In this week’s episode, Joe and Alexa talk about the excitement brewing around our first conference-meets-festival, Convergence (March 30 – April 2 at the Wisdome in LA), and some of the sponsorships starting to come in (interested? email Alexa@psychedelicstoday.com).
Then, they dive into what intrigued them the most this week: a study looking into potentiality and possible causes of 5-MeO-DMT reactivation (and what reactivation actually is); New York cannabis farms sitting on $750 million worth of cannabis as the government drags its feet on licenses; and the story of a woman who used cannabis and psilocybin as an adjunct to standard therapy in the treatment of advanced metastatic breast cancer.
In this episode, Victoria hosts a bit of a microdosing roundtable, speaking with three champions of microdosing: “The Father of modern microdosing,” James Fadiman, Ph.D.; Adam Bramlage, Founder/CEO of Flow State Micro (a functional mushroom company and microdosing educational platform); and Conor Murray, Ph.D., a neuroscientist at UCLA who conducted the world’s first EEG microdosing study.
Fadiman and Bramlage recently launched a very popular course through our Psychedelic Education Center: “Microdosing Masterclass,” which covers the history and science of microdosing, as well as best practices for microdosing safely and effectively. They discuss the roots of microdosing, decriminalization and concerns over the corporatization of psychedelics, what we’ve seen so far in research, and how we’re finding ourselves in an era where people are going to be allowed to actually help themselves.
Murray is hoping to make big waves in the promotion of microdosing with the world’s first take-home EEG microdosing study: participants will be mailed a wireless headband that will be able to track brain activity in real world scenarios – the citizen science we’ve so desperately needed in comparison to lab studies that couldn’t be more different from how people actually live day-to-day. There is no criteria to participate, and, in contrast to lab studies, they want all data possible: people who are in therapy or not, people following different microdosing protocols, people microdosing for different reasons, etc. Will microdosing improve brain scores on cognition and emotion? Will participants see measurable improvements? And how will these numbers look when comparing scores months after initial peak neurological windows?
If you’d like to participate, head to psynautics.com and sign up. The first 50 people to do so will receive the wireless EEG to track their brain for one month for only $40.
“Because it’s inherently interesting for people to find that their consciousness can be improved (not necessarily changed) and that their whole physical system can also be improved, microdosing has found a natural niche which is: it might be good for you, and as far as we can tell, it’s very, very, very, very, very rarely bad for you. And that’s a nice risk/reward ratio.” -James
“It’s hard to fool the brain. You can maybe have a good placebo effect if you’re trying to ask someone: how much do you think your cognition’s improving today or emotion’s improving today? But it’s harder to fool the brain into having a different answer.” -Conor
“There’s so many people who will not buy into this until it’s proven by modern science, and that’s why Conor and his work is so important, and this new study with the wireless headbands and the idea that every citizen scientist on the planet can write Conor at Conor@psynautics.com and be a part of this study and get a wireless headband – I mean, that is fascinating. That is taking microdosing out of a sterile lab and putting it into the natural environment where it came from, as hunter-gatherers, for hundreds of thousands of years.” -Adam
“That’s really the metaphor, which is: the more windows, the more you see different views, and there’s nothing good or bad about any particular window except how clean it is. …We’re opening up bigger windows in more directions than has been the case in the past.” -James
This week features David Drapkin, Joe Moore (for the first part), and introduces Alexa Jesse, who you’ve probably heard in ads, but who makes her first appearance on the podcast.
They discuss two big political moves in the advancement of psychedelics: the creation of the Congressional Psychedelics Advancing Clinical Treatments (PACT) Caucus (led by Representatives Lou Correa (D-CA) and Jack Bergman (R-MI)), and the filing of the Breakthrough Therapies Act by Senators Cory Booker (D-NJ) and Rand Paul (R-KY).
And they talk about the story of Jim Harris overcoming paralyzation through psilocybin; NICE (National Institute for Health and Care Excellence) determining that Esketamine is not cost-effective; new progress in Germany and Finland; MDMA-assisted therapy (and other psychedelics) showing alleviation of chronic pain; a ramp up in LSD research for Alzheimer’s studies; and more.
