Sparking the Psychedelic Renaissance

We discuss previously underappreciated personal stories of how the Psychedelic Renaissance was sparked since 1971.

Description:

1971 was the year when drug prohibition came into force. Did we tell you the story of how the tables were turned against the prohibition of drugs? Or did we tell you the hurdles that were needed to be overcome.

Well, that’s exactly the point of the episode. We are here to bring to you how the road to psychedelic renaissance was built. And if you think, it came from overwhelming people with data, just like how a typical scientist thinks, you would be amazed at the personalities who paved the way, as much as the ones that broke it for themselves and for the world.

We discuss the unconventional paths taken by Amanda Feilding of Beckley Foundation, Rick Doblin of MAPS – Multidisciplinary Association for Psychedelic Studies and more importantly, the trailblazers who initiated the clinical studies before anyone did – The Heffter Research Institute. We interview the original members – Dr. Mark Geyer of UCSD to tell us the never-reported personal stories of the creation of Heffter Research Institute and the Psilocybin studies.

Transcript

JoJo:

So far, we have taken a deep look at psychedelics from a societal history perspective. That part of the psychedelics story is interesting in itself. There are the properties of the substances themselves that we explored in episode 5, but beyond the science that we will dig into a bit more, the fascinating thing about psychedelics is how they are misunderstood over and over by religious ideologies and cultural differences. More importantly, the very molecules that are supposed to be opening up the mind drove differences, for which the advocates passionately voiced their opinion triggering panic and paranoia among the excitement. So the damage was done. Psychedelics were lumped in with other psychoactive substances and organizations like the DEA and the governments world over pushed hard for keeping up the prohibition. But how did the world change from its prohibitionist stance to allowing a proper exploration of the use of these substances in some of the recent clinical trials?

That is the story that we are going to explore. And the path to where we are today, did not happen without a lot of hiccups, blood, sweat and tears.

This is PsychedRx, a SKRAPS original Podcast exploring the therapeutic potential of Psychedelics. An enthralling story of an improbable drug class, as old as human-kind itself, banished into exile, yet comes back soaring like a Phoenix from the ashes, to save mankind’s affliction with mental health disorders.

Arun:

The best place to start is just where we left off – the year 1971. We have spoken enough about the geo-political situation at this time. But what we haven’t spoken is how the world of psychedelic research came to a standstill. One could argue that in a world of chaos, such a reset is needed. A reset that was so hard that people needed to re-assess the impact of what had happened. Let me give you an example to help you understand.

Take a case of a heart that is fibrillating like a bag of worms, unable to get a single proper contraction. What does an emergency medical technician do? They assess the situation, the pulse and shock the heart. What happens in the heart once it has been shocked is this period of a delay between when the shock is provided to when normal activity resumes. This pause is a reset of all the electrical circuitry that was needed. So the field of psychedelic research needed this reset.

There could have been rationality that could have prevailed on all sides, but know what? When Science influences the mind, to influence society and politics, you cannot have it solely one way. The government could have of course, taken a more considerate approach. On the other side, the psychedelic evangelists, psychologists and psychiatrists could have run controlled experiments to show that what they believed in was good enough. After all, randomized controlled studies were being done around this time and this was not a foreign concept. Why did the chemists, psychologists and psychiatrists skip these steps and run observational studies and not bonafide clinical trials? This is something that can spur a healthy debate. Why was there a paucity of randomized controlled clincial studies to show the peers, the regulators and everyone involved that the effects were not subjective or made up, but one that has strong scientific grounding. Well, if you disagree, let me tell you that the first randomized clinical trial was done in 1948 which explored the role of “streptomycin for the treatment for pulmonary tuberculosis” .

You dont believe me. Here is what the book published in 1979 called Psychedelic drugs revisted, authored by Lester Grinspoon and James Bakalar said – “Many people remember vaguely that LSD and other psychedelic drugs were once used experimentally in psychiatry, but few realize how much and how long they were used. This was not a quickly rejected and forgotten fad. Between 1950 and the mid-1960s there were more than a thousand clinical papers discussing 40,000 patients, several dozen books, and six in- ternational conferences on psychedelic drug therapy. It aroused the interest of many psychiatrists who were in no sense cultural rebels or especially radical in their attitudes.”

JoJo:

Sure, but to our knowledge and through careful research that we have undertaken, none of the few thousand clinical papers discussing 40,000 patients were controlled clinical trials that were needed to approve a drug for clinical use. So in the absence of that, one could argue that the field brought all of this on itself.

Why do we say this? Not because we do not believe in the potential but because if the field of psychiatric medicine needs to make a claim, 40,000 patient administrations might provide a great feeling about safety in a clinical setting, but to clearly identify signal over noise, a proper clinical trial is needed. This is so cruicial to understand because no drug should ever be used without a proper study and if things were done without a good scientific rigour, it deserves to wallow in the wild.

This is the point we have a very critical pivot in the podcast. One from where the drugs went from the vial to the mouth, to one where the field realized that a more considered approach was needed. This is because the people who wanted to change the world’s view decided that to fight against the taboo, they needed to have a rock solid proof without passion or prejudice to build evidence. And that evidence should constructed like a fortress, whose bricks needs to be laid one after the other, fixed its place by mortar, all of which is to be done transparently and within legal means.

So can we dig in?

