Peyote crosses the border and causes a riot. Drug companies want their taste, and psychedelics reach the social elite. What could possibly go wrong?

In episode two of PsychedeRx, Peyote comes north to the good old US of A. And it’s not just for religious ceremonies anymore, either. Spanish conquistadors and European explorers, seeking to dominate the indigenous tribes, used Peyote to show force by banning its use and denying the tribes their spiritual practices. And we all know what happens when prohibitions are imposed – the use doesn’t stop, it just gets moved underground. James Mooney, an ethnographer dispatched by the Smithsonian Institute, is one of our best resources for this era. He committed to his diary first-hand accounts of the use of and backlash against peyote in tribal rituals.

As Peyote moved north, albeit underground, it became the catalyst for a series of events that were bloodier than an episode of Dexter. Wovoka and the Ghost Dance were the turning point. The execution of Sitting Bull led to the massacre at Wounded Knee – and it was all over peyote and freedom of religion – ain’t that an ironic twist?

Episode two also sheds light on the earliest interventions of the drug companies like Merck and Parke-Davis and their part in our little psychedelic drama. Arthur Heffter separates the resins from the alkaloids and isolates the first real information on dosing. We get a close-up look at how the psychiatrists and psychologists got involved – where they got it right, and where they got it all wrong. Psychedelics also make their way into the world of the social elites through folks like Aldous Huxley and Ken Kesey. 

We’ll close out this week with our first peek at LSD. So remember to “Turn on, tune in, and drop out.”

Transcript

JoJo: 

In the last episode, we had a glimpse of how the discovery of certain modern medicines evolved in today’s western society.  We also ruminated on the  western world’s fascination with recreational substances like nitrous oxide which started off as a medical experiment, became a tool for pleasure in Humphry Davy’s hands to the laughing parties, before ultimately becoming  an anesthetic. But nitrous oxide become an anesthetic agent  only after a tumultuous period that involved the suicide of the very physician who proposed it. /the journey of Nitrous oxide teaches us that even if a substance has a medical use, it is possible for it to be condemned within the medical and regulatory frameworks. Despite its value, even today nitrous oxide is illegal. 

We then travelled to the Peruvian Andes where we discovered that native american population used indigenious plants like the grand-daddy San Pedro Cactus and its dwarf cousin – The Peyote Cactus,  in communal religious ceremonies. The ceremonies served  a spiritual purpose to heal the mind of the native people.  The use of cacti dates back to the period even before Christ. However, Spanish conquistadors denounced the use of peyote and san pedro in an effort to exert control over the villagers they sought to rule.

Religion and perception clashed. While the Christian missionaries spoke ABOUT God, the Natives used these indigenious plants in order to speak directly WITH God. Intolerance, fueled by deep rooted misconceptions and fear, laid the groundwork for subjugation and even, to a large extent, driving these customs underground. 

Was that all? Centuries of use summarized in a few sentences?  How did the white man know that the peyote cactus could actually be synthesized into a crystalline substance that could open the doors of perception and that such a mind-opening experience would change modern culture through the voice of an English writer who ingested it. All I can say is that history, just like life, goes around in circles. 

What goes up, must ……. come down! 

<INTRO MUSIC> 

This is PsychedeRx, a SKRAPS original podcast exploring the therapeutic potential of the plant based substances that is sure to shake up the world of neuro-psychiatry and mental health. 

Arun: 

So, Peyote reached the United States from Mexico. You can almost track the route that Peyote took, if you look at the map and trace the Texas Railroad. It is here that the journey of the clash of cultures begins on a wider and much more violent scale. 

The Native Americans, as they are called today in the United States, had brought with them Peyote from their forefathers and ancestors while they migrated north and assimilated it into their cultures. There is very little known about how and why the natives migrated northwards but surely this migration must have happened over centuries. These native tribes brought the peyote practice with them and very little is known about how it has evolved from the original Chauvin civilization practice.  

Spanish explorers and conquistadors wrote extensively about the use of this strange plant in their journals and that is how we know about them. Their use in religious ceremonies evolved before the arrival of the Spanish Conquistadors. However, with the continuing war between white settlers and the NATIVES, PEYOTE became a suspicious character and a cause for a level of apprehension that bordered on hatred. 

Back in the 1500s and 1600s, when explorers arrived on the Indian sub-continent, they were spellbound by the vast wealth that existed there and decided to do business. But the  Spanish and white settlers who sailed westwards from Spain, took it upon themselves to domesticate the lands that they saw were untamed, and figured that conquering the land by defeating the natives would be the best way. The native people of South, Central, and North America, lived in more nature-friendly ways and had less opulence in terms of material wealth but had a rich cultural heritage with use of many plant based substances. Such use is still prevalent in many native tribes on the islands of Oceania. But in the Americas after the Spanish invasion, the natives were expected to fall in line. 

So it is not surprising that over centuries such behaviour had seeped into the European immigrants to the Americas. They took the view, along with their armies, that the natives were savages and needed to be defeated and indoctrinated. 

