A Brief History of Psychedelics
From defensive molecules to cultural conquest, the story of psychedelics is quite the trip — and it’s not over yet.
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The year was 1502. Montezuma was preparing to inherit the Divine Seat, an honor that for 16 years prior belonged to Ahuitzotl, another formidable battle warrior. The transfer of power was set to make Montezuma king of the Aztecs for years to come. A vast ceremony would follow.
Among those attending the ceremony were townsfolk, slaves to be sacrificed (of which there were many), and, in an ominous foreshadowing, several chroniclers of the Spanish crown. As Tenochtitlan, the bustling Aztec capital, prepared for the coronation, Fray Diego Durán, one of the chroniclers present that day, witnessed a peculiar festivity:
All the Lords and grandees of the province … ate of some woodland mushrooms, which they say make you lose your senses. … With this food they went out of their minds and were in a worse state than if they had drunk a great quantity of wine. … With the strength of these mushrooms they saw visions and had revelations about the future.
Naturally, Durán assumed these visions were the work of the devil. In reality, they were the result of an ancient and inveterate practice: the use of psychedelics to experience the otherworldly. And, as much as it might have chagrined 15th century Spanish friars, the same practices have existed in every great society — from the Aztecs to the ancient Greeks. To not use these substances was the strange choice.
The history of psychedelics takes us back to a time before you and me — a time before anatomically modern Homo sapiens. And from there, it follows the sinuous trajectory of human evolution, where it’s moved from ubiquity and worship to inquisition and censor. Today, we’re at the beginning of a renaissance, where efforts in legalization and clinical use are slowly marching forward. It’s quite the trip. And to think, all of it started with just a curious defense.
A Curious Defense
In 1994, a research scientist and lecturer at Edinburgh Napier University by the name of Paul Agutter decided to poison his wife. His substance of choice was atropine, a chemical derived from the herbaceous plant Atropa belladonna. Over the years it would develop a more telling moniker: the deadly nightshade.
The deadly nightshade is a species of fruit-bearing plant related to tomatoes, potatoes, and henbane that’s native to much of Europe and Eastern Asia. It grows around five feet tall, produces purple-black berries, and has a long history of use by Italian women as a mydriatic to dilate their pupils. (This is, in fact, the origin of the name belladonna, which means “pretty woman” in Italian.) But, more notoriously, the plant also has a history of use as a deadly poison. Agutter knew this, and resolved to mix its deadly chemicals into a drink for his wife.
On a presumably cloudy night in 1994 (it might have even been a date night), the deed was done: Agutter mixed the atropine into a large gin and tonic, gave it to his wife, Alexandria, and, over the course of the next five minutes, watched as she descended into dizziness, nausea, pain, and hallucinations — all symptoms of atropine poisoning. And, as you might expect of a would-be murderer, Agutter opted not to call the paramedics; rather, he called a primary care physician. While nobody answered his call, he left a message that was miraculously relayed to a nearby hospital. Alexandria was saved, and Agutter was sentenced to 12 years.
While Agutter would eventually serve his sentence and resume teaching, his story reveals an important lesson other than cosmic injustice: many plants, animals, and fungi evolved chemicals like atropine as a way to defend themselves. Some of these defenses are deadly, others hallucinogenic.
The earliest chemical defenses likely developed in the Archean Eon, when bacteria evolved around 3.5 millions years ago. They would show up a few billion years later in plants and fungi.
Chemical defenses were helpful to plants and fungi for many reasons — the most salient being a lack of mobility. Since neither plants nor fungi ever evolved the ability to flee in abject terror from vicious predators, noxious chemicals helped them defend themselves. Without these chemicals, herbivores and fungivores uninterested in biological diversity might eat them into extinction. While some species utilized thorny branches or towering heights, many others turned to chemicals (although, of course, many species embodied more than one of these defensive strategies).
