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IN 2009, CLARK MARTIN, a retired clinical psychol-ogist, took psilocybin—the psychoactive component of mushrooms belonging to the Psilocybe genus, better known to most as simply “shrooms”—for the first time. He did so, however, in a softly lit room in a research lab, comfortingly decorated with wall hang-ings, flowers, and family photos that he’d brought along from home. Soothing music was playing, and there were two therapists in the room with him, looking on as he pulled an eye mask over his face

and journeyed forth on the psychedelic. Martin had volunteered for a clinical trial, still ongoing, led by Dr. Roland Griffiths, a professor of behavioral biology at Johns Hopkins University, in Baltimore, to explore the effects of psilocybin on cancer patients struggling with depression and anxiety.

Like many of the subjects who participated in this trial and in similar ones conducted at New York University and at the Harbor-UCLA Medical Center, in Los Angeles, Martin responded well to the treatment.

Just Don’t Mention Timothy Leary Psychedelic drugs got a bad rap after too many people used them casually and carelessly.

But researchers around the world are now finding that “shrooms” may be effective for treating everything from depression and anxiety to addiction. BY NELL CASEY

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“IT WAS A COMPLETE STRIPPING AWAY OF IDENTITY RIGHT DOWN TO THE BARE ROOTS, UNTIL I FELT I WAS A VIBRATIONAL FIELD OF ENERGY.”

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In fact, the 68-year-old, who had been diagnosed with kidney cancer nearly two decades prior and had since struggled through chemotherapy and other difficult regimens, has come to feel that the drug not only lifted him out of his unhappiness, but also allowed him to carry his expansive mood forward to this day. “It’s natural for human beings to develop a rather static and narrowly conceived belief system in order to survive,” Martin says. “For the conscious brain to wrap itself around the complexity of life, especially in facing your own mortality, is just not possible.” He believes that psilocybin may suspend

the defenses you create throughout life “just long enough for you to have a sense of a more spontaneous, intuitive approach, like you might have had as a child.”

Naturally occurring psychedelics have been used to induce alternate states of consciousness in various cultures for millennia. It wasn’t until the 1950s, though, that the world

of psychiatry began to co-opt psychedelics for re-search. In 1960, Timothy Leary, then a professor and researcher, began his well-publicized Harvard Psilocybin Project, which produced results that struck people as both intriguing and dubious. Leary’s dismissal from Harvard, frequent arrests, and seem-ingly casual relationship to the use of psychedelics, in addition to the growing recreational use of the drugs among the “counterculture,” led to a general sense of distrust and suspicion about them. Until recently, serious research into psilocybin has been, as one psychiatrist put it, “frozen in time.”

But the high rate of success in the Johns Hopkins trial and others has led to a thawing of the ice, as researchers begin to consider the potential of psilocy-bin for treating a broader spectrum of mental health disorders, in particular, addiction and depression.

Though the published studies on psilocybin have been based on small samples, the results have been promising. A UCLA trial, comprising 12 late-stage cancer patients and first published online in the Archives of General Psychiatry in 2010, found a signif-icant reduction in anxiety among participants after three months and an improvement in mood up to six months after administration of the drug. In the trials for the Johns Hopkins studies, which were published in 2006, 2008, and 2011, varying doses of psilocybin were given to 36 “healthy normal” subjects with a spiritual orientation of some kind (ranging from attending church or synagogue to

participating in a meditation group); a primary goal was to examine whether core personality traits, traditionally considered to remain stable after the age of 30, could be altered by a psilocybin-induced

“trip.” At the 14-month follow-up in the 2011 study, 94 percent of volunteers ranked their high-dose ex-perience among the five most spiritually significant experiences of their lives. Eighty-three percent reported that it had increased their sense of well-being or life satisfaction overall.

The participants in the trials seem to have been able to access a privileged realm of emotion and experience that they had previously been unable to tap into, and one that positively affected their moods and perceptions in the long-term. They tend to characterize the experiences as “spiritual” or

“mystical.” Ben Sessa, a 40-year-old psychiatrist in London who not only researches how psilocybin alters the brain but has also acted as a trial subject, describes it this way: “It was a complete stripping away of identity right down to the bare roots, until I felt I was a vibrational field of energy. It was deep-ly spiritual and incredibly frightening at the same time. ... I felt as if I were on my knees facing God.”

