving Dr. Robin Carhart-Harris’ REBUS model and cortical reorganization, which is what happens when a stimulus results in the creation of a new cortical map (essentially a vertical column in the brain cortex consisting of neurons performing specific processes). 

Both of these discoveries are crucial because cortical reorganization (or remapping) and inflammation are key drivers of chronic pain. Conditions like depression and anxiety are characterized by rigid, fixed beliefs or frameworks where the same negative thought loop keeps reoccurring repeatedly, with no amount of incoming contrary information able to alter that belief. It becomes what’s known as a “strong prior” in neurology, becoming a top-down driven process in the CNS, actively suppressing any bottom-up sensory input error correction. The same mechanisms of action occur with chronic pain, where, despite the healing or resolution of an injury; a rigid, fixed pain signal is continually being sent out by the brain as a maladaptive response of the CNS’ protective suite. These are referred to as nociplastic or noxious neurological conditions. The same is true for multiple chronic pain conditions where inflammation causes maladaptive signaling and perceptions, leading to negative structural or nociplastic changes in the peripheral and central nervous system. In psychedelic-assisted psychotherapy, a non-rigid, chaotic state is induced, which allows the cortical landscape to reorganize into a more efficient and positive state.

Landmark Study in Pain and Psychedelics Confirms Insights

As everything was becoming more and more clear – in what had to have been one of my most transpersonal moments after my dosing session – a landmark review paper was published. “Chronic pain and psychedelics: a review and proposed mechanism of action” by Dr. Joel Castellanos, et al. was released from the Psychedelics Health and Research Initiative (PHRI) at UC San Diego in May of 2020, barely two months after my dosing session and pain revelation. It was an amazing overview of all the possible mechanisms of action that could be at play in psychedelics being an effective analgesic and resolver of chronic pain, but the most revelatory moment was when I found, buried within the heart of the paper, a link to the case study that had set PHRI in motion. It was written by the world-renown neuroscientist VS Ramachandran, the clinical faculty at PHRI, and by its case subject, Albert Lin, who had used high-dose psilocybin coupled with mirror box therapy to put his intractable phantom limb pain into full remission.

I sat speechless for at least five minutes, shaking my head in a feeling of wonder and disbelief, as if the universe itself had just delivered this paper to me. Other than my remission and the pandemic, I had thought of nothing else but the application of how these two approaches could be combined. Of course someone else had invented it well before me; of course they had. I knew that resourceful, capable people had been working on this for a while, and chronic pain is a singular motivator, but it was still astonishing to see my vision so vividly applied and executed.

I had learned in 2015 that cluster headaches had been effectively treated with psilocybin for 25 years, and of mirror box therapy a few years before that. I had even blogged about it because people in the rehab and training communities thought that my using visual inputs to treat pain was so weird they called it “voodoo.” But there is a neural hierarchy, and many pain and performance conditions in the body actually have higher-order components within the visual and vestibular systems. That’s often why, no matter how much manual/physio therapy one does, it is often a downstream compensation within the body in order to reconcile perceptual discrepancies between the visual and vestibular system. The visual system lets you assess the surrounding environment and predict any threats that exist within it, and the vestibular system helps you orient within that space, keeping your body in balance so that you might be able to execute any motor actions in response to any perceived threats. If your eyes are telling you the horizon is 5° tilted to the left, but your vestibular system, a.k.a. your inner ear, is telling you that it’s 5° to the right, your body will compensate so that those discrepancies are reconciled and you maintain a stable, level “sight picture” – your viewscreen of the world. Having an unstable sight picture makes for poor predictions; in other words, in an evolutionary survival context, having a “shaky cam” is not so great for avoiding saber-tooth tigers.

So, those downstream bodily compensations that keep your viewscreen steady are creating distortions and possible maladaptations in the structure of your body, and are now being cemented due to repeated compensatory use. The nervous system will protectively reduce motor output and increase pain perception as a response, to slow you down in order to avoid potential injury and survive another day. Ultimately, the body has evolved towards survival, not performance. And pain is an alarm/action signal designed to keep you alive.

Mirror Box Therapy and Pain as An Output of Perception From the Brain

When we look at phantom limb pain, what we’re seeing is the phenomenon known as deafferentation: the loss of afferent or ascending inputs from the peripheral nervous system up to the brain. No limb equals no signal, and the loss of signal is very dangerous within an evolutionary context because limb loss due to injury or infection will mean, at the least, loss of sensation and loss of coordination for motor outputs/muscle contraction/movement, meaning a lost ability to gather food or to avoid threats. Or worse, it could mean signaling that you’re going to bleed to death in a matter of minutes.

Multiple pain conditions could be considered sub-clinical deafferentation: peripheral neuropathy from conditions like diabetes or shingles, or different types of phantom limb pain where the limb is still present but the nerves are so injured that they no longer transmit afferent signals – such as we see in cancer, stroke, or crush injuries. That loss of signal gets hardwired into the cortical representations of that limb, and never gets a counterbalancing signal, so the CNS registers it as an ongoing sense of threat. That creates a huge alarm signal in the form of pain perception.

What mirror box therapy does is replace that loss of signal with the image of an intact limb, generating input that dampens down that pain signal. And when you touch the remaining limb (which is generating normal signals) while seeing it reflected in the mirror in place of the missing or injured limb, it can immediately cause the pain signals to cease; so powerful are visual representations within the somatosensory cortex of the brain. Essentially, through seeing a limb appear where it wasn’t before, one tricks their own brain into thinking it’s still there, and the pain signals from the CNS for that lost limb stop being sent.