Most of the chemicals plants and fungi use to defend themselves are secondary metabolites, which means they serve no immediate reproductive function in the organism: They’re produced solely to ward off foes. A few of these metabolites should sound familiar. Penicillin, for instance, the miracle derivative discovered killing bacteria in an abandoned Petri dish, is a secondary metabolite; it’s produced by the fungi Penicillium to ward off hungry bacteria. Nicotine is another good example. It’s produced in many plants, but in particularly aggressive quantities in nascent and wounded leaves — just what you’d expect of a plant trying to defend its most valuable components. Both of these secondary metabolites create a lingering sense of unease in predators that consider repeating such meals.
Unfortunately for plants and fungi, predators would eventually evolve biological workarounds to these defenses. And so, plants and fungi had to evolve new chemical modifications to address the ever-changing assaults. Insects evolved, so plants and fungi had to develop specialized insecticidal chemicals (which is why over 700 species of fungi now kill insects). Amphibians, reptiles, and mammals evolved, so plants and fungi had to develop specialized chemicals to target them. At what was likely many points over the course of these evolutionary arms races, these alkaloids — secondary metabolites evolved specifically to affect the central nervous system — turned hallucinogenic.
The list of hallucinogenic chemicals created by plants and fungi is too long to enumerate (and the full list is certainly unknown), but a few examples stand out. Psilocybin, for instance, comes from one of the most widespread mushroom genera — the psilocybe. Mescaline, popularly adopted by Native American communities in the 15th century and now smoked by millions across the US, comes from the buttons of the peyote cactus. And DMT, which is found in many plant species, is commonly derived from Psycotria viridis. Native tribes from the Amazon Basin combine the leaves of Psycotria viridis with the stems of Banisteriopsis caapi to create the famous ayahuasca tea.
Most of the psychedelic chemicals we talk about today (including the three just mentioned) are “classic psychedelics.” Other than their potent psychological effects, these chemicals are united by the unique way in which they affect the central nervous system: Each contains alkaloids that work on the same areas of the brain. These areas are responsible for our regulation of the neurotransmitter serotonin.
The serotonin system is widely conserved across the animal kingdom. As its name suggests, it operates via the neurotransmitter serotonin — or what the neuroscientists call 5-HT. In mammals, the molecule plays a role in mood, attention, aggression, sleep cycles, and the fight or flight response. (It is also the target of leading depression medications — for instance, the famed SSRIs, or selective-serotonin reuptake inhibitors.) But it also works as a neuromodulator, tweaking the way that other neurotransmitters (say, dopamine and acetylcholine) work and respond to signals in the brain.
When the classic psychedelics enter our bloodstream — whether through eating, drinking, snorting, or smoking — they pull at the levers of this serotonin system. At a molecular level, they work by binding to the 5-HT2A receptor, one of the many serotonin receptors in the brain. Once here, they block the receptors from receiving more serotonin. This creates a buildup of the neurotransmitter in the surrounding areas, creating a deluge of serotonin for all unclogged receptors. And voila, the classic psychedelic experience.
The psychedelic experience is not solely the domain of these serotonin agonists, however. Amanita muscaria, for instance, likely the most iconic hallucinogenic mushroom (known by its red cap polka-dotted with white spots), works through muscimol — an alkaloid that binds to GABA receptors, not serotonin receptors. Likewise, atropine, which in small doses is more hallucinogenic than deadly (something Agutter’s wife learned the hard way), works by blocking our brain’s receptors for acetylcholine. (As an interesting aside, witches of the medieval age mixed atropine into “flying ointments,” which they would subsequently rub onto broomsticks and “ride” to yield flying sensations.) The point is, many different substances are capable of producing psychedelic effects.
Regardless of the underlying chemicals involved, the psychedelic experience is aversive to most animals: There’s not much benefit to dancing around naked and listening to the Grateful Dead all day if your primary objective is to avoid being eaten by large predators. Moreover, many of these psychedelic chemicals accompany bitter and nauseating substances, making them doubly unpalatable to mammals like us. And so, most animals assiduously avoided them. But this wasn’t the case for every animal.
