But in 30% of the cases, the drug provoked harrowing experiences dominated by fear and paranoia. Two participants likened the episodes to being in a war. While these episodes were managed by trained monitors at the sessions where the drugs were taken, researchers cautioned that in less-controlled settings, such responses could trigger panic or other reactions that might put people in danger.
A report on the study, among the first to systematically assess the effects of hallucinogenic substances in 40 years, is being published online today by the journal Psychopharmacology. An accompanying editorial and commentaries from three prominent neuroscientists and a psychiatrist praise the study and argue that further research into such agents has the potential to unlock secrets of consciousness and lead to new therapeutic strategies for depression, addiction and other ailments.
In one of the commentaries, Charles R. Schuster, a neuroscientist and former head of the National Institute for Drug Abuse, called the report a "landmark paper." He also expressed hope that it "renews interest in a fascinating and potentially useful class of psychotropic agents."
Still, the research is likely to stir controversy. Though psilocybin mushrooms, which can be found growing wild throughout the world, have been used for centuries in some societies during spiritual rituals, they also were agents, along with such hallucinogens as LSD and mescaline, that fueled the "Turn On, Tune In, Drop Out" counterculture of the 1960s personified by Timothy Leary.
Researchers acknowledge that the study's positive findings may encourage inappropriate use of the agents. Roland Griffiths, the Hopkins neuroscientist who headed the research, warned against viewing the results as a green light for consuming the mushrooms. "We don't know all their dark sides," he said. "I wouldn't in any way want to underestimate the potential risks" of indiscriminate use of the drugs.
The National Institute for Drug Abuse, which co-sponsored the study as part of its support for research into drugs of abuse, also warned against eating psilocybin mushrooms. They "act on serotonin receptors in the brain to profoundly distort a person's perception of reality," the institute said, possibly triggering psychosis, paranoia and anxiety.
It was widespread abuse in the 1960s that led to hallucinogens becoming illegal, effectively shutting down then-burgeoning corporate and academic research programs that had suggested the agents might be valuable research and therapeutic tools. One of the last influential studies was the Good Friday Experiment in 1962 in which 20 seminary students were given either psilocybin or nicotinic acid during a religious service. The 10 who got psilocybin reported intense spiritual experiences with positive benefits; one follow-up study suggested those effects lasted 25 years.
"It's remarkable that we have a class of compounds that has sat in the deep freeze for 40 years," Dr. Griffiths said. "It seemed to me scientifically it was high time to look again" at psychedelic agents.
Known colloquially by such names as magic mushroom or sacred mushroom, psilocybin is considered a Schedule I substance under the U.S. Controlled Substances Act. That puts it in the same class as heroin and LSD, drugs that have a high potential for abuse and no known medical use. It isn't considered addictive. The psilocybin used in the study was synthesized by David E. Nichols, a professor of medicinal chemistry at Purdue University, West Lafayette, Ind., under a special permit.
After getting approval from the Drug Enforcement Administration, the Food and Drug Administration and an institutional review board at Hopkins, Dr. Griffiths and his colleagues circulated a flier seeking volunteers for a "study of states of consciousness brought about by a naturally occurring psychoactive substance used sacramentally in some cultures."
From among the 135 people who responded, 36 were eventually selected, based in part on their lack of a history of psychedelic drug use or family history of serious psychiatric disorders such as schizophrenia. The 36 -- 14 men and 22 women -- ranged in age from 24 to 64 years old, with an average age of 46; 97% were college graduates, and 56% had post-graduate degrees. All 36 participated at least occasionally in religious or spiritual activities. (Dr. Griffiths declined to make any participants available for interviews, citing privacy issues.)
Thirty of the participants were randomly assigned to receive either psilocybin or Ritalin (known generically as methylphenidate) as a control for the first eight-hour session; two months later, they were given the other drug in another session. Neither the participants nor the monitors who were present during their sessions knew which agent was being taken. To further reduce chances that participant responses would be affected by expectations they were getting psilocybin, a third group of six participants was randomly assigned to receive Ritalin in both sessions, followed by a third session when they knew they were getting the psychedelic agent. Ritalin was selected as the control agent in part because it can cause mood-changing effects similar to those of psilocybin, researchers said. It also takes effect at about the same time and lasts for about as long.
Participants were given the drug in individual sessions in a living-room environment with two experienced monitors. They were blindfolded, given headphones to listen to classical music and encouraged to lie down and direct their thoughts inward.
Researchers provided participants with a battery of questionnaires and mysticism scales, some of which were developed based on research from more than four decades ago, to measure their impressions of their experience at the end of the session and again two months later.
A third of the participants said the experience with psilocybin was the single most significant experience of their lives, and an additional 38% rated it among their top five such experiences -- akin to, say, the birth of a first child or the death of a parent. Just 8% of the Ritalin episodes were reported to be among the top five meaningful occurrences. Two months after the sessions, 79% of the participants indicated in questionnaires that their sense of well-being and satisfaction increased after the psilocybin episodes, compared with 21% for Ritalin.
Researchers hope the findings will spur other studies that will, for instance, compare the effects of other hallucinogens and use MRIs to observe how such drugs affect the human brain. Other efforts are expected to test the value of psilocybin as a therapy. Charles Grob, a researcher at UCLA, is heading a small study to see if the drug relieves anxiety, depression and pain among patients with advanced cancer.
Dr. Griffiths said another goal is to understand the consequences of spiritual experiences -- both drug-induced and spontaneous -- and to determine how long they last and whether they lead to personality changes.