JoJo: 

On the other hand, the newly established Bureau of American Ethnology, that later became the Smithsonian Institute, was interested in preserving the history of America. They dispatched an ethnographer by the name of James Mooney in 1885 to various communities to take stock of what the lives of the natives looked like, not with an eye to help them, but from a land and cultural heritage preservation standpoint. This is where the story gets really interesting. 

Mooney was so dedicated to this role that he even learnt the language of the Natives and slowly but surely, got his head around the Native American Tribes and their ways. He had chronicled lives of many tribes and their customs, and he witnessed many traditions surrounding the Peyote ceremony. Mooney documented the practices surrounding the peyote ceremony and became the first white person and non-native to be invited to observe one. 

Mooney chronicled many details including how and when these substances were used and even wrote up reports to suggest that this was not harmful as it had previously been reported. And more importantly, that there was nothing savage about these ceremonies. In one report, Mooney describes how he was even offered the Peyote powder and took part in the ceremony, only to realize that it helped him to see the community with more compassionate eyes. Mike Jay describes very eloquently the various episodes where even Mooney was apprehensive about taking Peyote but eventually he was so amazed at the ceremony that he convinced himself to ingest Peyote buttons.

I know what you are thinking. Why are we talking about one single ethnographer when there was a whole army that was hell bent on fighting the native tribes? Now, let’s go back to the societal situation at this point in time. 

Because forced assimilation had nearly destroyed Native American culture, some tribal leaders attempted to reassert their sovereignty and began new spiritual traditions. The most significant of these traditions was the Ghost Dance, pioneered by Wovoka, a shaman of the Northern Paiute tribe. 

Arun:

According to the book, Wovoka and Ghost Dance, written by Michael Hittman, during a total solar eclipse on 1st of January, 1889, Wovoka, a shaman of the Northern Paiute tribe, had a vision. He claimed that God had appeared to him in the form of a Native American and had revealed to him a bountiful land of love and peace.  Wovoka founded a spiritual movement called the Ghost Dance to conjure up the devotion of the tribe towards Peyote and to bring everyone along to defeat the invading white army. He prophesied the reuniting of the remaining Indian tribes of the West and Southwest and the banishment of all evil from the world.

I am currently looking at a painting of the members of the Arapaho tribe performing the Ghost Dance. Men and women stand in a large circle while some people look on and others dance in the center of the circle. The men and women danced themselves to a frenzy that was amplified by the banging of the drums and this communal ceremony took on additional dimensions when more people joined it. In one such description, James Mooney wrote that it looked and sounded as if everyone moved in synchrony, perfecting their movement and in pristine rhythm. As he had seen before in other ceremonies under the moonlight, after hours of peyote-induced dancing, people started collapsing to the ground limp and motionless for a few hours. Here is Mike with a recollection:

Mike Jay: Yes, well, James Mooney, when he was out in Oklahoma heard about the Ghost Dance starting to happen. It was these were huge gatherings, Pan tribal, lots of people from the different tribes getting together and dancing day and night for days with new channelled hymns. And it was, I guess, what we might call an apocalyptic or millenarian movements. It was based on the idea that if this, if you know, working up into a state that was going to precipitate a big change in the world where all the white people were going to be swept away, and the land was going to be restored to its original inhabitants. And James Mooney was, was very interested in this and went and collected the songs and talk to the prophet who had who had originally channelled them. But he was very worried that this was going to end in conflict that the Native Americans were inevitably going to lose. And indeed, it did.

Arun: As we’ve discussed, the white settlers were fearful of this primitive ritual that was in direct opposition to their own religious beliefs that was so foreign and utterly incomprehensible to them, that they forced the Natives into reservations and banned the use of peyote. As a result, the practice and use of peyote became more clandestine, gradually moving it from an open communal ceremony over a bonfire to an event that would happen inside a closed teepee to keep it a secret from the white invaders. Predictably, events around this time made the natives more anxious about inviting new people in. So we now know how the teepee ceremonies came to be, but did we say why? 

JoJo: Let’s go back to the Ghost Dance and Wovoka. According to the teachings of Wovoka, the Ghost Dance ceremony would reunite the spirits of the dead with those of the living, and the power of these spirits could be harnessed in battle against white settlers and their armies. Though the practice of the Ghost Dance originated with the Paiute tribe of Nevada, it quickly spread to other Indian tribes in the Southwest.  Wovoka’s most influential prophecy was that “the white man would be forever banished from the land, and that the buffalo”, which had been hunted to near-extinction by white settlers, “would return and bring with it a lasting revival of the Native American way of life”. While the Natives considered the land to be communal, the White settlers were spurred on by “Manifest Destiny” – an idea that proclaimed that the white settlers were divinely ordained to settle the entire continent of North America. 

Several wars followed between the white settlers and the Native Americans and Ghost Dance became the rallying cry behind the native Americans’ stand against the US Army. The last of the resistance that was initiated by Wovoka and the Ghost Dance happened at the Battle of Bighorn. Though Wovoka was the originator of the ghost dance, it has become so widespread that other tribes had adopted it as their rallying cry. 

Let’s travel across the plains to another native American tribe – the Hunkpapa Lakota tribe. 

