Where were you on June 18, 1971? Did you know that was when Richard Nixon, the United Nations, and other world leaders changed the course of popular culture, scientific experimentation, and mind exploration for the next five decades? Did you know that substances that have the potential to change the way we treat myriad diseases and conditions – ones that have little or no reliable treatments today – were fated on that day to be imprisoned like Hannibal Lecter?

Join us for the first of a series of Skraps Original episodes as we explore the use, misuse, and history of psychedelics. In this episode, we will cover the most important question of what these substances are, and begin to question why they were lumped in with other addictive substances by exploring the history of how curiosity-induced exploration on one side clashed with religious single-mindedness. This manifested itself in how these plant-based substances were viewed then and for centuries later, in the eyes of the western world. 

PsychedeRx will cover the ancient history of plant-based psychedelics including their religious, ceremonial, tribal uses and the dangers imposed by the European views of those uses. We’ll experience murder, mayhem, executions, displacement, and more. We’ll talk to psychedelic historian Mike Jay to get the full story of the full journey – one that started long before Nixon and other world powers set their limited, short-sighted fear loose upon the world.

Subscribe to SKRAPS on your favorite podcast platform to make sure you don’t miss a minute of this riveting journey.

Transcript

<Nixon’s announcement – War on Drugs declaring public enemy number one> 

18th June 1971

Spurred on by the decades-old prohibition laws, the 1960s counter-culture, anti-war protests, and self-induced paranoia, US president, Richard Nixon declared that drugs were public enemy number one! At this point, the anti-drug policy looks completely rational.

The world had come together to fight a common enemy. But this one did not have World War II or Cold War issues or undertones.  It was a battle, not against a government or a set of ideals. It was a battle against chemicals.  The social and cultural happenings after the second world war led to a certain class of mind-manifesting molecules being lumped in with other drugs like heroin and cocaine. 

 Nixon, in fact, went on to create the Drug Enforcement Agency to ensure these substances were controlled. The stories that you hear about psychedelics always portrayed to have begun here. But there is more to the story. 

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

(INTRO MUSIC STARTS)

War on Drugs! Drugs are public enemy number one, said Richard Nixon. He was not alone. He had the full support of the bipartisan congressional committee. In fact, he had the support of the United Nations. Just 3 months prior to Nixon’s announcement, on 21st Feb 1971 , United Nations had approved a treaty to control psychoactive substances. 

What followed the ban is what drives our behaviour and attitude towards psychedelics? You don’t believe me. Well, let’s go on a journey, shall we? 

<A MAN breaking an egg into omlette advertisement> 

Such television advertisements were relatively commonplace for the generation that grew up in the 1970s and 1980s. It touted that drugs were bad and discouraged people from using it. Seems fair, isn’t it? But why were psychedelics lumped in with opioid derivatives like cocaine and heroin. Was there enough evidence to demonstrate that addictive drugs like cocaine and heroin were the same as psychedelic substances? Everyone that you probably know of, in today’s world will hold up this as the starting point in history. Some individuals will go a few years prior to 1940s, but honestly, the story does not begin even in the 20th century. Let’s go for a journey to discover these drugs and see what led to that fateful day in May 1971, shall we? 

But let’s not get carried away a bit too much. We are not here to examine the actions of a specific government or a nation. We are here to talk about how the shifting timescale shaped by cultural, societal, religious, human, and political factors portrayed these plant derived psychedelics as villains. Was it really the villain? 

Well,  we are not going to say if they are or not, but will let you decide. 

So, to understand what these psychedelic molecules are, I think we want to take you on a historical journey with us. A small disclaimer: For every event we tell you about, think about whether it was use or misuse? Was it glorification? or mischaracterization? Ask yourself these as we view this story through the prism of science. And let’s apply scientific principles to demonstrate the various interpretations that were drawn about these molecules in history.. 

So let’s start. Can we start with our best friend, Google? Let’s ask Google what the term psychedelic means. And we did. 

The results offer,  what seems to be  fact-based authentic sources of information. So we have fact-checked that our sources are reasonably legitimate and then we start reading. 

New Scientist magazine, a very credible science magazine was the first result that Google threw at us and it said: – “Psychedelics refers to a group of drugs that unlock a peculiar mode of consciousness”. Did a science journal call psychedelics peculiar? Hmm…….. Interesting, so Nixon was right. There was something peculiar about it. I try to ignore it and read. But my mind was looking for reasons why it was peculiar. There was little evidence justifying the word “peculiar” in the article. 

You see!  Though the goal was to present scientific facts, they have inadvertently unlocked something visceral in your brain by using the word peculiar, that made you uneasy.  

A RED FLAG pops in the head. Should I be alarmed?

Ok, now let us move to Wikipedia. There, Psychedelics are referred to as quote:  “The subset of hallucinogenic drugs whose primary effect is to trigger non-ordinary states of consciousness (known as psychedelic experiences or trips) via serotonin 2A receptor agonism. This causes specific psychological, visual and auditory changes and often a substantially altered state of consciousness.” 

OK, stop stop stop…Did we just read Hallucinogenic?

Honestly, the only time someone says hallucinogenic is when someone in my friend’s circle or family says something outrageous and we say – “No way, you’re hallucinating?”  The term hallucinogen or the common parlance is used to refer to something unreal. 

I think we have unlocked something critical here. Even before I read anything factful that wikipedia provided, like the psychedelic molecule binding to serotonin 2A receptor and unlocking a different type of consciousness, I was so distracted by the word hallucinogen. 

Now, we go to some of the scientific publications, and even there, we are sorry to say that science is written for scientists and is not accessible to the average reader. It’s like explaining the Riemann hypothesis to an Algebra II student. , I need a glass of wine or a shot of mezcal to shed my high status and bring down the language. 

