A cast will help a broken bone to heal, a tourniquet will help to stop the bleeding in a limb, an aspirin will alleviate a headache, time (and ice cream) will help to heal a broken heart. But how do you heal a broken mind? Post Traumatic Stress Disorder (PTSD) is but one of the psychiatric indications with inadequate, frequently ineffective treatment protocols, that has been in the psychedelic spotlight.

There’s no shortage of heartbreaking stories about men and women who have dedicated their lives to the service of their countries and endured unfathomable trauma. Add to this population the other sources of PTSD like car accidents, witnessing or experiencing violence – or even the threat of violence, sustained stress in traumatic situations (hello, COVID frontline workers – I’m looking at you), and you have an explosion in an untreated or treatment refractory population. 

Enter psychedelics.

In this episode, we are privileged to hear from Jesse Gould, a former Army Ranger, and Keith Abraham, a former member of the UK’s Parachute Regiment. These gentlemen both served their countries in combat tours in the Middle East and have suffered the invisible injuries of war. Each found his way to ayahuasca as a means of resolving his PTSD when pharmacological, talk therapy, and wholistic approaches failed him. Ayahuasca healed them when nothing else could; now, through their connected organizations – Heroic Hearts Project and Heroic Hearts Project UK – they are helping other veterans gain access to this highly promising combination therapy of psychedelics and psychiatry in what is now known as psychedelic-assisted psychotherapy.

In addition, we explore the story of how MDMA assisted psychotherapy, pioneered by MAPS‘ pivotal trials were done in an interview with Dr. Jennifer Mitchell 

This episode will take you into the personal stories, the science, the history, the future, and the promise of psychedelic-assisted psychotherapy for PTSD. Grab a tissue, you’re going to need it. (And then go donate to Heroic Hearts Project so that we can help more people heal.) 

Transcripts

As the trails of RPGs  lit up the deserted bazaar in a southern town of Afghanistan, the commanding officer thought that lance corporal Bernie had stepped on an explosive. The three-day fight to reclaim this Taliban strong-hold was fierce; the blood and the bullets were relentless. Casualties and life-altering injuries were the norm and returning to base in once piece was the rarity. 

The squad had made significant advances in fighting the enemy back, but they now found themselves stuck under interminable and heavy fire. They had one wounded man and their location was perilous. They were on a narrow crossroad with insurgents hiding in an orchard ahead of them, buildings with possible snipers behind them, and a patch of recently turned earth in the middle. All of the soldiers knew that the patch of disturbed dirt was just as likely to be laced with IEDs as anything else. The Commanding Officer ordered his troops to advance to the cover of a mud wall and irrigation ditch. The bullets seemed to gain speed, momentum, and frequency as the last light of the day faded.

Jacobs, an embedded reporter, would write in her journal “That’s when I realized there was a casualty and saw the injured Marine, about 10 yards from where I’d stood. For the second time in my life, I watched a Marine lose his. He was hit with the RPG which blew off one of his legs and badly mangled the other. … I hadn’t seen it happen, just heard the explosion. I hit the ground and lay as flat as I could and shot what I could of the scene.”

Two Marines stood over their injured brother. Their protective stance gave cover to Bernie but left them exposed. Things were not looking good. The first tourniquet on the leg broke. They applied another. There wasn’t much to work with in terms of supplies or the leg.

The screaming was unbearable. The constant sound of human anguish can never be unheard and can never be forgotten. Troops belly crawled over rocks and under bullets to drag Bernie to the MRAP – a mine-resistant armored vehicle that accompanied the patrol. 

“You’re doing fine, Bernie. You’re gonna make it. You might have a limp,” they joked “But you’re gonna make it. We got you. Stay with us.” 

Connor, a Marine on his third combat tour, held Bernie’s head in his hands. He had been here before and knew what the last breaths that a man takes felt like. The pain in Bernie’s legs suddenly faded. His breath grew shallow and incomplete. He was cold. He was scared, but he was not alone. His brother would never leave him behind. No Marine ever would. Bernie’s last breath would live in Connor’s mind long after the bullets subsided. Long after he returned home, long after he tried to reclaim his civilian life. He would never surrender. He would never forget.

This is PsychedeRx. A SKRAPS original podcast exploring the therapeutic use of Psychedelics. An enthralling story of an improbable drug class, as old as humankind itself, banished into exile yet comes back soaring like a Phoenix from the ashes,  to save mankind’s affliction with mental health disorders. 

< INTRO MUSIC> 

How do you mend a broken heart? There seem to be endless tv shows, movies, advice columns, memes, and more about this subject – enough to fill its very own data lake. But how do you heal a broken mind?

Post traumatic stress disorder, or PTSD can happen to anyone at any time. It can be the result of nearly any traumatic experience – such as war or combat, rape, natural disasters, serious accidents, witnessing or experiencing violence, or even the threat of death, sexual violence or injury. 

PTSD can be the result of acute instances – like a car accident – or chronic events – like physicians nurses working the front lines through the COVID crisis. 

Feelings of sadness, fear, rage, tension, and detachment are frequent manifestations even long after the event that caused the PTSD is over. Other manifestations of PTSD include flashbacks, nightmares, intense distress, physical pain, sweating, nausea, panic, ease to anger, hyper vigilance, sleep disturbance, irritability, aggression, difficulties concentrating, anxiety and more. 

Do you remember our discussion of the croc brain in episode one? It’s the brain telling you when to pay attention to a possible threat and when to take action. In the case of PTSD, the body continues to produce cortisol and adrenaline long after the danger has passed. And the amygdala, which is the region of the brain that processes the emotional response, trigger that defensive response and over time contributes to the symptoms of PTSD especially during any triggers of sight or sound that trigger memories of the trauma, triggering hyper vigilance. 

While there is a growing realization of PTSD now, would it surprise you if we said the groundwork for understanding PTSD was laid in the 1800s – around the same time that the conflicts between Native Americans and white settlers took place? The pioneer in this area was Jean Martin Charcot, a French neurologist, dubbed by many of his time as the “Napoleon of Neuroses.”  If you are a neurology speciality inclined., Many medical students would know Dr. Charcot from his descriptions of various phenomena in the field of medicine like Charcot-Marie-Tooth Syndrome or Charcot’s disease which later was called Lou Gehrig’s disease. Or if you have brushed up on basic gastroenterology during medicine curriculum, Charcot’s triad described in gall bladder infection, or his description of another triad in neurology to help diagnose multiple sclerosis. So Charcot was a very important figure in medicine. 

Charcot was a physician at Salpetiere hospital where he worked with traumatized women.  Through hypnosis in one of his most famous female patient with hysteria, Louise Augustine Gleizies , Charcot demonstrated that hysterical symptoms characterised by sudden paralysis, amnesia, sensory loss and in some extreme cases, convulsions were due to psychological symptoms and not physiological. 

 He noted that traumatic events could induce a hypnotic state in his patients and was the first to “describe both the problems of suggestibility in these patients, and the fact that hysterical attacks are dissociative problems — the results of having endured unbearable experiences”. In fact, this is the first time we are talking of dissociative symptoms. It refers to the manner in which the subject who has experienced trauma dissociates themselves from their current surroundings and gets transported back to the original trauma. 

In fact, his thoughts ran contrary to the prevalent thinking of the time. In fact, the way physicians approached hysteria itself was by hysterectomy. The simple reason for performing hysterectomy in the worst cases of hysteria is due to the opinion that female hormones triggered these emotional responses. 

Even Freud became a student of Charcot’s philosophy on trauma and called the presence of dissociation found in patients with hysteria as a splitting of consciousness, which he termed hypnoid hysteria. But the world was about to change their view of hysteria or trauma in general. 

If you are a fan of war movies like me, or a huge fan of Steven Spielberg, or even the most recent Oscar nominated 1917, you would have noticed that most soldiers in world wars experienced “shell-shock” phenomenon which was observed at the time with symptoms of uncontrolled weeping, screaming, memory loss, physical paralysis and lack of responsiveness. These veterans after the world war took to substance abuse or alcohol abuse and many physicians blamed their poor moral character as the reason for the symptoms. But one physician, Abram Kardiner at the time, thought differently. Dr. Kardiner called it as he saw it – “the subject acts as if the original traumatic situation were still in existence and engages in protective devices which failed on the original occasion”.  We bring up Kardiner, because he was one of the first physicians who thought carefully about the choices he had to pursue in treating these shell-shocked veterans. He had to decide in treating these patients whether he should bring back traumatic memories into the patient’s consciousness or focus on stabilization. We will explore the results of both approaches in this episode. 