The Hunkpapa Lakota tribe was led by the man we know as Sitting Bull. On December 15, 1890, 40 policemen arrived at Sitting Bull’s house to arrest him. These were not white policemen, mind you – they were Native American policemen in the service of the US army.  When Sitting Bull refused to comply, the police used force on him. His soldiers and the tribes were enraged.  Catch-the-Bear, another Lakota tribesman, shouldered his rifle and shot a lieutenant, who reacted by firing his revolver into the chest of Sitting Bull. Another police officer, Red Tomahawk, shot Sitting Bull in the head, and he dropped to the ground.  After Sitting Bull’s death, 200 members of his Hunkpapa band, fearful of reprisals, fled Standing Rock to join another tribe under the leadership of Chief Spotted Elk on the Cheyenne River Indian Reservation. 

Spotted Elk and his tribe, along with 38 Hunkpapa, left the Cheyenne River Reservation on December 23 to journey to Pine Ridge Indian Reservation to seek shelter with their chief, Red Cloud.  This set off a wave of alarm across the enemy lines and the US Army grew increasingly concerned about another standoff. It is said that Colonel James Forsyth intercepted Spotted Elk and his tribe, which had grown to 300 members due to the inclusion of the Lakota tribe whose chief, Sitting Bull, was now dead. They escorted these tribes to Wounded Knee Creek and a camp was made, with the intention to ship the Natives by train to another part of the country to live on a reservation. 

Arun: 

What happened the next morning is a matter of intense debate. Small disagreements broke into minor arguments between the army troops and the Natives over searching and confiscating any guns that the Natives had. The army retrieved 38 rifles and when it came to one deaf tribal man, who did not speak English, who refused to give up his gun and a scuffle broke up that ended in a bullet being fired. 

In a fit of rage fueled by panic, the army soldiers indiscriminately opened fire. Some men, around 120 women and children ran through the grassland and were hunted down and killed by the US army. The total carnage at Wounded Knee was in excess of 300. 

Despite the gory nature, The American public were largely supportive of removing the natives from their land.

Here’s the thing: All through this, the white settlers had perceived that dried peyote buttons turned the natives into savages.  Even though peyote had already had a long and significant history,  its stupendously serendipitous journey was only just beginning. 

In the latter half of the 19th century, a Native American named Quanah was born to a Native American Father, a Comanche Chief, and a white mother, Cynthia Ann Parker. Young Quanah had a traumatic childhood. At about the age of 15, his tribe was attacked by US forces at the Battle of Pease River, during the attack, his white mother and his sister were kidnapped and sent to live with Cynthia’s brother. His sister, Topsana, died of an illness three years later and Cynthia reportedly refused reassimilation and committed suicide in 1871. 

Young Quanah, seeing the destruction that the Ghost Dance had cost him personally, was a massive skeptic of peyote. But as a teenager, he was gored by a raging bull in Texas and fell ill. The local curandera, or the native healer, was summoned. In order to prevent the onset of fever and sepsis, the medicine man is said to have provided Quanah with a peyote tea which cured him. After that incident, he became an advocate for the legal use of Peyote. Ok, so what does this young native american guy have to do with Peyote you might ask. Here is Mike Jay again. 

Mike Jay: There was a huge massacre of a ghost dancer, Wounded Knee. And after that, James Mooney went back to Oklahoma, and he became particularly interested in the use of peyote in native religious ceremonies. He was invited to observe the ceremonies by a group of Kiowa people in Oklahoma because he’d been very sympathetic towards the Ghost Dance. To attend a ceremony, which he describes very beautifully, is fascinating. He was the first white person to attend a peyote teepee ceremony. They were   quite a new thing at that time. It was there that he met Quanah Parker. What is interesting was that quanah had I had made exactly the same decision when the go starts and started quite I had stayed away from it, because he could see where this was going to go. And he said, you know, has kind of said, I’ve brought, you know, I’ve brought those to get settled my people and you know, we’ve got a bit of prosperity. And we’ve, you know, we’re a bit of stability, we’ve got a chance of rebuilding our lives and our culture, how stupid would I be to throw this all away on something that’s just going to end up, you know, in a massacre. So I think from their different perspectives, both Mooney and Quanah had the same idea that the Ghost Dance was tragic, but they were in the in the peyote meeting and the parity ceremony, there was a sense of something much more sustainable, something that could be used to grow and restore the old ways in the context of forced captivity and new white America.

JoJo: So Quanah Parker, in concert with Mooney, started aligning his people in peace against the white settlers and got to keep Peyote in return. 

Quanah, in return for all of Mooney’s efforts in convincing the authorities, gave him samples of dried Peyote buttons, which Mooney carried to Washington DC, that transaction is what eventually served as the gateway to the western world. 

Did I say that the fun and confusion was only just starting? Around the time that James Mooney brought back the dried peyote buttons given by Quanah Parker to Washington DC, a physician called John Rawley Briggs decided to try a red berry, referred to as the mezcal berry. 

Briggs had consumed the red berries and documented an alarming reaction. The symptoms included: 

• constricted blood vessels
• dilated pupils
• nausea
• raised body temperature and blood pressure
• fast or irregular heartbeat
• tremors and muscle twitches
• restlessness

He called it a near-death experience and rushed himself to the office of another physician friend who treated him. Briggs, from his experience, concluded that nothing good was going to come out of this plant. But little did he know that he was referring to an entirely different plant. 

