The Psychedelic Renaissance is here, with powerful medicines like psilocybin, lysergic acid diethylamide-25 (LSD), and 3,4-Methylenedioxymethamphetamine (MDMA) back en vogue. But how did we get here? (Hold onto your seats, cosmonauts; we’re going on a trip.)
The Debut of Psychedelics in the West
The history of psychedelic medicines is perhaps as old as humanity, with evidence of the shamanic use of mushrooms dating as far back as 5000 BCE in Algeria. The soma drink mentioned in the Indian Rig Veda between 1500 and 1200 BCE was likely a brew of psilocybin-containing mushrooms and honey. Mushroom-shaped statues from 1500 BCE are evidence of the medicine’s sacred use in Central America.1,2,3,4
Psychedelic roots have also imbued elements of our modern-day practices, with the red-and-white color scheme of the Amanita muscaria mushroom reflected in Santa Claus’ suit. The early shamans of Siberia were thought to use the mushroom to engender mystical visions and “fly” in the realms of psychedelic insight. Rather than eating the mushrooms directly and risk being poisoned, however, the healers likely collected and drank the urine of reindeer that had consumed the mushroom – hence the Christmas trope of the flying reindeer.5,6
Despite the long, rich history of entheogenic use around the globe, however, the so-called developed world was rather late to the proverbial party. It was not until 1941 that the Harvard-trained ethnobotanist Richard Evans Schultes published his doctoral thesis on the identity of two hallucinogenic plants of Oaxaca, Mexico. His paper on the mushroom teonanácatl (Psilocybe mexicana) and the morning glory species ololiuqui (Turbina corymbosa) was groundbreaking yet largely ignored at the time, perhaps on account of the eruption of World War II in 1939.7
It would not be until at least 1957 that Americans would take an interest in psychedelic mushrooms, when Maria Sabina became the first Mexican modern-day curandera to serve los hongos (mushrooms) to a Westerner. Her client, the American amateur mycologist R. Gordon Wasson, husband of Dr. Valentina Pavlova Wasson, published a photo essay in Life magazine in 1957 describing his experience with the so-called “magic mushrooms” – and the rest, as they say, is history. It is rumored that the Beatles, Bob Dylan, and a host of other gringos (both famous and not) flocked to Sabina’s home village of Huatla de Jimenez, Oaxaca, to consume los hongos (this author being one such adventurer, though decades later than the celebrities).8,9,10,11
But back to the late 1930s, when Schultes’ papers were published and the world was rattled by the War, across the ocean, a Swiss chemist by the name of Albert Hofmann was working with various derivatives of ergot in hopes of developing a new cardiovascular drug. In the fall of 1938, Hofmann synthesized the twenty-fifth derivative of ergot, lysergic acid diethylamide-25 (LSD-25, or simply LSD). Initially dismissive of the derivative’s value, Hofmann forgot about it for five years. Inspired perhaps by intuition, Hoffman revisited the molecule in 1943, intentionally ingesting what he believed to be a miniscule amount of the substance. Hofmann then rode his bicycle home in the throes of what is now understood to be the world’s first-known “acid trip,” and which to this day is celebrated annually on April 19th as “Bicycle Day.”12
Although the psychedelic trip Hofmann experienced was more terrifying than glorious, it was clear he had stumbled upon a powerful compound. LSD-25 was branded “Delysid,” and Sandoz Laboratories began an international crowd-sourcing project to research commercial applications for the drug. Between 1949 and 1966, Sandoz Laboratories provided researchers (and clinicians willing to take notes) virtually unlimited quantities of the drug in exchange for their observations and insights.13,14,15
Between 1953 and 1973, the United States federal government too took interest in LSD-25. Four million dollars were spent funding 116 studies on the drug in research involving 1,700 subjects. Those numbers do not include the Central Intelligence Agency (CIA)’s classified research, done under the code name MK-Ultra. With the country engaged in the Vietnam War (November 1, 1955 – April 30, 1975), MK-Ultra focused on how LSD-25 could be used for mind control or otherwise weaponized. Some of the MK-Ultra studies were illegal; others downright unethical.16,17,18
One MK-Ultra research subject was Ken Kesey, who in 1960 was paid to take LSD-25 in a study. Kesey’s novel One Flew Over the Cuckoo’s Nest was published two years later, in 1962. (The novel, Kesey explained, was less a book about mental illness than a story of how society pushes away those who do not conform.) In 1964, Kesey banded together with his friend Neal Cassady and their entourage of “Merry Pranksters” to introduce thousands of people to LSD-25 at “Acid Test” parties, which were often graced by the music of the Grateful Dead. Their Day-Glo painted Furthur bus is to this day an icon of the Hippie Generation.19,20,21