So, to recap,  the first treatments for  PTSD was via psychological first aid for world war 1 veterans and in Charcot’s case for women with sexual abuse and trauma, through hypnotherapy. 

Kardiner and his colleague Herbert Spiegel argued that the most powerful intervention against overwhelming terror was “the degree of relatedness between the soldier, his immediate fighting unit, and their leader” (Herman, 1992, p. 25). Consequently, treatment for traumatized soldiers during the Second World War focused on minimizing separation between these soldiers and their comrades and providing brief intervention methods such as hypnosis. Kardiner and Spiegel warned, however, that cathartic experiences and hypnosis by themselves, without consistent follow-up, were not sufficiently helpful and that unless the traumatic memories were integrated in consciousness the improvement would not last (Kardiner & Spiegel, 1947, cited in Herman, 1992). During World War II, psychiatrists reintroduced hypnosis as a treatment for trauma, and the U.S. Army instituted the use of “group stress debriefing” (Shalev & Ursano, 1990, cited in van der Kolk, Weisaeth, et al., 1996, p. 59).

But beyond sexual abuse or physical trauma experienced in civilian life, or by solidiers in a combat setting, the first realization that a tragic event could trigger PTSD came from another sad story in 1942, a year before Hoffman took his LSD laced bicycle trip. A fire broke out in a night club called Cocoanut Grove in Boston and it took the lives of 493 people with it. Dr. Lindemann, who treated a number of survivors , observed many common responses. After the initial sadness of losing a close friend or a relative in the club , combined with expression of guilt, disorganization and physical complaints like cramping, Lindemann made some key observations that pertains to our diagnosis. 

1. Identification of a stressful event that cannot be undone. 
2. The problem overtaxes the psychological resources with repeated memory recalls of the event. 
3. The situation is perceived as a danger or a threat to self or to the family or community. 
4. The crisis period which is characterised by tension which mounts to a peak, then falls 
5. And probably, more importantly, the crisis situation awakens unresolved key problems from near and distant past. 

So now, you can make a correlation to many symptoms felt by victims of war and other forms of trauma. 

On top of this physical trauma, there can be developmental trauma that is characterised by emotional or sexual abuse in children and this over time can lead to insufficent development of neuronal structures necessary to process information, regulate emotions and categorize experience. All of this leads to poor impulse controls, aggression, difficulty in interpersonal relationships, inability to concentrate and in some cases, poor academic performance. As a result, some of these subjects might take to substance abuse to regulate their emotional arousal, an effect observed and brought to light by Dr. Gabor Mate in Canada. 

Not everyone with PTSD is easily or officially diagnosed. But the DSM-5 Diagnostic Criteria for PTSD is a fairly easily administered self-check that can help point someone in the direction of help. The DSM-5 looks at the following:

1. Exposure to actual or threatened death, serious injury, or sexual violence
2. The presence of one (or more) of the symptoms we mentioned a few moments ago, that are associated with the traumatic event or events, beginning after the trauma occurred
3. Persistent avoidance of stimuli associated with the traumatic event beginning after the even occurred as evidenced by avoidance of the distressing memories or avoidance of external reminders such as people, places, activities, etc.
4. Negative alterations in cognition and mood associated with the event
5. Marked alterations in arousal and reactivity associated with the traumatic event
6. Duration of the previously mentioned disturbances for longer than one month
7. The disturbance causes clinically significant distress or impairment in functioning
8. The disturbance is not attributable to substance misuse or other medical condition

But let’s just take the case of a soldier whose PTSD is caused by events in combat. Soldiers are trained to never let their guard down – to never surrender – to never give up.  As one combat veteran recently told me, hypervigilance in Iraq is what keeps you alive.”  Vigilance is as much a part of their protective gear as their bullet-proof vests. A state of readiness is constant. How are they treated currently? No marks for guessing the current standard of care – it’s with anti-depressants and talk therapy with psychologists. 

First, I’d like to acknowledge that we recognize there are many, many causes of PTSD and many groups seeking to help find new treatments and improve revising ones. Because we only have limited time with you, dear listeners, we’ve chosen to focus on the military population and on one organization of many that are advocating for this group and for new treatments. There has been sensational work done with non-veterans by the legendary, Dr. Gabor Mate and you can gather a lot about this from his two best sellers – “In the realm of hungry Ghosts: Close encounters with addiction” or “When the Body says No: The cost of hidden stress”. 

First, we would like to introduce to two outstanding gentlemen and veterans of the wars of Middle East. 

Keith Abraham, a former member of the Parachute Regiment, a combat unit in the UK and Jesse Gould, a former US Army Ranger. First, it is important to understand the stories of  Keith and Jesse and their journey. 

Jesse and Keith head up Heroic Hearts and Heroic Hearts UK respectively – two nonprofit organizations dedicated to helping veterans address their PTSD through psychedelic-assisted therapy. 

Keith and Jesse aren’t just servicemen and philanthropic-minded individuals. They both suffered from PTSD as a result of their time in service to their countries and both found help in some very unconventional ways that speak  volumes of how our healthcare systems and society work in the era of the “War on Drugs”. 

Here is Keith Abraham.

Keith Abraham:

I i’ve never labeled myself as actually having PTSD, even though I would say, it’s pretty clear. I have PTSD, but I definitely never had a diagnosis.

“So I was a member of the Parachute Regiment, which is a combat unit here in the UK. And is during my career, I had a wonderful career very rewarding career. During that career, I served in Iraq. And I also served in Afghanistan in 2008. And Iraq, was not really a combat campaign, by the time that I got there. Afghanistan really, really was. And so I came back home from Iraq, just feeling very positive about life in my career, and didn’t really experience anything overly difficult for me to deal with. But in Afghanistan is an entirely different situation. It descended into extreme violence, which I was trained for, we’re all trained for which something that I actually wanted as well at that point. But you got to be careful what you wish for in these sorts of roles. And it really, our area of operation actually became known as the mouth of hell. by a by the Taliban, we could hear them talking. And they would always refer to this to our area as the mouth of hell because it was so extremely violent. And from a British Armed Forces, ground forces perspective, our small little area of operation became the main effort of the whole brigade. And we also made use of international forces as well, it was that extreme we drew everyone sort of was drawn into it. And like I say, I can’t I signed up for that experience. We all did. We you wouldn’t join a combat unit unless you actually wanted combat. But it wasn’t To be honest, if I’m very honest, it wasn’t too long. Before I realized that it was more than I actually wanted. In my first contact with enemy forces to my very good friends died immediate. And that was my first experience of combat. And so shocking and overwhelming and traumatic because I had to deal we had to deal with their, their bodies. And they were very close friends. And and that was the first incident. And we had many of those incidences. And so I knew even while I was out there, though I was overwhelmed, and very tense, I was still able to perform a role. But I recognized that I was I was having to hold I was holding on. And so I still perform the role very well, but I was holding on. And so was very grateful. By the end of the tour, I was very happy to be going home. When I got home, I found myself really resentful of society, UK society, normal society. I saw them puttering around supermarkets and carrying on about their daily lives. And I felt really resentful of that, that they had no knowledge of the trauma i’d experienced. And that’s an unfair evaluation, of course, but it’s my perspective at the time. And I felt resentful, I was grieving the loss of many friends. And I was in shock. Because of that those experiences. And I suppose the skill that I didn’t really have was an ability to convey to express myself and to articulate what I’d experienced. Actually, that’s a very different, difficult thing to do. Anyway, even if you are articulate and warfighting experiences, that’s a hard thing to articulate. And I mentioned this because in the circle of loved ones, and people that cared about me, they obviously saw that I was struggling wanting to help. But they had no, you know, they could have no idea really. And so that was really frustrating. So I was resentful, I was angry, I was grieving, I was in shock. And I was frustrated, because I couldn’t tell people what I was experienced what I was suffering from an experiencing adequately. And so they couldn’t help me.” 

I don’t think that one can ever get used to hearing the traumatic stories of combat. But combat doesn’t seem to end when the battle is over. The conflict continues in the memories of our soldiers. 

Here is Jesse Gould and his post-combat experience of re-entering civilian life. 

Jesse Gould: 

“My name is Jesse Gould. I was an Army Ranger. And my time in service included three combat deployments to Afghanistan. When I got out of the military, I decided to adapt to civilian life, go into finance, that was my academic background. But around that time, a lot of issues, mental health issues really started to flare up. And I quickly came to see to be faced with the fact that there’s very limited options for people like me, in terms of actual comprehensive care and healing to get past these mental traumas. So I found myself in the situation where I was just really struggling with anxiety, depression, alcoholism, you know, I was diagnosed with PTSD, I assumed all sorts of other issues, undiagnosed, were also going on and just found myself in this situation life where I was just very unhappy, and more days are starting to become dark than light. 