Such recounts of experiences were common as the western scientists were looking at three different substances all of which had mescal in their name – mescal – the alcohol derived from Agave plant, Mescal berries, the ones ingested by John Briggs which are red, and finally, the compound that would be isolated from the cactus a few years later. It wasn’t just Briggs; “mezcal” was widely used to refer to all three of the above, and was widely misunderstood by many others. Its reputation for causing physical discomfort was believed to be its only effect and scientists to the conclusion that it was a toxic substance.

John Briggs published his results of self-experimentation and this caught the eye of the pharmaceutical company, Parke Davis. 

Mike Jay reports that Parke Davis tried procuring dried peyote buttons from peyoteros, and had even dispatched its employees in search of obtaining more of these buttons as a therapeutic. Remember, I said that digitalis was described a century ago by the British botanist and physician, William Withering. It is also interesting to know that by this time, the anesthetics we described in the previous episode had blossomed with the advent of bromide, chloroform and ether.  Morphine was isolated from the opium plant as a painkiller and even cocaine was a product that was marketed by Parke Davis as a cardio-stimulant. Cocaine. Parke Davis even successfully made a tincture of peyote and marketed it as a cardio-stimulant and as a better alternative to cocaine. 

Mike Jay:  No surprise that Parke Davis were the first pharmaceutical company to try and make a peyote      based product because that was what they did. They made plant products. And they, and they had a very advanced laboratory down there in Detroit, producing different tinctures and with control, you know, very similar, highly controlled sort of dosages, and batch numbers, and they were really the leaders in this kind of medicine, and Peyote turned out to be quite different. They had that lovely living working for them. So I had, you know, the top pharmacology sort of pharmacologist in the world. And they were and they were very interested, I thought that there was something going on here. And, and it was partly to do with that lower doses, its cardiac effects. And so from in 1893, they put a pod tincture on the market. And it stayed it was available in catalogues for for a long time, but never became very popular. It was at a lower dose than the hallucinogenic dose. And that, which was a stimulant, and that’s kind of where that cocaine comes in. Because they were at this point, the leading suppliers of cocaine in America, just as Merck were in Germany, but they were starting to run into problems with the fact that cocaine was so people were describing cocaine addiction for the first time at this point and starting to realise that if you took it in large doses, it could be very, very toxic and damaging. So I think they were also always on the lookout for something that could be a stimulant like that, but less dangerous and less prone to abuse. And it’s interesting, I think, to look back at this pod tincture in this sort of age of micro dosing, you know, which could hardly have been, you know, which which you know, which nobody really thought about until very recently, but actually, it may well be that that peyote e tincture that was on the market You know, 130 years ago was kind of an effective psychedelic micro dose. And it could have been maybe quite good for general energy levels and moods, there were certainly some doctors who used it as a remedy against depression and fatigue.

Arun: Are you wondering, what a strange world and place it must have been? My question to you is…is it any different today? Can we talk some science now? 

Cocaine, much like the mescal berry that John Briggs took, has a boat shaped tropane backbone and is a very interesting molecule. Cocaine is a cardio-stimulant, but is also extremely addictive. But let’s not dismiss cocaine altogether. 

Would you be surprised to know that some of the drugs that benefit humankind today share a very similar backbone structure to cocaine? Well let me recount to you why. 

Atropine – a commonly used anti-cholinergic drug used in surgery. and scopolamine derived from the Datura species, and is an anti-emetic drug, has structural similarities to cocaine. Both belong to a class of molecules that has the same backbone, called tropane. Why am I telling you this? Because it is premature to dismiss something as useless, as John Rawley Briggs did, without knowing fully what something is useful for. 

So back to the cactus. Quanah gave some peyote to Mooney, who brought it to Washington DC. Mooney had provided the peyote to Smithsonian Institution and this in turn, was disseminated to the Harvard Botanical centre and a number of botanists and scientists who took an active interest in this cactus with a historically colourful past. 

From here, Peyote took a life of its own. 

The first clinical study was done by a noted Physician in Washington DC, Daniel Webster-Prentiss, who gave the peyote to a subject marked down as “scientist”.  The subject ingested 3 dried buttons at around 9-11 PM and in a matter of couple of hours, saw all sorts of designs, that had all features of kaleidoscopic patterns  and ever changing colours. The subject reported his mind was clear. This was so contradictory to the white settlers description who thought of peyote as an intoxicant like opium.

 But when he closed his eyes back again, the colours re-appeared and he could willfully mold the visions into a recollection of a stage play that he had recently seen. This then morphed into a dark side, where he saw gruesome monsters and gruesome human shapes. By 4 AM, the effects wore off and insomnia persisted for a day. 

Subject 2 was even more fascinating. He described similar colorful patterns followed by geometric figures. But he described a rather strange double personality – one where he could see himself as an outsider, almost an out of body experience and while he was looking at himself, he found the doctors in the room to be laughing at him and almost resorted to violence and declined to take the 8th peyote button. 

