In April 1960, a Dow Chemicals biochemist named Alexander Shulgin consumed 400mg of a compound called mescaline, and had his first psychedelic experience. He saw “hundreds of nuances of color” that he had never seen before. “The world amazed me,” Shulgin later wrote. “I saw it as I had when I was a child. I had forgotten the beauty and the magic and the knowingness of it and me.” He found the encounter so extraordinary, that he dedicated the rest of his life to uncovering the secrets that psychedelic chemistry could contain.
“I understood that our entire universe is contained in the mind and the spirit,” Shulgin recalled. “We may choose not to find access to it, we may even deny its existence, but it is indeed there inside us, and there are chemicals that can catalyze its availability.” However, it struck him as curious why scant work had been done on compounds, known as phenethylamines, which are similar to mescaline—the psychedelic derived from peyote that was first isolated in 1897. The trip, “unquestionably confirmed the entire direction” of his life, he wrote in his 1991 classic PiHKAL: A Chemical Love Story. “I had found my learning path.”
Shulgin, known as “Sasha,” was a hero to the psychedelic counterculture, but not necessarily a movement insider, went on to make the psychedelic experience more accessible than anyone else in history. He worked out of a ramshackle backyard lab on his 20-acre ranch in Lafayette, California, and discovered more than 200 new psychedelic compounds. A number of his compounds became popular, notably 2C-B (also known as “tripstasy”). He also tripped several thousand times himself, before he died in 2014 aged 88.
He informally established the Alexander Shulgin Research Institute (ASRI), during the 1980s at a time when “the mere mention of psychedelics, even in the freedom-of-thought world of academia, was a career killer,” the ASRI says on its website. Today, the institute continues Shulgin’s psychedelic legacy. It was officially incorporated on Bicycle Day on 19 April 2021 by his wife Ann, before she died in 2022. Two of his long-time research colleagues, Paul Daley, and Nicholas Cozzi, took up leadership roles following Shulgin’s death. The institute is creating new psychedelics, which it is patenting, and scouring the vault of Shulgin’s creations for any overlooked gems.
Shulgin and Ann would test his new creations personally, taking tiny doses that incrementally increased over the course of weeks if the drug’s effects aroused curiosity. Later, he would engage his wider “research group” of friends and professional acquaintances to trial new compounds. “There is nothing illegal about synthesizing new compounds,” Shulgin told the Guardian in 2005. “I don’t know if they’re going to be psychedelic or not until I taste them. And there’s nothing illegal about my tasting them.” Twice, he used an anticonvulsant on himself during these trips into uncharted territory, all for the purpose of finding new drugs that would give him, “the pleasure of composing a new painting or piece of music.”
In 1977, Shulgin thrust MDMA from the backwaters of niche chemical literature to the dance floor. MDMA was created by scientists at pharma giant Merck in the early 20th century but never adequately investigated. Shulgin became The Godfather of Ecstasy when he identified its therapeutic potential and gave it to psychotherapist Leo Zeff, who became an advocate. “An easily controlled altered state of consciousness with emotional and sensual overtones,” Zeff wrote with fellow chemist David Nichols in the first paper to publicly detail the drug’s effects on humans.
“Sasha found a way, with DEA people in attendance, to present the results of human studies on psychedelics,” Rick Doblin, founding president of the Multidisciplinary Association for Psychedelic Studies (MAPS), told Wired, recalling one of the first hearings to permit human clinical testing of MDMA. “It was one of the more heroic, in-the-lion’s den moments I’ve ever seen.” Shulgin then provided the MDMA for its first clinical study, conducted by George Greer; the results were published in the Journal of Psychoactive Drugs.
It seems like another life from the one where he made millions for Dow by creating the world’s first biodegradable insecticide, Zectran. Shulgin was henceforth effectively given free rein to pursue his interests by the company. He began to alter the structure of mescaline, before his innumerable other forays into the frontiers of psychedelic science. He left Dow in 1966 after DOM, a psychedelic amphetamine he created, was reportedly sold on a mass scale without his blessing by the Hell’s Angels after production by underground chemists, according to the chemist Hamilton Morris, the last person to interview him. The pills were reportedly excessively strong, leading people to panic, and even have to go to hospital.