And I just fortunately had the the warning signs go off in my brain that that wasn’t a sustainable formula. So I started looking at options. And again, I just kind of hit walls, the the VA had very limited options outside of medication. Everything else I tried to do holistically, just sort of had helpful aspects, but limited.”

Guess how they are treated. Here is Keith again. 

“And so I did seek professional help. I, I again, I see this as a very typical experience of many people, not just veterans, but we struggle with mental health, we go and see our GP, we’re in the UK or a physician. And we usually get the two options of talking therapies, and pharmaceutical assistance. So and I tried them, neither of them were very helpful for me, I’ll go into the reasons for that in a second. But talking about that ability to convey and to express myself adequately, that was actually one cause of the, at the breakdown of a very, very significant relationship for me. And when that broke down, that was kind of my my anchor to reality. And so I read, I struggled even more than I was grieving of an important the loss of an important relationship on top of everything else. So I was very depressed, anxious, still hyper alert of all of my surroundings, because that’s how you have to operate in Afghanistan, or in any combat environment. And so then, after I sought, professional help, the pharmaceuticals do not sit well in my system. They, they numbed me of all emotion. And I didn’t feel like it was worth living then. And that’s dangerous for me when I was already depressed if I didn’t think life was worth living. Because I couldn’t feel anything. It was almost no, it wasn’t almost it was more. I wanted to feel something and if I had to feel my trauma again, that was more important to me than feeling nothing. So I came off of them. I came like sertraline is why I was prescribed. They felt toxic in my body anyway. But emotionally It was very dangerous for me took me down a path of Have you had that that would have ended in suicide, I think even on the antidepressants themselves would have taken me to the root of suicide, which is doesn’t necessarily make sense. But that’s how I experienced it. “

Can we pause for a second here and take stock? The antidepressant market is projected to be over $28 billion – and is widely prescribed almost as the first choice medication.  Keith described how it numbed him of all emotions. On top of this a typical antidepressant medication or SSRIs (selective serotonin reuptake inhibitor) like Paxil, have other side effects that reads like a grocery list of untoward effects – sleepiness, drowsiness, tired feeling, nervousness, insomnia, dizziness, nausea, skin rash, headache, diarrhea, constipation, upset stomach, stomach pain, dry mouth, changes in appetite, abnormal ejaculation, impotence, decreased sex drive, difficulty having an orgasm, dry mouth, and weight loss. 

[Take an audible breath]

While I know that all sounds like fun, some of the more serious side effects of Zoloft include [read quickly]: rigid muscles, high fever, sweating, confusion, fast or uneven heartbeat, feeling you might pass out, agitation, hallucinations, overactive reflexes, tremors, vomiting, feeling unsteady, loss of coordination, trouble concentrating, memory problems, weakness, fainting, seizure, shallow breathing, or breathing that stops.

Yes, this definitely sounds like the vacation you need from your PTSD. And we’re not picking only on Zoloft. Paxil’s side effects are no less horrifying. With Paxil you can also add nasal irritation, yawning, and ringing in the ears – oh, and please call your doctor immediately if you are experiencing suicidal thoughts.

None of this sounds like a solution. So, what alternative treatments are there for PTSD? I’m glad you asked. 

The American Psychological Association has issued clinical practice guidelines strongly recommending four interventions for PTSD – all of which are variations of cognitive behavioral therapy or CBT. CBT is the frontline recommendation. Behind that are Cognitive Processing Therapy, Cognitive Therapy, and Prolonged Exposure. Riiiiight…. So – and I’m simplifying here – what we’re asking for is usually 12-16 sessions wherein we’re telling people to confront their fears and change their behavior. I don’t deny that this method is beneficial for many but it works less for veterans. Here is Keith Abraham again. 

“Yeah. And so I’m talking therapies, like I was saying about articulation and being able to express oneself. They’re very professional. And I know you don’t have to have corresponding life experiences to be a therapist. I understand that. But as veterans are notorious for these for this, and I’m no different. So I really struggled to, to form that working relationship. That’s so important. Actually is a big, there’s a massive amount of luck in that finding that relationship. I did find one in the end years later, I found one. In the end, I had 12 weeks with her, she was very helpful. But again, I always I see talking therapies as a management tool instead of a healing therapy. So they’re important. Talking therapies are important, but they’re limited. I knew it would never heal me. And I really needed healing. I couldn’t go on the way that I was going on, because I was spiraling downwards by that. And so I reached a point of pretty much hopelessness, because I recognized that talking therapies wasn’t going to wasn’t going to heal me, even though it was interesting and valuable. pharmaceuticals, I had no further interest, I gave them another go, just to make sure that I had the same experience again. And so I knew, I know there’s other options, that body based exercises, which I now I’m now a teacher of that are important, and very valuable in that thing. There are other therapeutic methods, of course, and I’ve tried the vast majority of them like hypnotherapy, sound therapy, lots. But for me, personally, none of them, I recognized that none of them on their own, or collectively, were actually gonna help me. “ 

The hopelessness and despair is something that I can only barely imagine. With the veteran population in particular, there is a taboo – a discomfort and reticence within the community to even ask for help. It’s important to note that while Jesse was diagnosed with PTSD, Keith was not. But an official diagnosis in these cases seems a little like asking Captain Obvious what’s the date of Cinco de Mayo. Both Jesse and Keith explored the recommended interventions for PTSD – pharmacological, talk therapy, and even holistic options. While they both ultimately found relief through a very unconventional path. Let’s hear from our two veterans – Keith Abraham first. . 

“ I heard about so because I was visibly struggling. While I was holding on before I was now visibly struggling externally, it was quite clear, my behavior changed. And it was clear to anyone that care to look. So a friend of mine in the US, she saw that and suggested that you know that there’s another option.  There is still hope, and hope is all I really need. We know it’s all most of us really need is a little bit of hope to just keep going. And so I didn’t do any research. I trust her implicitly. I would. I would always suggest people do their own research, of course. But I was so hopeless. I trusted her implicitly. I didn’t do any real research on iOS. I just told my boss, I’d left the military. And I was actually working for JPMorgan in London, told my boss I was going to take two weeks off, I flew out to Peru. And I had been put in contact with two local people, not not indigenous people, just local Peruvians in a city called tarapoto. And they very, very, very kindly gave me use of their hu t in the jungle. So I had to make my way by car from Terra portal to a place called Jota, which is a jungle town. And then from choosing tide to get onto a little boat and outboard motor boat up river further into the jungle for another hour or so. I got off a tiny little village where I didn’t know it at the time. But the shaman of that village, he would be my host.

So I had to carry all of my food and water with me as well. But I was I’d only been out in the military a year and a half. So carrying heavy equipment into the jungles and this is what I do anyway. So it’s kind of like good. I feel nature. Yeah, this is my nature is what I can do. This is my skill set. So that didn’t faze me at all. And so, I did have someone that checked in on me nearby. One, he was a cow farmer. He lived forever at river about 500 meters or so. Other than that, I was actually left to my own devices. There was a river next to the heart. So I just sat by the river I spend time in nature. And I was there for about 10 days and twice during that period, the shaman, he wanted already obviously told him that I was there at some point, he came up. And he brought this really dirty, it was an old Coca Cola bottle. And it was full of this look like mud from the outside, really disgusting. And he came up and he took out a shot glass and laid me down in the heart. So he was laying down with me, gave me a shot of this drink that was Iosco sang, started singing, and then everything changed. So that’s how I found myself there. Yeah, and that that is then when the catalyst kicked off.”

So what is this mud coloured liquid that handed to Keith. We do know that Ayahausca tea as it is referred to by the Western world is a brew of the two plants, which is rich in DMT or Di-methyl tryptamine. And where does this come from. It comes from a plant, called Psychotria Viridis or commonly referred to as the Chacruna plant, whose leaves are rich in di-methyl tryptamine.  But we told you in our last episode that DMT experience is very short lived and hence referred as “Businessman’s Lunch” in common parlance. 

So the indigenous people of South American through centuries of trial and error found that 

Another plant, Banisteriosis Caapi,  a woody vine that grows climbs and twines around a large tree. So the stems of Banisterosis Caapi can grow 24 inches in diameters and 100 m in length. 

Remember, our first two episodes on Mescaline, where discussed that the alkaloids present in San Pedro and Peyote, much like coffee and tea plants are made with a idea to either store water and nutrients for the plants, or to concentrate nutrients, and in some cases, to repel animals. 