The first personality that we are going to pick up is Amanda Feilding. Amanda was born in the same year that Albert Hoffman took his first dose of LSD and had the famed bicycle trip. But Amanda’s life would read like a novel, except that none of her life was fiction. She was born into a well-to-do British family that possessed a Tudor hunting lodge and possessed a peerage. Amanda’s father was an Earl. So it is fair to say that compared to the rest of the society, she had a privileged upbringing. Growing in a Tudor Lodge and being exposed to parents who held mysticism and books about eastern religions, young Amanda was thought to have been lost in mystical thoughts so much so that in search of such a life changing experience, she left the UK to see her uncle who was stationed in Ceylon, as Sri Lanka was called back then. But with a mere £25 in her purse and no passport, her journey only got halfway to the Syrian Border. There she is said to have met a group of drunk bedouins who owned a cadillac and were in utter shambles and sixteen year old Amanda’s driving is said to have helped the group to drive out of the desert to their encampments. There, Amanda found some interesting learnings about the nomadic lifestyle and the free-spiritedness that came from it. A year later, she arrived back in the UK to pursue comparative religious studies and mysticism degree at Oxford. Much like the stories we heard about social and recreational use of LSD, Amanda had her first LSD experience at a party in the 1960s. This experience was so bad that ultimately she had to cocoon herself in her paternal home near Oxford in the UK. A few months later, she met a medical student from Holland, who had some radical notions. This young medical student, Bart HUghes had a huge influence on Amanda’s life. Bart and Amanda experienced many LSD experiences. Bart Hughes was massive influence on Amanda’s life. Bart was convinced that alterations in cerebral circulation and the cerebrospinal fluid led to changes seen in adulthood and predominantly, the personality changes associated with ego. Bart Hughes reasoning was that a process called as trepanation which involved drilling of holes in the skull would lead to normalization of the cranial blood and cerebrospinal fluid ratio and improved cerebral circulation. Before you wince, we must say that trepanation is a process that was undertaken in many ancient cultures dating back to the prehistoric, neolithic period around 6500 BC, Ancient Chinese, Middle EASTERN AND mesoamerican cultures. In fact, today’s neurosurgical practice to treat hematoma in the brain involve a variation of trepanation. Bart and Amanda’s hypothesis was that just like how the childhood mystical experiences decrease with closure of the fontanelles, when the cranial bones fuse, trepanation was said to unlock a form of mysticism by altering the blood circulation in the brain. Why are we bringing this aspect into the podcast? It’s because these very thoughts were the foundations of Amanda Feilding’s fascination with psychedelics. These were so radical at the time that the popular tabloids and establishment did not take very kindly to either LSD or trepanation. Amanda and Bart are said to have escaped to Netherlands via a boat and after a few months, the pair split and Amanda move to the UK to live in her tudor estate.

Arun:

But the following years, according to her own admittance, were a bit revelatory. Amanda, driven by her father’s struggles with diabetes, had an inspired moment whereby she decided that the best way for her to understand and manage her cognitive function. Through the period in the 1960s when LSD was still legal, Amanda was said to have self-experimented with LSD and assess her performance in a competitive game of Mahjong against her friends and house help. She made the conclusion that LSD somehow altered the circulation in the brain that was similar to trepanation. While there are more colourful accounts of Amanda Feilding in popular press, her realization after the 1971 ban is something that needs to be admired. Through her art, she made quite a few acquaintances and managed to maintain a reasonably low profile with trepanation attempts surfacing from time to time. All of it came to its head when she realized that she needed to fight the battle against the prohibition of psychedelics in a way that would look scientifically credible.

Spurred on by what she perceived as a bad policy that prevented humans from approaching their right to have a mystical experience and with an indomitable spirit that had confidence in the ability of psychedelics, Amanda set out to chart a plan in 1998. We will come to this in just a bit. Until then, hold on. We need to tell you another parallel story.

JoJo:

The scene now moves to 1970s America to explore the impact a twenty year old man born in Chicago had on the field of psychedelic research. Rick Doblin was born in a conservative jewish family to a pediatrician and a school teacher. Doblin, the eldest child of four, decided to drop out of college after to study realms of consciousness and an LSD trip. Though his parents, like what most parents were shocked, they let Rick follow his dreams. Rick enrolled himself in liberal arts college in Florida. Unlike other universities that follow grades, evaluations at New Florida State College were contracts between the student and the counselor. Young Rick was said to have been introduced to the noted Psychologist, Stanislav Grof’s book = ~Realms of Human Unconscious: Results from LSD experiments and was said to have been fascinated by it. But here, buoyed on by careful experimentation accounts, Rick understood the value of preparation and integration in psychedelic practices.

As is the case with people who search for a goal, Young Rick attended to some immediate priorities by working in construction for a few years before his interest in psychology peaked again. He approached Stanislav Grof and worked with him to understand non-ordinary states of consciousness as one would experience through practices like yoga, meditation and psychedelic experiences. Rick Doblin through his work with Stan Grof became a holotropic breathwork practitioner. All of this fascination in psychology were realized in a key fundamental principle – that the key to an effective psychedelic experience was the presence of adequate psychotherapy and support. Rick’s realization came from two specific historical studies that he went back to. We alluded to one of them in episode 4, where Rick Doblin was the first one to interview the prison inmates from Leary’s Concord Prison experiment, to find that the prisoners received little to no after-care or integration sessions. And, Timothy Leary fudged the data. Rick Doblin published these results in 1998.

Another study that pointed Rick’s outlook to how a psychedelic therapeutic session must be conducted came from the Good Friday Experiment. Rick Doblin published these results in 1991, a few years before the results of the concord prison experiment. If you are wondering what this is, it was an experiment that was conducted by a Harvard theology student, Walter Pahnke, under the supervision of – you guessed it, Timothy Leary and Richard Alpert as part of the Harvard Psilocybin Project.

Arun:

Walter Pahnke, along with ten other graduate students who served as research assistants in the study recruited 20 graduate students to take part in two groups. Subjects were randomized to two groups – one active drug group – psilocybin and a placebo – nicotinic acid. Nicotinic acid was chosen as the placebo it provides with a vasodilatory response over the skin resulting in a warm feeling. The students were then asked to take part in the Good Friday service and upon Leary’s insistence, the religious leaders were also provided with either a drug or a placebo with the psychedelic group leader having half a dose of psilocybin and the other group leader having a placebo. This was according to Rick Doblin’s paper – “to provide a complete mystical experience and lend necessary confidence to the subjects” However, the group leaders were not followed up with any questionnaires but all the study participants were. If you think, this is a serious pitfall, I think you are not alone.