Plus, we hear a bit of Alexa’s story, wish Joe and Johanna happy birthdays, and talk about what’s most immediate in the PT world: Early Bird pricing ending today for our first conference, Convergence (use code PTINSIDER10 for a 10% discount!), and the next round of Navigating Psychedelics launching next week.
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
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.
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.
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.
An NYU psilocybin depression study participant discovers an unforeseen application for psychedelics: the treatment of chronic pain. Part 1 of the series: Psychedelics and Chronic Pain.
Everything Worked, but Nothing Lasted
In the fall of 2020, I was living a pretty successful and happy life – on paper. I had co-founded a very popular, leading-edge CrossFit gym in NYC; one of the first in the world. I held multiple advanced certifications in applied neurophysiology through Z-Health, helping clients with challenging pain and performance issues. As an early adopter of kettlebell training, I became a nationally top-reviewed instructor and trained Team 6 Navy SEALs, astronauts, pro athletes, wounded veterans, and members of the FBI, NYPD, NYFD, and ROTC. I was featured in Men’s Fitness, the NY Times Sunday Routine, and USA Today. I had 30 years in the pain & performance field, training and teaching at a high level, and was becoming widely known for helping people with difficult mobility problems or chronic pain, using unique methods from the leading edge of neurological rehabilitation. On top of all of that, I was 17 years sober.
However, not all that glitters is gold. A now ex-business partner was committing a Ponzi scheme to the tune of millions, and his case followed him like a shadow, turning my life’s passion into an emotionally and financially toxic nightmare that economically devastated my family. My best friend, Kirk MacLeod, who I had completely rehabbed from chemo & cancer surgery, died six months after being declared in remission. My first son had developed undiagnosed GERD and couldn’t sleep more than an hour and half at a time, which meant my wife and I slept even less.
Unsurprisingly, my episodic depression returned after more than a decade and a half, and I was now increasingly treatment-resistant; unresponsive to psychiatric drugs that had previously worked. All my pain neuromodulation interventions that worked on my clients no longer worked for me, and I had developed chronic pain myself.
I share all my background here to demonstrate that I was not under-resourced in either knowledge, networks, or diversity of approaches, practice, or experiences. I poured over all my certification materials looking for anything I had missed, but had fallen into an increasingly deeper recovery hole; everything worked, but nothing lasted. I was hitting a new bottom in my life, deeply sinking into the midst of an increasingly treatment-resistant depression episode that had likely been ongoing for five years.
But then I became aware of ongoing studies on psilocybin for depression happening locally in NYC. I had experienced a few high-dose psychedelic sessions nearly a quarter century ago and had been an avid Terence McKenna fan (even speaking with him directly after a lecture in Seattle), but I had never taken psychedelics therapeutically, and my recreational interest had effectively vanished once I became sober from alcohol. Intrigued, I connected with the local clinical research coordinator, Leila Ghazhal, at the NYU for the clinical trial of Psilocybin for Major Depressive Disorder study (sponsored by the Usona Institute), and took all the online and over-the-phone assessments, passing them easily. The primary investigator (PI) on my study was Dr. Stephen Ross, who had been leading psychedelic research at NYU for more than a decade. Amazingly, I made it into the trial within a month and a half, learning that I’d actually beat out 8500 other applicants for just 100 spots nationwide.
Trying Not to Hope
When I first entered the trial, I was in a state of denial about how severe my depression was, but once I took the MADRS assessment, there was no avoiding that I had moderate to severe depression with suicidal ideation.
