Chemical enlightenment: line up for the scientific, psychedelic mystical tour.

The comfortably furnished room in a corner of the Johns Hopkins University School of Medicine in Baltimore seems an unlikely setting for spiritual transcendence. Yet one after another, volunteers last year entered the living room-like space, reclined on the couch, swallowed a pill, and opened themselves to a profound mystical journey lasting several hours. For many of them, the mundane certainty of being a skin-bounded person with an individual existence melted away. In its place arose a sense of merging with an ultimate reality where all things exist in a sacred, unified realm. Participants felt intense joy, peacefulness, and love during these experiences. At times, though, some became fearful, dreading unseen dangers.

The pills that enabled these mystical excursions contained psilocybin, the active ingredient in so-called magic mushrooms that some societies have used for centuries in religious ceremonies. Psilocybin boosts transmission of the brain chemical serotonin, much as LSD and some other hallucinogenic drugs do.

Johns Hopkins psychopharmacologist Roland R. Griffiths and his colleagues have taken psilocybin out of its traditional context and far from the black-light milieu of its hippie-era heyday. Griffiths' team is investigating the drug's reputed mind-expanding effects in a rigorous, scientific way with ordinary people.

In the group's recent test, psilocybin frequently sparked temporary mystical makeovers in volunteers who didn't know what kind of pill they were taking. What's more, some of these participants reported long-lasting positive effects of their experiences.

As a control in the test, the researchers used methylphenidate-an amphetamine known as Ritalin when used to treat attention-deficit hyperactivity disorder. Methylphenidate rarely produced a mystical experience, although the researchers were intrigued that a few people did have that response.

Griffiths' study, published in the August Psychopharmacology, combines research on psychedelic-drug effects--which have received little attention in the past 40 years--with a burgeoning scientific interest in the roots of spirituality (SN: 2/17/01, p. 104). The new findings put psychedelic studies on the road back to respectability, Grittiths says. In the 1950s and 1960s, preliminary research had suggested that LSD and related substances--now regarded as powerful but nonaddictive drugs--aided in psychotherapy, addiction treatment, and creativity-promoting programs.

However, the excesses of researchers such as the late Harvard University psychologist Timothy Leafy, as well as widespread illicit use of psychedelic drugs, led to legal restrictions that halted most psychedelic research.

Now, the scientific and clinical promise of drugs such as psilocybin can be fully explored, in Griffiths' view. "With careful preparation, you can safely and fairly reliably occasion a mystical experience using psilocybin that may lead to positive changes in a person," he says. "Our finding is an early step in what we hope will be scientific work that helps people."

SPIRIT TRIPS Griffiths' recent work was inspired by an unusual 1963 investigation conducted by physician and minister Walter Pahnke. Half of 20 Protestant seminarians randomly received psilocybin before listening to a radio broadcast of a Good Friday service. The rest took a B vitamin that caused the skin to flush.

After the service, many members of the psllocybin group reported unusual spiritual experiences. Four of them had full-blown mystical reactions, which they said included ecstatic visions and a feeling of oneness with God.

In interviews conducted 6 months and 25 years later, members of the psilocybin group attributed many more positive changes in attitude and behavior to the Good Friday service than vitamin takers did. Psilocybin-induced mental states had apparently triggered lasting improvements in people's lives, researchers concluded.

During Pahnke's study, however, participants sat together during the broadcast and could easily tell whether others were acting out of character. Such observations could have affected their reactions to what they had ingested. Griffiths' team tried to minimize the power of expectation by not telling most participants which drug they were taking and by administering pills to one volunteer at a time.

The team recruited 36 physically healthy adults, ages 24 to 64, who had no serious mental disorders themselves or in their immediate families. All but one volunteer had graduated from college. None cited any previous use of psychedelic drugs. Each reported at least occasional participation in religious or spiritual activities, including church services, prayer, and meditation.

At the start of the study, each volunteer met several times with a psychologist or social worker, who later sat with participants during drug sessions and offered support if needed.

Each of 30 randomly selected volunteers attended two 8-hour drug sessions, the second occurring 2 months after the first. At one session they received a strong dose of psilocybin and at the other a high dose of methylphenidate. No participant was told which drug he or she ingested--only that it might be either of the two substances.

The remaining six participants received methylphenidate at the two sessions without being told what the pills contained. At a third session, they took psilocybin pills after being told what was in the tablets.

After taking psilocybin, 22 of the 36 volunteers described having mystical experiences, the scientists say. All but three of these cases occurred in volunteers who didn't know what kind of pill they were taking. Mystical events typically included a sense of merging with an overarching reality, perceiving unity in all things, transcending time and space, and basking in overwhelming feelings of love and other positive moods.

At the end of psilocybin sessions, 25 participants--including 3 who hadn't reported mystical encounters--rated the experience as among the five most meaningful and spiritually significant events in their lives.

After taking methylphenidate, four volunteers reported mystical experiences as well. They, too, ranked the experience among the top five in their lives.

Feelings of extreme fear or dread emerged in 11 of the 36 volunteers after taking psilocybin and in none after taking methylphenidate. Those who encountered negative reactions nonetheless completed the sessions with assistance from the psychologist or social worker.

Positive effects of psilocybin seemed to last beyond the sessions. Two months after their last drug session, 29 participants reported moderately or greatly increased well-being and satisfaction with their lives as a result of psilocybin experiences. The others cited no such changes, but none described any declines in well-being in response to the psilocybin use.

Interviews with family members, friends, and coworkers of each volunteer confirmed the reports of long-lived improvements in mood, attitudes, and behavior.

The researchers are now analyzing results of a 1-year follow-up of participants.

