Can psychedelics meet their potential for treating mental health disorders?

Kanu Caplash was lying on a futon in a medical center in Connecticut, wearing an eye mask and listening to music. But his mind was far away, tunneling down through layer upon layer of his experiences. As part of a study of MDMA, a psychedelic drug also known as molly or ecstasy, Caplash was on an inner journey to try to ease his symptoms of post-traumatic stress disorder.
On this particular trip, Caplash, now 22, returned to the locked bathroom door of his childhood home. As a kid, he used to lock himself in to escape the yelling adults outside. But now, he was both outside the locked door, knocking, and inside, as his younger, frightened self.
He started talking to his younger self. “I open the door, and my big version picks up my younger version of myself, and literally carries me out,” he says. “I carried myself out of there and drove away.”
That self-rescue brought Caplash peace. “I got out of there. I’m alive. It’s all right. I’m OK.” For years, Caplash had experienced flashbacks, nightmares and insomnia from childhood trauma. He thought constantly about killing himself, he says. His experiences while on MDMA changed his perspective. “I still have the memory, but that anger and pain is not there anymore.”
Caplash’s transcendent experiences, spurred by three therapy sessions on MDMA, happened in 2018 as part of a research project on PTSD. Along with a handful of other studies, that research suggests that when coupled with psychotherapy, mind-altering drugs bring some people immediate, powerful and durable relief.
Those studies, and the intense media coverage they received, have helped launch psychedelic medicine into the public conversation in the United States, England and elsewhere. Academic groups devoted to studying psychedelics have sprung up at Johns Hopkins, Yale, New York University Langone Health, the University of California, San Francisco and other research institutions. Private investors have ponied up millions of dollars for research on psychedelic drugs. The state of Oregon has started the process of legalizing therapeutic psilocybin, the key chemical in hallucinogenic mushrooms; lawmakers in other states and cities are considering the same move.
New ways to help people with PTSD, depression, anxiety and other mental health disorders are desperately needed. An estimated 30 percent of people with depression, for instance, don’t get relief from current treatments. Psychedelics, some researchers and clinicians believe, may help.
“The promise is incredible,” says Monnica Williams, a psychologist at the University of Ottawa, who ran the clinical trial Caplash participated in at UConn Health in Farmington. “Psychedelics have the potential to really completely revolutionize mental health and change everything.”
But a cloud of questions hovers over the research. It’s not known how the therapy works or who it might work for. Even if these new treatments perform well in clinical trials, the drugs, and the mind-bending experiences they bring, won’t appeal to everyone. What’s more, the drugs may not be available, or they may cost too much.
Psychedelic drugs, including MDMA, psilocybin and the hallucinogen LSD, which is also being studied as a treatment for depression and other mental health disorders, are illegal under federal law, classified as Schedule 1 substances by the U.S. government — with high potential for abuse and no currently accepted medical use. Many people may be reluctant to take an illegal drug that lowers their defenses and makes them vulnerable, no matter how great the promise of healing.
Social and legal hurdles, barriers to access and scientific questions make it unlikely that psychedelics will replace current mental health treatments, many experts agree. More likely is that with enough research, psychedelic substances will become another tool for doctors and therapists.
Caplash remembers what MDMA did for him right after his sessions. “I wasn’t as angry as I was before. My muscles were a lot less tense. I could literally see clearer,” Caplash says. “As I went through the study, I was also becoming a different person.”
The benefits are still with him. Caplash no longer thinks of suicide. A biology major at the University of Connecticut, he has big dreams and advocates for more accessible mental health care for others. “I feel like I’m at peace, to an extent,” he says. “I know who I am and what I want to do.”

Psychedelic drugs are not new. Scientists at the pharmaceutical company Merck made MDMA in 1912. Swiss chemist Albert Hofmann synthesized LSD in 1938, and Aldous Huxley popularized his experience on mescaline, a psychedelic compound made by certain cacti, in his 1954 book The Doors of Perception. When people talk about the psychedelic renaissance, they often begin with Hofmann and Huxley, says Sutton King, who advocates to include Indigenous voices in discussions about psychedelics and is an Afro-Indigenous member of the Menominee and Oneida Nations of Wisconsin.
But the story of psychedelics starts long before then. Indigenous communities around the world have used psilocybin and other consciousness-changing compounds for healing for thousands of years.
“The traditional Indigenous Nations … have had these connections to these medicines,” says King, who is cofounder and president of the Urban Indigenous Collective, a nonprofit advocacy group in New York City.
Belinda Eriacho, a wisdom carrier of Dine’ (Navajo) and A:shiwi (Zuni) descent, believes that psychedelic drugs, called sacred plant medicines by some Indigenous groups, are catalysts to help align mental, physical, spiritual and emotional health. “We were the knowledge keepers,” she says. “A lot of our understanding about these medicines is through practical experiences. They are not something you can read in a book.”
But around the middle of the 20th century, medical researchers, dissatisfied with existing mental health treatments, began trying to quantify these drugs’ effects on mental states. A flurry of research yielded promising hints, but many of those early attempts didn’t yield solid data. Some experiments were poorly designed; worse, some were deeply unethical, forcing high doses of psychedelics on people who were incarcerated or experiencing psychosis. Many of those study subjects were people of color.
In the 1960s, social and political sentiments began turning against these drugs — and the counterculture they represented — in both non-Indigenous and Indigenous communities. The U.S. government criminalized the use of psychedelics to keep them out of the public’s hands. The new restrictions kept the drugs out of researchers’ hands, too.
That social shift stigmatized the drugs and whatever promise they held, says neuroscientist Rachel Yehuda, who has studied PTSD for decades at the Icahn School of Medicine at Mount Sinai in New York City. Current drug treatments for PTSD, such as antidepressants or sleep medications, don’t work well for some people, she says. These medicines may help with symptoms, but don’t get at the root of the problem. Psychedelics might do more, she’s come to realize.
Two years ago, when Yehuda began studying psychedelic drugs, she faced a lot of skepticism. But those dismissals have disappeared. “The general attitude in academic medicine right now is, ‘Gosh, let’s try it. Let’s see. Maybe it will be good. Wouldn’t that be nice?’ ”
In some ways, psychedelics can outperform approved psychiatric drugs such as Prozac and other selective serotonin reuptake inhibitors, or SSRIs. And so far, the data suggest psychedelics work quickly, appear to be safe and have lasting effects, says Atheir Abbas, a psychiatrist and neuroscientist at Oregon Health & Science University in Portland. “That is hard to come by. I think that is extremely exciting.”
In the last five years, a handful of high-quality, albeit small, studies have suggested tremendous benefits from the psychedelic psilocybin for depression, anxiety and PTSD. The studies differ in their details, but many follow a similar arc. Generally, the studies begin with talk therapy sessions, followed by several therapy sessions in which participants are under the influence of a psychedelic drug. More psychotherapy comes afterward. At certain points in the process, researchers measure the participants’ symptoms.
Psilocybin-assisted therapy quickly reduced signs of depression among 24 participants with moderate or severe depression, scientists reported in 2020 in JAMA Psychiatry. Four weeks after two psilocybin sessions, 71 percent of the participants had maintained a drop of at least 50 percent in their scores on a depression rating scale called the GRID-HAMD.

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