75 Years After First LSD Trip, Psychedelic Science Is Making a Comeback
Sidelined for decades by the War on Drugs, LSD and other psychedelics are regaining their original reputation as effective therapies for depression and addiction.
On April 19, 1943, Swiss chemist Albert Hofmann intentionally ingested 250 micrograms of Lysergic Acid Diethylamide-25, a chemical compound that he first synthesized back in 1938 from the parasitic fungus ergot. Three days earlier, Hofmann had accidentally absorbed a few drops of the chemical — known by its shorthand LSD — through his skin or eyes, causing odd sensations. But it was nothing compared to what he would experience at a much higher dose.
“I had to struggle to speak intelligibly. I asked my laboratory assistant, who was informed of the self-experiment, to escort me home,” Hofmann wrote later, describing the effects of the world’s first acid trip as he gingerly rode his bike home from the lab. “On the way home, my condition began to assume threatening forms. Everything in my field of vision wavered and was distorted as if seen in a curved mirror. I also had the sensation of being unable to move from the spot. Nevertheless, my assistant later told me that we had traveled very rapidly. "
It’s been 75 years since that fateful spring day, now celebrated by LSD enthusiasts as “Bicycle Day.” And after a decades-long dark age for LSD, in which psychoactive substances were criminalized and dismissed as a dangerous relic of the hippie sixties, psychedelics are coming back into the light. Researchers and recreational users are rediscovering the drug’s curious power to unlock the subconscious and potentially cure intractable psychological conditions like depression, addiction, and even the fear of death.
Although Hofmann’s first trip wasn’t an entirely positive experience — it turns out that 250 micrograms of pure LSD is a whopper of a dose — it was clear to Hoffman’s lab, Sandoz, that LSD had the power to alter consciousness and perception in ways that could be useful to scientists, particularly psychiatrists and psychologists. Unsure how to market the drug, which Sandoz called Delysid, the company gave away massive quantities of LSD to researchers to see what they could make of it.
The result was an LSD research boom that flowered from the late 1940s through the 1950s and into the mid-sixties. In the US alone, more than 100 government-funded studies explored the use of LSD in treating depression, alcoholism, schizophrenia, autism, and obsessive-compulsive disorder, with tantalizingly positive results. The US military and the CIA also famously experimented with LSD, the latter as a mind-control weapon to use against the Soviets.
By the late 1950s, therapists were incorporating guided LSD trips into their practice, with celebrities like Cary Grant claiming life-changing results after dozens of LSD-aided therapy sessions. Stanislav Grof, a pioneer of LSD psychotherapy, wrote that “the potential significance of LSD and other psychedelics for psychiatry and psychology is comparable to the value the microscope has for biology and medicine or the telescope has for astronomy.”
LSD also played a pivotal role in the birth of modern psychopharmacology. In the early 1950s, scientists first discovered the neurotransmitter serotonin, identifying large amounts of it in the human gut and some in the brain. But it was only when researchers noticed that serotonin had a similar chemical structure to LSD that they began to wonder if serotonin levels had something to do with brain function and behavior.
“Up until that time, mainstream psychiatry had no idea that behavior might arise from neurochemical events in the brain,” wrote pharmacology professor David Nichols. “If neuroscience can be said to have a beginning, one could argue that it occurred in 1954, with the idea that the action of LSD might be related to its effects on the brain serotonin system.”
But the mind-opening properties of LSD couldn’t be confined to university labs and therapists’ couches. Scientists-turned-evangelists like Timothy Leary believed that the whole world would benefit from seeing reality through an altered consciousness. In the early 1960s, author Ken Kesey and his Merry Pranksters traveled the United States in a tie-dyed school bus conducting their “acid tests” — LSD-fueled parties performed to the music of the Grateful Dead. The psychedelic hippie sixties were born.
Jesse Jarnow is the author of Heads: A Biography of Psychedelic America, which explores the widespread cultural influence of LSD in America, from its well-known role in music to its illuminating effect on the minds of tech pioneers (Steve Jobs) and scientific heavyweights (Kary Mullis, a Nobel prize-winning chemist). Once LSD was associated with the anarchy of the hippies, though, it sacrificed some of its scientific legitimacy.
“In the 50s and early 60s, acid is treated as this miracle drug, this unprecedented way to get insight into the human mind,” Jarnow told Seeker. “Gradually, over course of the early 60s, you see this shift in attitude. Acid is starting to leak out into the counterculture and the underground, and finally it’s criminalized in late 1966.”
In 1970, Richard Nixon signed the Controlled Substances Act, creating the Drug Enforcement Agency and listing LSD as a Schedule I narcotic — defined as having “no accepted medical use” and “a high potential for abuse” — along with heroin and marijuana. With the War on Drugs declared, funding for LSD research dried up and acid was driven deeper underground. A few rogue psychiatrists continued to treat patients with LSD, but they did so quietly and couldn’t publish the results of their practice.
In 1986, the non-profit research organization MAPS (Multidisciplinary Association for Psychedelic Studies) was founded to revive the rigorous scientific study of psychedelics. Rick Doblin created MAPS in direct response to the criminalization of MDMA (the active ingredient in Ecstasy), which he believed held tremendous potential as a therapeutic agent. The mission of MAPS was to combat the War on Drugs by proving that Schedule I drugs like LSD, psilocybin (magic mushrooms), and MDMA had legitimate medical uses.