The problem with this experiment was that the psilocybin’s effect was obvious to those who received it as the subjects were talking to each other and the blinding was broken during the ceremony. But Rick Doblin, in his follow up interviews surmised that none of the subjects were prepared in any shape or form for the experience and this led to acute episodes of panic among the study subjects.

Secondly, the questionnaire created by Pahnke and Leary was unlike anything else at this time. It did not measure anything that could be denoted as Christian and was dismissed by experts later on, who developed more pointed questionnaires. As a result, the two experiments that Leary spearheaded, despite the whole “set and setting” were not conducted well. So, Rick Doblin asserted to himself that an effective psychotherapy with psychedelics should include preparation, support during an experience, followed by integration and follow through. Despite all this, one thing was clear. The Psilocybin treated volunteers did unanimously agree that their experience was unlike any other than they experienced in their life, coming back to the effects of salience that we explored in the pharmacology episode. I think we should also mention to you the conversation Rick Doblin had with Timothy Leary in the 1990s chronicled in the Boston Magazine a couple of years ago.

JoJo:

“. In 1990, I asked Leary, “Based on your long experience with psychedelic research, what is your advice to us about how to try to bring back psychedelic research and make it into medicine? How do you suggest we work with the government?” He said, “I am so far past asking the government for permission for anything, but I’m glad you’re doing it.” So he’s like, Fuck the government. And we’re like, Let’s become mainstream.”

Arun:

But Rick Doblin’s journey beyond these realizations are unlike any other. We will come to that again in a few minutes. But to understand this convoluted yet legal path that Rick Doblin took, we must go one level deeper. We must rewind our clocks back to 1960s to a very industrious chemist, who made a very profitable pesticide called Zectran for the Dow Chemical company and was referred to “As the most important scientist of the 20th century”.

Dow Chemical company, in return for the discovery of their most profitable pesticide patent gave the chemist utmost freedom. Until the 1940s, when this young scientist went on to start his career for Dow Chemical company, there were two psychoactive substances – one was mescaline and the second was cannabis. LSD came in 1943, psilocybin in 1959. But by the time, the 80s ended, the world had come to know of more than 200 synthetic compounds through the work of this chemist who synthesized molecules that were, are you ready for the list ??

Stimulants, depressants, aphrodisiacs, ”empathogens,” convulsants, drugs that alter hearing, drugs that slow one’s sense of time, drugs that speed it up, drugs that trigger violent outbursts, drugs that deaden emotion — in short, a veritable lexicon of tactile and emotional experience.

The scientist that we are talking about is Alexander Shulgin. In plain sight of the DEA, Shulgin synthesized most of these substances in his backyard laboratory. You can call Shulgin the unwitting genius or the Heisenberg of Psychoactive substances.

JoJo:

Shulgin’s first psychedelic experience was with mescaline and it was said to have influenced a lot of his work, including the famed patent for Zectran, the block buster pesticide. With new found freedom that Dow Chemical company provided, Shulgin decided that it was time to indulge in making psychoactive substances of his own and even published influential journals like Nature and Journal of Biochemistry. Dow Chemical company is said to have been slightly alarmed at their name being used widely in papers on psychoactive substances and asked Shulgin to not use their name as an affiliation. It is weird, to think of it. Shulgin was using Dow’s resources to publish research but Dow Chemical company requested him to not use their name. Requested? Don’t think this would ever fly today.

What did Shulgin do? He parted ways with the company and set up a lab in his backyard called as “The Farm” where in plain daylight, he could carry on with synthesis of new psychoactive substances while still serving as a consultant to the DEA. During this time, he synthesized many of these substances and provided it to the DEA. Was it a conflict of interest? If you think there isn’t one, let me tell you a bit more to see if I can persuade you to change your mind.

Through these processes, he managed to published two books that were cult classics of the scientifically inclined in the 1970s called TIHKAL and PIHKAL – standing for tryptamines, I have known and love & Phenyl ethylamines I know and love. So, in the face of the prohibition, as a DEA funded analytics lab, Shulgin manages to avoid scrutiny. Or was Shulgin such an amazing operator that he managed to have both DEA on his side and also publicize his books. Shulgin always maintained, right up until his death that he did not intend for any of his substance for recreational use. But talking the talk is different from walking the walk.

Just like Hoffman, Shulgin does something weird and wonderful. I sometimes wonder why people would ever do anything like this. Shulgin knew that he was researching amphetamines and amphetamines by nature, would mimic the effects of adrenaline. Somehow, he assesses what would be a safe and tolerable concentration and manages to take a lower dose of the drug himself. Once again, serendipitously the world gave rebirth to a molecule that was synthesized in 1912 but was now tested by shulgin himself. Shulgin noted a remarkable sense of euphoria and recommends it to his psychologist friend, Leo Zeff. MDMA through Shulgin’s network in California had spread to use in many psychologists who found the empathy heightening nature as a tool that could be used in couples therapy. Once again, a drug went from the vial to the mouth to popular usage, right under the DEA’s nose, but neither did the establishment nor the scientists think it was time to test in a formal way.

Arun:

There is a counter argument for this, too. Many will say that when Shulgin recommended the drug to his psychologist friend, Leo Zeff, it was still legal. Zeff, a former US colonel in the US army prior to being a psychologist, did not do anything illegal. But honestly, if one needs or wants to develop a clinical use for a synthetic molecule, one should not implement it without performing appropriate safety and dose ranging studies. It was not illegal then, but runs a fine line of whether or not it was ethical, as there wasn’t even an investigational study protocol or a peer review. But Zeff was not alone at the time, many psychologists were using MDMA in clinical practice.