The psychologist Timothy Leary, PhD, was also among those experimenting with psychedelics. After reading Wasson’s Life article, the Harvard University professor traveled to Mexico in 1960 to try the psilocybin-containing mushrooms for himself. With the approval of the psychology department’s chair, Leary and his associate professor Richard Alpert, PhD, founded the Harvard Psilocybin Project. The two professors then administered psilocybin – and later LSD-25 – to hundreds of people in studies that often lacked a control group. Their research was criticized not only for its party-like atmosphere, but also for the researchers’ tendency to take drugs themselves alongside their subjects, some of whom were undergraduate students at Harvard. In 1963, both men were fired from Harvard University, but it was too late: the psychedelic movement had escaped the lab. Leary continued his work with psychedelics; Alpert went to India and returned as the spiritual teacher Ram Dass. In 1971 Ram Dass authored Be Here Now, a book on yoga, meditation, and spirituality that some have described as the Bible of the Hippie Generation.22,23,24
Unsurprisingly (at least in retrospect), turning thousands of young people on to powerful psycho-active substances did not always yield sunny outcomes. By the mid-1960s American emergency rooms were regularly visited by distressed and bewildered folks complaining of “bad trips” – an phenomenon that turned much of the medical community off of psychedelics altogether.
Nineteen sixty-seven (1967) marked the Summer of Love in the United States, with approximately 100,000 people converging in San Francisco. Two summers later, in 1969, the Woodstock Music Festival took place, at which half a million people gathered for “three days of peace and music” (plus sex and drugs). In November of that same year, growing opposition to the Vietnam War climaxed in the largest antiwar demonstration in United States history.25,26
The War on Drugs
Despite the US government’s initial enthusiasm for researching psychedelic compounds, the merits of the drugs were ultimately dismissed with Nixon administration’s Controlled Substances Act of 1970. It has been suggested that Nixon’s anti-drug stance had less to do with a legitimate concern for public safety than with a disdain for certain demographics – namely Blacks and anti-war hippies.27
John Daniel Ehrlichman, counsel and Assistant to the President for Domestic Affairs during the Nixon years, once summarized it like this:
The Nixon White House… had two enemies: the antiwar left and black people. You understand what I’m saying? We knew we couldn’t make it illegal to be either against the war or blacks, but by getting the public to associate the hippies with marijuana and blacks with heroin, and then criminalizing both heavily, we could disrupt those communities. We could arrest their leaders, raid their homes, break up their meetings, and vilify them night after night on the evening news. Did we know we were lying about the drugs? Of course we did.28
Nixon – who was himself no stranger to alcohol or prescription drugs – once described Leary as “the most dangerous man in America.”29,30
The 1970 Controlled Substances Act created five schedules used to classify drugs based on their abuse potential, accepted medical use in the USA, safety, and potential for addiction.31 Drugs placed in Schedule I became illegal overnight, categorized as having a high potential for abuse and no accepted medical use. Medicines categorized as Schedule I drugs to this day include LSD-25, cannabis, and heroin.32
The term “War on Drugs” was popularized by the media after a press conference on June 18, 1971, in which Nixon referred to drug abuse as “public enemy number one.” In 1973, the Drug Enforcement Administration (DEA) was created.33,34
During the presidency of Ronald Reagan (1980 – 1988) MDMA, the active constituent of the street drugs “Molly” and “Ecstasy,” was added to Schedule I, despite the fact that the drug had shown promise as an powerful adjuvant to psychotherapy.35
History of MDMA
3,4-Methylenedioxymethamphetamine (or MDMA) was first synthesized from an extract of sassafras by Anton Kollisch, a German chemist working for Merck. On December 24, 1912, Merck filed two patents on the molecule under the name “methylsafrylaminc.”36