Additional patients followed – Subject 3 saw suppression of muscle activity and felt weak, subject 4 had no effect of taking peyote and subject 5, took to drumming and kept drumming and described that the drumming enhanced his feeling of euphoria. You can ask why was this such a contradiction. The physicians in the study much like anyone wanted to performed a randomized study, so picked subjects at random. But nature had an interesting lesson for them – the outcome was as random as the subjects themselves. 

There was one unifying factor. The physicians noted marked dilation of pupils and an absolute loss of sense of time in their subjects  – minutes seems to fold into hours, almost as if they were caught in Christopher Nolan’s movie Inception where dreams reside inside a dream.. 

The physicians concluded that the drug effect was similar to cannabis, which also produced dilation of pupils, but was not sedative like cannabis. This made Daniel Prentiss to conclude with his co-authors that Peyote can be used as a cerebral stimulant to treat depressed conditions like melancholia, hypochondriosis and some cases of neurasthenia, nervous headache, nervous irritable cough and could be seen as a substitute for opioids for active delirium. It was a laundry list, and not explored further. If you think this is confusing, I will give you another weirder example. 

One of the recipients of the cactus was an agricultural chemist, Harvey Wiley. I am bringing up Harvey WIley, because he ran a lab that was working on analysing food adulterants, that much later on in 1906 became the current FDA. Mike Jay describes in his book on Mescaline that Harvey Wiley was a big proponent of increasing American intake of sugar in food and even is said to have proclaimed that “A childhood without candy, is like heaven without harps”. 

The cactus reached Wiley, and he, like a big boss of a lab passed it on to a younger scientist called Euel, who decided that the best way to test what this peyote button did, was to test it on himself. One night, EUel’s roommate is said to have rushed him to WIley’s home, and according to Wiley, Euel was said to be smiling and talking to himself saying -,”how beautiful, How splendid,  I can see the angels and the streets of gold. “

Wiley concluded that peyote was an active deliriant poison, contradicting Prentiss’ view that it could be used to treat delirium. So within a span of a year or two, Peyote went being an intoxicant to being a deliriant. 

JoJo: At this stage, the scene shifts to Germany where a race to discovery was brewing. The race was unequal and we will come to that inequality in just a second, but the purpose of the scientific race was to understand the constituents of the peyote cactus. The first person who obtained this was Lewis Loewin in the 1888, who was introduced to the peyote buttons by Parke Davis, the pharmaceutical company that wanted to isolate the compound rather than selling dried buttons. It wanted to make a purer version of the chemical, but did not know what it was made of. Lewis Loewin was a rock star chemist and was a charismatic teacher who packed lecture halls. He tried the cactus in animal experiments and was unsuccessful in eliciting any effects. However, he did succeed in convincing the funder Parke Davis through a few experiments but failed to describe anything notable. Parke Davis was eager to appease its star scientist, so changed the name of the cactus from Anholonium Williamsii(William-C-I) to  Anholonium Loewinii (Lewin-ni-eye), in honour of Lewis Loewin. And in 1891, that star status was about to be challenged. The challenger however, was a very diligent chemist from Leipzig  who did not mean to make it into a feud. He just saw all the natter around peyote cactus and decided that it was time to give it a go to figure out what it was made of. 

We will come to this remarkable scientist’s other accomplishments in a later episode, but for now all you have to know is that he was so industrious that he was labelled as boring. Here is Mike Jay again. 

Mike Jay: 

I think it’s a wonderful story. Of course, some Germany was where your pharmacy was really happening at this time, and particularly the isolation of pure drugs from plants that had happened in Germany with tobacco with with caffeine and nicotine and cocaine. So as soon as pierotti appeared, and it was this captors that produced visions and had these spectacular effects on the mind, of course, and the race was on to identify, you know, the, the compound that was producing this, and it turned out to be very difficult because the coyote cactus has a lot of different alkaloids and a lot of different resins. A lot of people suspected that the drug would be in the resin as it is in cannabis in in hasheesh. And the Louis Levin, who was the really the world leader in toxicology, and plants and drugs at that time, made various different extracts and isolated compound that he called an alanine, which was probably a mixture of different alkaloids, and then didn’t get any further. And then Arthur hefter, who, as you say, was much less well known, you know, younger, very thorough, but the other really big difference, I think, was that Louis Levin, never self experimented with drugs he’d spent in his early career in the 1830s. He’d seen a lot of the first morphine addicts, and he says he’d seen so many people take drugs out of curiosity and then get into difficulties with them. So he never went down that route himself. So it’s very different difficult for him with this because how would you identify which compound in the cactus is psychoactive, he was feeding them to laboratory animals and then trying to observe from them whether they were hallucinating or not.  “ 

Arthur Heffter, the guy who was responsible to tell the world about what was in the cactus has arrived in our story. So what did this shy, industrious, almost boring scientist do? Well, as they say, it is one thing to sell the science like a good salesman, but doing good science is a different matter – One that requires thought, self-reflection and humility. and Arthur Heffter possessed these qualities by bucket loads. 