I remember a specific moment very well during this process, when I was finally cleared to enter the study and the study coordinator was speaking with me about the results of my assessment and my upcoming participation. I asked what would happen if I didn’t receive psilocybin during my session, and he reassured me that they would not just drop me off in the middle of the ocean to dog paddle – that there were other interventions and studies available and they would be sure to find me something, but there was a good chance I would receive psilocybin and hopefully get some good results. At this point, my mask cracked a little bit and some protective cynicism came out, and I quipped with a bit of a shrug: “Well, we’ll see.” I hadn’t meant it to be dismissive or sarcastic but it came out that way, and the conversational atmosphere rapidly shifted. He looked right at me and suddenly he wasn’t the primary investigator anymore, lost in the myriad details and logistics of a very involved study. Now he was the deeply experienced clinician and therapist, and, having heard something within the tone of my voice, dropped all the way in and asked softly: “What’s going on behind that, Court?” Suddenly, all the masking dropped and there was no more place to hide because I was so, so tired at this point, and had been waiting for this moment. In and out of therapy for years, dozens if not 100 self-help books, so many modalities, so many somatic systems, and here I was with a chance for something new to help me. When I realized why there was cynicism behind my statement, my voice cracked, I started crying, and I answered him: “Trying not to hope.”
The one glimmer of hope I did have was reading a 2018 paper by lead author Calvin Ly describing psychedelics’ neuroplastic activity in the prefrontal cortex. As someone who had studied the neurology of pain for years, this was revelatory. Many pain conditions are, in fact, nociplastic or noxious conditions arising out of the central nervous system (CNS); there’s no more injury or damage if there ever was, but your CNS is still continuing to put out a maladaptive alarm signal that is perceived as pain. So learning that psilocybin was creating actual structural change within my cortex – not “just” psychological change – was completely astonishing.
My dosing date was on March 5, 2020, and I remember looking down at the capsule sitting in the cup, saying to it: “I really hope that’s you.” I was terrified inwardly that I would receive the placebo, that I wouldn’t respond to the psilocybin, or that it would only work just a little bit, only for its effects to slowly fade. But within half an hour, there was no denying that I had received psilocybin, and I earnestly pursued all the procedures everyone on my care team at NYU had worked with me on for weeks in preparation for this day.
I was genuinely shocked at the sheer volume of psychological material from my childhood and early adulthood that came up. I had profound transpersonal experiences and healing, revisiting instances that were pivotal in my childhood. I had an encounter with the first woman I had ever loved, who had committed suicide three years after we had broken up. Her death had caused a profound grief in me that drove my drinking for a decade after. I thought I had released the majority of my grief around her once I got sober, but clearly, there was so much more to heal that had been deeply suppressed as I tried to move forward with my life.
Reset, Renewed, and Reborn
The biggest shock of all, though, was waiting for me at the end of the day when one of my facilitators casually pitched a seemingly routine question while closely watching me out of the corner of his eye: “So, how do you feel?” Without thinking, I reflexively replied, “Good,” but then, just as reflexively, scanned more deeply inward, and in a sudden rush, realized my depression was completely gone – not just better, but vanquished, exclaiming: “Good! That fast? Are you fucking kidding me, that fast? Is it gone already?”
It felt as if a huge mass had been surgically removed from me or as if an entire continent within my interior was now suddenly revealed. No matter how many times you read the word “remission” and the percentages behind it in scientific studies, very little will prepare you for the shocking reality of it. The contrast between before and after was profound. All of the iterative rumination was gone, and it took no effort for that to happen. And it only seemed to strengthen as the days passed. Miraculously, all suicidal thoughts ceased on that day and never returned.
Shockingly, only ten days after my dosing session, NYC went into a complete pandemic lockdown, my entire industry closed, and my two young boys were now at home with me 24/7, tele-learning. I cannot imagine what 2020 would have been like for me if I had received the placebo. It’s almost unimaginable.
But here is where the story takes an even more profound and impactful turn. During the session, my leg started intensely tremoring/spasming. I had been evaluated for musculoskeletal pain and dysfunction that I had acquired through a host of injuries over the years of my performance career, and in fact, had just been in the doctor’s office a few months earlier trying to determine if I had arthritis or something worse. But right there in the session room, I started having a neurological revision, with my muscles and nerves in my right inner thigh firing in an effort to recalibrate the sensory and motor inputs and outputs in that part of my kinetic chain. It was almost like a self-generated TENS unit (Transdermal Electromagnetic Nerve Stimulation, used to generate muscle contractions and neuromodulate pain signals with micro-electric pulses) getting my leg back online by creating intense motor activity in the muscles of my thigh.