Griffiths also plans to explore how brain processes unleashed by psilocybin compare with neural activity in people who experience drug free spiritual epiphanies. "There's good reason to believe that similar brain mechanisms are at work during profound religious experiences, whether they're produced by fasting, meditation, controlled breathing, sleep deprivation, near-death experiences, infectious disease states, or psychoactive substances," he says.

DEEP HYPNOSIS Although it's not news that psilocybin stimulates mystical experiences, Griffiths' study offers important improvements over earlier studies, asserts psychologist Etzel Cardena of the University of Lund, Sweden. First, in most instances, neither the participants nor those assisting them knew which drug was being administered. This approach enabled researchers to distinguish genuine drug effects from placebo reactions. Second, the researchers verified participants' reports of psilocybin-induced improvements by talking to their families, friends, and coworkers.

Cardena studies yet another way that people enter life-changing spiritual realms. Some folks spontaneously undergo mystical experiences during periods of "deep hypnosis," he contends.

From a group of 147 college students, Cardena identified eight women and four men who entered trance states with ease. Dubbed hypnotic virtuosos by Cardena, such individuals can direct their thoughts inward and, in no more than a minute or two, become hypnotized on their own. None of the 12 students in the study reported being in a meditation program or currently using psychedelic drugs, although 3 had ingested such substances years ago.

In a silent, dimly lit room, each participant induced a self-hypnotic state under three conditions,while lying on a bed, pedaling a stationary bicycle at a comfortable rate, and sitting on a stationary bicycle equipped with a motor that propelled the pedals, moving participants' feet at a moderate rate. Sessions ran for 17 minutes.

Participants reported an initial period of moderate hypnosis characterized by spinning sensations, a feeling of lightness, loss of touch with the external world, and perceived bodily changes, such as enlarged hands.

They then reached a state of deep hypnosis, which became more intense when the students were lying still, Cardena says. The experiences while in deep hypnosis closely resembled mystical journeys taken in Griffiths' psilocybin sessions. Reports included a sense of floating or flying, of one's mind leaving one's body, of merging with a light, and of being one with everything, as well as powerful feelings of love, wonder, and freedom.

In another parallel to Griffiths' findings, participants occasionally noted that the unusual occurrences of deep hypnosis seared them.

Still, at the end of the experiment and 8 months later, the volunteers mentioned only positive effects of the deep hypnosis, Cardena reported in the January 2005 Journal of Clinical and Experimental Hypnosis. Favorable results included increased personal insight, fewer nightmares, and enhanced inner peace. In other words, these people enjoyed the inner benefits of a self-induced mystical encounter without ingesting any mind-altering drugs.

"It's about time that psychology and related fields started taking seriously mystical and other anomalous experiences," Cardena says.

LIFE CHANGERS In 1935, a man named Bill Wilson cofounded Alcoholics Anonymous. He had recently undergone a self-described spiritual revelation that caused him to stop drinking alcohol. Two decades later, before legal restrictions largely ended studies on psychedelic drugs, Wilson backed research that suggested a use for drug-induced mystical experiences as part of alcoholism treatment.

Griffiths and his colleagues now plan to follow up on that research. They will try to determine whether psilocybin indeed fosters a spiritual insight that people can use to break alcoholism's grip. They also want to examine whether psilocybin sessions ease depression and anxiety in end-stage cancer patients.

A few treatment-focused investigations of psilocybin are already under way. In pairs of 6-hour sessions separated by 1 month, psychiatrist Charles Grob of the University of California, Los Angeles administers either psilocybin or placebo pills to patients with life-threatening cancer. Patients then typically lie still with their eyes covered while listening to relaxing music. Grob and two assistants sit with each patient during these sessions.

Grob has studied six patients so far, tracking them for 6 months after completing the sessions. He plans to investigate six more patients before publishing his findings.

"Even without having a classic mystical experience, these patients do pretty well after psilocybin sessions, and their anxiety often decreases," Grob says.

Another study, directed by psychiatrist Francisco Moreno of the University of Arizona in Tucson, is examining psilocybin as a treatment for obsessive-compulsive disorder. This condition is marked by anxiety and a need to perform repeatedly certain behaviors, such as hand washing. Results are promising, Moreno says, although he won't discuss the findings in detail until their upcoming publication in the Journal of Clinical Psychiatry.

In the meantime, Griffiths' paper has attracted some surprising supporters. Psychiatrist Charles R. Schuster of Wayne State University School of Medicine in Detroit says that the new investigation will hasten explorations of the neural basis of drug-induced altered states of consciousness. Schuster, the former director of the National Institute on Drug Abuse, calls the treatment of drug addiction with psychedelic substances "entirely conceivable."

Psychiatrist Herbert D. Kleber of Columbia University in New York City agrees. Former director of the White House Office of National Drug Control Policy, Kleber cautions that only well-prepared individuals--such as those in Griffiths' study--are likely to reap lasting benefits from drug-related mystical states.

Kleber looks forward to investigations of whether mystical experiences triggered by methylphenidate and psilocybin activate the same brain regions. Activity in the brains of people who show minimal reactions to psilocybin should also prove intriguing, he says.

Not everyone finds Griffiths' study enlightening, however. The new data simply confirm the longstanding knowledge that psychedelic substances disturb perception, cause disorientation, and sometimes instigate fear and paranoia, remarks David Murray, special assistant to the current director of the White House Office of National Drug Control Policy. Clinical benefits of psilocybin have yet to be demonstrated, he asserts.

"Psilocybin might grow hair on bald men--we just don't know," Murray says with a chuckle.

Even ardent proponents of psychedelic-drug research acknowledge that, after lying dormant for decades, the field faces many unanswered questions. It's been a long, strange trip, and it's far from over.