The Human Exception
The Tassili n’Ajjer caves in Algeria are a remarkable archaeological discovery. They are recognized as part of a UNESCO World Heritage site that hosts everything from beautiful geology to over 15,000 cave paintings — several of which document flora and fauna that have since gone extinct. Even more remarkable, however, is the discovery of the “Matalem-Amazar figure” (more colloquially known as the bee-faced shaman), an ancient mural of a bee-human hybrid with an unusual relationship to mushrooms.
The bee-faced shaman, presumably unlike many other shamans, has mushrooms drawn all around its body — sprouting from its arms, legs, and even its ears. Scientists suspect these mushrooms are Psilocybe mairei or Psilocybe cubensis, two species of psychedelic mushroom native to areas of Northern Africa like Algeria and Morocco. Carbon-dating suggests the mural is between 7,000 and 9,000 years old, making it and its fungal appendages one of the oldest known tributes to psychedelics yet discovered. But such tributes are by no means unique to ancient Algeria.
The number of archaeological discoveries suggesting a psychedelic past defies counting. Archaeologists have unearthed golden crowns in Egypt with images of mushrooms engraved into them. In Central America, missionaries and archaeologists documented countless “mushroom stones,” basalt statues of men shaped like mushrooms (likely the native Psilocybe zapotecorum species). The ancient Greeks even had temples thought specifically dedicated to psychedelic ritual.
Many of the sites and artifacts archaeologists have uncovered suggest that our relationship to psychedelics was spiritual. The Tassili n’Ajjer caves, for instance, were located in remote areas far removed from nearby society, making them hidden and difficult to access. Such conditions are typical of sacred spiritual sites. At other locations, archaeologists have found psychedelic paraphernalia thrown into graves — another sign that psychedelics held spiritual value.
More explicit evidence of this spiritual relationship comes from ancient texts. Ancient Buddhists, for instance, wrote of an enlightenment elixir you can obtain from reindeer urine. Because eastern reindeer eat Amanita muscaria, the psychedelic mushroom mentioned earlier, the reindeers’ urine contains distilled psychedelic compounds: their liver and digestive tract break down Amanita muscaria’s most toxic components, leaving a purified psychedelic compound — er, “enlightenment mixture” — in its wake. How the Buddhists discovered this elixir is a topic for another day.
But the spiritual connection between psychedelics and ourselves is also found in the names and ways that societies talked about it. In Mexico, the Aztecs called their mushrooms teonanacatl, meaning “flesh of the gods.” Peyote was widely described as a “portal to the spirit world.” And ayahuasca, the psychedelic tea of the Amazon, is extracted from the so-called “spirit vine.” Psychedelics, in other words, bring profound spiritual experiences. And these experiences were in no way confined to peoples of the distant past.
Gerardo Reichel-Dolmatoff, once a Nazi soldier who later changed his ways to fight the Nazis, eventually moved to Colombia and founded the discipline of Colombian Archaeology. He knew more than most at the time about the religious importance of psychedelic chemicals to non-westernized communities. Having lived in the Amazon Basin for over 60 years, he studied a variety of Native Colombian tribes — each with little, if any, exposure to the outside world. The affiliation of these tribes to their psychedelics was clear. This was particularly true with Yaje, a potent psychedelic concoction similar in character to ayahuasca.
Here’s how Reichel-Dolmatoff described Yaje and its significance to the various tribes he studied:
The use to which these hallucinatory trances are put by the different Indian tribes varies from curing rituals to initiation ceremonies … from the violent frenzy of warriors to ecstatic religious experiences. In all cases … Yaje is thought to provide a means of being transported to another dimension of consciousness, which, in the daily life of the individual or of the group, acquires great importance.
The Yaje provided “ecstatic religious experiences”; it transported its users to “another dimension of consciousness.” The drink acquired “great importance” in the everyday lives of tribe members. The profundity of these experiences was an integral, inextricable aspect of daily existence.