While I partially understood what had happened, I was understandably beyond eager to learn more, and to see where else this realization could take me: Why did this work so well? Has our understanding of chronic pain been wrong? And if psychedelics are the answer, what does treating chronic pain with psychedelics actually look like?
This is part 1 of a 2-part piece and part of a larger series on chronic pain and psychedelics. In part 2, I will dive into the research around remapping and mirror box therapy, and why my psychedelic experience seemed to be so effective.
Future articles will focus on:What is pain and what causes chronic pain, old assumptions vs. new science, 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.
In this Veteran’s Day episode, Joe checks in with two members of the Heroic Hearts Project: Founder and President, Jesse Gould, and Chief of Operations, Zach Riggle.
Heroic Hearts’ mission is to create a healing community that helps veterans suffering from military trauma recover and thrive through helping them gain access to psychedelic treatments, professional coaching, and ongoing peer support – and we’re always happy to have them on the podcast to remind listeners about the extremely important work they do.
Among other projects, they are currently running several studies: psilocybin for gold star wives (spouses of fallen soldiers), ayahuasca for combat veterans, and ibogaine for special operations veterans through the University of Texas at Austin Dell Medical School’s Center for Psychedelic Research & Therapy; a study with the University of Georgia on personality change through psychedelics; a gut microbiome study with University of Colorado Boulder; and a psilocybin for head trauma study through Imperial College London. And today, they released the short film, “It’s Time – A Documentary of Veterans and Pro Athletes Seeking Healing Through Psychedelics.”
Gould and Riggle discuss the growth in interest and acceptance in psychedelics they’ve seen over the last few years; the importance of people telling their stories; relative trauma and how people too often wait to seek help; how trauma isn’t always due to a single event; Colorado’s Proposition 122 (which passed!); the need to have standard measurements in psychedelic studies; and how people who go through trauma together can heal together.
“At what point do we ask for help? I think, just as a society, we feel like things have to be in full-on crisis before we need to seek some sort of assistance. And we want to put [it] out there that that doesn’t have to be the case – that if you’re able to look at your life and realize that there may be some areas where things could improve and you might need some help in improving them, then don’t be afraid to reach out, because we’re not going to turn you away.” -Zach
“In the standard medical world, the physicians [or] the psychologists are looking at that qualifying incident and trying to heal that, trying to address that. And there’s some things that are pretty effective …but they’re working largely on that single incident, and ignoring all the other things that may have happened over time. And that’s where psychedelics can be so beneficial, is that they address that whole issue with a full system reset.” -Zach
“You take a population that largely (due to their illness) has been isolating, pushing everyone away, and just sitting back and looking at how amazing everyone else’s life is while theirs continues to deteriorate. Well, we plug them back into a community, bring them in, and help them to heal together. That’s a powerful thing to realize: that communities that were traumatized together; they heal better together.” -Zach
In this episode, Joe invites Court Wing to co-host, interviewing two members of UC San Diego’s Psychedelics and Health Research Initiative (PHRI): Joel Castellanos, MD (Associate Medical Director of PHRI and board-certified physical medicine and rehabilitation and pain medicine physician), and Timothy Furnish, MD (Medical Director of PHRI and Associate Clinical Professor of Anesthesiology and Pain Medicine).
As one of the early participants of a psilocybin-for-depression trial in NYC, Court Wing (of REMAP Therapeutics) discovered that immediately after the session, his chronic pain had miraculously gone away. He began researching how psychedelics could be used (with or without other therapies) to continue the alleviation of pain psychedelics had brought him. Through the Psychedelics and Health Research Initiative, Drs. Castellanos and Furnish are following that that same road, and are currently recruiting for a randomized controlled trial on psilocybin for phantom limb pain.