Banisterosis Caapi vine, being a tropical vine has this amazing vascularised system that conducts water over large distances from the ground. So you can imagine how the plant and nature has devised the presence of these alkaloids to enable some of these functions. So the Banisterosis Caapi stems are rich inan alkaloid called harmine. Guess what the interesting property of Harmine is…It is a blocker of one enzyme subtype  called Mono-amine oxidase A , which is heavily involved in metabolism of serotonin and other adrenergic compounds in our body.  And if you stare at the structure of Harmine, for a few seconds, you will notice the similarity of the harmine molecule to the indole structure we spoke about, with a six carbon hexagonal benzene ring attached to a pentagonal ring with nitrogen at the vertex. There are other side chains, so the harmine alkaloid is a beta-carboline. I think that’s enough chemistry for now. 

It prolongs the amount of time that the psychedelic molecule can be present in the body. 

Over the course of this podcast, we’ve had several inquiries about what a psychedelic trip is like. The answer, as with many good things, is – it’s complicated. Not only do the different substances produce different outcomes, but as we’ve already covered, set and setting have a great deal to do with the trip. Let’s also add intention. In the case of psychedelic assisted therapy for PTSD, most go into the experiences with a goal in mind. But for you to understand the power of ayahuasca and the feelings or emotions or access that comes through the experience, and how it adds to healing, perhaps Keith’s experience will help to answer your question. 

Keith Abraham: 

But once I had laid down on the floor in that heart with my shaman, and he started singing, I and I went there, you mentioned, trust, you’re absolutely right, it does take a certain amount of trust you write. And for certain other people that can be quite difficult, I all I know is that I was hopeless. And so anything that was even potentially helpful, I was going to go and give it my very best shot. And so I went, I went with an open heart. And when we have an open mind, and I just trusted that something valuable would come from it. And so it’s it was obviously night when the ceremonies took place. And the songs were, the songs are kind of vehicle, a vehicle to take you further into the experience that the medicine brings about. And the way that I remember it really is that I, I lay down, close my eyes, I started listening to him sing. And I was thinking, I got to a point where I was thinking, actually, this is a bit of a waste of time, because I don’t feel anything but it’s not unpleasant, because his songs, they’re lovely songs. I love listening to him, but nothing’s actually happening. Next thing I know, I just recognize that I’ve woken up. But I haven’t woken up here. In this reality, I’d woken up in the realm of what I now call spirit. And so this is a this is a massive shift, just even waking up in that environment. And it being real to me, so that, to me, the experiencer that was as real as this is, I believe it now is as realized this is. But for me that was in itself. Shocking, but wonderful and exciting, and incredible. And so I recognized that I was actually unconscious in my physical body, but I was awake in the realm of spirit. And in the realm of spirit I can do as I please I was, I became aware of an understanding of time and space. And I watched the planets revolve around our stars, our solar system. And then at one point, this is actually in the second ceremony. At one point, a voice came out of the darkness and said, “Have you finished? As alluding to have I finished playing? And I recognized it as a voice of authority. It wasn’t stone, it was just plain. Have you finished? And I thought are this is it? Okay, so I’m here to work. This is it. Yes, I have finished playing. I’m ready to do some work. That was my non vocal response, non verbal response. Then I woke up. I just woke up again, in a classroom, like a Victorian classroom. I sat at desks like this. And there was a blackboard in front of me. And then there was a woman, a teacher, and she was clearly the teacher, I was alone, but she was a teacher. And I recognized that she was the spirit of the medicine,

manifested as a woman in front of me. And again, so I accepted that she was the authority. And that she was the medicine is theoretically understood that she was the medicine itself talking to me. And she highlighted. So the way that it worked was that she would highlight things in my life that were causing me trouble. So my behavior being one of them, and my responses to certain stimuli, in society and relationships. So she would show me I would relive experiences in my life, the conflict, the heartbreak, any sort of something that I was resistant to or found difficult in my life, but they normally conflict between myself in someone and another, or how I dealt with heartbreak or adversity in some in some way. She was I would relive it with her. And she would ask me, if I felt that that way, the way that I dealt with it was still valuable and rewarding. And I would having relieved it then I would say no No, that’s not healthy. Because normally I would become aggressive and violent and angry. And I recognized that it wasn’t healthy for me. So then she would ask me if I would like to learn how to change that behavior and live differently and respond differently. And if I said, Yes, she would then take my place in the experience. And I could observe her as me experiencing that conflict, that adversity. And she would then respond in a healthier way. I hope this makes sense hope I’m articulating myself correctly, sufficiently, she would respond in a healthier way that would resolve the matter in a in as healthy way as you as anyone could expect. Having observed that, she would then ask me, do you agree that that is a healthier way of behaving? If I said, Yes, she would then teach me how she did it step by step. And then if I accepted that I understood those lessons, she will put me back into that situation as myself. And I would have to as I was being tested by this, any whatever stimuli stimulants, I would have to remember each of the lessons and respond in a more healthy way, each time. And if I passed that test, then I could move on to another test and another lesson in a different environment. If I failed, she very patiently said, I think we probably need to do that one again. And I would say yes, I know! , because I would have resorted to anger and violence or some frustration. And, and we would redo it again, and she would revisit the lesson very patiently. Are you ready to go back and be tested? Yes, I am. Okay, here we go. And I would revisit it again. And the same situation would be played out in front of me, and I would have to manage my emotions, manage my ego, and respond from a place of compassion and forgiveness and gratitude and patience and love. Love is what we’re talking about trying to respond from a place of love. But the tests were specifically, can you have compassion for someone else? Can you have compassion for yourself, if you can have compassion for yourself in someone else, the next step is that you can, you can learn to forgive yourself in someone else. After you’ve learned to have compassion and forgive someone else and yourself, you can become grateful for the experiences that they present you, and that you yourself, experience. And then once you become grateful, everything changes because trauma, you can become grateful for the traumatic experience. And once you can do that, you no longer label it as traumatic. It’s just a learning experience.

And why did Keith have to go all the way to Peru to access Ayahausca. Is that a question you thought of, too? Aren’t you curious? I am glad you asked. To explain that, here is Jo Neill, our pharmacology expert and a professor at University of Manchester who has a very personal story of her own. 

Jo Neill:  

So a friend of my daughters, and he very smart chap had when he came out of the military, I mean, I learned a lot about the experience of the pick somebody who’s a soldier. I’ve been in Afghanistan, I’ve been a paratrooper, so they are on the front line, seem unsure, seeing some terrible things. Fine. That was his career, left school at 16. He was very committed to a military career, which I think many of these these people are. came out of the military though, and then the PTSD hidden so not sleeping nightmares. Not being able to be Eitan public really hypervigilant. And not really being able to access the help that he needed on the NHS. Very long wait for psychotherapy for the talking therapies, and offered antidepressants, and he trained with the green berries and of course, the Americans with the maps programme. MDMA, Rick Doblin treatment for PTSD in the military. He had learned an awful lot about psychedelics, and he had educated himself was so felt that this was something that he would help him with his trauma, as opposed to an antidepressant. 

So anyway, long story short, his girlfriend eventually said, I cannot live with this, I can’t be on a bus with you, you know, without you being hyper vigilant. And I can’t have a conversation with you if we’re out in public, because you’re just checking everything, you know, looking for, I guess, the enemy. So she persuaded him to go to Amsterdam. And he sat in a hotel room and took two doses of truffles over a weekend, which is absolutely not how we would recommend that you do this. I mean, at least you’d learned a lot of it, it was probably the right mindset to do it. But he, you know, he should have had loads of integration and loads of help. And he should have been supported by the NHS and by our society. And he wasn’t so this is as Crispin blunt says, he signed a blank check on his life, he fought for us. And he couldn’t get the help that he needed on the NHS in the UK, he had to go out of the country at his own expense, and sit in a hotel room and not have all the support that he deserved. And I was that was one thing that struck me I was horrified that he hadn’t been supported better. But the other thing was that he healed himself. And for anybody who who would donate them the importance of this medicine, you have you just need to talk to somebody like this. Of course since then, I’ve talked to lots of people, hundreds of people, you know, we’re doing an event today where we’ll be talking to a former cancer survivor. So I spoke to him he had been in January. I spoke to him in August. He’d not gone near a psychedelic again, he’d come home. And he transformed his life, basically. And he enrolled in medical school.

Keith and Jesse both had the benefit of healing through psychedelic assisted therapy. Sadly, through the DEAs scheduling policies, psychedelics are not widely available in the US or even in most developed nations. Both Jesse and Keith moved into action to find a way to help other veterans achieve freedom from their PTSD. And so the Heroic Hearts Project was born. Heroic Hearts has outlets both in the US and the UK – with Canada coming on line soon. The mission of the organization is to connect military veterans struggling with mental trauma to psychedelic therapy. The seek to provide hope and healing to veterans that have been left hopeless by the dearth of other effective treatments.