From the Aztecs to the Amazonians, and from the ancient Algerians to Buddhist enlightenment elixirs, psychedelics have influenced an untold number of human populations. We find evidence of their use from the far reaches of Siberia to the distant islands of the Pacific. Their presence in our history is unequivocal. The question now is how far back does this history go.
Around two million years ago, we humans were a different breed — in fact, we were multiple different breeds. The hominin line that eventually culminated in us had yet to narrow, hosting a broad range of species from Homo erectus to Homo habilis. These early hominids were the first hypothesized to start deliberately eating psychedelics.
While the details surrounding this early hominin use are difficult to completely unravel, there are a few lines of evidence that suggest a deep and affiliative history. One of these is the global dominion of a certain genus of psychedelic mushroom.
The psilocybe mushroom is one of the most widely distributed mushroom genera on Earth. It contains the compound psilocybin, a chemical that, like other classic psychedelics, binds to the 5-HT2A receptor in the brain. These mushrooms are found everywhere from New Zealand, Australia, and Thailand to Siberia, Alaska, and South America.
Some scholars believe the psilocybe mushrooms evolved their hallucinogenic properties to aid in their propagation: early humans would eat them, have profound, life-changing experiences, and spread their spores as they migrated out of Africa and Eurasia. The profundity these mushrooms offered, then, helped spring their global dominion: Once we tasted their sacred properties and fashioned traditions around their use, we made sure to keep eating (and spreading) them wherever we went. The result was the transport of their spores across the world. And so, we have the global ubiquity of psilocybe mushrooms.
Another line of evidence for such a history is found in our neurochemistry. Some research suggests that our hominid lineage gained unique adaptations in the serotonin system to bring us an amplified reaction to the classic psychedelics. These adaptations suggest that our ancestors might have ingested psychedelic alkaloids so frequently that those who possessed an amplified response toward them had a stronger survival advantage. We are the descendants of those with the amplified response.
The primary finding of these researchers is that different serotonin receptors in our brains respond more strongly to the classic psychedelics than serotonin receptors in the brains of our closely related primate cousins like the gorilla, chimpanzee, and bonobo. It is possible, then, that our history with these drugs became so intertwined that they changed the chemistry of our brains.
However far back our history with psychedelics goes, it didn’t take long before they became an omnipresent fact of life. Unfortunately, the great age of spiritual exploration would not last.
The Fall of Psychedelics
The Spanish Inquisition began in 1478. Started by Pope Sixtus IV, the authority began with the Vatican but eventually moved to the crown, often used as an arm of political oppression rather than pure religious orthodoxy. The trials disseminated into the recently conquered “New Spain” in 1536, 15 years after Montezuma forfeited Tenochitlan to Cortez.
The “Indian Inquisition,” as it was then called, officially began when the Spanish crown granted inquisitor status to Fray Juan de Zumárraga, a Bishop who salivated at the idea of a Christianized New World. While many were skeptical of his abilities to convert the natives (and even of the natives’ cognitive ability to be converted), Zumárraga’s zealously was undeterred. Shortly after he was granted authority, his inquisition began.
The most frequently punished crimes under Zumárraga’s rule were sorcery, bigamy, idolatry, concubinage, sacrifice (whether animal or human), and dogmatizing — trying to dissuade others from adhering to the dictates of the Catholic Church. He launched campaigns to seek out and destroy idolatrous art and edifice, including sacred scripts, temples, and artifacts like mushroom stones. Those tried and found guilty were often subject to lashes, banishment, long prison terms, or, as happened in the infamous case of Don Carlos, burning at the stake.
The early years of the Mexican Inquisition, as it has since been renamed, didn’t last long; Zumárraga’s authority was revoked in 1543, nine years after it had begun. But the persecution did not stop there. Similar trials would unfold sporadically throughout the 17th, 18th, and 19th centuries; colonizers and missionaries had an unfortunate penchant for terrorizing those who engaged in such “Satan-inspired” rituals. The relentless persecution successfully drove the once thriving culture of psychedelics — and every other aspect of culture, for that matter — underground. The same happened in more than just Mexico.