I think the system is broken because psychedelics have historically demanded intricate interpretations and intricate interpretations confuse people even more. Let’s face it, history agrees with our view. 

You know why this is important? Because the field of psychology and specifically, articles on psychedelic science is littered with such nuggets that distract the reader. And before we go any further, we need to realize one thing. Human brain is definitely well developed compared to the lower order species in the animal kingdom, but we retain some of the primal instincts. 

Though, our outer layer, the neocortex can process information, analyze it and also reason. It is precisely for this reason why the arguments we put forward always appear to be the most thought out, to US.  But when someone hears that information for the first time, they do not hear reason.

You know why? Because, the primitive part of the brain, one that is evolutionarily present in humans and let’s say for lack of a better animal, a crocodile, is very similar. This primitive brain is the deepest structure but has the primary function of survival and danger detection. 

You see, a crocodile brain, has three modes – attack, ignore and mate. If the information shared, however wonderfully wrapped in rationality, triggers my primitive crocodile brain, I attack the source just like how a crocodile does not like provocation. If it is not interesting, I ignore. And if I love it, I am going to mate with the idea. 

The mid-brain which involves regions of the brain like the amygdala process the emotions associated with an event but in this case, the crocodile brain told you to be wary of psychedelics because it was peculiar and was hallucinogenic. So your emotional process is tuned to perceiving it as a something not so good, tnerefore the mind gets entrenched in these ruminations of the idea. 

So when the words peculiar and hallucinogen were uttered, the majority of the people either attack it by countering with all examples like the ads from the 1980s or ignore it and as it is not interesting enough. 

The same thing happens when you hear someone yells or shouting, say when you are walking to your parked vehicle. Your first feeling is one of feeling startled, a little bit of fear. That’s your primitive brain, then you mid brain looks for social cues – Am I being yelled at? Or is it someone else that is getting yelled at? Do I know this person etc? Then your neo-cortex finally kicks in to analyse – OK, its some random guy yelling to his friend across the parking lot, so I can carry on. 

See, just with that example, we just told you that your mid-brain or your neocortex did not even get a chance to assess the information first. It was the primitive brain that locked into survival or danger mode.  So it is crucial that distracting words must be avoided, especially in the context of psychedelics. Because, honestly, the evidence is there to show that it is neither peculiar nor is it hallucinogenic.

So what exactly are these substances and what is the right way to describe them?  Let’s go back to high school chemistry. Every element in this universe has a valency. Don’t worry, if you forgot, we got you covered. Valency is the combining capacity of an element, and this can be used to arrange the elements that we know of in nature into a table and this is called as the periodic table. 

Similarly,  we need to redefine the definition of the psychedelic. Before, we go any further, I must tell you that even the term psychedelic is a recent one.  It was coined by two people in 1950s, a psychiatrist and a hollywood screenwriter trying to communicate a complex phenomenon and the experience. It’s like describing the feeling of being in love to someone who has never experienced it. 

I digress!  We will share with you the very exchange that led to the coining of the term psychedelic later on. But for now…. 

what in the world is a psychedelic?  

Let’s start with a basic definition of psychedelic and build on it during the course of this podcast, together. Are you ready? 

Psychedelics refers to a group of natural plant-based or synthesised substances that, at any given dose (as known for other medicinal products), modify basic neurological functions to enhance the user’s sense of perception. 

Now, what is different about this definition? I have not used the word drugs. Though every medicine is a drug, I have not appealed to the crocodile brain that attack or ignore. I said it enhances user’s sense of perception. Ooohh….enhancement! So I have set up the intrigue by saying it. Is my statement true? Yes, absolutely. Can it be polished further? Absolutely, we are going to do that with you as we go through the evidence. 

I have said substances because that’s what they are. Every drug is a substance.  And I have brought in the concept of dose. We all know that even Paracetamol or Aspirin if taken in the right quantity is a drug or if taken at a higher dose, causes digestive discomfort like nausea or vomiting, and in overt overdosing, is an emergency. Note I have not mentioned the word addiction as yet, not only because I think the word addiction needs to be examined through the prism of cultural, historical, or therapeutic use, but also because addiction is not a property generally ascribed to psychedelics. We will spend a substantial time looking at the evidence during the podcast. 

So going back to our old friend, valency. Just like valency is a combining capacity of an element, we have broken psychedelics down to say exactly what it does; and not left it to subjective interpretations by using loaded language. Psychedelics are substances that modify basic neurological functions to enhance the ability of the user to perceive their thoughts and the world around them. 

Now, the critical question! What evidence was there to group these psychedelic substances with heroin, while their more devastating cousins like cocaine, methamphetamine, and fentanyl enjoy a more relaxed place at number two on the schedule? 

High potential for abuse is a major factor in drug classification. No evidence to support high levels of physical or psychological dependence exists to demonstrate why psychedelics that ended up on DEA Schedule I listing. Schedule II narcotics like cocaine, meth, and fentanyl on the other hand demonstrate their addictive qualities on the streets of nearly every major city in the world.

Scientifically speaking, the word narcosis refers to a state of stupor, drowsiness, or unconsciousness. The classic narcotics – let’s take morphine, reduce pain but can also cause sleepiness. Therefore,  drugs that cause narcosis are referred to as narcotics as they have an overall inhibitory effect on the brain state, molecularly and functionally. 

But Psychedelics don’t seem to produce any of the above. So where did it all go wrong? 