They talk about the relationship between the mind and chronic pain: how people confuse pain with the simple act of nerves firing, but how it’s so much more. And they discuss how pain can become part of one’s identity (and how the Default Mode Network could be contributing); how physical therapy is related to neuroplasticity; mirror box therapy; microdosing for chronic pain; the unusual nature of phantom limb pain; and where the mystical psychedelic experience may come into play. If this topic is as fascinating to you as it is to us, stay tuned – we will be featuring much more on chronic pain and psychedelics, including a blog series from Court Wing coming soon.
“One of the things that may be unique about or interesting about chronic pain is that the longer it goes on, the more people start seeing pain as a part of their identity and that Default Mode Network is probably playing a role in that. And it’s possible that something like psychedelics could open up the possibility of changing that internal story so that pain is no longer so much a part of one’s identity.” -Tim “I think that people oftentimes confuse pain with simply nerves firing. …[But] there is this rich interplay between the way we think about pain, the way we perceive pain, and how we feel about it.” -Tim “When you’re not really dealing with chronic or severe pain on a daily basis, it’s really hard to think about how life-changing that is or can be.” -Joel
“When we hear things like ‘It’s only just in your head,’ I don’t think people quite get [that] the head can be a scary place to be trapped sometimes.” -Court
In this episode, Joe interviews the Co-Founders of Tesselate Therapeutics: Dr. Rochelle Hines, Ph.D. (also the CEO and an Associate Professor at UNLV), and Dr. Dustin Hines, Ph.D. (the CSO as well as an Assistant Professor at UNLV).
While Tesselate’s primary objective is the development of novel psychedelic molecules, the Hines’ work goes much deeper than that, as they are researching the ways the brain communicates with itself and other parts of the body: how neurotransmitter systems interact, why synaptic partners find each other, and how certain substances may be able to modulate the actions of specific receptors. They are exclusively studying phenethylamines and using EEG to isolate signatures that could help predict the outcome of a therapy session. Additionally, they’re attempting to build a “tripnogram,” modeled after the hypnogram that explains the stages of sleep.
They talk about the reductionist base of neuroscience; the biodiversity in human populations and how heterogeneous depression can be; the reliability of the head twitch model; the structure of the cerebral cortex; neuroplasticity; the price of bringing new drugs to the FDA and the strategy of “failing fast,” and much more. You’ll likely learn a lot from this one, especially if terms like polypharmacy, laminar, ocular dominance columns, synaptic pruning, and “psychedelicitivity” (thanks for that one, Joe!) are new to you.
“I’m really fascinated by these connections that cells form with one another in the brain. And I’m really fascinated by how they form these partnerships so reliably, and all the right equipment gets there. And generally under typical conditions, we have this really high fidelity system so that [a] neurotransmitter gets released, and the right receptors are there to receive it, and the signal gets passed on. That always struck me as just this incredibly cosmic process. How do we make it right all the time, hundreds of thousands of times during development?” -Rochelle “The average drug that gets into the clinic costs about 3 billion. And most of that cost is racked up from failures that get pushed along, pushed along, make it into clinical, a lot of money goes into them, and then they ultimately fail. So I think a big strategy now is to see how quickly you can get something to fail, because then you’ll save yourself some time and money in the long run.” -Rochelle “If you want the answer, you should listen to everyone. You should be [a] skeptic, but you should listen to everyone.”-Dustin “I’m not at the stage where I think this is our last hope; I think there’s other hopes. But I see a revolution here. I really do, because it’s impacting the basic science that we’re doing also. People need this. People deserve it.” -Dustin
In this episode, recorded in-person at the recent From Research to Reality summit, David interviews one of the more well-known figures in the psychedelic space (who somehow hasn’t been on the show yet), David Nutt: Psychiatrist, Founder and Chief Scientific Officer at Drug Science, Chief Research Officer at Awakn Life Sciences, and Edmund J. Safra Professor of Neuropsychopharmacology in the Division of Brain Science, Dept of Medicine, Imperial College London.