“There was this tranquil sense of presence but no auditory or visual,” Martin recalls of his deepest period on the drug. “It was very comfortable and somehow familiar. ... If there were any words to de-scribe it, they might be curiosity or awe.”

Others have undergone more traditional transfor-mations, or “autobiographical experiences,” in the parlance of psychiatrists. “One woman said, ‘I want to do more art, I want to travel more, and I want to improve my relationship with my daughter,’ ” explains Jeffrey Guss, a psychiatrist at New York University who is working on a trial with cancer patients. “At first, those intentions existed among other anxieties and preoccupations and a feeling of being over-whelmed by what was going on. After taking part in the study, though, patients found that those intentions rose up and became intensely focused.” Another subject was able to acknowledge that he could no longer go it alone and moved so that he could live with a friend. “He settled relationships with his family,” says Guss, “and began feeling loved and safe in a way he hadn’t in years.”

SUCH PROMISING EMOTIONAL SHIFTS—and the consequent ability to clear a path toward making better decisions and then acting on them—are largely responsible for influencing other researchers to ex-tend the exploration of psilocybin. “The studies with

the healthy patients at Johns Hopkins were probably most influential for me,” says Michael Bogenschutz, an addiction specialist at the University of New Mexico who has just received funding for a psilocybin-assisted therapy trial to treat alcoholism. “Well over half of the people had this complete mystical experi-ence, and fourteen months later they reported lasting change in attitude and mood and behavior,” Bogen-schutz says. “That resonates with addiction treatment, this idea of sudden change and spiritual awakening .... You can imagine that, coming out of this experience, which really shakes people up, they may have a greater appreciation for the adverse effects of alcohol on their lives and the need for change.”

Bogenschutz is also inspired by a series of studies from the 1960s that used LSD—a synthetic drug whose effects are similar to those of psilocybin—to treat alcoholics. A 2012 study in The Journal of Psy-chopharmacology provided a meta-analysis of these trials and found that LSD, taken as a single dose, offered help for people struggling to quit drinking.

“People with addictions can have an abused sense of self,” says Matthew Johnson, Ph.D., a researcher looking into the effects of psilocybin on smokers at Johns Hopkins. “If they’ve failed countless times to bring their behavior in line, it can become a very self-defeating mentality. [The drug] allows them to get out of their own way and reevaluate the big picture of their life.” The anecdotal results of the Johns Hopkins pilot study on smoking cessation seem to corroborate this theory: Four people, once considered heavy smokers who were unable to quit the habit, since taking psilocybin, have re-mained abstinent at follow-ups for six months and up to a year (the research is ongoing).

Robin Carhart-Harris, a psychopharmacologist and the lead author on two recently published reports about the psychedelic from the Imperial College of London, used an MRI to track movement in the brain when under the influence of psilocybin. Carhart-Harris’s team discovered that the drug decreases ac-tivity in two areas, the medial prefrontal cortex (mPFC) and the posterior cingulated cortex (PCC). The mPFC, in particular, is known to be more active during depression, and the PCC is understood to play a role in consciousness and self-identity. “This is a network in the brain that activates when we think about our personal past as well as project our-selves into the future, make social judgments, and are faced with moral dilemmas,” Carhart-Harris explains. “Heightened activity in this region corre-lates with excessive introspection, being stuck in

one’s own head and detached from the outside world.” In other words, psilocybin slows down the part of the brain that becomes hyperactive in depression. The reason this is also useful in con-quering addiction, Carhart-Harris theorizes, is that it alters the brain’s habits, or patterns. When there is a compulsive behavior such as addiction, there is also a well-trod neural pathway that under-lies this behavior. Psilocybin may beat an entirely new path in the brain and knock a person from his or her “overly reinforced trajectory.”