Although both Merck and the United States Army experimented with the molecule – mainly in the 1950s – it was not until the mid-1970s that MDMA’s psychotherapeutic potential was first glimpsed. In search of an alternative to 3,4-methylenedioxy-amphetamine (MDA), which was made illegal in 1970 by the CSA, the American chemist Alexander T. Shulgin began tinkering in his laboratory. Shulgin re-synthesized MDMA and, in 1978, co-published a paper with David Nichols on the molecule’s psychoactive properties. Appreciative of the benign, heart-opening, and non-hallucinatory properties of MDMA, Shuglin referred to the drug as his “low-cal martini” and passed it on to psychotherapists like Leo Zeff, PhD (AKA “The Secret Chief”), and Shulgin’s own wife, Anne, a Jungian psychologist who is celebrated to this day as the matriarch of the psychedelic movement. The use of MDMA spread to other therapists, who used the substance with their clients as a therapeutic “lubricant,” especially within the context of couples’ therapy.37,38,39
Like many consciousness-enhancing substances, MDMA held value not only therapeutically, but also recreationally: in the 1980s MDMA (or “Ecstasy”) became popular in the techno dance cultures of the United States and United Kingdom.
At the same time, the crack cocaine epidemic was ravaging inner cities of the USA, and the Reagan Administration was keen to respond. Nancy Reagan launched her Just Say No campaign, and the Drug Abuse Resistance Education (DARE) program was launched.40,41 (Curiously, a meta-analysis from 2004 concluded “that D.A.R.E. is ineffective,” and a 2009 meta-analysis of 20 controlled studies revealed that those who attended the DARE program were just as likely to abuse drugs as those who had no intervention.42,43)
In 1985, MDMA was added to Schedule I, in a move perhaps akin to throwing away the proverbial baby with the bathwater (the baby being MDMA; the bathwater crack cocaine). The American psychotherapist Rick Doblin, PhD, sued the DEA in an attempt to block the total criminalization of MDMA. Many witnesses testified in support of the molecule, including psychiatrists who spoke of the drug’s compelling therapeutic applications. Doblin won: DEA law judge Francis Young ruled that MDMA should be classified as a drug with a moderate to low potential for physical and psychological dependence, available prescription-only – and ergo placed in Schedule III. (Other drugs in Schedule III include acetaminophen with codeine, testosterone, and ketamine.44) Young’s recommendation was rejected by the head of the DEA, however, and MDMA was categorized as a Schedule I drug.45,46
In 1986, Doblin created the Multidisciplinary Association for Psychedelic Studies (MAPS), an organization that has since fought effortlessly to encourage more research on MDMA and other psychedelic compounds.47
Nineteen eighty-six (1986) also marks the year in which the Anti-Drug Abuse Act was passed. The law, which was signed by Reagan, substantially increased the number of drug offenses (including those related to cannabis) with mandatory minimum sentencing. This zero-tolerance policy directly contributed to an increase in nonviolent drug arrests and higher rates of incarceration in America. The Act instituted a five-year minimum sentence – without parole – for those convicted of possessing either five grams of crack cocaine (a drug more commonly used by poor Americans, in particular Blacks) or 500 grams of powder cocaine (an expensive preparation more commonly used by affluent Caucasians). This penalty disparity of 100:1 has been criticized as inherently racist. Regardless of the intention, the Anti-Drug Abuse Act certainly affected the Black community more adversely than the White: Prior to the enactment of the Act, African Americans were subject to 11% higher federal sentences for drug possession/sales than Whites; by 1990, that rate swelled to 49%.48
The War on Drugs did not stop the personal and recreational use of psychedelic substances so much as it drove it underground. What the War did do, however, was thwart decades of research – research that the medical community desperately needed, given the alarming rate at which depression and other mental illnesses have been steadily climbing (even pre-pandemic).49 The criminalization of psycho-spiritual medicines like psilocybin, LSD-25, and MDMA did to psychological research what kinking a hose does to the flow of water.50
Water Returns to the Well: The Psychedelic Renaissance
Due to the persistent efforts of groups like MAPS and the Beckley Foundation, the generous donations from private parties like Tim Ferris, the courage of clinicians and researchers willing to risk it all, and a robust awareness-raising campaign (sweeping from the Joe Rogan podcast to Michael Pollan’s two most recent books), we are once again able to research these unique molecules and consider their therapeutic applications.