For those of you who are not convinced, who maybe think this is an excuse to use and abuse psychedelics for entertainment – I can’t begin to tell you how wrong you are. Heroic Hearts goes through well considered, highly developed protocols that screen participants to ensure safety, prepare for optimal outcomes, and optimize the opportunity for genuine healing. While a formal diagnosis is not required to participate in the program, it is strongly encouraged. The program provides information, services, access, and guidance throughout the process – beginning before the retreat, through the retreat and after. 

Let’s hear from Keith about the process.

Keith : 

So yeah, again, we we don’t These aren’t trials, they’re certainly not clinical trials, even though I did reference that we’re doing observational research study, but that’s on a, that’s something else, just generally speaking on an operational level for us, prior to retreat, but after successfully passing our own vetting process, and then the vetting process of the retreat center staff themselves, there’s two vetting processes that they’ve got to pass. And we run a default, no, no prescriptions, no supplement policy as well. So each participant needs to withdraw themselves from their prescriptions prior to the retreat, and they need evidence that they’ve done that responsibly with the guidance and help of a qualified physician as well, they can’t just do it cold turkey, we need evidence, they’ve been doing this under guidance. So they’ve passed vetting, they’ve passed the second round of vetting, they’re clear of any supplements and pharmaceuticals, then we have, and we load, we’re loading them onto the retreat. Now. That group, that group will be a mandatory in preparatory group video calls to them prior to the retreat that will involve her oakheart staff, that will also involve for the sake of continuity staff at the retreat center. So this before we’ve even got, says, our staff and their staff, and it’s our staff who will actually be on the retreat with them as well, again, for continuity of relationships. And there, we discussed about what needs to happen prior to the retreat, and how you can best prepare for these sorts of experiences, be that mindset be that diet, because some significant dietary changes need to need to happen, otherwise, you’re going to probably have quite a difficult, you might have a difficult experience anyway. But if you’re taking on board, lots of alcohol, and sugar and caffeine and other drugs, right before an iOS cake ceremony, you could well be in line for something of a difficult experience. And so we discussed the importance of changing diet, mindset, the introduction of practices like journaling, things like this. It’s simply preparatory calls. Okay, so that’s the first step, then we will go on to the retreat ourselves. And again, those people that were on the call from the retreat center, they’re going to be the people that are hosting a retreat. And then, immediately after each ceremony, there will be integrative coaching from the retreat staff who are obviously very experienced and qualified and trained. And that’s after every ceremony. And then after the retreat itself, we have numerous and increasingly longer intervals, integrative group calls, digital group calls, to help with that further integrative process, which is fundamental to the psychedelic therapeutic process itself. Interestingly, in addition to that is not in place yet. So that is our that’s our core operating procedure, or to be a standard operating procedure. In addition to that, what we’re trying to achieve now is to provide a course through the faculty of one of the doctors at Manchester University, trying to create our own integrative coaching program that will train people, anyone anyone can go on the course is not yet up and running. Anyone go on the course get coaching in how to help others and themselves integrate psychedelic experience, the psychedelic healing experience. And then we’ve got we’ve created a community and nationwide community of real people that exist across the nation that can offer actual in person support. Because that can be you know, that’s ultimately what we need. We need connection, we need human connection. And so it’s all well and good doing digital integrative coaching, that then we hope to have a nationwide community of ambassadors and coaches. They’re not necessarily, it’s not an accredited course. But you don’t always need an accreditation to help someone. And if you just need to have a go and have a cup of tea and tell someone that you’re struggling and that the experience still hasn’t settled inside your body, and you just want to express yourself, then hopefully, we’re going to have a great deal of trained and compassionate people across the nation are prepared to help, which is

wonderful.

So, now you know what to expect logistically. But what is the experience from a participant’s point of view? How does ayahuasca help someone who is trained to never surrender, actually surrender? Jesse has a pretty good description for us. 

Jesse Gould: 

Were with a group of veterans and very intense, I lost the ceremony. And one of them was a ranger with with a number of deployments. And that actually came up mid ceremony, he was like a ranger will never surrender. until we figure that we kind of just have to rebrand that word. So maybe surrender is not the best one to appeal, but maybe like acquiesce for the time being. But aside from the words or how you frame it, that is I think the beauty and the power of why this is so effective, is because one veterans are very good across the board at compartmentalizing and sort of pushing down those emotions. And so that’s a lot of the barriers that just traditional talk therapy by itself can reach is that you’re you’re almost like hitting against this wall that’s been training to compartmentalize these feelings for so long. And that’s why it can take 10 years 20 years, even to get the slightest benefit from from the talk therapy and they hit these walls. And that’s where I think also psychedelics can really be an enhancer and not you know, we never say it’s one or the other. You know, but if you go through talk therapy, and you work with psychedelics, they just really work off each other very well. And so when you’re in the situation, and you know, you drink it, or you eat the mushroom, you’re in that world for the next three, four plus hours. And the thing about Iosco in a therapeutic setting is that it’s very poignant is that of the other ones, it tends to be more in the term of like, it’s very hard to ignore the trauma or whatever you’ve been very good at avoiding, because it just throws it right in your face. And you can almost like fight against it, like those finger traps, like, the more you fight against it, the more it will throw at you. And you know, eventually at some point, you’re not going to win against that, because it’s you against the Ayahuasca gets you against your mind. And you kind of have to get pushed to that point where you’re just like, Alright, like, What are you trying to tell me? What am I trying to learn? Like, why am I making this so hard. And so when you get to that point of friction, and you’re almost introducing it that to yourself, you you have to move, you have to change, you have to like let go. And then once that let go position happens. And I would say that it’s more of a let go than a surrender, you’re working with it, as opposed to an opposition of it. And you’re realizing like, your brain is your friend, as long as you figure out how to work with it, and you’re not being in the self destructive mode. And so once that is in coordination, that’s when so much comes out, and you just see, you know, you see this build up, build up, you see, like, people coming from the ceremonies like man, what the hell is that. And then when they have that break, that let go moment, a twin a lot, so much work comes out. So much change, transformation, peace of mind. It’s a continual process. Again, it’s not magic, but that is, I think the power of this that were in like some other therapy could just walk away or just shut down. Whereas this, you can’t do that. 

And it’s also you, it’s like anything else, we believe ourselves the most, oftentimes to our detriment. But when you are faced when you are, your brain is pushing this thing in front of you in a way that you understand and interpret. There’s no way to ignore it. It’s there. It’s it’s in your language. And you know, you know, it’s true.

Heroic Hearts is also invested in supporting the science of psychedelic medicine. They have partnered with scientific organizations that are performing well considered, scientifically rigorous research in order to advance the understanding of how and why these substances are working. MAPS – the Multidisciplinary Association for Psychedelic Studies is one such organization. You might remember some of the MAPS work that was mentioned in previous episodes. If you’re thinking that this is a fly-by-night organization that has just recently glomed on to a recent fad, you’re definitely wrong. MAPS was founded in 1986 with an aim to create safe and legal opportunities for the use of psychedelics. Their studies look at MDMA, marijuana, LSD, ibogaine, ayahuasca, and other psychedelic substances. In fact, in May of 2021, MAPS published their Phase 3 Trial results for MDMA-assisted therapy for severe, chronic PTSD.

The experiences of Keith and Jesse, while poign ant, are far from rare. PTSD has reached crisis levels around the world while new treatment research has stagnated. With the exception of the application of psychedelics. 

As of the time of this broadcast, there are over 300 clinical trials in various stages of completion that are using psychedelic medicines to treat a variety of conditions including PTSD, depression, addiction, OCD, and more. These trials are happening in some of the premier institutions around the world including Johns Hopkins, Imperial College, Yale, and more. In short, psychedelics are seemingly, finally getting the positive attention that they deserve and they are being put through the rigorous research and reviews that have long been ignored. 

According to the Military Times, suicide rates among veterans continues to rise despite the myriad programs, funding, and attention being directed toward the issue. And even the most recent data is two years old. 6,435 veterans died by suicide in 2018. 

I want to introduce you to Jon, a 42 year old retired combat veteran who was injured in an explosion in Iraq in 2005. Upon return to civilian life, his PTSD advanced so dramatically that he had five suicide attempts – two of which actually included pulling the trigger. Of those two trigger pulls, one failed due to faulty bullets from the manufacturer and the second one, thankfully failed due to a broken spring. Jon eventually found his way into a MAPS sponsored study of MDMA for PTSD. His experience allowed his psyche to sufficiently allay the fight or flight reaction in order to allow him to address his issues. In his words, “This therapy is what ensured that my step-son has a father instead of a folded flag.”