Why are we talking about this? Because once Alexander Shulgin’s methodology of synthesis became known to other underground chemists, the market for MDMA grew exponentially. The question remains should “The Farm” run by Shulgin have freely disseminated the information on synthesis that laid the groundwork for recreational use in the 1980s. Now popularized by the happy 80s disco and concert cultures, MDMA found a new use at bars and music festivals. What was iinadequately addressed, was the non-psychoactive side effects that are associated with MDMA that led to many deaths predominantly via dehydration and hyperthermia – both are which are classic symptoms of hyper-adrenergic response driven by amphetamines.

So was Shulgin an amazing scientist or a person who miscalculated the effect he could have on popular culture? Well, as we always say, we are the gardeners sowing the seeds, you as the intelligent listener can make a decision.

JoJo:

So, the slow to react DEA, bans the substance in 1985 and placed it in schedule 1 of the DEA drug classification. And guess who was at the centre of its legal appeal. Yes, Rick Doblin, of course. The 1985 ban and scheduling of MDMA into schedule 1 meant that the substance had addictive psychoactive properties and did not have therapeutic value.

But MDMA as per the psychologists of the time, had a therapeutic value. There were multiple clinical experiences and discussions in conferences that rendered it to be useful in clinical practice. So was the DEA wrong and did it over-react? So what were the logical next steps?

Many proponents of MDMA psychotherapy filed for a legal appeal and Rick Doblin spearheaded the effort. But Rick, who was 32 years old at the time, decided that things needed to be done formally to change the view of the world. This I think was the seminal moment in Rick’s career. Rather than falling into the trap of all those who came before him who evangelized the use of psychedelics, Rick Doblin decided that the best way to counter this was to fight the battle the right way. But as you can imagine, the battle was largely disproportionate in nature and Rick Doblin had to resort to philanthropic donations to restart this lonely path to legalization of MDMA as a therapeutic tool.

Between 1985 and 2011, Rick Doblin and his team at MAPS, a charity organization that he founded single-handedly, took up the case for performing studies as it needed to be done for a new drug. The toxicity studies were published in 1987. Through formal engagement and extremely tough negotiations, Multi-disciplinary association for psychedelic studies launched it formal Phase 1 clinical trials in 2002. But the path to pivotal trials to test the efficacy took another 15 years. We will come to the results and the efforts in a later episode, but the efforts of Rick Doblin in unpicking the past studies and figuring how to legalize psychedelic treatments should serve as an inspiration to all.

But that was the case of MDMA, an atypical psychedelic molecule. It is atypical because, it does not affect the 5-HT2A receptor that we discussed in the last episode. So what happened to the other molecules like psilocybin or ayahuasca derived tryptamine – known as DMT? How did they accomplish initiating clinical trials with psilocybin or employ the synthetic substance that caused the psychedelic experience in Ayahausca – DMT or Di-methyl tryptamine?

Well to understand this, let us go to an expert – Dr. Mark Geyer. Dr. Geyer is a psychopharmacologist at University of California, San Diego and has been one of the few behavioural neuroscientists who employ both pharmacological and behavioural approaches to study drugs.

Here is Mark Geyer, detailing how and why he got interested in psychedelic science.

Mark Geyer:

\Sure, I grew up in Oregon and I went to school at the University of Oregon and then the University of Iowa. moved on to finish my PhD and at the University of California, San Diego, in 1970, I came to San Diego. It was at that time because I moved here because the founding chairman of the Department of Psychiatry, 34 years old, recently discovered an enzyme in the brain of rats that was metabolizes serotonin into a psychedelic one that if given, just technically would be passed, spread blood brain barrier, but basically, it’s a compound related to was the active ingredients and I Alaska, by the taxi, and then dimethyltryptamine or just straight, and then dimethyltryptamine or DMT, the so called spirit molecule, and at that time, I was coming out of the 1960s.

Well, I was interested in psychedelics are a number of reasons. Some personal, some academic, so I joined Arnold Mendell, the new chair, as a graduate student, just studied this new binding,

which turns out was not a real binding. I mean, it was not a robust binding, it turned out to be an artefact in layer chromatography, at the time, so the actual data were dismissed. But I went on to finish my PhD there, rather rapidly working on what was then kind of a newly identified neurotransmitter called dopamine. But I began working explicitly on psychedelic compounds in 1974. But my first psychedelic paper was on and then dimethyltryptamine, and rats in 1975. And it got a grant in 1976, from the National Science Foundation to hire about a dozen undergraduate students for a summer programme, in which we studied the effects of LSD primarily in a variety of behavioural tests. Matt moved on to starting a course in the next year and the University of San Diego, California, San Diego, dimensions of consciousness, which is the really successful one term course for which I still have the syllabus today and would be as relevant today as it was that I think, the dimensions of consciousness and those questions have not changed all that much in the decades since.

Mark gave us some great insights. He started his graduate student research career just when the 1971 war on drugs came into force and he mentioned that he was working on some of the psychedelic substances all the way until 1975. So was the ban really, not a ban? Or was the enforcement slow?