At first, that mission seemed like a longshot. Double-blind, placebo-controlled research studies are expensive and no government funding agency would touch psychedelics. Plus researchers had to win approval from the FDA and the DEA to treat study participants with a Schedule I drug.
Brad Burge, communications director at MAPS, told Seeker that back in the 1980s and early 1990s, psychedelics researchers would submit all the required protocols to the regulatory bodies, “and the applications would just disappear.”
But groups like MAPS and other psychedelic advocates kept at it, submitting and resubmitting research applications while educating academics on the therapeutic potential of compounds like LSD, which showed so much promise before the hippie acid tests and criminalization shuttered the psychological studies.
All that work finally seems to be paying off as psychedelics, including LSD, are experiencing a full-blown research renaissance. The tipping point came in 2006 with an article published by Roland Griffiths, a respected psychopharmacologist at Johns Hopkins University School of Medicine, which showed that a single dose of psilocybin — also first isolated by Albert Hofmann from psychoactive mushrooms in Mexico — can trigger “mystical experiences” that have a lasting positive psychological effect.
James Fadiman, author of The Psychedelic Explorer’s Guide, credits the Griffiths article — which was the product of a years-long effort among psychedelics advocates to cultivate relationships with mainstream researchers — with shifting the scientific and cultural conversation around LSD. It also helped that an estimated 26 million Americans, mostly well-educated, had experimented with psychedelics since their criminalization with no ill effects.
“The people who started what’s now called the ‘renaissance’ did it very carefully, found an impeccable institution, and someone with 30 years of publication around other kinds of drugs, and proceeded totally inside the cultural rules,” Fadiman told Seeker. “And since 26 million Americans already knew that it wasn’t dangerous, there was no pushback.”
Griffiths paper paved the way for a raft of groundbreaking psychedelics studies, including a 2016 study out of New York University that tested psilocybin on terminally ill patients experiencing acute anxiety about death. Again, a single psychedelic experience, guided by trained therapists, was enough to significantly improve the patient’s end-of-life outlook, freeing them to reap the most joy from their remaining time. Other recent studies have confirmed 1950s-era research that psychedelics can help smokers and alcoholics kick the addiction.
But some of the most exciting data has come out of Imperial College London, where Robin Carhart-Harris and colleagues administered psilocybin to people who had lived for decades with treatment-resistant major depression. Two weeks after psychedelic therapy, two-thirds of participants met the criteria for remission, meaning no symptoms of the disease. And nearly half remained depression-free three months later without any further treatment.
With funding from the psychedelic-friendly Beckley Foundation, Carhart-Harris has also done some of the first detailed brain scans of individuals on LSD and psilocybin. Functional MRI scans and magnetoencephalography reveal that psychedelics suppress the activity of something called the Default Mode Network, described as the “conductor” of the brain’s symphony of synapses. Carhart-Harris theorizes that the quieting of the Default Mode Network leads to the classic psychedelic experience of ego dissolution and a feeling of oneness with the universe.
Without an overbearing conductor, the brain on LSD and psilocybin is also free to strike up conversations between normally unrelated regions. The visual cortex, for example, instead of just analyzing data from the eyes, might play with auditory signals creating a colorful musical synesthesia. Or the visual cortex might retrieve images from the brain’s long-term memory to create convincing hallucinations of long-lost loved ones or childhood figures. In the brain scans, the LSD brain lights up like a Christmas tree.
When Fadiman published The Psychedelic Explorer’s Guide in 2011, he included a short chapter on LSD microdosing, Albert Hofmann’s idea that very small doses of LSD taken every few days could sharpen cognition and improve mood. Fadiman launched a website, microdosingpsychedelics.com, where people who wanted to try microdosing — defined as five to 10 micrograms of LSD every three days — could report their experiences. So far, 1,800 people from 59 countries have submitted reports.
“They say their lives work better,” said Fadiman. “We’re not seeing the life-changing attitude changes you get with high doses of LSD. No insights, no visions; people just feel better. One comment said, ‘I don’t care if it’s a placebo or not, I haven’t felt this good in 30 years.’”
The Beckley Foundation is now raising money for a placebo-controlled, double-blind clinical trial to carefully study the effects of microdosing.
The psychedelic renaissance has also been good for MAPS. Burge says that it’s much easier now to get approval from the FDA and DEA for psychedelic research studies, although there’s still no government funding. MAPS has raised $40 million in donations from individuals and family foundations mostly for clinical studies into the efficacy of MDMA therapy for people suffering from post-traumatic stress disorder. With a stage-3 clinical trial set to launch in 2018, MAPS is hoping to win FDA approval for doctor-administered MDMA by 2021.
The dream is that FDA approval of MDMA could start a domino effect that leads to a widespread rescheduling of psychedelics for therapeutic use.
“That’s why we’re pursuing the FDA drug development process,” said Burge. “Because once the FDA says, ‘Yes, MDMA has a medical use,’ the DEA is going to be forced to reschedule it.”
Methadone, for example, is a Schedule II narcotic, allowing it to be administered by doctors in a clinical setting. With the wave of new data from psychedelic studies, it’s not hard to imagine that if MDMA gets the DEA’s blessing, soon will drugs like LSD and psilocybin.
That’s not to say that LSD, like marijuana in some states, is ever going to be legal for recreational use like it was before 1966. One reason is that there may not be much interest. According to the Monitoring the Future Report, LSD use among high-school seniors peaked in 1996 with 8.8 percent saying they’d used the drug in the past year. By 2003, that number plummeted to 1.9 percent. By 2017, it had crept up slightly to 3.3 percent.