In fact, even before Nixon announced it in May 1971, the UN convention held in Austria in February the same year,  clubbed psychedelics with narcotics as psychoactive substances. It looks like“psychoactivity” is defined in social terms based on perceived danger, going back to the crocodile brain; rather than real danger. It also pays no attention to the effects that these substances were causing. Unfortunately, as you can see, the US had the support of the rest of the world too.  

The UN convention set out certain criteria for assessment too. They were: 

• The extent or likelihood of abuse,
• The degree of gravity in the public health and social problem,
• The degree of utility of the substance in legitimate medical therapy, and
• Whether international control measures as provided in the treaty would be appropriate and useful.

It did not just stop with clubbing all psychoactive molecules in one bundle but also left the door open for adding new substances to the list. Of course, it all seems logical doesn’t it? Well, I am not going to tell you what you think or conclude, but I am going to tell you something that will make you reflect? We are going to read a paragraph from this UN article. 

“If the World Health Organization finds: 

• (a) That the substance has the capacity to produce 
  • (i) (1) A state of dependence, and (2) Central nervous system stimulation or depression, resulting in hallucinations or disturbances in motor function or thinking or behaviour or perception or mood, or
  •  (ii) Similar abuse and similar ill effects as a substance in Schedule I, II, III or IV, and 
• (b) That there is sufficient evidence that the substance is being or is likely to be abused so as to constitute a public health and social problem warranting the placing of the substance under international control, the World Health Organization shall communicate to the Commission an assessment of the substance, including the extent or likelihood of abuse, the degree of seriousness of the public health and social problem and the degree of usefulness of the substance in medical therapy, together with recommendations on control measures, if any, that would be appropriate in the light of its assessment.”

Ok did you get that? It basically said, we can add more to the list if it caused dependence, brain stimulation or depression, produced abuse or if it posed a public health problem. 

Alright, now we are talking! Can you just close your eyes for a moment and think of anything that you know of, that fits into the criteria above? 

Well, let me help you. The coffee that you drank was a psychoactive substance and is also a cardio-stimulant. The cigarette or vape that one might enjoy contains nicotine and, it’s 5:00 PM somewhere so let’s talk about alcohol. 

Guess what was said about nicotine or alcohol? 

• Alcohol does not ‘warrant’ that type of control because it is not ‘suitable’ for the regime of the Vienna Convention. It appears obvious that the application of the administrative measures for which that treaty provides would not solve or alleviate the alcohol problem.
• [Tobacco] is not suitable for the kinds of controls for which the Vienna Convention provides, and which if applied would not make any useful impact on the tobacco problem. That problem, however serious, therefore does not ‘warrant’ the placing of tobacco ‘under international’ control, i.e. under the Vienna Convention.

If you are going, OH REALLY? I must say, you are not alone. 

Prohibitions on alcohol were tried in the past and resulted in increased violence, crime, and abuse. Smoking, until it ostensibly fell out of fashion, we loosely regulated and now taxes in lieu of bans are being used to reduce or eliminate smoking.

Conservative estimates put societal costs (healthcare expenses and lost productivity) of nicotine addiction in the U.S. at approximately $193 billion a year.

And that is just in the US alone. EU numbers are similar, 7.2 percent of people ages 12 and older who had Alcohol use disorder in the past year received any treatment in the past year.  

You, I am sure, are qualified enough to dig more and make your own judgment. 

All of these factors lead to a very interesting question: 

How did plant-based substances that had been in vogue for centuries across South American, Greek and even South Asian cultures all of a sudden become taboo? These substances were naturally occurring and were not cultivated specifically to change the mind, but like many others – coffee, tea, cacao beans all of which contain alkaloids with a psychoactive property, get marginalized. 

Anyways, I am getting ahead of myself. 

Let us see what the impact of Nixon’s announcement was. Remember, the special governmental agency called the DEA. For a few years, it reported to Nixon directly and it used some of the $1.1 billion it received during the 1970s  to crack down on select cultural happenings – the anti-war protests, post-civil rights movement, cultural segregation that serve as the underpinnings to racial tensions we see today. Once again, I digress. I promised to stay within the realms of science. 

Where were we? Yes, The DEA! They graded substances into schedules. The lower the number, like schedule I, meant that it had no known medicinal use and has a high potential for abuse. It slowly goes down as one goes from Schedule 1 to 2, so and so forth to Schedule 5. Ironically, marijuana, also a Schedule 1 substance, has enjoyed a series of legalization victories that originated with claims that it was for ‘medical use.’ And don’t even get us started with the addictive qualities of methamphetamine – a schedule II substance.

We are not here to question the benefits or detriments of the existence or methods of the DEA or organizations like it; those are drug policy and policing issues and ones that you as a listener can research on your own through sources like the Drug Research UK website. 

But we are here to question some of the scheduling of molecules that we believe are wrongfully placed and we want to outline why psychedelics shouldn’t be scheduled as they presently are. We also seek to highlight how a more accurate rescheduling would help treat mental health disorders, particularly those for which there is presently inadequate treatment or no treatment at all. 

Treatment efficacy of existing treatments for mental health disorders like depression is rated differently depending on whether you ask the physician or the patient. Can I tell you a startling figure? 13% of adults in the US take anti-depressant medication. It’s higher in women than men. In the UK, the number is not all that different, slightly lower but at a comparable 11%. In all of Europe, the number of prescription antidepressant use is 20%. Now add in post-traumatic stress disorder and people who get prescription opioids for pain, and those numbers skyrocket. I haven’t even gone to Asia yet, folks. 

Blame does not fall on a single culprit. The burden is shared among governments, their agencies, and the governed themselves. We will share examples of this later in this series. But times have changed since the DEA implemented its classification system, and so has the evidence. So just as the rational beings that we are, now that we have gone past the crocodile brain and I showed you the discrepancy in the we need to reconsider this DEA scheduling of drugs. We will deal with the why now. We will tackle the How in later discussions. 

