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F or the last 30 years, it’s been fashionable to say psychedelic drugs are on the rebound. There’s reason in 2023 to believe it may finally be true. Leading research universities such as Johns Hopkins and Imperial College London have opened research centers for psychedelic study, asserting the long-exiled psychoactive substances offer effective treatments for depression, addiction, and post-traumatic stress disorder, or PTSD. John Oliver recently sang psychedelics’ praises on HBO’s “Last Week Tonight.” And Prince Harry’s embrace of psychedelics in his new biography, “Spare,” threatens to make mushrooms cool again.

Sonja Lyubomirsky, a world-leading researcher on happiness and social connection, agrees the momentum is building, and she says it’s about time. A journal paper she authored this past year, “Toward a New Science of Psychedelic Social Psychology: The Effects of MDMA (Ecstasy) on Social Connection,” has spurred discussion within and beyond the halls of the academy. Her paper focuses on MDMA, a psychoactive drug sometimes classified as a psychedelic and better known by the street names of “Ecstasy” and “Molly.

“Psychedelic social psychology is an exciting new frontier,” Lyubomirsky, a distinguished professor of psychology at UCR, wrote in the paper. “I propose that MDMA can be valuable in mitigating the social obstacles or problems endured by individuals with a variety of conditions, including social anxiety, panic, depression, autism, substance abuse, and even schizophrenia.”

Those conditions, she writes, make healthy interactions impossible. MDMA has also been shown to be effective at treating PTSD. Some researchers think that because prolonged grief has many similarities with depression and PTSD, psychedelics could be useful for treating it, too.

The First Bad Trip

The subject of psychedelics often begins and ends with Timothy Leary and his famed phrase, “Turn on, tune in, drop out,” which became a slogan of counterculture. But Leary’s foray into psychedelics — beginning with his 1960s tenure at Harvard — came hundreds of years after Indigenous people first partook of psilocybin in the form of mushrooms, ayahuasca, and peyote, and a full generation after the start of serious academic exploration in the 1940s. It will surprise many to hear that, until the mid-1960s, there was no stigma attached to psychedelics, and little fear of its misuse. Only promise.

The first research exposure to psychedelics was an accident. In 1943, a Swiss chemist named Albert Hofmann synthesized lysergic acid diethylamide, or LSD-25, for its medicinal potential. He accidentally ingested a trace amount, experiencing “a dreamlike state.” He then, less accidentally, ingested a larger dose. He thought the second dose — a conservative .25 milligrams — was miniscule, but he was wrong. What followed was a profound sensation of succumbing to madness. It was, in fact, the world’s first recorded really bad trip. “A demon had invaded me, had taken possession of my body, mind, and soul,” he would later report. But the experience softened into a pleasing afterglow.

The variables of “set” and “setting” had not yet been introduced. The effect of psychedelics varies depending on expectations for the session, and on where, how, and with whom a person takes the drug. That is to say, rigid sessions administered in sterile clinical settings don’t often yield the stuff of kaleidoscopes and daisies.

By the 1950s, there were a dozen or so hubs of LSD research at universities. One of those hubs, at UCLA, linked up with Bill Wilson, the co-founder of Alcoholics Anonymous, or AA, to further research LSD’s potential to address alcoholism. By the end of the 1950s, LSD had come to be viewed as a “miracle cure” for alcohol addiction. Wilson lobbied his AA board to accept LSD therapy as a treatment, though the board wouldn’t go for it.

With grants from the federal National Institutes of Health, Spring Grove State Hospital outside Baltimore conducted experiments with hundreds of patients struggling with mental illness and alcoholism in the early 1960s into the mid ’70s. Many related studies were published in the esteemed, peer-reviewed Journal of the American Medical Association, and in 1965, CBS News broadcast an admiring report, “LSD: The Spring Grove Experiment.” The onboarding process for Spring Grove employees included a couple of LSD trips, to get the gist of the research.

The Czech-born psychiatrist Stanislav Grof found his patients could uncover childhood traumas and buried emotions with moderate doses of LSD. He predicted psychedelics would be for psychiatry what the microscope was for biology, or the telescope for astronomy. But Timothy Leary was soon to interrupt the therapeutic trajectory of LSD and psychedelics.