But instead of us describing it to you, can we talk to Dr. Jennifer Mitchell, who was the leading author of the paper that was published in Nature Medicine. Jenny Mitchell  is a Professor in the Departments of Neurology and Psychiatry and the Deputy Associate Chief of Staff for Research and Development at the San Francisco VA. She recently became a member of the UC Berkeley Center for the Science of Psychedelics and the UCSF Neuroscape Psychedelics Division. She received her PhD in Neuroscience from UCSF, where her doctoral research focused on understanding how stress and anxiety influence opioid tolerance and addiction. 

Here is Dr. Jenny Mitchell: 

Sure, my name is Jennifer Mitchell and I work for UCSF in San Francisco. Oh, absolutely. So yeah, Adam Gazzaley runs neuroscape, which is a group of divisions, and the newest division is psychedelic science. Right, so I’m a neuroscientist and behaviour pharmacologist by training and have spent the last 25 or so years identifying and developing novel therapeutics for a number of what we used to term access one disorders. So stress, anxiety, depression, PTSD, alcohol and substance use disorders and then related comorbidities like impulsivity and compulsivity. And so we’ve been studying most recently with past like four and a half years, the effects of MDMA on PTSD. And then we’re also interested in looking at the impact of psilocybin on alcohol use disorder. So Adam approached us, oh, gosh, a little over a year now and asked if we wanted to team up and join neuro scape. And we were delighted to do so because it allows us affords us the opportunity to work with all these really incredible neuroscientists at UCSF.

So we asked Jenny Mitchell, why she was interested in psychedelic research and more importantly, what was so different about MDMA compared to all the other psychedelics that we spoke of, like LSD, Psilocybin or DMT which affect the 5HT2A receptor. 

Dr. Jenny Mitchell: 

I think it’s fair to say I didn’t actually hone in on MDMA. Back when I was a graduate student, I was sort of fascinated by this idea, people were talking about whether or not it was neurotoxic, and it didn’t seem like it. The evidence was really rock solid. And I remember looking into it as part of my thesis project and writing up a paper on on the impact of MDMA and what it was actually doing. And at the time, we were already looking for novel therapeutics for the indications that I just mentioned. And so we were very interested in some of the psychedelic compounds, because there were anecdotal reports that they were really very effective. And, and so it was for that reason that I was reading so much about MDMA. But at the time, we couldn’t get our hands on any of those compounds. It’s not like you could, you know, go down to CVS and, and buy a bunch. So I asked NIH at some point, if we could perhaps have enough for her preclinical studies for use in animal models, and they didn’t need that request. But you know, ever since then, I’ve been interested in following up with those compounds. And so now it’s taken, you know, however many years we finally have the opportunity to do so. Well, they’re both similarities and differences. So on a on a similarities level, they all affect their energic neurotransmission. To some degree, right. And there are just a tonne of Sarah Turner toning receptors. I don’t even remember how many maybe 1417 serotonin receptors. Every time I turn around, it seems like there’s a new one. And so the impact of each of these compounds on that array of serotonin receptors, still needs to be elucidated, better elucidated. So we have some idea. And, of course, we think that one particularly important receptor for the effects of psychedelic compounds is the five htt to a receptor. But with respect to MDMA, in particular, its actions are primarily on a presynaptic transporter pump. And instead of that transporter pump, taking serotonin, this neurotransmitter from this sort of extracellular area that we call a synaptic cleft and putting it back into the cell, it winds it down and so it sort of spins in reverse, and Sarah And instead comes out of the of the presynaptic terminal and sits in the synaptic cleft. So basically you get a lot of serotonin and endogenous serotonin release following MDMA administration and that itself can act on your, you know, sort of inherent system. Basically, they all use this neurotransmitter system, right? It’s search energic.

But before we go any further, we wanted to come back to one major myth and a cause for taboo,  that people hold about psychedelics. We addressed this in episode 3 when Albert Hoffman’s recollection of what the visions were, and again with Bryan Roth in episode 5 where we discussed pharmacology. Both those answers were that psychedelic visions were not hallucinations and we even addressed that with some definitions of what hallucinations were. 

So can we now ask a clinician researcher about psychedelics and the so-called “hallucinations”? Are they really hallucinations?  Here is Dr. Jenny Mitchell again. 

Dr. Jenny Mitchell: 

that’s a really good question. I mean, I don’t really also know how we’d ratify a definition. psychedelic, we can all raise our hands take a vote, Aye. Aye. For me personally, it does mean that it can be transformative. And it is sort of an inner window into your subconscious working. It’s not really a great definition, I guess it’s easier to say what it isn’t. But to me, it’s different than hallucinogenic. Which just sort of suggests that you see things that aren’t there or hear things that aren’t there, right. And psychedelic really means it is so exposing, to some degree. And that allows you the opportunity, perhaps, to see yourself more clearly or from a different vantage point and then hopefully work on yourself to to better yourself and to become the best possible version of yourself.

When we conducted this interview with Jenny Mitchell, it was just a few days after the pivotal study for MDMA, sponsored by MAPS was accepted for publication. This was also before the rest of the world started singing the praises of MAPS and MDMA for PTSD via two New York Times column. Since then, it has received massive publicity. 

Dr. Jennifer Mitchell: 

Oh, absolutely. So I will tell you then, separately, but it’s in math has lots to say about this, too. It’s under embargo. Let me just check my email here and see if they’ve changed anything. Nope, it’s still embargoed. I have 24 hours to get the prospective nature medicine and then they are going to give us the publication date, they said within another 24 hours. So in about 48 hours, we should know when that paper is going to come out.

Now that we have established that we arrived at the clinician who led the trial, who was also the first author of the published study looking at MDMA in PTSD population, can we dig a bit deeper on what it takes to do a trial? After all, you can read in the press or the actual paper where 90 patients with severe PTSD, so essentially the worse of the worst patients due to their symptoms were enrolled in this study. It is very sobering to learn that these subjects in the trial has 14 years of PTSD on average. And if we go back to what we said about causes of PTSD earlier – combat trauma, abuse trauma and developmental trauma, the trial had representatives of all classes. In fact, 84% of the subjects or the vast majority had  developmental trauma. MDMA was administered three times as part of an 18-week study with Forty-six out of 90 participants receiving MDMA therapy and forty-four participants received therapy with placebo. All of Rick Doblin’s inferences of talk therapy, preparation and integration practices were included much like what they did in an earlier stage clinical study. 

At the end of 18 weeks, The primary efficacy endpoint was based on the change from baseline in an independently assessed clinical interview of PTSD severity. Average change in functional impairment in work/school, social, and family life. Want to know how amazing the results were…Among the participants in the MDMA-assisted therapy group, 67% no longer qualified for PTSD diagnosis after three MDMA-assisted therapy sessions and 88% of participants experienced a clinically significant reduction in symptoms, while in the placebo group, 32% no longer qualified for PTSD diagnosis at the two-month follow-up and 60% experienced a clinically significant reduction in symptoms. The results were so substantial  that  the tests applied by scientists to assess impact were 0.0001, meaning that the possibility that this result  was by chance was one in 10,000 – This outcome substantiates the years of hard work by the folks involved. 

Can I give you another example such a result was obtained? It is also the only example and I hope people from MAPS, the general public and scientists should know. The only other example in history when heart failure was a scourge in the 1980s and 1990s, and it had no treatments. In fact, 50% of the people die within 5 years after diagnosis, if inadequate treatment is provided. And one drug changed it all. It was the story of a drug called as Carvedilol, a beta blocker that was trialled in thousands of patients and in their early pivotal trials of 1094 patients, the P-value was similar that the FDA at the time, decided that it was unethical to withhold the therapy from the subjects in the placebo group. Guess what the person who spear-headed the effort, did. Bob Ruffolo Jr, the lead discoverer of the molecule, when he heard of the FDA DECISION,  spent the evening  in a London Hotel room crying in joy and you can find that interview in our earlier episodes of our parent podcast, SKRAPS. 

But for people like me, attrition in clinical trials is common. Patients who enroll into clinical trials especially in the diseased population for testing efficacy have to adhere to strict protocols and testing. So, one can imagine that this can catch up to them and as a result, patients can drop out of therapy. We asked Jenny Mitchell about this problem and how psychedelic clinical trials are different to other drug trials. Here is her answer. 