Beginning in the eighth century BCE, the Temple of Demeter went through several successive changes, each making it larger and more exclusive than the last. The protected complex eventually grew so large it allowed thousands of Greeks and Romans to sit and watch its mysteries, the famed Eleusinian Mysteries, unfold. While the celebration took place over nine days and nights from Athens to Eleusis, it was the last two days in the Temple of Demeter that brought something truly strange.
While nobody knows for sure what happened in those final two days, many suspect that they involved ergot, a parasitic fungus that grows on rye wheat (which explains the temple’s association to Demeter, a goddess of wheat). Ergot is significant because it contains the alkaloid LSA, the same alkaloid Albert Hoffman would later synthesize into LSD in the 1930s. Once ingested, ergot can produce profound psychedelic experiences — but also, if not carefully purified, death or gangrene. (In fact, the “possessions” of the Salem Witch Trials have been attributed to ergot poisoning.)
Unfortunately for us, the initiates — a group including a litany of esteemed figures from Pythagoras to Plato — were sworn to secrecy, so the exact nature of the rituals are lost to time. What we do know, however, is that the initiates left the temple with a newfound perspective on life. Their experiences should sound familiar.
The “Eleusinian Rites,” according to Egyptologist and British Classicalist Terence DuQuesne, would “facilitate the making of a bridge between earth and sky and earth and the netherworld, to underscore the point that humans are also, or can become, deities.” Pindar (518–438 BCE), another famous Eleusinian initiate, wrote; “Happy is he who has gone through the Mysteries, for he knows the source and the end of life.”
By the fourth century BCE, the Eleusinian Mysteries had become the most widely celebrated tradition in the Greek and Roman world. But, after a few prominent conversions to Christianity, the celebrations would end.
Rome conquered Greece in 146 AD. But because they ascribed to the same pagan traditions, they upheld the mysteries and even expanded the temple’s walls. When Constantius II, one of Constantine’s sons, gained power in 337 AD, all of that changed. He criminalized the worship of pagan gods and the rites that appeased them. No longer was it legal to sacrifice in their name or even wander their holy temples. Doing so could be met with “fines, torture, or, death.” Things predictably grew worse from there.
The next great pagan persecution came from Theodosius I at the end of the fourth century AD. Toward the end of his reign, he tightened religious strictures even further, killing thousands of Greeks and Romans in the process. He destroyed numerous temples and places of worship, forced baptisms into Christianity, and, as if to add insult to grievous injury, disbanded the Olympics, the once glorious tradition of games and competition held to honor the gods.
When Theodosius I was on his deathbed, he cleaved Rome into Eastern and Western administrations and gave each (gasp!) to one of his teenage sons — Arcadius, 16 years old, and Honorius, 11 years old. To help them manage such imprudently assigned responsibilities, he entrusted each an advisor. This is where things go south for the Temple of Demeter and the Roman more generally: Each advisor wanted to wrestle complete control of Rome by killing the men in charge of the opposing administration. Bad news.
In the tumult and chaos that followed, Stilicho, the advisor to Honorius, decided it was wise to destroy the Temple of Demeter — a gesture to signal total allegiance to the Christian god. To carry out his plans, he recruited Alaric the barbarian. Guided and encouraged by Christian monks who harbored similar animosities toward the pagans, Alaric and his crew carried out the orders: The temple was destroyed, and ancient Greco-Roman traditions dashed.
The early antagonism toward psychedelics (called entheogens when used for spiritual practice) was largely a product of xenophobia and religious intolerance. Those party to the prevailing religions did not want people adhering to gods, cultures, and traditions other than their own. We saw this with the Mexican Inquisition, and we saw it with Christianized Rome. In more recent memory, the antagonism has taken a different shape.