After a lull of decades, in 1998, researchers led by Franz X. Vollenweider, PhD, at the University of Zurich published the first post-Drug War study on psilocybin,51,52 effectively cracking the seal on a new generation of psychedelic research. Since then, Vollenweider has authored or co-authored over 90 studies on psychedelic compounds.53
In 2000, researchers at Johns Hopkins University obtained regulatory approval to research the effects of psychedelics in healthy volunteers. Psilocybin studies were followed by research focused on LSD-25.54 Research into ayahuasca, MDMA, and other entheogenic substances quickly followed: Scientifically robust studies on psychedelics are now easy to find in PubMed. Most of the current studies are funded by non-profit organizations like Johns Hopkins’ Center for Psychedelic and Consciousness Research (CPCR), the Centre for Psychedelic Research at the Imperial College of London, the Beckley Foundation, and MAPS. A newcomer to the effort is the Center for Neuroscience of Psychedelics at Massachusetts General Hospital, the original teaching hospital of Harvard Medical School.
What was once a choked garden hose is now a steady stream of science.
Psychedelic compounds have been shown to effectively help with a variety of ailments, including depression,55,56,57 treatment-resistant PTSD,58 social anxiety in those on the autism spectrum,59 eating disorders,60 obsessive-compulsive disorder (OCD),61 anxiety in those with terminal illness,62 and Parkinson’s disease.63 Psychedelics have also shown promise in the treatment of various drug addictions,64 including nicotine,65 opioids,66 alcohol,67 methamphetamine,68 and crack cocaine addictions.69 (Note: the references peppering this paragraph are far from an exhaustive list of indications or studies.)
The research has also shown that these once villainized compounds are not nearly as dangerous as once believed. In fact, a 2020 German analysis ranking the risk of harm associated with various drugs ranked methamphetamine, heroin, alcohol, and cocaine as the most harmful drugs. At the opposite end of the graph, non-steroidal anti-inflammatory drugs (NSAIDs) and triptans were found to be the least likely to cause harm. Psychedelics and cannabis fell somewhere in the middle.70
A similar analysis out of the United Kingdom ranked various “recreational” substances in order of most to least harmful, including both risk to the user and risk to others.71 The authors ranked alcohol as the most harmful drug, with heroin and crack cocaine in second and third place, respectively. The least harmful drugs on the ranked scale were ecstasy, LSD, and mushrooms.72
[Caption: Image from Nutt DJ, King LA, Phillips LD. Drug harms in the UK: a multicriteria decision analysis. Lancet. November 6, 2010:376(9752);1558-65. Used with permission.]
Psilocybin (the active constituent in “magic mushrooms”) has been granted breakthrough therapy status twice by the United States Food and Drug Administration (FDA) – first in 2018 for the treatment of treatment-resistant depression, and again in 2019 for the treatment of major depressive disorder.73 Cities around the country are voting to decriminalize the psychedelics, and in 2021 the state of Oregon not only decriminalized the possession of all “recreational” drugs in small quantities, but also legalized psilocybin-assisted therapy, being the first state in the USA to do so.74
The legalization of MDMA at the federal level is perhaps soon to follow.75 In January 2020, the FDA approved an expanded access program for MDMA-assisted psychotherapy, allowing 50 patients with post-traumatic stress disorder (PTSD) to legally access treatment outside of Phase 3 clinical trials. The purpose of the Expanded Access program (which is also called “Compassionate Use”) is to allow people living with a serious or life-threatening condition to access potentially helpful investigational therapies.76 A similar program was approved in Israel in 2019.77
The secret is out: psychedelic substances are medicines.
The Psychedelic Dark Ages are behind us.
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