At Awakn Life Sciences, amongst other projects, Nutt is working to set up clinics for legal psychedelic therapy (so just ketamine for now), and, after a successful study on MDMA in the treatment of alcohol use disorder, he’s doing something nobody has really done before in seeing if improvements can be made to MDMA. He tells the story of when he was fired as chair of the Advisory Council on the Misuse of Drugs due to telling the truth about the differences in harm between alcohol, tobacco, and “bad” drugs like LSD and cocaine, which led to the birth of Drug Science (and embracing the truth about drugs even more).
He covers a lot of ground in this episode: how serotonin seems to affect the default mode network; glutamate, cortexes, and the flexibility in the human brain; Robin Carhart-Harris’ “Trial of Psilocybin versus Escitalopram for Depression” study and the realization that psychedelics were doing something different in the brain; Measure 109 and the importance of how Oregon establishes a new paradigm around legal mushrooms; drug hysteria in the US and UK and how drastically that differs from Portugal’s incredibly successful approach to drugs; why real world evidence is the core of science; and why psychedelics seem best at disrupting internalizing disorders.
“The reality is that the psychedelic impact on depression has been so powerful, it’s changed the whole narrative about how we think about depression. Our one study in [treatment]-resistant depression spawned 40 companies now [that] are working on psilocybin for depression, which is amazing. …It’s been a spark to this amazing expansion. Why? Because for the last 40 years, there’s not been any innovation in terms of mechanisms in treating depression, ever. All the drugs we have today are essentially safer derivatives of the drugs we invented in the 1950s. So this is a new approach, and that’s really, really exciting.” “We’ve got to get our politicians, our policymakers to admit that these drugs should never, ever have been put in Schedule I. They were put in Schedule I [because] we said they were ‘very harmful’ (which they’re not), and they have no medical value (which they do), and it’s actually immoral now, reprehensible that politicians could not see that.”
“They just said, ‘Let’s try a different approach. Let’s try decriminalization and let’s treat drug addicts as human beings and help them get off the addiction rather than put them in prison.’ And that’s been one of the greatest success stories in the history of drug interventions. In the 15 years we have data since the Portuguese experiment was instigated, the Portuguese have reduced opiate deaths to one third of what they were before. In the same 15 years in Britain, using prohibitionist policies, we’ve doubled our deaths from opiates. And that, frankly, is an insult to humanity that we’ve pursued policies which we know are actually killing people.” “Real world evidence is the core of medicine.”
David Nutt is a psychiatrist and the Edmund J. Safra Professor of Neuropsychopharmacology in the Division of Brain Science, Dept of Medicine, Imperial College London. There, he uses a range of brain imaging techniques to explore the causes of addiction and other psychiatric disorders and to search for new treatments. He has published over 400 original research papers, a similar number of reviews and books chapters, eight government reports on drugs, and 36 books, including one for the general public, Drugs: Without The Hot Air, that won the Transmission Prize in 2014.
In this episode, Joe interviews Miriam Volat, MS and T. Cody Swift, MFT; Co-Directors of The Riverstyx Foundation: a charitable organization focused on funding psychedelic research and ensuring integrity and reciprocity in the psychedelic space.
Volat and Swift cover a ton of ground in this conversation; from philanthropy, research, and the hurdles of funding in the psychedelic space, to the unintended consequences of the quest for holistic healing (e.g.: iboga & peyote over-harvesting), to plant medicine biocultures and the Good Friday Experiment, to changing our relationship with waste with green funerals. They discuss psilocybin’s ability to ease distress related to cancer and death, toad conservation efforts by the Yaqui; the true sacredness of peyote amongst Native Americans, and Indigenous-led structures for future biotechnology companies.
They talk about the ever-present reality (and ripple effect) of the decimation of the Native American way of life, and break down the critical considerations for the survival of Indigenous culture; looking at the Nagoya Protocol and how sustainable harvesting structures, better relationships with the land and surrounding communities, benefit-sharing, and, most importantly, partnerships with Indigenous leaders can help to ensure a culturally respectful and informed future for the psychedelic field.