Heffter went to a local horticulturist and obtained some cactus that looked like Peyote. Then he also obtained a sample from another German CHemist called Karl Helmholz, who had obtained samples form Huichol (pronounced as “Which-ol”) people in the United States. Unlike Lewis Loewin, Heffter believed that the best way to get to the bottom was to ingest the cacti, by himself. It is also said that he first came to this conclusion because he dosed a  frog and saw that the frog did not show any changes, much like what Lewis Loewin did. Therefore, he decided that it was time to take the matters into his own hands. Call it luck, call it intuition, call it serendipity, it was a stroke of genius! 

By sampling one species that he obtained from the local horticulturist, he figured out through experiments that the alkaloid in the original Anholonium Williamsii, the one that was originally provided to Lewis Loewin as pellotine. Pellotine alkaloid was a mild sedative. 

Whereas , Heffter was convinced that Anholonium Loewinii had two alkaloids but he could not separate them them as yet  prompting him to conclude they were two different species of cacti, very similar looking but had completely different constituents. And just like every scientist, he wrote it up, published and managed to piss off the older, charismatic scientist. 

Arun: So, if some of you are privy to some heated debates in scientific journals, I say that things have gotten a bit less spicy over the years. I have seen some near fist-fights at Biophysics Meetings that I have been to while people discussed the nitty gritties of cellular processes. Coming back to Heffter and Lewis Loewin now…what happened was the following. Lewis Loewinii fired off a furious letter to the editor where he wrote – “I have neither time nor do I feel inclined to make Mr. Heffter understand the results of my work”. It was a fiery rebuttal to a study that disproved Lewin’s studies that showed there was just one species of cactus. 

I am really curious to know what would Arthur Heffter be thinking when he came to know of this letter to the editor? It would have demoralized any scientist, but not Heffter. Here is Mike again. 

Mike Jay: <Meantime Arthur Heffter was self experimenting so he methodically separated out the resins from the alkaloids and took a small amount of each and noticed that the resins only made him nauseous, so he moved to the alkaloids and methodically trialled half a dozen different ones on himself, and eventually established the one that was causing the  visual hallucinations. And he worked his way up in doses until he had an active dose. And he then got to name it because the PRT captors was often referred to as the mezcal, which was a term that was used quite a lot. So he called the alkaloid mescaline. 

Arun: So what did Heffter do? Can we dig a bit deeper? It surely makes a case for careful and diligent science. Heffter managed to isolate not two, but five alkaloids. And as a careful chemist, he placed them in a order. On one end, he had Lophophorine – a strychnine like stimulant. Strychniine for the pharmacologically inclined is a classic human and animal toxin, that causes seizures, cramping, stiffness, hypervigilance, and agitation.

On the other end, he placed Mescaline, which he initially thought of was having morphine like sedative properties, based on what Prentiss has suggested his papers around this period.  In, between, he placed the notorious pellotine that he isolated that put Lewis Loewin into a fit of rage, Anholonidine,  and Anholonine. 

Now that he had the alkaloids, he had to go one step further. He needed to, oh no, he wanted  to figure out which alkaloid was the responsible for the psychoactive effects. 

On 5th June 1897, Yes, it is that fateful month of June, the same month that Nixon announced war on drugs in 1971. Anyways, on 5th June 1897, he took 16.6 g of cactus that was equivalent of 5 buttons that caused occipital headaches, dizziness, clumsiness and when he locked himself in a darkened room, he saw mosaics and winding colour ribbons to scenery, banquet halls with gems which turned upside down just like CHristopher Nolan’s Paris dream scene in the movie Inception. His sense of time was scrambled, a few minutes seemed like hours. So this was the experiment with whole cactus. It was time to figure out how to separate the effects of the resins from the alkaloids.

A month and    half later, he took the cactus and combined them to a chemical reaction with ammonia and chloroform to digest the alkaloids and got a slurry of resins. He took the resins wrapped in chocolate paper, and felt just a mild discomfort and weakness, but in two hours, it was gone. By this experiment, he concluded that resins were responsible for physical symptoms and the alkaloids were responsible for the colorful visions. 

Two days later, Mike Jay Notes in his book that Heffter drank all the alkaloids he isolated as a mixture with water, and sat down to read. The green and violet patches started appearing all over the page, evolving into a kaleidoscopic vision that then evolved into a very distressing nausea and confirmed his hypothesis that the visions were from the alkaloids.  

Then, by this time, he had the nagging feeling and then started experimenting with the purified alkaloid that he had isolated called  mescaline. He carefully titrated the doses starting with 20 mg, and gradually increased the dose to 100 mg. At the lowest dose, he experienced mild symptoms, heaviness, headache, nausea and mild visions. 

But then on 23rd November, five months after he first started systematically started his quest to understand the molecular constituent of Peyote cactus, Heffter took 150 mg of mescaline and the strong violet and green patches came back. Images of carpet patterns and architecture ensued and this lasted for hours. In fact Heffter described that he could control the kaleodoscopic patterns and could cause them to change by opening or closing his eyes. 

THIS IS HOW MESCALINE WAS ISOLATED AND DEFINED TO THE CONSTITUENT OF THE PEYOTE’s kaleodoscopic VISIONS. And now what was left is the synthesis of Mescaline into a crystalline substance by an Austrian Chemist, Ernst Spath and this literally blew the doors wide open. 