The band wasn’t an instantaneous event. It was a process. So initially, it wasn’t Very difficult. I got a grant from the National Science Foundation to do this study on psychedelics with only undergraduate students and lab assistants basically. And it got us one licence from the Drug Enforcement Agency in order to obtain the compounds through nyda. Not at that point, it wasn’t very difficult. And then the next year, the California research advisory panel sent my mentor Arnold a letter saying to cease and desist his work on mesclun because he had published a paper I will author but because it was a paper on the effects of mescaline and pigeons. And he had done this without the approval of this California legal committee approval Committee, which we didn’t know existed. So we’re Wait, it was in a sense, ironically, we just asked for things and got going without much difficulty, partly because we are ignorant of the newly established regulations. So once we learned that there was a California required California State approval process, well, then we, of course, submitted our application to them, and they got approval, but we got the first letter, warning us about it. Without having done it they have their existence. So it gradually became a little more difficult, but I think I kind of got in under the wire before the rules had been changed, but the implementation hadn’t occurred. So I’ve had that schedule one VA licence ever since. And I’ve kind of been grandfathered into that programme. And of course, I submit my annual reports and my annual reports to the state of California as well. They’ve changed their name from California research, advisory and electric works, we always call crap as an axiom. So now that the research advisory panel of the state of California rap sheet, but we are beholden to them, and we’re very beautiful. It’s critical to cross all the T’s and dot all the i’s and be very, very cautious. And of course, a lot of the reason my work was acceptable was it was only an animal I was interested in psychedelics. Because of what I thought we could learn about naturally occurring psychosis is very impressive to me that a compound in milligrammes or micrograms even could change one’s mental state, so dramatically, and in ways that were reminiscent of the reports of, especially schizophrenia patients that a number of different definitely labelled psychiatric patients with psychosis. And I thought we could understand something about how the brain functions normally and that normally, by studying the mechanism of actions of what we then called hallucinogens for psychopathy mimetics. But the National Institute of Mental Health wouldn’t consider such work. They had dismissed the notion that we could learn anything about psychosis from these compounds out about the time in the 1970s, mostly because of the rapid and profound tolerance onesies with these compounds in both humans and animals. So they dismissed the psychotomimetic bottle. So my research then needed to be funded through the National Institute on Drug which

they are not interested by definition, and studying psychiatric conditions other than substance abuse. So I had to, of course, couch my research applications in terms of negative aspects effects that I had funding from the National Institute on Drug Abuse to study hallucinogens, beginning in 1981. And ending basically with my formal retirement. So I was able to continue my work. Addressing the mechanism of action of listening genomes and the packages and DNA and others, the cycle of AIDS and other psychotomimetic was support from the National Institute on Drug Abuse, obtaining all the compounds through and through the VA, and really had no particular problems are typically the ones we were working in units. And it was a band, if you could call it a band that was not very heavily enforced. for ethanol research. There were four or five labs all throughout the US decades from the 70s to the 90s. In the US that had NIH support for research on those regions. So there were many of those. Turned out later when Rick Strassman decided he wanted to do some studies with DMT in humans, he kept asking for what the rules were preventative. Turns out that the federal government didn’t have actually explicit rules that prevented that research it was they had these constraints, application and approval processes, but there was actually no formal prohibition in

in the law, and the federal law.

Ok, so we now know two things – One, there was some research that was undertaken in the US but under a very careful watch and the enforcement of which is comical in itself. That DEA found out when these studies were undertaken and decided to ensure all future studies obeyed the guidelines they set forth.

Second, after working through animal studies as new neurotransmitters like dopamine and serotonin, when investigators wanted to study these compounds in humans, suddenly it was taboo. It is like what I call in a group meeting – zombie decision making, where no one knows who made the decision but somehow there is a perception that something cannot be done, when nothing was written down in law, especially one pertaining to prohibition of exploration of Di-Methyltryptamine in human clinical exploration.

Arun:

Mark Geyer, mentioned the name Rick Strassman, whom many in the area will know from his extensive work on DMT. DMT or Dimethyl Tryptamine is seen as a spirit molecule because experience with DMT was so quick due to its pharmacological properties. DMT also was called as a spirit molecule because it opened up the world to a very unique spiritual experience. While with LSD and Psilocybin or even peyote, the visions were one of grand scale kaleidoscopic patterns, DMT triggered visions of spiritual beings from ancient mythologies and in some cases, even sentient beings that resembled aliens like a clock elf or the machine elf. DMT was so unique that the half life was literally a matter of a few minutes so it became referred to as a businessman’s lunch in urban parlance because a psychedelic trip with DMT would fit within the lunch break of soulless cubicle slave.

So how did Rick Strassman get into DMT testing in humans? Well, here is Mark Geyer again recounting the occurrences of the time.

Mark Geyer:

For psychedelic research in humans, Jed Wyatt and Chris Gillan, when Chris was at the intramural programme at the National mental health, hospital, had done a study image with DMT. And Chris was joined our department

After I arrived, he’s genuinely a wonderful person and a very good scientist. He had mentored Rick Strassman, some and noticed that paper on what he called the spirit molecule that will publish from within the National Institute of Mental Health. So maybe there’s a way to do this. And it took a lot of dialogue for education. Finally, the government had to acquiesce because they couldn’t find the rule within their books that was actually permitted and what was perceived as a ban wasn’t actually a horrible ban. Everybody just acquiesces to the presumption of a ban. When there was not.

Yeah, yeah. Yeah. Well, I think he had something of a similar path. Of course, Rick was interested, not in a classic tech show. He was a detective called MDMA or ecstasy. And I don’t remember what year it was, but MDMA had been used, but not by ISIS, scheduled as a forbidden substance in our schedule, one substance and psychotherapists. Were using it clinically, with great efficacy apparently. So a lot of psychotherapy, several psychotherapists in the US and abroad, are using it in clinical interviews to increase the transference of the connection between therapist and patient and to enable the patient to get in touch with his or her feelings and experiences and share them. And it was thought to be a very, very effective adjunct to psychotherapy. But then the DEA, I guess it would be the DEA took note of the fact that people were starting to use recreation and schedule one compound technically is supposed to have abuse potential and be utilised in the subculture and therefore require control. So once it kind of hit the streets, then it became more widely known by the lay public. The DEA stepped in and put it in this go to one category, thereby precluding the psychotherapeutic use, about the time the wreck, who is passionate about the values, clinical values and experiential values. Not necessarily patients have just heard of MDMA took up the fight in a sense and laboured long and hard and successfully, to re resumed enables a resumption of the psychotherapeutic use of MDMA, with a goal of course of enabling the resumption of the recreation or personal choice use of MDMA, even outside of a psychotherapeutic setting. I believe that say it’s fair to say that rape isn’t only interested in having MDMA available to therapists but to people in general. And rarely, clearly, he’s been effective, that he’s been a determined dog and advocate for the use of the impact in that type of setting. And the work you’ve done with the Getty is remarkable and very promising.