Right, so I think in terms of attrition, one of the things that I’m hoping is going to become clear over time with the psychedelics in general, not not just MDMA. But it is the idea. I mean, first of all, for many of the psychedelics, if you’re only doing a single administration, you don’t really have to worry so much about attrition. But for those that involve a lot more work, and again, those that are placebo controlled, so that somebody would have to keep coming back again, and again, even if they were just receiving placebo, you have to worry about attrition. And I think that that is probably going to turn out to be a an infant test animal a smaller problem in psychedelic therapies than it is in current standard of care. Because when you For example, if we’re just taking PTSD, as our example, if you look at dropout rates for prolonged exposure therapy, or even CBT, those are, are actually quite high. It’s hard to get through the the, you know, the 10 weeks of standardised PE, for example, and keep going through and revisiting that trauma over and over again, it’s a complicated process, and many people don’t feel that they can do it. So by comparison, my my guess is that by the end of, you know, 2024, so we’re going to be able to sit down and look at all of these psychedelic therapies and say that well, there’s a real difference here in terms of attrition. So that’s the first thing but I think that in general, with face trials, one of the problems that we’re still having is a surrounds inclusion and inclusion of people from marginalised communities, inclusion of people of colour, inclusion of people that are themselves spread so thin, that they really cannot figure out how to get treatment into their lives. And so sort of a bigger philosophical question, how do we make sure that these treatments actually get to the populations that need the most? And I think that’s something we’re all going to have to you know, put our heads together to figure out over the next few years.

Isn’t it amazing? So we definitely know that it can comes down to the dose and more importantly the next three words. It’s psychedelic assisted psychotherapy and not just psychedelics or psychotherapy that is useful but the combination. Jenny also raised an interesting question about access and reach of these therapies and how does one get these therapies to marginalized populations, where they need the most? 

Once again, this is fundamentally different to how existing healthcare is delivered. Healthcare is delivered by resources that one has bought, for example insurance policies or by a queue and prioritization in nationalised healthcare systems or simply in some parts of Asia, self-funded. 

So it is truly remarkable that when MAPS initiated the clinical trials for MDMA, they planned to perform two phase 3 trials. The first one was just published and second one is just starting off and this time with the European Medicines Agency. The remarkable and forward thinking EMEA regulators have advised MAPS to include refugee population and MAPS and the leading trial site, Charite’ in Germany have gladly accepted that challenge. So you can see how this still-to-be-approved MDMA assisted psychotherapy is trying to change the world AND MAKE IT a better place. 

But there is one challenge to delivering tehse therapies. Due to the lack of availability of these treatments on existing healthcare systems, organizations like Heroic Hearts  charity in US and UK are organizing retreats for the military personnel. We heard from Keith Abraham abiout how he is planning to expand this to first responders. While it is a noble cause to have these systems in place via existing healthcare systems, there is a bottleneck. The bottleneck to delivering these therapies are due to the availability of trained psychotherapists. So how are people thinking about this? We will come to that in just a couple of minutes. 

First, we asked Jenny, is psychedelics really a tool that takes out the subjectivity of psychologists and the rapport & trust they can build with a patient? Because we know, in the example Keith gave about himself, he did try talk therapy for years but was not successful. So we asked Jenny Mitchell, how does psychedelics help establish a level playing field so that a patient in USA is treated no different to one in far east corner of Europe or Asia. 

Dr, Jenny Mitchell: 

I think you are making sense. Absolutely. So and I think it is a really good question. I think that you know, I I cannot say enough great things about our our therapy team at our study sites. I am impressed by them every single day that I work with them. And I think they’re among the best in their field. And even so I think that they would say, if they were sitting here with us that those compounds definitely facilitate their ability to create a therapeutic rapport with their patient, and to feel like they have established a bond with them, and to trust with them, and enable the patients to to feel closer and more open with them. And that also facilitates the work that they’re going to do together. So I would say that, you know, that’s definitely a benefit to the therapist or the provider is, I’m sure it is a horrible struggle. I’m, again, not a therapist, and I always tease and say no one would ever want me to be. But I respect those that are and I see how hard they work, how hard they work to reach a subject who has gone through so much and is so close, and is so terrified of being open, and how hard to process that is, if anything could make it slightly easier. I think we’d all be very delighted to to try that. And so I’m sure that that is a component of why they themselves do this work and why they are so interested in it

So, how does a therapy session work? 

Well, it’s an all day session typically runs a different amount of time. If you’re administering MDMA, then if you’re administering psilocybin, the psilocybin sessions are often an hour or two shorter than the MDMA sessions. And that is, in part because the approved protocol for MDMA administration right now for clinical use involves a supplemental half dose which is administered about an hour and a half in to the experimental session after the primary dose. So that also pushes the session out it makes it a little bit longer. But in general, the subject typically comes in in the morning, first thing in the morning and To sit down with a therapy team, they’re usually two people in administering therapy for most of these treatment sessions. And they sit in a room that looks a lot like a very comfortable living room. So there’s usually a sofa, sometimes a sofa bed, the lighting is typically dim, there’s often music playing, the participant is given things like a warm blanket and eye shades and the pillow and made comfortable. And they talk a little bit about intentionality about what they’re hoping to accomplish, or again, what the session might provide them with the reason that they’ve come to therapy in the first place. And then they take the compound. And then the rest sort of happens organically. In other words, most of these therapeutic sessions are not very intense in terms of manualized therapy, they’re not very focused on if you’re, if you’re used to manualized therapy, if you’re used to cognitive behaviour therapy are used to prolonged exposure therapy or some other form of manualized therapy. It’s sort of like a cookbook at times where you, you know, you read through and in session three, you’re supposed to hit these four topics, and then session five, you’re supposed to sort of wrap it up. And it doesn’t work quite like that it’s very participant guided. And so over the course of these several hours, as it unfolds, the participant usually begins to revisit the trauma on their own. And that’s one of the things that’s so fascinating about psychedelic compounds is they seem to take you to where you need to go. And so you don’t need somebody to keep pointing that out, right, it just sort of hap pens. And then they go to where they need to go. And they start talking usually, either they’re quiet for a while, or they start talking about what they had previously experienced. But again, it was sort of fascinating is that and this is just my, my personal subjective perspective is that what happens is, they can do it from a slightly different vantage point or slightly different point of view. So whereas before, when they’d relive that trauma, they felt shame, or embarrassment, or fear, or anxiety. In these moments, they typically have a different perspective, and they have a lot of self compassion and a lot of self empathy. And that seems to lead them to some self forgiveness as well. The acknowledgement that maybe the whole thing wasn’t their fault, or the acknowledgement that may be it, you know, they’re validating their their feelings, and also acknowledging their ability to get past them. So that’s sort of how a session unfolds during the day. And then, you know, at the end of a five to eight hour experience, the subject begins to return to baseline. And it depending on the therapeutic protocol, at that point,

In fact, what MAPS is doing currently is training every single site psychiatrist and psychologists and therapists via their training program. The program was devised by Michael and Annie Mithoefer, who are husband and wife combo of psychiatrist and a therapy nurse. So they cover all aspects of training and here is Jenny Mitchell recounting her training program. 

Correct? Yes, I can’t, I’ve actually got, again, not a therapist, but I have gone through the training programme myself and found it to be fascinating. It’s a five part training programme ABCD and E that the sponsor provides that allows therapists to really feel comfortable using those substances in their practice. And that also allows them to partner with other therapists that have previously delivered those treatments, or that are currently delivering those treatments and give them supervision as they work with subjects in this context. And, you know, therapy, hours, role play, all sorts of different things that I think the therapists find to be invaluable. Most of the sponsors, not all of the sponsors, because some of the sponsors in this field right now, don’t, I think values the therapeutic component or the role of the therapist, the facilitator, perhaps as much as others, but Matt most certainly does. And so the the process of training therapists is an important process to them, and I know one that they’ve really committed themselves to over the next couple of years to bettering and they’re trying to get more people trained up so that they can act as facilitators so that Fingers crossed, if their therapeutic ever is going to come to market. There are providers there that can help people immediately and we don’t have a huge bottleneck as we wait for more people to get trained up. So did you have like, What other questions can I answer for you about the therapist training because I actually think it’s it’s fabulous.

We did ask jenny MItchell more questions and she confirmed that to roll out the MDMA therapies, while there is not an existing botttleneck for the trials, there will be a bottleneck for broader access. In fact, it is estimated that for optimal reach of the MDMA therapy to every state in the US, approximately 24,000 therapists need to be trained keeping in line with existing population of the United States and you can imagine what this number means for the rest of the world. 

And for the recreational users of psychedelics, we have a very strong message from Jenny Mitchell. 