“Sometimes in the psychedelic space, people are just focused on this organism or brew or something, and that’s the focus. But really, for thousands of years, those things aren’t separated from a way of life or a cultural container that guides many things through a territory, through language. So that’s why we’re really using that term, ‘bioculture,’ so as not to dissect these things into little parts that are actually very interconnected.” -Miriam
“If we arrive in a psychedelic future 20, 30, 50 years from now and we haven’t done our work to empower those communities to survive and stay strong and stay rooted in their own traditions, we’ll be at the same place of not knowing where we came from: What were the original ways of holding these medicines? What were the original songs? What were the original protocols? And once again, [that] will have been lost. And that’s not healing, that’s more disconnection.” -Cody
“White cultures, especially on the West coast; we’re blessed with …so many amazing medicines from MDMA and LSD and ayahuasca and 2C-B, and all the 2Cs, and 5-MeO, and just– it’s incredible. And the Native American communities have, at least in this country, they have peyote. They do not regard it [as] a psychedelic. This is a sacred, sacred plant medicine. And they have no interest (from all the leadership that we’ve talked to); absolutely no interest [in other drugs]. It would be a sacrilege to consider the other pathways. All they have is Peyote. We really need to keep that in mind.” -Cody
Miriam Volat, MS, serves as Co-Director with Cody Swift of the Riverstyx Foundation, Interim Executive Director of the Indigenous Peyote Conservation Initiative, Director of the Indigenous Medicine Conservation Fund, and she is on the Board of Directors of MAPS Public Benefit Corporation. The RiverStyx team undertakes deeply engaged relational philanthropy supporting social justice; ethical and innovative integration of the psychedelic movement into broader society; addressing mental, spiritual, and ecological crises through biocultural responsibility; and respectful allyship with Indigenous traditional knowledge holders. Miriam Volat works personally and professionally to promote health in all systems. Her background is as a complex systems-facilitator, soil scientist, educator, and community organizer. Her work aims to increase broad-based community and ecological resilience through supporting high leverage initiatives at the intersection of biological, socio-cultural, and psycho-spiritual diversity.
About T. Cody Swift, MFT
T. Cody Swift, MFT is a philanthropist, qualitative researcher, and licensed psychotherapist. Through the Riverstyx Foundation, he has collaborated extensively on projects addressing healthy society through working with stigmatized populations and issues – those most likely to be overlooked for funding and support. Since 2007, he has helped to fund over 20 psychedelic research trials. He has served as a therapist-guide in the Johns Hopkins psilocybin and cancer-anxiety study, and has conducted dozens of qualitative interviews with study subjects into the subjective aspects of their experiences with psilocybin and MDMA. He has a passion for reinvigorating religious traditions through psychedelics, and has also worked for over 7 years supporting Indigenous communities in the conservation of their sacred plant medicines, such as the Native American Church in the preservation of Peyote and the Indigenous Medicine Conservation Fund.
In this episode of the podcast, Joe interviews the CEO of Mindset Pharma, James Lanthier.
Mindset Pharma is a 3-year old biotechnology company built on discovering and developing new psychedelic compounds to be used as medicine for a variety of indications. While the efficacy of the psychedelics we know can’t be denied, the goal of science is to improve, and Lanthier believes optimizing these drugs will make them safer, more predictable, and more palatable for a far greater portion of the population. He envisions these new molecules leading to a future of highly personalized medicine, where people who would never eat a mushroom would likely take a related drug prescribed by their doctor.
Lanthier discusses what’s going on at Mindset Pharma; why patents alone will not be sufficient protection from competition; the long game of biotech, psychedelic stocks, and overreaction to slow growth; the Nagoya protocol; mescaline; the need for big pharma and capitalism; the art of formulation; and how microdosing could soon be revolutionized.
“I had some fairly well-known psychedelic investors say to me, ‘You’re just building a better mousetrap.’ And my reaction was: ‘Well, that’s the march of science. That’s what science is trying to do.’ Take the example of what the German scientist [Felix Hoffman] did in the nineteenth century to go from the bark of the willow tree, eventually going through a whole bunch of intermediate chemical steps to eventually get to Aspirin. Science hopefully tries to make things better, and that’s what we’re trying to do.”