JoJo:

So Rick Strassman moved to researching DMT because MDMA was in the schedule 1 category. Now do you understand how the various personalities and journeys of people are intertwined. The journeys of Rick Strassman and Rick Doblin ran in parallel, while one argued from a patient advocacy and clinical psychology angle, another argued from the point of pharmacology.

So in a series of three papers in the late 1990s, Rick Strassman demonstrated the safety, tolerability effects of DMT and documented the psychedelic effects of DMT. DMT, as Mark Geyer noted, is an endogenous serotonin-like molecule, and is an active ingredient of the Ayahausca vine. We will have more about Ayahausca in a later episode because we wanted to bring you the journey of psychedelic through the prism of people and their experiences who brought about the change.

So Mark and his colleagues decided that it was time to start something on the other prohibited molecule, Psilocybin. One of Mark’s close friends and peers in the area was another pharmacologist called David Nichols, who also happens to be at University of North Carolina, Chapel Hill. Here is Mark Geyer again, recounting some pivotal personal and professional moments that are previously unchronicled in the history of psychedelic renaissance that we see today.

Mark Geyer:

Dave and I were friends and colleagues, because of shared scientific interests, and worked together. Somewhat before we began discussing creation of Institute and the idea of creating and certainly originally, he contacted a few of us to see if we might be interested in Another and the original motivation was recognition that most of us were products of the 60s had been determined throughout the dark years to keep the science of psychedelia alive. Feeling intellectually, potentially very important. We learned a lot about brain consciousness from the study of these compounds. But there was no nobody following in your footsteps, students would come and say, Well, how do we get into this field? We had to say, we can’t recommend it, because it was so difficult to come by that it’s not a very viable career path. We were aware that when we retired, this field would dry out by at least in the United States, there was still ongoing work in Europe. So Dave did some arm twisting that we all felt it might be good to develop, an institute that would try to rehabilitate psychedelic science and bring it back into the mainstream. We were aware of Rick’s efforts, and Rick was a much more politically oriented person. We wanted to be a very mainstream science or organisation, literally to overcome the bad reputation that the overly enthusiastic reports in the 60s from the 60s generation from Tim Leary and others have given the science of psychedelic research a bad name and a lack of acceptability within the scientific community. So we wanted to create an organisation that would do mainstream research on mental illness. So the presentation of psychedelics is that we have to be holier than the pope. We had to, we were aware that we needed to have the highest quality science in order to rehabilitate perception of psychedelic research in the United States. So we started after this to the early stages, we were thinking that there would be a physical building property in New Mexico, we thought about talking about maybe getting an architect renderings that we could go to funders because the regulations were simpler, because of the Native American church presence there. constituency population are accepted because originally retracement and then written stay with you have to add he was that George Greer took over kind of the position records brought to the original thinking. So it was that we didn’t start out thinking we’re going to be doing. We thought that a living course that worked had important implications for not just psychiatric research, just understanding of human consciousness and experience and rating mechanisms controlling perception that affect important functions that were abnormal in psychiatric disorders. Our original goal was specifically to identify therapeutic treatments, understanding treatments, and several of us were very sceptical that there would ever be a clinical treatment outcome. So

1983 was when we formally had our first meeting, and event Centre in Mount Baldy and there had been discussion I think it was Dave who had done the reading mounish meterpreter karkos Carpathia history adapter, we wanted a name that had no much baggage. And so we muddled along for an identity and a narrow mission, we started with a very broad mission. To get a bunch of people interested in consciousness and psychedelics, we have a plethora of ideas and, and notions and directions on to go. And we kind of went all of them. And none of them in particular, we had one dedicated person who joined us at partly as a funder. And he said, You need to take the captain be the captain of the ship and decide which direction to go not let the funders dictate it. And identified more narrow mission. By that time, and pretty much given up on the idea of instantiating, a physical Research Institute, it was hard enough to get going to get enough funds to to fund a number of research studies, we developed a portfolio kind of a menu of research studies that people had worked on that we had reviewed, not very systematically but well through a very systematic, orderly review process. And be offered that kind of programme menu of opportunities for funding programmes and studies that with different people might be interested in helping funded, some of those were successful, they started getting some money. And we had some sustaining money from Bob Wallace, who was number six man at Microsoft. And he was also very astute and chemistry not just computers and fascinated by altered states of consciousness in general and psychedelics in particular. So he was the sustaining funder of Heffter for a number of years prior to his early demise, unfortunately. But that that steady stream of money especially funded basic research 93 was a pivotal year, not just for the dramatic in my life, not just for the inception of Heffter. But I was invited to a very quiet meeting in the south of Switzerland. Write the 50 year anniversary of Albert Hofmann the discovery of LSD was actually paid for by Sandoz, but even Danny Santos didn’t know it was happening. You had to invitation only if you’ve done research on LSD, then you’re on some less than some set of organisers had. I don’t know exactly who those organisers were. But at any rate, we had a very interesting meeting that maybe 100 people.

Sandoz didn’t advertise or publicise the fact that they were funding and supporting. And it was a pivotal time for me personally, because I met profitable and better and as soon as we had our top five, Anita and a number of other researchers established a couple of collaborations with us, because they were mostly in Europe. They continued the Swiss tradition of funding human research. For us in the US, it was the dark years and so there was a tradition and I was able that time to start working with rigidity, Germany with bronze. By virtue of that collaboration, I began collaborating because of that meeting, and then that person, maybe once I got going with Ron’s writing prompts into After a few years later, he became a critical part and we raised enough money to take a day tonight. sizeable checks to process Chairman, secondary research institute scissor church is ready it was intended probably on the other side doesn’t work. Still there and retirement. Human psychopharmacology has great reviews. And we were able to take this substantial Chapman.

So, the Heffter Research Institute was started in 1993 and Mark Mentioned some very seminal names in the field. Franz Vollenweider who contriubuted immensely to this area via brain imaging scans and neuropharmacological studies was funded by Heffter research Institute.