Totally Yeah, yes. Right? No, I think I yeah, no, I think I understand that what you’re saying and I, I am a huge fan of studying set and setting. And I’m a very firm believer that the environment plays a major and important role in the therapeutic efficacy of these compounds. So I think that’s something that we all need to look at that that really should not be discounted. So I recognise that there are commercial entities in this space now that would like to disagree with that. And they would like to say, you can just, you know, go home and, and, you know, put your feet up and take a psilocybin and go to sleep and everything will be fine. And you can go walk your dog, and to maybe, you know, chat with your neighbours, I, I, you know, and more power to them if it if it happens, but I personally am concerned about not considering the setting, when you are talking about administering these compounds. I think setting is particularly important. And I think that, you know, certainly one of the things that people say that I hear a lot when they talk about these compounds, and they doubt their efficacy for these indications is, oh, I dropped shrooms in high school. And I didn’t find that I got over all of my trauma, or I did MDMA at Burning Man. And I gotta tell you, it didn’t do any of these things to help me. And I think well, why would it have? That was not the setting that you would really want to be thoughtful about creating, if you we re looking to address your trauma, right. And so I think that that’s something that we need to really delve into further is what’s the appropriate setting in which to take these compounds? And how can it benefit the the therapeutic outcome. And so it would be nice, if in a perfect world, what I keep hoping and maybe it’s just my foolish pipe dream, scientific pipe dream is that there would be a process maybe by which providers would be licenced, to work with these compounds, not just by the study sponsors at present, but you know, in a more generalised way, the way we expect our doctors to have additional training before they administer buprenorphine for opioid abuse, for example, or for opioid use disorder that they have to in addition to holding an MD they have to undergo a certain number of hours of training, and they’re only allowed to administer buprenorphine to a certain number of people per year so that we know that we don’t have to worry about deviation, you know, of the substance, etc, that they’re really being thoughtful and that there’s really appropriate oversight. So maybe maybe someday psychedelics would be like that and the providers would have some additional training and they would be able to sit down with their their, you know, with their what would you even call them with their participants and and go through walk through the the best way to design the setting to have as much therapeutic impact as possible.

And research is going beyond this. We did tell you in episode 5 that serotonin is made from tryptophan and there is a strong role for the gut microorganisms TAHT  make 95% of the serotonin. So the role of gut microbiota and its link to serotonin was known well before the microbiota’s role in other disorders. 

Can we tell you a bit about HOW THE  scientists put together some pieces of the puzzle while ideating? Here it goes! 

It is now known from a 2014 paper  that inflammation prior to or at the time of trauma exposure increases the risk of developing PTSD symptoms. The study included 2,600 war zone-deployed Marines, and their propensity to develop PTSD was assessed. Marines with a higher blood concentrations of C-reactive protein, a biomarker of inflammation, at boot camp had higher risk of post-deployment PTSD symptoms. CRP or C-reactive protein is a very non-specific marker of inflammation but definitely the easiest to measure. 

WHat comes next is even more interesting! Another paper in 2019 which was a report on a working group of a scientific body published in Journal of Nutrition that  reduction of  “alpha diversity” of the microbiome drives inflammation. The consensus is that a microbiome characterized by high alpha diversity is a healthy microbiome (McBurney et al., 2019), and that stress, by decreasing alpha diversity, makes the gut microbiome more vulnerable to opportunistic pathogens. Opportunistic pathogens can cause gut inflammation, “leaky gut,” resulting in translocation of bacteria from the gut into the body, and subsequently, systemic inflammation (which can be detected by increases in biological signatures of inflammation, including C-reactive protein; Myers et al., 2004). More studies have pointed to the fact that trauma and stressor exposures can increase proliferation of “pathobionts”, microorganisms that typically behave themselves, but under some conditions become pathogenic leading to the cascade of effects and causing increased inflammation. We do know that microbiome population take years to stablize. Yet Ayahausca treated veterans via the work that organization like Heroic hearts are doing is driving remission from PT SD. 

And since Ayahausca brew blocks the mono  amine oxidase enzyme in the gut and increases the DMT levels in the body, scientists are also currently investigating what impact ayahuasca therapy have on gut microbiota. 

]Here is Jesse Gould, CEO of Heroic hearts who is pioneering this work. 

Absolutely. Yeah, we’re actually we’re working I think we’re one of the first that’s doing we have IRB approval to do the effects of Iowa, Tosca and down the line psilocybin as well on the gut microbiome. So we’re working with University of Georgia and University of Colorado Boulder. So there’s a Chris Lowery, who has the Lowry lab. And so we have a think about 12 samples of gut microbiome there right now, we’re going to try to increase those over the year and just see if this this substance if it has any sort of ascertainable effect or discernible effect on on that, and then maybe, you know, figure out if there’s connections, it’s again, it’s very early, but even if there’s small instances or inclinations, it’s it’s all fascinating stuff.      

The field of PTSD has wallowed in lack of good available treatments and Heroic Hearts organization is involved in a Psilocybin therapy in a retreat setting for military veterans, to be conducted in collaboration with Prof. David Nutt’s group at Imperial College. 

The sun is definitely shining bright on PTSD sufferers with all these efforts pointing to a potential help that has long been missing. 

A controlled psychedelic assisted psychotherapy and integration session can change all of that. 

Finally, there is one aspect that we haven’t discussed in great detail – the spiritual aspect of psychedelic. Here is Jesse Gould, a US army veteran. 

I mean, that’s a big one especially, I think it’s pretty common in Ayahausca and I feel like I have a maybe a little bit different definition of spirituality. And so, I mentioned before that, in my opinion, this is my hypothesis as a non doctor or psychotherapist. But I think at the very least, psychedelic treatment works on three different layers. And so we kind of talked about the psychotherapy side of things where you might see these these issues that you’ve been struggling with, and it will show you them in sort of different approach, or you might be able to handle them or move past that story. The physical side, you know, we mentioned the gut microbiome, there is also initial evidence that it might, you know, heal the brain actually with neurogenesis, possibly reduce inflammation, we’re doing some studies around that. But then the third, and I think this is an important spot that often gets neglected or ignored, is the spirituality side. And my definition of that is kind of more of a connectivity. And different people need to connect to different things. So some might take the form more of the religious connection, sort of your spot in the world, your spot and sort of the cosmos and life. For other people, it’s really maybe more on a grounded level, the community around you, your brotherhood, your sisterhood, your fellow veterans. And, you know, there’s also even what you see with a lot of indigenous tribes or through the psychedelic process, connection to nature connection to the world in general, like, Hey, you are a something moving these microcosms forward, and you are a part of that, you know, you can be this, you’re drinking this plant, and it’s having this profound effect on you making you see all this other information that you never even knew was there, there’s this inherent connection to it. And so again, I think that’s why it works, because it works on your level. So for, for maybe a more religious or Christian theme kind of thing, probably wouldn’t affect myself, because that’s not you know, my necessarily belief system, but for somebody that how that’s how they translate the world. And that’s what they need in terms of comfort and connectivity, then that might be the thing that gets them to there. And so I do think that is important. And you see that with a lot of that’s, and that’s why we found similar things with athletes is they leave these worlds these professions, these lives, and they lose all that they lose their sense of purpose, they lose their community, they lose self identity. And there’s not a lot of mechanisms in modern society that help you recapture those, it’s kind of more you have to go in the system. And, you know, you go into the corporate job, and you’re gonna be there for 10 years and your rank up. There’s not this focus on connectivity or, or, you know, sort of the broader side of you what what is outside of you, not just in this ego centric me I am this is what I did.

And We hope we have shown you through glimpses of people’s work and experiences that psychedelics can help. BUt there is more to reveal in studies from depression and substance abuse. And we shall do just that. 

<END of the episode> 

You have been listening to PsychedeRx. PsychedeRx is a SKRAPS Original podcast produced and narrated by Arun Sridhar and JoJo Platt. 

SKRAPS is a volunteer run organization created by Arun Sridhar and JoJo Platt to disseminate factful stories of science, scientists and innovators as a service to the world. 

Select research for this podcast series was performed by Sharena Rice.  The producers thank Clara Burtenshaw for her invaluable input. Multimedia services were provided by Dr. Romeo Racz. The scripts were written and edited by Arun Sridhar and JoJo Platt.  Financial support to cover the production costs was from Cybin, Inc and a kind donor, BB. We thank Mr. krish Ashok for letting us use some of his music. 

Recordings were done at Caprino Studios in the UK and Slightly Red Studio in San Francisco. Swaminathan Thiru Gnana Sambandham performed the mixing and mastering. All recordings including interviews are properties of the producers and should not be reproduced without permission. The show notes, transcripts and useful links pertaining to the episode are located at the podcast website –  www.PsychedeRx.com.