Albert Hoffman first synthesized LSD in 1938. Five years later, he ingested the substance (on a date now affectionately called “Bicycle Day, given Hoffman’s post-trip bicycle ride). From that moment forward, for nearly three decades, scientists would stretch and expand their understanding of psychedelics and their apparent medicinal effects. Psychedelics looked like a miracle cure for everything from addiction to depression — disorders notoriously difficult to treat. But, because of a growing hysteria that began to surround the drugs and their affiliated counterculture (motivated in large part by iconoclasts like Timothy Leary), propaganda and fear would undo it all.
By 1966, LSD was made illegal. By 1970, Nixon passed the Controlled Substances Act, which put many other classic psychedelics on Schedule I — claiming they had no medical benefit and a high probability of abuse. While a few facilities maintained a license that allowed them to continue careful studies, psychedelics were largely battled out of the academic and public spheres. While the battle wasn’t as physically oppressive as that employed by the Spanish inquisitors or the volatile Roman elite, the stigma was nonetheless stifling. Fortunately for many, the taboo wouldn’t last.
A New Day
In 1988, Dr. Rick Strassman decided to try something new: He petitioned a governing research body to conduct a study on the psychological effects of DMT. Much to his surprise, his petition was successful. By 1990, Strassman began preliminary research, intravenously testing participants with varying amounts of DMT. His efforts, more than any specific result, showed the research community at large that the taboo around psychedelics was beginning to fade. More good news was quick to follow.
Throughout the early 1990s, academic interest in psychedelics continued to grow. In 1993, a group of researchers founded the Heffter Research Institute — named after Arthur Heffter, a famed chemist who, in 1897, synthesized mescaline from the peyote cactus. The sole aim of the institute was to study the classic psychedelics and their ability to change us for the better. Five years later, in 1998, a Zurich branch of the institute formed, compounding the organization’s research efforts.
This second wave of research into psychedelics was beginning to show all the initial promise of the first wave in the 1940s. Collectively, it showed that psychedelics could help with everything from trenchant addictions to intractable depression. The data continued to build, as did the positive attitudes of governing bodies in the research community.
By the early 2000s, the revival of psychedelics was well underway. Institutions like Johns Hopkins University, Imperial College London, the University of New Mexico, and the MacLean Hospital at Harvard had all begun allocating resources to their study. The “dark ages” of psychedelic research, as they have since been called, were finally coming to an end. Soon, researchers would start to decry the criminalization of these drugs and urge public officials to reconsider their Schedule I classification. Their cries have not gone unheard.
Today, research into psychedelics has resumed the fervor it initially maintained during the first wave catalyzed by Albert Hoffman. Between 1943 and 1966, over a thousand papers were published on psychedelics and their medical potential. Today, that number is quickly getting dwarfed. Now recognized as a potential remedy for some of the most confounding problems of the mental health crisis, psychedelics have opened up new doors — to health and perception.
The most promising avenues of research for the revived psychedelic program are similar to those brought by the first wave — to alleviate maladies such as addiction, end-of-life stress, PTSD, and depression. But, as we could have gleaned from historical examples and anthropological findings, the second wave is also beginning to show that it’s not just those with mental illness or end-of-life stress who can benefit.
Because psychedelics work — simply put — to encourage new synaptic formations and to weaken old ones, they can quickly alter a person’s perspective. In the medical world, this is what we see with treatments like addiction therapy, where many people come out of extended retreats with guided psychedelic practice and can’t imagine returning to their addictions (and accordingly show low rates of relapse). But it’s also what we see in many clinically “normal” people, who walk away from high doses in controlled environments (and sometimes only the high doses) thinking they have just had one of the most profound experiences of their life.
Given the apparent abilities of psychedelics, many scientists now think the legislative bodies in power will continue to recognize the many benefits — to the sick and to the healthy — of psychedelics. And it looks as if many parts of the world are beginning to catch on. With this slow march forward, we might eventually ease back into that ancient state in which all cultures partook, looking at their connection with nature and their surroundings with newfound adoration. Whatever the conclusion, the story of psychedelics is far from over.