Arun:

But for a moment, can we stop and reflect on the name Heffter research Institute? Why was the research institute that these researchers saw the last bastion of passing on the knowledge in a formal way to the next generation called Heffter Research Institute? WHy was it not called something else?

According to Mark Geyer, it was a brain child of Prof. David Nichols. David Nichols and the leadership group established the institute in New Mexico as it was the state with least degree of legal resistance owing to the Native American church. But why did the research organization needed to be called the Heffter Research Institute.

Well, if you guessed half the answer that peyote contains mescaline and New Mexico’s Native American church connection, that is only part of the answer. The other more important part was in the real work beyond the discovery of mescaline that Arth ur Heffter performed. After all, we promised that we will come back to this in episode 2.

Arthur Heffter’s seminal contributions in pharmacology and toxicology is still in vogue today. Can we list some of his seminal contributions? If you are a scientist, this should really pique your interest.

Heffter was the chemist and pharmacologist who developed chloralose, the anesthesia used in many animal experiments and also one that is used by many large animal physiologists to this very day. Why, because chloralose as against every other anesthetic agent does not impact the autonomic tone. He also figured out a way to measure lecithin concentration in the liver as a means to understand phosphorus poisoning. This is used clinically to this very day.

He measured the lactic acid concentration in muscles in response to paralytic toxins like strychnine, curare and carbon monoxide. So you can imagine how these tests have an impact in forensic toxicology. He was also instrumental in isolating other alkaloids from fern root that was used as an anti-helminthic agent to combat intestinal worms. So if you have been to a pediatrician and have used a de-worming therapy in tropical countries in children who lose weight rapidly, Heffter discovered one of the first medications for de-worming.

Furthermore, later in his career, through a collaboration with his dermatologist friend, he became incredibly interested in the impact of chemicals and its metabolism in the human body and how it can be detected. What did this lead to? Well, Heffter documented the the absorption, distribution, and excretion of iodine, and the excretion of lithium, mercury, and quinine. And if you watched enough of crime series on TV, Heffter was the first to recognize the deposition of arsenic in hair, which led to the well known forensic test for arsenic poisoning by hair analysis.

So, In David Nichols’ minds, if they wanted a non-controversial name and one that would unlock the prolific potential of psychedelics. So Heffter Research Institute became the logical choice.

Here is Mark Geyer again:

Mark Geyer:

So it was through that mechanism that we began to see the opportunity to do human research. And then, in the spirit of becoming the captain of the ship and steering it rather than opening the doors broadly to investigator initiated studies, we decided, well, strategy would be to get some psychedelic out of schedule in one category. So the end of the hands of clinicians so that we can find out what it might be good for. silicided was chosen, not because it’s the best compound, but because of practical, we already we have hundreds of already kind of focused on silicided because that long history of us and humans with no concerns for safety, Sandoz have actually run that through toxicology and marketed as a compound was called sensor. Long time before psilocybin psilocin. So 1000 Yes. So there was, you know, a track record of safety, not speeding standards and today’s toxic toxicology. But of course, there’s a track record of use through mushrooms with very, very, very few very untoward consequences, it was relatively safe, it didn’t have the political baggage of LSD has, the scary perception in the community. And it was short acting relatively, you’re going to do experimental medicine and studies to have to keep the volunteer overnight, there’s a lot of expense. And if you have to do a study, brain imaging or whatever, with LSD, you’re not going to be able to let them go at the end of a four hour day, or a six hour day. But with psilocybin, you could. You could have come in at nine in the morning and do the study and let them go home. monitor them to make sure they’re ready to go home by the end of the workday. The trip is gone because the time course was critically valuable to enable the early experimental medicine studies of mechanism and phenomenology. So it became our target compound, one that we thought would be the fastest and easiest to establish possible political advocacy. And thereby break the scheduling barrier because schedule one requires a compound not have medical use. So we had a compound that had been psychedelic, that had medical use. And we reasoned that by definition, it would be in the scheduling category anymore. We’ll see if that works out. The initial studies that are out there are amazingly impressive in their efficacy. Through the years, Franz and I in particular, have been among the most sceptical within the Heffter community, reaching, demonstrating clinical work pleasantly amazed and surprised.

What’s amazing and surprising is not that they can help someone in the short term but that their clinical effects seem to be so long lasting. And it has gotten us into this neuromodulation neuroplasticity and to try to understand that a lot of us love to understand how that’s happening and there are ongoing debates as to whether one needs to psychedelic experience or just just need to a agonist activity to occasion this whatever the centering modulatory neural plasticity change that must be mediated by the brain to change, emotion, affect mood, behaviour, three or four months later, after one or two administrations. Those effects are not pharmacological in the sense of the compound is still present in the patient. But the patient has been transformed. And most of us feel that that is a transformation occasioned by the profound experience that is produced over the course of several hours by the psychedelic pharmacological action.

Arun:

So,if you have read any of the recent publications that detail patient interviews from the psilocybin studies, this is how it came to be. But what patients did they study first and how did they move into clinical practice and convince the FDA that there was something useful for patients who volunteered without impacting safety.

And these amazing scientists took a very pragmatic approach, but their approach was also a brilliant one. This was also around the time that the field of safety pharmacology was coming into focus and anti-cancer agents was coming into vogue. While anti-cancer agents of the time were supposed to be cellular toxins and therefore as a result affected the cancer cells more, but the function and the molecular actions meant that they were producing side effects. Such side=effects would not be tolerable in an otherwise normal person, say who is ingesting medication for hayfever, but a cancer patient might be willing to take such a treatment, tilting the risk-benefit ratio to a more favourable one.

So the Heffter funded studies looked at impact of psilocybin in end stage cancer patients who by nature of their prognosis had some form of mental depression. So it was reasoned that if there was any impact of improvement, this might be a logical first step in clinical exploration.