Following the prohibition of psychedelics in 1971, he obtained a rare Drugs Enforcement Agency (DEA) schedule 1 analytical research license. Shulgin was remarkably close to the DEA over a number of years. He supplied samples of various compounds to forensic teams, gave internal pharmacology seminars, and wrote a definitive federal law enforcement manual on controlled substances.
The head of the DEA’s western laboratory presided over his wedding, and held his own on Shulgin’s lawn. But when Shulgin started to go public about what he was doing in his backyard lab, and wrote the first of two opuses, cult sensation PiHKAL (Phenethylamines I Have Known and Loved), alongside a pro-drug legalization message, the DEA’s feathers were irrevocably ruffled. After all, he published what were step-by-step psychopharmaceutical guides on how to create a slew of psychedelics, including accompanying trip reports.
“It is pretty much our opinion that those books are pretty much cookbooks on how to make illegal drugs,” a spokesperson for the DEA’s San Francisco field division said at the time. “Agents tell me that in clandestine labs that they have raided, they have found copies of those books.” In 1993, Shulgin’s lab was raided by the DEA. Many of his chemicals were confiscated and he was given a fine of $25,000. But he kept making and testing new chemicals, letting the data speak for itself.
Shulgin would spend the rest of his life researching and advocating for psychedelics. His wife Ann, a lay therapist who co-wrote PiHKAL, outlived him by seven years. “One of his greatest legacies is his inspiration to young chemists—including myself, as a younger man—to follow this path,” Cozzi told DoubleBlind, echoing the sentiment of scientifically sophisticated psychonauts who also followed in Shulgin’s trailblazing footsteps.. “We continue Sasha’s legacy with the hope that other people will be inspired and, in turn, create new molecules, both for their potential therapeutic value and as tools to deepen our understanding of consciousness itself. These unusual molecules speak to how we’re put together as human beings, how our brains work.”
It’s unclear exactly how Shulgin, who was not averse to IP protection and held patents for the drugs Ariadne and methylone, would feel about the massive corporate influence in today’s renaissance, the scale of which was unimaginable a decade ago. The ASRI has been synthesizing and supplying various psychoactive drugs to universities and research organizations to study, while also providing psilocybin and dimethyltryptamine (DMT) to top US universities undertaking FDA-approved clinical research. Now, however, it is embarking upon a new frontier.
At the Multidisciplinary Association for Psychedelic Science (MAPS) conference in Denver in June, Cozzi presented on two ASRI compounds that are currently in late-stage preclinical testing. “Our first compound, ASR-2001, is an orally active, non-hallucinogenic, highly potent 5-HT2A receptor activator,” he said in a press conference. “It demonstrates exceptional selectivity over the problematic 5-HT2B receptor and displays no overt psychedelic effects. Yet it produces a state of mental clarity without the frank psychostimulant effects of drugs such as Adderall or Ritalin.” The other, known as ASR-3001, is short-acting and is said to induce “an internal psychedelic cognitive state with little or no sensory involvement.”
Many other drug development companies are in the business of identifying, creating, and patenting novel psychedelics. But the ASRI says that it’s able to create entirely new compounds far beyond the confines of known psychedelics. “This ambitious undertaking stems from our unique heritage, a deep-rooted partnership with the legendary Sasha Shulgin, the pioneer who revolutionized psychedelic research,” Cozzi said.
The ASRI is also trawling through the Shulgin vault of novel psychedelics–a painstaking and expensive task, but one which could herald riches. There are more than 500 compounds, well above previous estimates. Some are already in the public domain and others are protected by patents. Many have not been subject to rigorous testing using modern methods. “Our knowledge of how the brain works is much more detailed than it was at that time,” Cozzi said. “There were only two serotonin receptors recognised then, whereas we know now it is 14. Drugs which were thought to previously be inactive might be hidden gems.”
Whatever happens with the ASRI, with the likely emergence of MDMA as a legal therapeutic drug, Shulgin has played a pivotal role. The man denounced by some as “at best a curiosity and at worst a menace” will be vindicated. “It’s the excitement of discovering something totally unknown,” Shulgin said of what drove him. “I feel an incredible tingle when I look at a white solid I’ve just synthesized that I know has never existed anywhere in the universe before this moment … And I’ll be the first to know what it does.”