A Dose of a Hallucinogen From a ‘Magic Mushroom,’ and Then Lasting Peace

Octavian Mihai at his home in Las Vegas. Mr. Mihai began experiencing anxiety after he finished treatment for Hodgkin’s lymphoma.

Appeared on the front page of the New York Times on Dec. 1, 2016

On a summer morning in 2013, Octavian Mihai entered a softly lit room furnished with a small statue of Buddha, a box of tissues and a single red rose. From an earthenware chalice, he swallowed a capsule of psilocybin, an ingredient found in hallucinogenic mushrooms.

Then he put on an eye mask and headphones and lay down on a couch. Soon, images flew by like shooting stars: a spinning world that looked like a blue-green chessboard; himself on a stretcher in front of a hospital; his parents, gazing at him with aching sadness as he reached out to them, suffused with childlike love.

Psilocybin has been illegal in the United States for more than 40 years. But Mr. Mihai, who had just finished treatment for Stage 3 Hodgkin’s lymphoma, was participating in a study looking at whether the drug can reduce anxiety and depression in cancer patients. Throughout that eight-hour session, a psychiatrist and a social worker from NYU Langone Medical Center stayed by his side.

Published Thursday, the results from that study, and a similar small, controlled trial, were striking. About 80 percent of cancer patients showed clinically significant reductions in both psychological disorders, a response sustained some seven months after the single dose. Side effects were minimal.

In both trials, the intensity of the mystical experience described by patients correlated with the degree to which their depression and anxiety decreased.

The studies, by researchers at New York University, with 29 patients, and at Johns Hopkins University, with 51, were released concurrently in The Journal of Psychopharmacology. They proceeded after arduous review by regulators and are the largest and most meticulous among a handful of trials to explore the possible therapeutic benefit of psilocybin.

Dr. Jeffrey Lieberman, a past president of the American Psychiatric Association, and Dr. Daniel Shalev of the New York State Psychiatric Institute are among leaders in psychiatry, addiction medicine and palliative care who endorsed the work. The studies, they wrote, are “a model for revisiting criminalized compounds of interest in a safe, ethical way.”

If research restrictions could be eased, they continued, “there is much potential for new scientific insights and clinical applications.”

Although cancer patients will not have access to therapeutically administered psilocybin anytime soon, the findings add vigor to applications to expand research in a multicenter trial with hundreds of participants.

Some medical professionals held the studies at arm’s length. Dr. William Breitbart, chairman of the psychiatry department at Memorial Sloan-Kettering Cancer Center, questioned this use of cancer patients. “Medical marijuana got its foot in the door by making the appeal that ‘cancer patients are suffering, they’re near death, so for compassionate purposes, let’s make it available,’ ” he said. “And then you’re able to extend this drug to other purposes.”

Psilocybin trials are underway in the United States and Europe for alcoholism, tobacco addiction and treatment-resistant depression. Other hallucinogens are also being studied for clinical application. This week, the Food and Drug Administration approved a large-scale trial investigating MDMA, the illegal party drug better known as Ecstasy, for post-traumatic stress disorder.

Cancer-related psychological distress, which afflicts up to 40 percent of patients, can be resistant to conventional therapy. Mr. Mihai’s anxiety began when doctors finally told him he was in remission.

He would keep touching the nodules on his neck, where the cancer had announced itself. He flew to Europe to celebrate the end of treatment and his graduation from college, but abruptly returned to New York, terrified to be away from oncologists. He began drinking daily, hard, jeopardizing his fragile health.

Alarmed, doctors suggested the psilocybin study.

He took the capsule and began tripping. After seeing himself on a hospital stretcher, he recalled: “I had an epiphany.”

“Why are you letting yourself be terrorized by cancer coming back? This is dumb. It’s in your power to get rid of the fear,” he told himself. “That’s when I saw black smoke rising from my body. And it felt great.”

Three years later, Mr. Mihai, now 25 and a physician assistant in Las Vegas, said, “I’m not anxious about cancer anymore. I’m not anxious about dying.” The session, he added, “has made my life richer.”