JoJo: The western world did not have to grapple with a silly plant that produced physical symptoms. They could skip all that and go straight to the chemical and ingest it, test it and experiment with it.  

Here is Mike again as to how the world went nuts! On one side, you had the psychiatrists giving it to patients without knowing how much to give them, and ended up triggering psychosis like symptoms acutely or mislabelling mescaline as a psychotomimetic like Kirk Berenger. In fact, Kirk Berenger coined the term – Der Mescalinrausch which translates to mescaline intoxication. All of this despite Heffter’s careful studies and showing that it did not produce psychosis. Well anyway, the psychiatrists saw a chemist’s work as an opening but wanted to push the boundaries themselves. 

 On the other side, you had other psychiatrists use mescaline as the model to understand schizophrenia by using mescaline as a psychoto-mimetic. And you might ask why?  Around this time, it was thought that schizophrenia was caused by imbalance of neurotransmitters in the brain and that adrenaline which is produced by stress, would somehow undergo a chemical reaction that heightened the hallucinations seen in schizophrenia patients. Therefore, how could one mimic such states, well mescaline might provide an answer, people thought.

This included the british psychologist, Humphry Osmond who had migrated to Saskachetuwan in Canada to become the associate director of the psychiatric ward. He teamed up with another psychiatrist called Abram Hoffer to test mescaline on themselves to understand how it felt like to be in the mind of a schizophrenic patient they thought and if this could let them empathize more with their patients. On the other side, you had careful researchers like Heinrich Kluwer,  who moved from Germany to Minnesota who looked at the impact of mescaline on visual patterns by looking at its impact on optic nerve signalling and impact on visual cortex using EEG. 

Above all, mescaline became widely available as Merck and another pharmaceutical company that was the precursor of today’s GlaxoSmithKline, called Burroghs Wellcome started manufacturing and this became a medical tool which fell into the hands of the societal elite – the artists, the writers and eventually to counter-culture evangelists, who started questioning authority after a mescaline experience.

Mike Jay: 

I think, it’s interesting. It’s what we now call the psychotomimetic model. And you can follow it further back, I think there was a psychiatrist in mid 19th century France called jack Joseph Morrow who really developed this with hashey. She noticed that if you took large doses of it, you had all kinds of hallucinations and delusions and altered perceptions of time and space. And he said, isn’t it curious how these correspond to the symptoms of psychosis? And I think one of the reasons that a lot of psychiatrists and neurologists and psychologists started to look at mescaline in the 1920s was because it produced these hallucinations. And hallucinations were a very, very hard thing to study. Because most people suffering hallucinations are in some kind of delirium. They can’t really talk about what’s going on. But mescaline produced what, Joseph Morrow called an etat mix or mixed state where people could be hallucinating. But at the same time, if you ask them, if you said Close your eyes, what are you seeing, then they’d say, Oh, I’m just seeing all these little golden spirals rotating outwards. And then I’m seeing these sort of dancers legs appearing. And then now that’s changing if people could talk, you know, very coherently and articulately. So you could get information about these extraordinary states of mind, which you could take in different directions. Heinrich kluever, who was much more interested in the mechanisms of AI and brain and where these hallucinations were coming from, what was generating these patterns. Kurt Behringer, who ran the biggest study in the 1920s, in Heidelberg, was much more interested in who had what kind of hallucination and what you could tell about them from that. And so this was something that ran all the way through, as you said, to the 1950s, and to the early days of the rediscovery of psychedelic weapons use the term psychedelics being coined, but then it started to be pulled apart. Particularly, you know, in the early 1960s, by researchers who said, Well, actually, maybe this term hallucination is a bit misleading. It sounds very medical and specific, but there are actually so many things we’re talking about here. And if people are suffering from psych psychosis or sort of skits, or delusions, then they’ll often find that things taste funny, or they’ll hear voices speaking to them, although I think that people are poisoning them. That’s very, very different from what that doesn’t happen to people on psychedelics, if you give them that, you know, normal subjects, psychedelics, you know, they’ll see extraordinary visions, and they’ll have peculiar thoughts, and they’ll have, you know, tonnes of great, expensive changes of mood, but that’s not the same as psychosis.

Arun:  There was one person who was carefully watching all of this. It was Aldous Huxley, the writer and the step-brother of the Nobel Prize winning Physiologist, Andrew Huxley. Aldous had just finished writing his third book, Point Counter Point which was said to have drained him. He was fascinated with the results of the research published by Humphry Osmond, Abram Hoffer and John Smithies. The three physicians were world leading experts in mental health disorders at the time and were proponents of the idea that mescaline provided the perfect psychotomimetic model to under schizophrenia. They concluded via their experiments that the substance that causes schizophrenia was chemically modified adrenaline or nor-adrenaline derivative that they called as adrenochrome and later as M-substance to denote something similar to Mescaline. 