THE CARHART-HARRIS STUDY also showed that psilocybin was capable of granting swifter and livelier access to personal memories. Ten volunteers were offered cues that spurred links to happy childhood recollections. These were much more intense for people while on the drug, and, in a two-week follow-up, those who had had the most vivid psilocybin-induced memories reported a stronger sense of well-being. “Under the influence of psilocybin,” Carhart-Harris suggests, “pre-existing memories are sharper. In this case, they were positive memories. In depression, people struggle to remember the good times in their lives. So they may have a view that they’ve never been happy. The idea we’re run-ning with is that we could use memory cues in depression patients to wake them up, to let them know they were happy before and could be again.”

Carhart-Harris is in the planning stages of a psilo-cybin trial of people with depression; the aim is to have it in place by early 2013. “The long-term goal would be to use this to treat depression,” he explains.

“But you want it to treat patients who don’t respond to first-line medication. We’re looking at it as a complementary treatment.”

Even as a last resort, psilocybin-assisted therapy could prove to be revolutionary if it were discovered that one dose might alter the brain enough to allow a reprieve from depression. There isn’t enough evi-dence yet to know whether the brain is permanently affected by psilocybin, but Carhart-Harris believes that the real change comes from the wisdom granted

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while on it. “It may be that those insights stay with you, so you’ve learned something about yourself and your existence in the world,” he says. “As you come

down and your brain goes back to normal functioning, it may be that new connections are formed.”

Of course, psilocybin doesn’t come without its hazards. The language of the published reports is circumspect, carefully warning of the potential for an uncomfortable response to the drug. “Although hallucinogens are relatively safe physiologically and are not considered drugs of dependence,

their administration involves unique psychological risks,” one study states. “The most likely risk is over-whelming distress during drug action (‘bad trip’), which could lead to potentially dangerous behavior such as leaving the study site. Less common are prolonged psychoses triggered by hallucinogens.”

Martin found he was most concerned when coming back down from the drug. “In the last two hours or so, I had a lot of anxiety about whether I was going to be able to pull the everyday reality fully back into focus,” he says.

Researchers go to great lengths to minimize the risks in the studies, employing a selective process in choosing volunteers—participants cannot have, for example, any family history of psychotic condi-tions such as schizophrenia or bipolar I or II disorder. They also nurture a feeling of trust and safety, with a series of lengthy therapy sessions before and after the administration of the drug, and they have trained professionals sit with subjects throughout.

Still, even in a scenario in which things go as planned, there can be an inherent discomfort in surrendering to the will of the psilocybin. “I just wanted everything to snap back into place,” Martin says of his initial reaction. “There was no sense of time, and I realized the drug was in me and there

was no stopping it. ... Had it not been for the two experienced researchers in the room, I probably would have had a full-blown panic attack and lost the larger experience.” Two of the volunteers in the first Johns Hopkins study compared their time on psilocybin to “being in a war.” Three made it clear they would not want to repeat the experience. And yet none of these participants rated the session as having decreased their overall sense of well-being.

“It’s important to understand that the psychedelic experience isn’t a guaranteed journey into bliss and light,” explains NYU’s Guss. “There can be very frightening experiences of loss of things that make you feel secure, and when you are reorganizing your way of seeing yourself in the world, there can be anxiety. There is usually a good bit of crying, but that’s not bad. Nobody has had fear without a revelation or worthwhile experience.”

It is unusual to consistently find such encouraging results, but professionals in the field are temperate

in discussing the future. They acknowledge that the studies have been limited and that the use of psilo-cybin still needs to be explored and challenged. It is important too that they tread carefully so that they might continue to dismantle the prejudices that built up around the use of psychedelics in the 1950s and ’60s. Psychiatrists also cite the difficulties of gathering the resources to conduct these studies, all of which have so far been privately funded.

But they do have dreams for what psilocybin research might deliver in a distant future. “As we understand more about the brain, it may be that one day—we’re talking way down the road here—we could put someone under a magnet and stimu-late a part of the brain to have this experience,” researcher Johnson says. “So we’re building a knowl-edge piece beyond the drug that is very helpful.”

nell casey is the editor of 2002’s best-selling Unholy Ghost and of The Journals of Spalding Gray, published last year.

PSILOCYBIN COULD PROVE TO BE REVOLUTIONARY IF IT WERE DISCOVERED THAT ONE DOSE MIGHT ALLOW A REPRIEVE FROM DEPRESSION.

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