Hmmmmmmm, I did warn you that this was a heavy topic and one that has a history like no other class of substances known to man. Are we ready to get into the story? 

By the mid-1950s, psychedelics had moved from the laboratory to more of a cultural use and used by many considered to be members of the middle and upper classes. One such person was a noted English writer and poet called Aldous Huxley. For me, Huxley is an interesting character, not because he was a poet but because he was the brother of the famous neuroscientist, Andrew Huxley. 

Older brother Andrew along with Alan Hodgkin were the folks who first described and measured the first voltage recording of nerve transmission in a giant squid axon. It is said that they went to Southampton along the southern English coast, fished for squid and did all their experiments by the sea in the summer, and brought the recordings and lab notebooks back to Cambridge for analysis and writing up their papers. 

Talk about work-life balance, these two had taken work as fun to a new level back in the 1940s. 

The younger brother, Aldous also wanted to be a physician but suffered from an eye condition, Keratitis punctata and he decided to take up writing instead. Aldous became a famous writer and moved to California where, through his neuroscience and eastern cultural inclinations, he became friends with many psychiatrists. Although Aldous enjoyed critical success with his first two books in 1921 and 1923, it wasn’t until 1953 that he was exposed to an experience that was so rousing that it prompted him to write the book “Doors of Perception”. Western readers in England and the US celebrated this book as a cult classic. Aldous embraced the revolutionary experience and described the crystalline drug that he ingested, mescaline, as a “drug for the elite”. Whether he meant ‘elite’ in the contemporary sense of the word is a topic for further discussion but one that we won’t address now. There is no doubt that his book influenced many other cultural events, recreational use and ultimately ties into the 1971 announcement by Nixon. 

Let’s fast forward to 2021.  Remember the schedules of drugs that were created? The following is verbatim from the US Drug ENFORCEMENT AGENCY website:

Schedule I drugs, substances, or chemicals are defined as drugs with no currently accepted medical use and a high potential for abuse. Some examples of schedule I drugs are: heroin, lysergic acid diethylamide (LSD), marijuana (cannabis), 3,4-methylenedioxymethamphetamine (ecstasy), methaqualone, and peyote

This gradually decreases in potential severity of abuse. 

Schedule II drugs, substances, or chemicals are defined as drugs with a high potential for abuse, with use potentially leading to severe psychological or physical dependence. These drugs are also considered dangerous. Some examples of Schedule II drugs are:

Combination products with less than 15 milligrams of hydrocodone per dosage unit (Vicodin), cocaine, methamphetamine, methadone, hydromorphone (Dilaudid), meperidine (Demerol), oxycodone (OxyContin), fentanyl, Dexedrine, Adderall, and Ritalin

So you get the picture, Schedule III, IV and V are substances that have decreasing dependence and lower abuse potential.

OK, so now you know what the DEA drug scheduling text says. And, I did tell you that we, as a society, are responsible for this. But why? To understand this, we must really understand what got us here. 

Humankind’s tryst with substances that modify the state of mind is as old as humankind itself. This is important to know in order to understand how our relationship with drugs has been shaped. Back in the late 1700s, spurred on by the renaissance period, the field of science was blossoming. It was not just arts and literature that the renaissance had a hand in, but also in science, especially physics, chemistry, and biology. One of many notable examples was the explosion of an area of science that brought to the fore, today’s branch of biology – botany, physiology, pharmacology and ultimately the convergence of all these on treating patients in medicine. Many English and German botanists were instrumental in these advances. One of the first known examples was the discovery of the Foxglove plant by Leonard Fuchs, a Bavarian physician in 1542, way before William Withering, an English botanist laid his hands on the plant to treat patients with hydropsy – or what we know today as end-stage heart failure. 

I bring this example up to signify two things – one, is to show that around this period in the 1500s, Europe was learning that there was a world outside of its own landmass, and explorations to the far east and far west started. Second, when these plants were discovered, they were misunderstood for their toxicities (most of them included nausea or vomiting) due to humans or animals ingesting them. It wasn’t until the late 1700s when the white settlers were fighting their colonial rulers in the US, that scientists pursued further investigation and used these plants to treat patients. And all of this, was for diseases like heart failure or hydropsy as was called back then, which was seen as a matter of life or death. In fact, you might also be really interested to know that even drugs like cocaine were once marketed as a cardiac tonic, way before its addictive properties came to light. 

Why am I saying this? Because it is important to note that medicine and especially plant based substances were met with suspicion, skepticism and systematic study were performed. It is in the systematic study that our topic gets really interesting when it comes to mind-altering substances. 

Now let’s focus on the late 1600s and through the 1700s, chemistry and chemical reactions were only starting to be described. And by late 1700s, interest in a form of gaseous matter that was seen in various chemical reactions was gaining momentum and prominence. So one area of medicine, where gases became really important, and one where chemistry and medicine came together was in the discovery and deployment of anesthetics and the first major mind-altering description known to scientists was documented.  And the person who was at the centre was a young, dashing and almost flashy, extroverted Humphrey Davy. 

Around this time, most of us can’t imagine undergoing an invasive procedure like surgery, without anesthesia. Today, It would literally be a crime if someone performed surgery without it, but that was not always the case; historically, pain was considered essential to healing. So are we ready to rewind the clock to late 1700s. 

