Jon Kostakopoulos had been trying to stop drinking since his late teens. Nothing — not inpatient programs, outpatient programs, Alcoholics Anonymous or pharmaceutical treatments — seemed to help. So when his concerned mother heard from her new doctor at NYU Langone Health about a small trial of something totally different, she passed on the information. That’s how he found himself, at age 25, undergoing a succession of three therapist-supported experiences with psilocybin, a psychedelic component of magic mushrooms that is now being tested for conditions including addiction, cancer-related anxiety and depression.
Kostakopoulos didn’t have the kind of 3D, multicolored, reality-distorting head trips that some report — and the 1960s stereotype would suggest. “I pretty much knew where I was the whole time,” he says. In one session, he had a kind of death-and-rebirth experience, with the sense of starting over with a clean slate. “Parts of it were great, full of optimism and hope,” he says. And parts of it were upsetting, full of “guilt and embarrassment for what I’d put my friends and family through,” he says. He felt flooded by the need to recalibrate his priorities, and was able to look at himself — and his alcohol problem — more objectively. Kostakopoulos says his last drink was 11 days before his first supervised experience with the drug. That was five years ago.
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But you shouldn’t take Kostakopoulos’ story as proof that psilocybin is the next great wonder drug for treating addiction, depression, post-traumatic stress disorder or anything else. The larger trials that the Food and Drug Administration requires before considering new treatments are ongoing or in the planning stages.
“We don’t know if it works for any of these things,” says Stephen Ross, an associate professor of psychiatry and director of the Addictive Disorders and Experimental Therapeutics Research Laboratory at NYU Langone Health. What researchers do have is a collection of promising small studies evaluating just a few doses of psychedelics — including MDMA, also known as ecstasy — in conjunction with therapy in carefully selected patients, for specific conditions. And these scientists seem to have the wind at their backs in terms of popular and institutional interest in their work. In 2019, Johns Hopkins Medicine — with $17 million in promised funding from individuals including podcaster and “The Four-Hour Workweek” author Tim Ferriss — launched the Center for Psychedelic and Consciousness Research to study the therapeutic potential of psychedelic compounds. Imperial College London launched its own center earlier that year. Researchers at NYU Langone, the University of California-San Francisco and UCLA are also studying the medical potential of psychedelics.
Psilocybin and MDMA are the two drugs that have gotten the most research attention, says Charles Grob, a professor of psychiatry and behavioral sciences at UCLA’s Semel Institute for Neuroscience and Human Behavior. Both now have breakthrough status from the FDA — psilocybin for major depression and treatment-resistant depression, and MDMA for PTSD. That means the agency recognizes the potential based on early studies and promises an expedited review. The drugs have different chemistry and effects, but they have the potential to be used in a similar way: a small number of doses paired with psychotherapy for long-term change, says Josh Woolley, an associate professor of psychiatry at UCSF.
As journalist Michael Pollan describes in his 2018 bestseller “How to Change Your Mind,” psychedelic substances were used in certain rituals by other cultures (including in South and Central America) for centuries. In the U.S., psilocybin and its lab-synthesized cousin LSD were embraced as “miracle drugs” in the 1950s and early 1960s by the psychiatric establishment, notably for alcoholism and cancer-related distress, before becoming inextricably linked to the 1960s youth counterculture movement. “The dark side of psychedelics began to receive tremendous amounts of publicity — bad trips, psychotic breaks, flashbacks, suicides — and beginning in 1965 the exuberance surrounding these new drugs gave way to moral panic,” Pollan writes. “As quickly as the culture and scientific establishment had embraced psychedelics, they now turned sharply against them.” The drugs were criminalized. “In all of my training, the only things I ever heard about psychedelics was that they’re dangerous and that they cause problems,” Ross says.
But in the past few decades, some researchers — backed by nonprofits such as the Multidisciplinary Association for Psychedelic Studies, or MAPS, and the Heffter Research Institute — found their own way to the promising early science and decided to take a fresh look at the drugs. Roland Griffiths, director of the new Johns Hopkins center and a professor of psychiatry and behavioral sciences, got “deeply curious about non-ordinary states of consciousness” after developing a meditation practice about 25 years ago. He did some research on comparative religions and various meditative and contemplative practices, and came across the old medical studies on psychedelics. “I was kind of a skeptic going into it,” he says, referring to the potential of the drugs. But in 2006 he and his colleagues published a double-blinded study showing that administering a high dose of psilocybin under “comfortable, supportive conditions” reliably produced mystical experiences in healthy, religiously or spiritually oriented adults. Griffiths was stunned to find that about two-thirds of the volunteers rated the experience to be “either the single most meaningful experience of his or her life or among the top five most meaningful experiences of his or her life” — on par with the birth of a first child or death of a parent. Participants also reported enduring positive changes in moods, attitudes and behavior, suggesting a potential therapeutic role.