Mirror box therapy is often not enduring though; only being effective for as long as you do it, and that was the case with Albert Lin. It often takes a lot of repetition for it to become “sticky.” Neuroplasticity requires novelty and intensity, usually in the volume of work. But that can be hard to achieve, thus the issue in pain treatment that I had experienced directly as a practitioner and as a patient; everything works, nothing lasts. When it was suggested to Lin that psilocybin had strong neuroplastic properties that could impact cortical reorganization for chronic pain, he tried it a few times, taking a high dose of psilocybin mushrooms, which gave him approximately 3-12 pain-free hours, depending on the dose. But then the pain came back with a vengeance. Within the cluster headache communities, this is known as a “slapback effect” and can actually be a sign that the nervous system is adjusting and more permanent relief could be imminent.

Then, Lin’s wife suggested combining (stacking) mirror box therapy with psilocybin. He went out to the desert with a closet door mirror, and while under high-dose psilocybin, he would stare at the reflected image of his remaining leg and then at the space where his amputated limb had been, while repeating the phrase “You are safe. You are totally safe,” for approximately 45 minutes. This met all the conditions for driving neuroplasticity: novelty, intensity, and volume of work with deep assurance of emotional and physical security. Amazingly, it worked, immediately putting him into remission for the next 20+ hours, with 50% reduced pain for nearly two weeks. He shared his success with the lab, and experiments with different types of visual neuromodulation while under high-dose psilocybin quickly began.

Lin was dealing with a persistent pain in his phantom foot that felt as if a railroad spike was being driven through, suspected to be a sensory remnant from when the bones in his foot were surgically pinned together as they attempted to save it before ultimately deciding to amputate. An artificial foot and a pen with a telescoping pointer was introduced, and they covered the space between his stump and the plastic foot with a blanket, then “pulled” the telescoping pen out of his foot at the site of pain, mimicking the action of removing pins (or really, removing the pain). He felt instant relief.

Another experiment involved a novelty Halloween-store “flame” (bright light with orange and yellow fabric and a fan underneath that makes it flutter). Lin chuckled when he saw it, but when they brought it near his representational foot, he actually felt heat from the “flame,” which was intensely relieving.

Through these experiments and continued work, Lin went into full remission after five weeks, and has been free of chronic pain ever since. It’s worth noting that he had a top research team working with him that was extremely creative in creating novel inputs, and he is known for being an almost Michelangelo-type character, with a high degree of inventiveness and novelty-seeking, allowing him to discover unique, lateral approaches to solve problems. And, it bears repeating: chronic pain is a singular motivational force.

Additionally, post-dosing, cortical reorganization was happening during a psychedelically-induced “critical period reopening”; when the brain has a metaplastic quality that allows it to reset to an almost-new condition. As described in the work by Dr. Gül Dölen, critical period reopening happens during crucial phases of nervous system development in childhood, such as when toddlers can learn multiple languages without an accent or when adolescents are uniquely sensitive to social cues from peer pressure (and/or support), allowing them to quickly adopt different social customs and frameworks. This reopening is also seen post-stroke, when there is a limited window for rehabilitating from brain injury, so this likely applies very well here with chronic pain. We know that veteran groups like the Heroic Hearts Project, VETS (Veterans Exploring Treatment Solutions), and The Mission Within, who are employing psychedelics for treatment, are having striking results both in recovery from combat-induced PTSD as well as traumatic brain injury – typically seen as treatment-resistant conditions.

Conclusion

If there’s anything I would like you to understand after reading this article, it’s that:

We don’t have to prove that psychedelics are effective for treating chronic pain; we have to establish that this has already been proven.

Psychedelics are not an instant cure for chronic pain, but they are strong impact boosters for neuroplasticity and can make physiotherapy/neuromodulation become “sticky,” creating enduring relief.

We know that many mechanisms that create psychiatric conditions that are responsive to psychedelic-assisted psychotherapy are extremely similar in nature to the same mechanisms that generate chronic pain; it’s just that psychiatric conditions have gotten far more focus in psychedelics, perhaps because the non-ordinary states of consciousness they are known for producing seem more applicable to conditions more traditionally thought to be related to the mind.

But both arise out of the central nervous system and are rigid, fixed states of cognition and perception. With depression, you have negative outlooks and self-perceptions: “Nothing I do makes a difference,” “People are just saying that to make me feel better,” etc. At one point, these thoughts may have helped you to cope with a traumatic incident, environment, or upbringing, but now they’re maladaptive, weigh you down, are out of step with reality, and have actually caused (or are the result of) structural deficits in the neurology of your brain. It’s the same with chronic pain: when there is an acute injury or even the possibility of one, pain is part of the protective suite of responses from our nervous systems to prevent further injury and allow healing to occur – an alarm bell/action signal to change a behavior. But it can be so overprotective that it gets embedded and cemented with movement, emotions, and surrounding environments long after all tissue healing is done – getting triggered by seemingly innocuous events, maladaptively hardwired into your neurology in a negative loop of conditioned responses.

This is exactly what happened to me when I went through NYU’s psilocybin trial; an adverse financial and work environment, repeated (and under-recovered) musculoskeletal stress/injuries, and (likely) sub-clinical post-concussion syndrome and PTSD, all topped off by the sudden death of a close friend releasing long-suppressed grief and leading to a significant nociplastic output in the form of increasingly treatment-resistant depression and moderate chronic pain. Many recovery efforts were attempted using every modality I knew, but there was too much of a deficit to overcome – until psilocybin was introduced to the mix. That life-changing experience allowed for metaplasticity, cortical reorganization, descending inhibition, and anti-inflammatory properties to take root, giving all post-dosing interventions the opportunity to gain traction and for me to flourish once again.

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Future articles in this “Pain and Psychedelics” series will focus on old assumptions vs. new science, additional case studies, the suspected mechanisms of action behind the interaction between psychedelics and pain, and best practices and safety concerns for working with psychedelics to alleviate chronic pain.