So who was  young Humphry? To the chemistry and engineering inclined, Davy was one of the early faculty of the Royal Institution,  dubbed by its creator – as one which will serve as an Institution for diffusing knowledge. Davy, served around the same time as Henry Cavendish. Cavendish was the chemist who discovered the world’s lightest element and gas – hydrogen. He was also a contemporary of Antoine Lavoisier who discovered oxygen and played a seminal role in understanding the density of inflammable air that produced water on consumption. 

Here is one of our guests, Themis Prodromakis who holds a Royal Engineering Professorship and works at the University of Southampton.  

< Themis Prodromakis describes Davy and Faraday>

Ok, Humphry Davy was a very respected figure,  But young Humphry did not start there. He was born in today’s Cornish coast – in the southeastern portion of England and moved to Bristol. His father died when Humphry was 16. It is said that he and his siblings got into a lot of trouble, and have been described as a group of boys who loved hunting, shooting, wrestling, cockfighting, and getting drunk. Young Humphry reportedly had little interest in literature and even less in science. 

When Humphry’s father died, Humphry’s godfather decided to put him to work. Humphry was a servant and an apprentice at an apothecary of a local physician called John Bingham Borlase. The godfather’s plan was to make a physician out of young Humphry. While working in the apothecary, Humphry became interested in Chemistry and taught himself the field as an extension of what they did at the apothecary. Humphry became so adventurous that his boss said – “This boy is going to blow us all up.” 

The world must have seemed like an amusing place for young Humphry.  Around this time, a young  twenty year old Humphry was exposed to a physician called Thomas Beddoes who published a paper with another physician James Watt titled – Considerations on the Medical Use and on the Production of Factitious Airs. The goal was to build a pneumatic machine that would be used to burn two ingredients – in this case ammonium nitride over boiling water. This would heat up the ammonium nitrate and produce nitrous oxide. This gas could then be trapped in bags and used for medicinal purposes for patients with lung diseases. All of this was going to be done at a new institute that Beddoes and Watt created in Bristol called Pneumatic Institution. 

But Humphry, the lab technician was not going to be just standing by, watching. Where young Humphry was, there was sure to be mischief. He had tried to inhale the gas a few times. It gave him a very pleasant feeling, but now he was ready to take in more! 

On boxing day, 1799, In the centre of the laboratory, Davy had set up a chemical reaction: ammonium nitrate bubbled in a heated retort, and the escaping gas was being collected in a hydraulic bellows before seeping through water into a reservoir tank from which the sealed box was filled. Davy was said to have inhaled twenty quarts of the gas from a series of oiled green silk bags.

While seated in the box breathing deeply, Davy had felt the effects that had become familiar from his many previous experiments since he had first inhaled the gas earlier that year. At first, he felt that his mouth tasted sweeter, and then a gentle pressure in the head followed as he continued to inhale. Within thirty seconds the sensation of soft, probing pressure had extended to his chest, and the tips of his fingers and toes. This was accompanied by a vibrant burst of pleasure, and a gradual change in the world around him. Objects became brighter and clearer, and the space in the cramped box seemed to expand and take on unfamiliar dimensions.

Now, under the influence of the largest dose of nitrous oxide anyone had ever taken, these effects were intensified to levels he could not have imagined. His hearing became fantastically acute, allowing him to distinguish every sound in the room. In his field of vision, the objects around him were teasing themselves apart into shining packets of light and energy. Young Humphry felt that he was rising effortlessly into new worlds whose existence he had never imagined before. 

Somehow, the whole experience was irresistibly funny: he had ‘a great disposition to laugh’, as all his senses competed to exercise their new-found freedom to its limit.

At the newly founded Pneumatic Institute, Davy was very meticulous in his observations. He performed experiments on animals, himself, and many other individuals. Due to the gas’s euphoric effect, it did attract quite a bit of social attention. Soon men from high class, poets, and writers started meeting at the Pneumatic Institution which became much more than just a place to use factitious air to treat patients with lung diseases. Some of the prominent figures at the time included Samuel Coleridge and William Wordsworth. 

This, to date, is the first known experimentation with a mind-altering substance outside of alcohol or opium. 

Humphry did not stop there. His connections and his penchant for being a young experimenter, enabled him to lead many science-based parties at the homes of the rich and the famous. Humphry succeeded in turning it into a business enterprise. His distribution of nitrous oxide at these parties caused people to become veritable bags of laughter, thus Davy coined the term “laughing gas” – a term that has stuck to this very day.It is this social connection that led young Humphry Davy to the Royal Instituition and eventually, he became the head. What a turnaround! 

 It is also said that while people were laughing so upon inhaling this gas that both consumers and witnesses might slap themselves to bring themselves out of laughing state. It was noted that Nitrous oxide increased the threshold for pain, so seeing people slap themselves made both themselves laugh more and it must have also sent other members of the party into a laughing frenzy. 

Now! In all the laughing, I almost forgot about the meticulous self-experimentation and experiments on others. Humphry Davy published an 80-page paper titled Researches: Chemical and Philosophical in 1800  where he detailed the effects of nitrous oxide including reduced pain sensitivity. But it would be another 50 years before nitrous oxide had a medical application. 

I want to share a bit with you to show, not just the fun part of innovation, but also about the sad stories. The laughing parties had become so famous that they had spread to the US in no time. It was at one such party that a young dentist called Horace Wells figured out the pain-reducing potential of nitrous oxide in his practice – he had to routinely yank out people’s teeth with no anesthesia. In those days, surgeons would amputate limbs with no anesthesia. It is said that some surgeons would have severe anxiety before engaging in these procedures – vomiting and sweating profusely prior to performing the surgery. 