Here is Mark geyer again:

Mark Geyer:

So Charlie Grob was one of the original Heffter people. And Charlie Grob was at Harvard. UCLA, and he did the very first study, a safety study and got FDA approval to do a safety study with in end of life stage cancer patients. It was a safety study, but it was a safety study to consider the possible application to end stage of life, anxiety and depression. So the only clinical readouts that they used were anxiety and depression scores. That was 11 patients. And, you know, there were never changes in the DMD. And, obviously, anxiety scales, but there was no control group, there was no, it wasn’t a proof of concept study. efficacy, it was a safety study. And of course, being in that population, the FDA is concerned about risk and benefit greatly mitigated. So the population was in part chosen, because it was a population that the FDA would allow someone to take the risk of the Minister silicided, to humans. So Charlie, a really gifted child psychiatrist was actually able to get the study guide, he and Dennis McKenna had done a lot of similar epidemiological work with Iosco in Brazil. And that’s been his major scientific effort before doing this one safety study. But he wasn’t much of a statistician, he didn’t know how to analyse the data. So a postdoc of mine, Albert Halberstadt, was on the paper because they handed all the data to Adam because the clinician didn’t know what to do with the data, politically.

So that paper was published in the archives psychiatry team in 2011. Not sure about the date there, but there was a little report, not very long afterwards. Hector supported study.

Francisco Marino, I think six patients with OCD. That was fairly early that followed the initial cancer study, data study. And there were claims of clinical benefit and the LGD study, but statistically, there was absolutely no, nothing that one could publish data to support such a claim successfully. I think it was accepted. So that there was enough, you know, write about it actually done. raised the possibility by simply doing the study. And somehow the possibility was bigger than the outcome in terms of the impact.

So that opened the door to studies in bill populations we recovered, were transplanted who had been the Pioneer to do the first humans have been healthy volunteers, in the US with DMT. DMT didn’t have the kind of safety track record, only lasting less than an hour. So the risk there was he was cut off, he cut off those studies when he tried to do interaction with a beta blocker, which he got permission to do I had to do the animal study that FDA required This is that he couldn’t find any evidence of any mammal ever having been receiving both the beta blocker and DMT. And the FDA wanted to know that that wouldn’t kill people or animals. So I’ve never published it. But he started when he started doing those studies. He had a patient or subject non patient with hypertensive crisis so that he cut off those studies. There was some interaction that he was concerned might be dangerous. So that work never continued to try to understand that.

There was a pharmacodynamic motivated study. But other than Rick’s study, I don’t recall anything between that and Charlie’s first foray into psilocybin and to help heal populations, potentially patient population. So anxiety and depression, I think, the very first indications that show is a hint of efficacy. Because the study wasn’t designed yet.

Arun:

So this is how the journey of psilocybin in regimented and legally transparent psychotherapy clinical trials came to be.

But, we aren’t done yet. We have left a loose strand hanging from the beginning of the episode. Do you remember? It is the story of a lady, Amanda Feilding who did not have a few letters behind her name but how did she spark the psychedelic research?

Just like Rick Doblin and the Heffter Research Institute founders, Amanda Feilding realised that the only way to accomplish any demonstration of efficacy of psychedelics was to explore this as a proper scientific endeavour. With an eye to lobbying on drug policy reform, she set out a process of setting up the Beckley Foundation in the UK in 1998. A couple of years later, she led a seminar series to educate the drug policy experts and to influence political leadership, in the House of Lords. It was one such meeting that also had presence of US scientist, who also happened to be a former director at One of the NIH’s institutes – called as NIDA or National Institute for Drug Abuse. The former NIDA director is said to have mentioned at this meeting that psychedelics would face an uphill battle due to political pressure in getting approval for any studies while still accepting that his own psychedelic experience was the most profound experience of his life and one that he is grateful for.

Seeing the diabolical nature of the global drug policy, She was one of the early vocal proponents of drug policy reform arguing for more regulated and non-prohibitive use of substances classfied under Misuse of Drug Substances act, a UK analogue of DEA’s policy.

Despite all this, Amanda’s interest into exploring psychedelics did not materialize until a young man, by the name of Robin Carhart-Harris made an acquaintance with her and expressed his interest in psychedelics, consciousness and Freud. If people did not trust in destiny or being at the right place at the right time, the following story should make them think again.

One of her academic friends, Professor David Nutt at the time was advising the British Government on the Misuse of Drugs. He had performed a formal study outlining the risk of psychoactive substances and their harms against existing regulated substances like Alchohol, nicotine and comparing them to other drugs.The results revealed something remarkable. Psychedelic mushrooms from which psilocybin was derived was low, probably ranked last in terms of harm compared to alcohol or other addictive substances. Prof. David Nutt in an effort to be provocative suggested that the harms might be lower than that of horse riding. This led to a furore in the establishment and dismissal of David Nutt from the advisory committee.

JoJo:

While all of this was happening and the data for this study was being collected, Amanda Feilding’s acquaintance, Robin-Carhart Harris enrolled himself into the PhD program at University of Bristol. And the two unlikely pioneers in David Nutt and Amanda Feilding joined forces to raise money to perform the first MRI brain imaging study using LSD and psilocybin. In the last episode, we discussed some of the changes in cortical blood flow, increase in connections and overall decrease in brain entropic state.

But since then, Amanda Feilding and other philanthropists have funded multiple studies that explored the effects of these compounds using brain imaging techniques and exploration of the use of these substances to treat alcohol addiction and depression.

Amanda Feilding now currently is a founder of a small pharmaceutical company called Beckley Psytech that explores the therapeutic potential of other psychedelic substances.

These stories really do paint a great picture in how when the going gets tough, the tough gets going and more importantly, the tough got going with a dose of rationality that did not exist in the area until the 1970s.

So, now we have told you how these notable people sparked the renaissance through their efforts, but is there more to say from the patients themselves? Should we dig in?

Well, you gotta wait for a bit for that to unravel.

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.

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.