In the 1940s and 1950s, hallucinogens were studied in hundreds of trials. But by 1970, when those drugs were placed in the most restricted regulatory category, research ground to a near halt.

Since about 2000, investigators have begun studying them, mostly with private funding. These two studies built on a 2011 UCLA psilocybin pilot project with 12 cancer patients.

Both share similarities. All volunteers had diagnoses of cancer-related anxiety or depression. Patients were randomly given a placebo or synthetic psilocybin, and not told which. Within seven weeks, they were given the other sample.

All patients were educated about the drug, monitored by two people throughout the placebo and psilocybin sessions, and seen for follow-up evaluation.

Researchers created seven-hour music playlists, paced to the anticipated rhythms of the drug reaction. N.Y.U. leaned toward New Age and world music — Brian Eno; sitars; didgeridoos. Johns Hopkins favored Western classical.

At N.Y.U., psychotherapists tried to layer the session into patients’ memories by asking them to write about their visions in a journal and discuss the experience in meetings. The Johns Hopkins study, led by Roland R. Griffiths, a psychopharmacologist, had monitors who urged participants to “trust, let go and be open.”

The N.Y.U. researchers assessed patients the next day and found the effects to be immediate in most of them.

Dr. Stephen Ross, the lead investigator and chief of addiction psychiatry at N.Y.U., pointed out that antidepressants, by contrast, can take weeks to show benefit.

“Cancer patients with anxiety and depression need help immediately,” he said, “especially if you consider that they are at elevated risk for completed suicide.”

A chalice used in a study on psilocybin, an ingredient found in hallucinogenic mushrooms.

Some experts questioned the reliability of the results. Dr. Breitbart said that because diagnoses ranged from early-stage cancer to imminent terminal illness, it was impossible to know which patients might have come through their psychological ordeal without psilocybin — whether some might have adapted to the new norms of their disease; felt stronger once chemotherapy side effects, including depression, had abated; or even experienced an improvement in health.

None of those possibilities fit Kevin, who had a bone-marrow transplant for acute myeloid leukemia. It sent his cancer into remission, but left him with graft-versus-host disease.

Suffering from chronic pain and fatigue, Kevin, 57, who lives in central Michigan and asked that his last name be withheld because he had been in law enforcement, had to retire. Four years after the transplant, he despaired.

“Going through a near-death illness is similar to returning from combat,” he said. “It damages who you are, to the core of what it is to be human.”

“I was hoping to get out of this funk of waiting for the other shoe to drop,” he added. “You’re looking up to the heavens, saying ‘What else can I try?’ ”

In 2013, Kevin entered the Johns Hopkins trial. During his session, he saw spirals of iridescent spheres that folded in on themselves.

The experience did not restore him to his former life, he said, “but I have a greater sense of peace of what might come. I’m very grateful, beyond words, for this trial. But you have to approach the session with the right intentions of why you’re doing it. Because you’re going to meet yourself. ”

Researchers do not know why psilocybin has worked in these settings. Neuroimaging scans of healthy volunteers show areas of the brain lighting up or resting during dosing. Hallucinogens activate a serotonin receptor that can lead to the alterations of consciousness reported routinely.

One theory is that psilocybin interrupts the circuitry of self-absorbed thinking that is so pronounced in depressed people, making way for a mystical experience of selfless unity.

The studies received funding from the Heffter Research Institute, an alliance of scientists interested in the medical study of hallucinogens. Dr. George Greer, the co-founder of Heffter, does not see a commercial future for psilocybin, even if it is eventually approved for therapeutic use, because these patients needed only one dose.

Instead, he envisions a nonprofit manufacturer, with distribution restricted to specialized clinics.

Researchers were emphatic that these results should not be interpreted as condoning hallucinogenic mushrooms for self-treatment. Dr. Griffiths noted that patients received extensive support, which may have deepened and secured their life-affirming transformations.

“People will take psilocybin at a rave or at Burning Man” — the art and performance desert festival — “but the effect,” he said, “evaporates like water running through their hands.”