Now, Horace Wells thought that Nitrous oxide provided the answer. He had used it once to remove a tooth and lo and behold, he found that the patient did not feel much pain. He went on to use the gas on another 15 patients and is said to have failed in producing pain relief in 2 out of the 15 patients. I would say, for a drug that was new and one for which Horace had no information, it was a pretty good result. It would even get venture capitalists in today’s world to invest in his endeavor. But that’s not what happened. 

Like many skilled physicians of the time, Horace arranged for a demonstration in Boston. The patient was laid down in a dentist chair in the middle of a packed auditorium and Horace proceeded to administer nitrous oxide. He then started using the surgical tools to pull out a tooth The patient let out a noise which was perceived by a few members of the audience as pain and they shouted “Humbug” which was, at the time, incendiary and shameful. What followed is unclear – but Dr. Horace Wells committed suicide. 

In the years that followed, ether and chloroform were discovered and physicians learned that they were much more powerful than nitrous oxide. But a system that would allow them to mix gases would provide them with an opportunity to start with nitrous oxide so the patients felt good, before putting them to sleep with ether and chloroform and bring them out of anesthesia with nitrous oxide so that the pain from surgery could be reduced. Nitrous oxide is still used as an anesthetic agent to this day! 

So why are we talking about an anesthetic agent on a podcast about psychedelics, you may ask? The answer lies in the message that this story provides – a gas was created for a specific use. It became a plaything for elites and party-goers before it was applied for therapeutic purposes. It was misunderstood and dismissed before someone else discovered its medicinal benefits.

This is not just the story of nitrous oxide, this is the fate that psychedelics have endured. 

So let us now take a deep breath and move from early 19th century England to America. This is a really interesting period in history. Around the time that Nitrous oxide was invented, used and abused and used again, England’s East India Company had landed in India. Prior to them, the Portuguese had landed, then the French and finally the British arrived. The British succeeded where the Portuguese and French did not. They did not just come to do business as the Portuguese and French did, but had astutely come to capture land. And they did. They used a policy called “divide and rule” to sow seeds of doubt among the kings of India and made them fight against one another, sought to support one and once the opponent was defeated took over the lands of the  puppet king. Why is this important? Because it shows a slightly similar pattern with a different ending happened in the Americas; only because the indigenous people were seen as savages and not as ones from  a civilized and wealthier society like the far east. The tricks that the mind plays on us…We are ONLY  just getting  started!  

Just like the Portugese, French and British, the Spanish wanted to come to India. They succeeded in following Magellan and Columbus and many other sailors into the Americas. If you remember,  Columbus rode on his ship, The Santa Maria, to make landfall in the Bahamas. A few years later, Amerigo Vespucci, an Italian who had emigrated to Seville in Spain, and was a big supporter of Christopher Columbus, captained voyages himself to discover what is today, referred to as the Americas. 

The Spanish and the Portuguese were the most successful maritime voyagers in the 15th and 16th centuries. They became so enthralled with the land that we know today as South America, and Amerigo Vespucci himself voyaged successfully to the Bahamas, Brazil, Peru and even into the Amazonian rainforests and high mountains of the Andes. The Spanish and Portugese knights, explorers, and merchants – known as Conquistadors or ‘conquerors’, began the process of colonizing and used religion as the way to do so. Unlike the British, who used the “divide and rule” tactic in India many years later, the Spanish and Portugese used christian missionaries and religion as the means to occupy the lands. 

This is where a fantastic book titled “Mescaline: A Global History of the First Psychedelic” comes in. Author Mike Jay is a renowned cultural historian of drugs and drug use in society past and present. 

Here is Mike, recounting why he has made it his career mission to research and study the history of drugs. 

Mike Jay: <Academics have not really spent a lot of time studying drugs, because I thought it was a bit beneath their dignity. So it’s actually full of great stories that nobody’s really looked at.>

It wasn’t just that. Here is Mike again recounting another reason why this interests him as a historian. 

Mike Jay: < Another reason why the history is so interesting because of self experiment. It takes you back to the time when scientists took come these drugs themselves to understand what was going on> 

It might seem like a far cry to you listening to this, but scientists in the 19th and early 20th century were operating as mavericks. They did try experiments in animals like how today’s scientists do, but chemistry., physics and medicine wasn’t as advanced. So to advance these areas of science, the scientists took it upon themselves to test their findings on themselves. It’s a throwback to when kings and generals used to fight on the frontlines rather than take a backseat. There are many such examples in history. In fact, the scientist who discovered that abnormal heart rhythms moved around in circles, like a snake biting its own tail and developed the first way to shock the heart as it is done with defibrillation today, died while self-experimenting. You needed to be bold and have high degree of self-conviction, much more than what it is today. 

This is where stories get very interesting. The subjectivity of the response makes for a very interesting history. Let us go step-by-step. 

Let’s go back to conquistadors and their plundering of the Americas, specifically the amazonian forests and Andes mountain highlands. Mike recounts a very interesting stage in history that preceded the conquistadors by at least 1900 years. This is the era of the Chauvin civilization, one of the most advanced civilizations of the time around 900-200BC. The history and the fascination with mind and the mind’s inner-working dates back to when humankind first set up shop on this earth. The most striking feature here is the temple located around 3,000m above sea level. Here is Mike Jay, again, describing the temple to us. 