Psiloscybin may affect people differently. But often, Griffiths says, the drug produces transcendent or mystical-type feelings characterized by a sense of unity and interconnectedness. People many times report feeling a sense of mystery and wonder at the very fact of being alive, and a sense of freedom to choose their own path, he says. That can be helpful for those who are “caught in habitual patterns of behavior or thinking,” whether it’s the fixation on an addictive substance, ruminative anxiety or depressive thoughts, he says. Experts aren’t sure precisely how psilocybin works, but it seems to temporarily produce a widespread reorganization of brain activity and communication, says Frederick Barrett, an assistant professor of psychiatry and director of neurophysiological mechanism and biomarker assessment at Johns Hopkins’ new center.
Most research on psilocybin has focused on addiction and cancer-related distress. Ross and Griffiths published research in 2016 showing that a single dose along with support from therapists helped participants achieve a 60% to 80% reduction in depression and anxiety that endured six months after the session. Sherry Marcy, now 77, was one of the volunteers. She was diagnosed with stage 3 endometrial cancer in 2010 and underwent surgery and months of grueling chemotherapy and radiation. The treatment worked, but the experience left her depressed and traumatized. She read about the Hopkins study and, after consulting with her wife, signed up. “I’m a child of the 60s, so I wasn’t appalled at the idea,” she says. Marcy took a dose of psilocybin in a special room with a couch, while wearing an eyeshade and headphones. She was monitored by two therapists. (She had two sessions, one with psilocybin and one with a placebo, and was only told which was which afterwards — though she had a pretty good idea based on what she felt.) Her primary experience was a sense of connectedness to her family. “That got me grounded,” she says. “Once I got connected to Nancy and the kids, I knew which way was up and how much I had ahead of me.”
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MDMA is also in phase three trials — of three doses accompanied by therapy — following promising results for use in people with PTSD. It’s “quite different” from the classic psychedelics like psilocybin and LSD, though in this context it’s delivered in a similar way (over many hours, with therapists, in a supportive environment), says Michael Mithoefer, a psychiatrist who practices in Charleston, South Carolina, and leads MAPS-sponsored trials of the drug.
The primary treatment for PTSD is psychotherapy that revisits the traumatic events. But some patients get so overwhelmed that they “can’t talk about the trauma without getting upset and anxious,” he says. Others may numb their feelings, which can reduce emotional connection and render therapy ineffective. MDMA seems to help people reach a sweet spot. “They’re activated and engaged enough to do meaningful work, but not overwhelmed,” Mithoefer says. That may be in part because the drug decreases activity in the amygdala, the part of the brain associated with fear, though the mechanism isn’t fully understood. The drug also increases trust and interpersonal connection, which can help build a therapeutic relationship. As with psilocybin, a therapeutically successful or meaningful experience isn’t necessarily a fun one. “The name ‘ecstasy’ is misleading,” Mithoefer says. “You’re not ecstatic when you’re processing trauma, but it’s bearable and productive when it wasn’t before.”
MDMA-assisted therapy helped Jonathan Lubecky, a U.S. Army veteran who served in Iraq and was officially diagnosed with PTSD in 2007. “Within 60 days of coming home, I had my first suicide attempt,” says Lubecky, now 43 and living in Charleston. More attempts followed, and he tried medication and various forms of therapy, to no avail. After hearing about one of the trials Mithoefer was leading and enrolling, he had three therapist-supported sessions with MDMA. “I would purposely stay away from trauma in therapy, because it would trigger panic,” he says. “The medication allows you to not have that occur. You can talk about it like you’re not going to die of a panic attack.” He says the experiences helped him look at things more objectively, without self-judgment. It helped him, although he says he worries that other veterans will hear his story and think they should just go get ecstasy on the street and that they’ll be fine.
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Researchers have the same concern. In clinical trials, patients are screened carefully for conditions including psychosis and cardiovascular problems. Obtaining and taking the drugs while not under medical supervision can be unsafe, and the effectiveness isn’t necessarily going to mirror the controlled conditions of the studies. In the context of supervised therapeutic use, there are prep sessions where the patient discusses his or her medical and psychiatric history and intention for the session. During the experience, therapists monitor patients closely to ensure safety — for example, that no one leaves or does something dangerous while under the influence. Afterward, there are sessions to process the experience. “I don’t see them as trivial drugs, or drugs to be used for trivial reasons,” Grob says.
If psilocybin and MDMA are eventually approved, researchers expect their use will still be limited in several ways, including the need for them to be administered by trained clinicians. They also worry about “irrational exuberance,” as Ross puts it — that people might believe the drugs will be a cure-all in one or two doses and get their hopes up. There is a concern that news of one person having a bad outcome in an uncontrolled setting could halt research progress into psychedelic medicine. “We’ve had thousands of terminally ill cancer patients calling us because they think we have a clinic,” Ross says. But trials are limited, and he doesn’t advise use outside of them. For now, all he and his colleagues can do is keep working.