In his book “How to Change Your Mind,” the bestselling food author and psychedelics advocate Michael Pollan writes that the leading psychedelic, LSD, too quickly “completed its speedy media arc from psychiatric wonder drug to counterculture sacrament to destroyer of young minds.”

Leary’s 1960s Harvard Psilocybin Project came on the heels of his graduate-level course named “Experimental Expansion of Consciousness.” Over three years, LSD was administered to several hundred study participants. Leary and his assistants wrote up accounts of their journeys, and several journal papers were published, though much of the research was later discredited. Leary’s experiments soon came under the scrutiny of faculty colleagues and then the press. By 1963, he was fired by Harvard.

LSD and psychedelics became a staple of counterculture and a pariah to mainstream America. Hyperbolic claims, such as that LSD would alter chromosomes, took hold. President Richard Nixon passed the Controlled Substances Act in 1971, and LSD and psilocybin were declared Schedule 1 substances, meaning they had no accepted medical use and carried high potential for abuse. In 1971, Nixon declared Leary “the most dangerous man in America.” MDMA, for its part, was declared a Schedule 1 substance in 1985.

A Mind-altering Shift

There are at last signs of a shift in the government’s perspective. The Food and Drug Administration OK’d studies of MDMA for PTSD and psilocybin to treat depression. There is serious discussion about MDMA being removed from the list of Schedule 1 substances in 2024, with psilocybin possibly not far behind.

“I started doing this research — beginning with a deep dive into reading everything I could get my hands on, including media articles as well as tons of empirical papers — in 2019, and I felt that it was a bit of a risky area to go into,” Lyubomirsky said. “But today, not only are people more enthusiastic and receptive, but the psychedelic space has almost become too trendy, at least in some circles.”

Lyubomirsky writes that MDMA has been shown to increase levels of serotonin and oxytocin — neurochemicals tied to well-being and social bonding, which reduces negative thoughts and emotions that serve as barriers to communication, intimacy, and warmth. MDMA’s influence renders a person less likely to interpret an interaction from a partner in a negative way, i.e., that they are bored, hostile, or judgmental.

MDMA dampens the response of the amygdala, which detects threat — and can shift into hyperdrive in the case of PTSD. With MDMA’s help, a person suffering from PTSD can better engage with difficult feelings and memories in a way that encourages perspective and not panic. One study found that, just two months after treatment, 67% of patients no longer qualified for a PTSD diagnosis.

Lyubomirsky points to MDMA’s low potential for addiction. A 2010 study in the prestigious journal The Lancet found MDMA LSD, and mushrooms among the five most innocuous of 20 harmful drugs listed. Alcohol and tobacco far outpaced them.

“Alcohol is the one that gets me, as it’s one of the most harmful substances that exists, and yet it’s the one that’s legal,” Lyubomirsky said.

She concedes there is a great deal still unknown about MDMA, and she does not believe its use should be unregulated. Like many who advocate for psychedelic research, she believes the drugs should be administered only under a therapist’s watch, with follow-up sessions. There is consensus that no psychedelic should be given to someone with a history of schizophrenia or psychosis. Finally, there is the potential for a bad trip — or as the researcher Roland Griffiths called it, “a Hell-realm experience.” Still, one of the benefits of MDMA, Lyubomirsky writes, is that it may not require frequent, or even repeat, use.

“Results from the Phase II clinical trials suggest that as few as one, two, or three doses administered over several weeks or months can have powerful and durable effects,” she wrote in the MDMA paper. MDMA’s effect, she writes, can be long-lasting. 1970s researchers concluded after a single session of MDMA: “Once you got the message, you could hang up the phone.”

Lyubomirsky doesn’t dismiss the prospect of UCR-administered psychedelic research. But she’s not concerned about where the research happens, only that it happens.

“This work has great potential as both basic research, e.g., to uncover the psychological and brain pathways underlying authentic social connection; and applied research, e.g., to help people improve their relationships and alleviate loneliness,” she said. “I definitely advocate for such research — whether at UCR or other universities.”

Her greater concern is the next crucial chapter in the still-unfolding history of psychedelics — that is, for its history not to repeat itself. Just like the counterculture movement’s association with LSD sank it, Lyubomirsky said its reputation as a 1980s “rave drug” pulled MDMA underwater.

“The next step,” Lyubomirsky said, “is cultural acceptance.”