Mike Jay: < Well, this is a very mysterious temple, it’s always been called Chauvin.. It’s quite high up in the Peruvian Andes. And it was always an archaeological puzzle, because it doesn’t seem it’s not fortified. It doesn’t seem to be militarised, and there is not much sign of settlement. So it looks as if it was a temple or a pilgrimage site. And it was only quite recently that it was discovered that people thought it was this must be connected to the Mayans or some other civilization that people knew. But in fact, it turns out to be what’s called a pristine civilization. And about 3000 years ago, the temple was was built, it’s still standing and in the central temple space. There is a little frieze of images carved in the wall, and they include a shamanic figure, which is kind of human, but with snakes for hair and Jaguar with claws and fangs, and holding a very obvious San Pedro cactus. This is the mescaline containing cactus species of the Andes. So I think this is probably the earliest iconographic representation of the of the San Pedro. And in that time, Chauvin culture and other sites, there is more direct physical evidence for the use of mind altering plants, particularly snuff trays and snuff tubes which are associated with snuffing the ground seeds of a shrub called Adenanthera, which contains DMT. >

Mike referred to quite a few plants. Importantly, he noted the San Pedro Cactus held by the jaguar in the sculpture seen at the Chauvin temple. Beyond that, many of the people who know a bit about psychedelics will know about ayahuasca. Let us hear from Mike again, on why the cactus-based alkaloid, mescaline is the grand-daddy of all. 

Mike Jay: <So it looks as if, in this same Chauvin temple, psychoactive psychedelic plants were probably used, there was a great find, I don’t know if you remember, it made the headlines a couple of years ago, of a mummy burial up in the high Andes in Bolivia, with a mummy bundle containing all kinds of roots and herbs and that turned out to contain traces of cocaine from coca leaf and of harming from the Ayahausca vine. And of this, these seeds of Adananthera. And also I think psilocybin so there’s quite a lot of physical evidence, you know, very unusual amount of physical evidence from that point in time to suggest that there’s mescaline containing cactus, San Pedro was one among a complex of psychoactive plants that were used at that time.

And, it’s always assumed that ayahuasca  is very, very ancient, but it may not be, it looks as if you know, probably 100 years ago, there were very few people in the Amazon who used Ayahausca. But there may have been quite a lot of people who choose the vine, while they also snuffed out, drank the seeds because they potentiate each other. So there’s a very interesting, early chemical synergy demonstrated in that bundle.> 

It is here that the real documentation of a peculiar plant starts. The hero of our story – The San Pedro Cactus has ARRIVED! 

San Pedro Cactus is thought to have been used as the first psychedelic that is documented well in history. There are other instances referenced in history, but clear evidence is lacking in both Greek and Indian cultures. For example, the Hindu religion and the scriptures called the Vedas refer to a drink called Soma. It is known that Soma did not have alcoholic properties but had mind-lifting properties. Note that I said “mind-lifting properties,” that could be interpreted to mean “spiritual.” We do not know exactly what that means, but as an Indian and a Hindu, I have always wondered about the vibrant representations of the deities – A blue deity in Krishna, the creator Brahma with four heads or Lord Shiva the destroyer who applied ash from cremation of fellow beings upon death, or the protector- Vishnu who slept on a massive serpent in the middle of the ocean or the female deities like Durga with eight hands, riding a tiger, and each hand holding a weapon to protect mankind or destroy demonic powers.

The colour, splendour and the variety of descriptions extend not just to the deities but also to the characters in spiritual stories – like the Indian equivalent of Elves, whose leader Indra always was drinking Soma. Many stories including the avatars of the the protector Vishnu or what most Indians describes as the first successful head transplant in Ganesha is not likely something conjured up by normal consciousness, or so I wonder. 

I digress. Where were we? Ah yes, the San Pedro Cactus.  The San Pedro Cactus is the granddaddy of psychedelics. San Pedro and his Mexican mate, Peyot, which grew in the Mexican desert, have had a critical role in shaping the world’s history. 

From a scientific perspective, here are two plants, the San Pedro native to the highlands and Peyote, native to Mexico and lower altitudes, that had evolutionarily developed mechanisms that we now know enable them to survive in dry climates. The spines and succulent stems contain alkaloids that serve various purposes like end products of metabolism, or storage reservoirs of nitrogen, but the most ubiquitous quality is providing protection from predators or in some cases, growth regulators. 

The Natives of the high mountains of the Andes had used the San Pedro cactus as a religious plant. There is ample proof according to Mike Jay’s book to suggest that the cactus was ingested in a communal setting.  Evidence is gathered from archeological finds that this temple was inhabitated by Shamans. As Mike said, the temple had no fortifications whatsoever; we believe that people visited this temple for a spiritual purpose. 

High priests of the temple administered the ingestion of San Pedro to help guide their followers through the process of self-reflection and enlightenment and to open up their senses and directly interact with their god. The enlightment journey was impacted by each devotee’s personal baggage. The high priests of Chauvin were said to have conducted the ceremony over multiple days to ritually cleanse the mind. The intention was to allow the people of the land to follow their individual path in life with an eye toward a common purpose and an aligned vision that humankind and nature were one and to take their part in that natural evolution. This was seen as a way to live in harmony with the world and people around you. 

Mike Jay: <The earliest reports we have that are from the, from Mexico, and for the with the peyote cactus. And where missionaries, particularly in the north of Mexico, where peyote comes from, who record ceremonies in the 17th and 18th century where a whole village would get together. And usually at night, usually around a fire, and everybody would eat the Peyote and then kind of dance around the fire all night. So I think  it’s possible from that to imagine that something similar might have happened with San Pedro in the Andes. 