“Big pharma has skipped right past psilocybin. Why? In my view, it would be because of the lack of strong IP rights. They’ve gone right to second and third generation drugs because they’ve made the assessment that even if you own the strongest IP in the psilocybin space, you’re still quite exposed, ultimately, to competition.”
“I think if there’s a future where you have relatively low-priced classic drugs potentially available alongside more optimized, specific drugs that have the full support of the medical community, that would be a great place to get to, I think – really great place to get to. And I think we only really get there with the machinery of capitalism moving forward.”
James Lanthier is the CEO of Mindset Pharma, and is a seasoned technology executive with strong expertise in corporate finance, public markets and M&A. Most recently, Mr. Lanthier was a co-founder and CEO of Future Fertility, an innovative early stage developer of AI applications for human infertility. As a C-Suite executive, Mr. Lanthier has assisted in the growth and successful exit of numerous technology-enabled businesses through the public markets, including Mood Media, the world’s largest in-store media provider, and Fun Technologies, a pioneer in online casual games.
Sensorium Therapeutics was created by professionals from Massachusetts General Hospital who started to wonder: With so many plants with rich, ethnobotanical history, what if we looked to those plants for answers instead of just analyzing the trendy psychedelics so many are focused on now? Why not fully research what already has established efficacy? Their goal is to have the largest collection of psychoactive plants (which they’re calling their Neuro-Natural Library), and use machine learning to figure out exactly which molecules are doing what, to then synthesize new drugs that are safe and effective; eventually bringing these new compounds through the FDA approval process.
Simon talks about how so much of what we know to be effective and beneficial is based on assumptions or best guesses, and while that doesn’t discredit very real benefits, it does beg the question: Is this all optimized as best as it could be?
He also discusses how recent advances in neuroscience and technology are catalyzing molecular research; how we can learn about other mental health indications from studying rumination; the benefits and challenges of nutraceuticals; geopolitical conflict resolution; organoids; the necessity of the FDA; why “them” can be a very dangerous word; the challenges of benzodiazepines; Burning Man; and the problem with people needing to be treatment-resistant or seriously ill to gain access to psychedelics. He hopes that what Sensorium Therapeutics learns over the coming years will help bring better medicines to more people.
“The goal here is to look at the 500+ plants and fungi and what their component elements are (what’s actually driving that efficacy, or signals of efficacy; signals that they make a difference in a high throughput way), to really assemble massive data. Then, we’re using machine learning to distill all that down to: ‘Alright, we have all this cool information; what does it mean? What does it tell us? And how do we convert that into a drug that helps people?’” “We operate under a lot of assumptions that are based on experience, but are not based on any controls on the experience. Even something basic like the assumption [that] music and playlists are really important – they’ve been used and they seem to work. We don’t really know if that’s true. …I’m not saying that music and a controlled playlist isn’t absolutely the best answer, but it seems like it’s something we really ought to know an answer to, rather than make assumptions.” “If I would have told someone ten years ago: “No, no, we’re going to have this company, Sensorium, and it is going to be able to, in a 384-well plate, take a look at groups of neurons growing, and we’ll have sophisticated microscopy to take a look at it, and we’ll be able to do it at a high throughput basis, and we can reliably do it and replicate,’ the question would have been: ‘Alright, what other drugs are you taking? That’s not going to [happen].’ [But] we’re there.”
“Even questions as to how important the psychedelic effect is to efficacy; the assumption tends to be that somehow or another, the intensity of the experience is related to the efficacy. …There are people now who are looking at: ‘What if you removed the psychedelic effect from psychedelics? Are you still getting the same neuroplasticity, neurogenesis, and much of the effect?’ I don’t know the answer, but I think those that are ideologues on either side of that [are] silly. Let’s figure it out. …Why don’t we find the answer rather than argue for whatever our position is?”