Aldous Huxley was watching all of this, and at once, wrote a letter to Humphry Osmond and learnt that Humphry Osmond was going to visit California soon.  So Huxley suggested to Osmond that, if he were to be visiting Los Angeles, Huxley would be very interested in ingesting mescaline and have an experience to liberate his mind. These experiences are well chronicled in history and Huxley’s influence in bringing mescaline to public attention and cult following cannot be understated. Huxley, a graduate of Eton College and Oxford, who had a privileged upbringing called it as a the “drug of the elite”. WHile there were instances where this was clarified to mean that the drug is only for ones that want to open their minds, liberate their consciousness and breakdown their  ego, the damage was already done. There are many instances where unfortunate, usage of words have led to people wanting the experience more. In fact, the worst part was, as we will come too, later, these plant based substances or their synthesized cousins aren’t even addictive, yet the perception and intrigue that mescaline created was one of a cult status. Huxley’s drug for the elite made people believe  that they would liberate themselves from the shackles of the mind, bordering on religious mysticism and as a result would make them realize that the world was beautiful. When science meets philosophy meets art, it took some disproportionate dimensions in the next decade, that the world had to grapple with. 

JoJo: Humphry Osmond to demonstrate the acute psychotomimetic and non-sedative nature, convinced a member of Parliament, Christopher Mayhew to take mescaline for a television program. Here is an excerpt from that interview where You hear Humphry Osmond asking Mayhew to count the numbers in 7 from 100. 

Here is Christopher Mayhew describing this experience, 30 years later. 

There was doubt in the minds of the BBC who had produced this event and in typical British fashion, independent committee was formed to review and make a recommendation. Since the experience was mystical in Christopher Mayhew’s eyes, scientists, psychiatrists and theologian were part of the committee. The chair of the committee was a Cambridge physician who felt that Mayhew’s mystical adventure was obtained on the cheap.  The rest of the committee agreed and  concluded that the film should not be shown as the Parlimentarian’s experience was not valid. 

There is an interesting story about the Two of the most influential figures, Humphry Osmond, the famed British Psychiatrist and Aldous Huxley wrote letters to each other where Aldous, raved about his psychedelic experience that he had with Humphry Osmond, It is said that that in one such letter, Aldous was reported to have said – “ To make the world Sublime, take half a gram of Phanerothyme” and Osmond who worked as a psychiatrist and one who believed that mescaline produced acute symptoms of psychosis and schizophrenia wrote back – “To fathom Hell or Soar Angelic, take a pinch of psychedelic”. Well, what can I say, a pinch of psychedelic, surely made sure all hell broke loose in the next decade. 

You don’t trust me. Well, lets talk about how? 

Arun: Let’s rewind a decade and a half to before Aldous Huxley ingested mescaline. The world was in the throes of the second world war. Bletchley Park, the place where the Enigma code was broken by the codebreakers intercepted a radio transmission that scopolamine was given at very high doses to induce a sense of scariness to make prisoners of war speak the truth and that Nazi doctors were on route to testing another crystalline substance, Mescaline. 

It was rumoured that Nazis got hold of mescaline, which was being made by Merck, a German pharmaceutical company and were trying to use it as a “truth drug”. One of their notorious scientists, was Kurt Blohme, the deputy surgeon general of the Third Reich, who spearheaded the mescaline exposure in concentration camps. And you would not expect what happened to Kurt Blohme after the end of the second world war. We will come to that in the next episode. But mescaline was used by Nazis who dose it to prisoners of war, turned friendly to the Nazis after ingesting mescaline. How is this possible? Well, this is not the first time that human kind had discovered that mescaline had triggered a sense of empathy and community. The native american tribes had long used it and the Native American church which had just been formed a few years ago, knew this as well. Well anyways, the Nazis dropped the experiment with mescaline as a truth drug. So the social and research use with mescaline continued long after the second world war culminating in the clinical research of Osmond, Hoffer and Smythies and eventual dosing of Aldous Huxley. 

But in 1950s, a tiger emerged to douse the pussycat. The tiger was another molecule derived from ergot fungus, called Lysergic Acid Diethylamide or LSD. LSD was so potent that only a tenths of microgram was able to provide the same effect as 400 mg of mescaline. And mescaline became an afterthought once LSD gained prominence, so much so that it fueled many things that would leave a lasting impact on society. 

Here is our chief mescaline expert, Mike Jay again detailing how CIA after the second world war took over the legacy of testing psychedelic substances and fueled the 1960s counter-culture. CIA funded a number of clandestine research studies and one of them was with a psychiatrist in Los Angeles who had a very nosy janitor. The psychiatrist was Leo Hollister and the nosy janitor, who was originally his research subject was Ken Kesey.  

Mike Jay:  So I think it was really people like Leo Hollister in the early 1960s, who studied the we remember him because he did the experiments on normal subjects, which included Ken keys he wrote about this in One Flew Over the Cuckoo’s Nest. But what Hollister was doing there was getting a group of normal subjects and a group of people suffering from psychosis and saying, Look, what you’re calling hallucination in one group of people is completely different from what these other people are experiencing>

So that was the story of the spiritual healing substance that blew down the doors of perception of the western world. In a few years, it was to be  overshadowed by a new-comer called LSD. More on that soon! 

Well, we are just getting started. I did warn you right at the beginning that history has a habit of going in circles! And it hasn’t stopped as yet. 

<OUTRO MUSIC> 

End credits: 

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.