And. mescaline is very different from other psychedelics and that it’s a phenethylamine. So it has a different chemical structure, it’s more adrenergic, you have to take quite a large dose, it takes quite a long time to come on. And it has a sort of physical body load that can be quite difficult to manage. And it’s getting together and dancing and singing is very helpful for getting the mood going for getting the phone working the plant through the system. And you build up if you do that in a rather hypnotic kind of the sort of the idea of a sort of a group mind ceremony in which everybody if they carry on doing the same three step shuffle around the fire for you know, for several hours, everybody gets into a really remarkable comical altered state.>

All was fine and dandy until the Conquistadors landed. Columbus and other Spanish explorers had trafficked tobacco which was widely smoked and consumed in Europe, but here the same plant was being consumed along with a bunch of other psychoactive plants including mushrooms, seeds of morning glories containing an alkaloid similar to another molecule that we will speak about soon called LSD, shrubs like datura, the toxic red mescal bean, and most important of all, dried, spineless cacti called as Peyote. While San Pedro had a distinct giant cactus look, Peyote was an inconspicuous cactus that could not be more dissimilar. How this inconspicuous cactus, that barely grows above the desert sands of Mexico, is going to change the world was something no one could have ever predicted. Peyote buttons are the moste widely used and the most visible part of the plant, but most of the plant grows under the ground. When the buttons are damaged by an animal or a human trodding on them, they can appear to be almost dead for years, but then could suddenly spring to life with new parts growing like budding yeast. 

Botanical survey of 1577 states that “This root scarcely issues force, but conceals itself in the ground as if it did not wish to harm those who discover it and eat it. The native tribes of the Andes and Mexico attributed wonderful properties to it, including the power to foresee and predict things. Such things as in, if the weather will continue favourable or to discern, who has stolen from them some utensils or anything else.” Others were more skeptical, another physician attributed the local beliefs regarding the powerful properties of peytote to its pharmacology, one that disturbed the anterior sense of the cerebra, which caused visions of monsters, bulls, tigers, lions and goats, and that is painful and harsh. 

 Let’s find out more. Here is Mike again! 

Mike Jay: <I find that fascinating because it’s really the first Western encounter with what we now call psychedelics. The Spanish Conquistadors arrived in a land that was isolated from the rest of the world, but extraordinarily rich in psychoactive cacti, mushrooms and other plants. And it was very, very interesting to see the ways in which they tried to make sense of this. And predominantly, as you say, they’re coming from Europe in the grip of a witch craze, they sort of see the devil everywhere. So once when they see people having visionary experiences on these plants and fungi, it’s, it seems obvious to them that these are not coming from God. So they must be the work of the devil. you can see how puzzling it was for the Spanish, that this looks really quite similar to the Catholic mass,  where people would stand around and sort of bow their heads and mutter prayers and then take the cactus or the mushroom, very reverently. So what was what was going on here? And there are different types of accounts, some that offer a more natural history perspective, trying to document what’s going on. But also from the Jesuits who were leading the Christian mission of the Conquistadors, and were very keen to mark this down as something that was the product of heathen and demolitions to convert the population to Christianity.> 

As with many examples we now know, religion was at the heart of the Conquistadors’ visions, no pun intended. Their vision was of one nation united by a common religion, Christianity. This is not new either. If you have visited the Vatican and Rome, you will see the various ways that Paganism was eliminated. So, as we said, History has a habit of repeating itself. Were the Spanish Conquerors successful? 

The Spanish conquerors and Jesuits saw the South American natives’ use of peyote as nothing but superstition and they believed that the Peyote was a plant that conjured the intervention of the devil and they called it “Raes Diabolica” or Devilish root. Missionaries saw communal ceremonies where groups of villagers would collect Peyote buttons, and then invite other villagers to join during harvest festivals. Villagers from multiple tribes would assemble together at night around a bonfire. They would then consume the peyote usually from a tea bark served primarily by young girls and old men. The group would then take part in communal singing and dancing. 

On one occasion it was noted that while there were around one thousand people at such a gathering, one could hear only one voice. One another occasion, the spanish missionaries noted that the villagers would then use a dried fish bone to impale their skin and draw blood and would smear the blood on each other. After many hours of singing and dancing, they would lie on the ground, as if they were dead which was interpreted as intoxication. While most of this ceremony was new to the conquistadors, almost any culture that had ancient roots would understand that singing, dancing, and chanting are part of many religious ceremonies. Yet the Spanish conquerors saw these ceremonies and the use of peyote as a way for the native tribes to summon the supernatural. These negative interpretations took root and  continued all the way to the mid-1850s. 

This is where the story of Peyote enters the modern era and it travels beyond the Rio Grande and across the US, from Texas to the east coast. 

The San Pedro and its sibling, Peyote were actively traded and as the conquest moved north from Peru, through Central America and into Mexico, Peyote grew in value. 

In 1620, the Mexican Inquisition banned the use of peyote and that is likely the first drug prohibition of the sort. The ban was partly to move the indigenous people away from their traditional beliefs and practices, which held with great tenacity, and to move them towards Catholicism. The Spanish population started to become suspicious of the way that plants like peyote were used for what they believed was divination and witchcraft. They attempted to draw a very clear line to say that this was incompatible with Christian worship. In doing so, they gave plants like peyote a very peculiar reputation. Indigenous people merely regarded peyote as a normal part of their cultural and spiritual ceremones; once the Spanish and the Catholics prohibited them, they became a marker of a distinctive, indigenous old religion.

There is ample evidence to show that Conquistadors were exposed to San Pedro through trade in the region. It is believed that these plants made their way to the United States through trade.. The Texas Railroad connected Texas to Mexico and the town of Laredo served as the entry point. 

It was through Laredo that a plant revered by the indigenous people of the Americas was on a collision course with the western world’s introduction to Peyote. What if we told you that this journey involved a masscare, war, a feud, questionable ethics, and served as the fuel to the fire of the 1960s counter-culture ? 

<END of the EPISODE 1> 

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 podcast 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 with inputs from Dr. Jo Neill.  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.