December 7, 2006
Researchers Explore New Visions for Hallucinogens
By: Susan Brown
Chronicle of Higher Education
The Chronicle of Higher Education published the article “Researchers Explore New Visions for Hallucinogens.” This article describes the current renaissance in psychedelic research, particularly Dr. Francisco Moreno’s recently-published Heffter- and MAPS-sponsored study evaluating psilocybin as treatment for OCD. The article also discusses the recent psilocybin/mystical experience study at John Hopkins, and Dr. Charles Grob’s ongoing Heffter’ sponsored study at UCLA evaluating psilocybin-assisted psychotherapy as treatment for individuals with anxiety disorders secondary to advanced-stage cancer.
Chronicle of Higher Education
Volume 53, Issue 16, Page A12
December 7th, 2006
Researchers Explore New Visions for Hallucinogens
By SUSAN BROWN
After a long hiatus, medical investigators return to studying the benefits of once-banned compounds
Recently, 36 people who had never taken hallucinogens before gave them a try. The pill they took launched a daylong psychedelic journey, sometimes fantastic, sometimes frightening. When it was over, a few who took the drug said it was the most meaningful experience of their lives, as momentous as the birth of a first child or the death of a parent. Others wished never to repeat it.
The drug they took was psilocybin, the hallucinogenic molecule found in "magic" mushrooms.
Their tales do not come from an all-night desert trance or a radical festival like Burning Man but from Baltimore, where they participated in an experiment at the Johns Hopkins University Bayview Medical Center.
The study, which began in 2001, explored the drug's ability to induce a mystical state. Published in the journal Psychopharmacology this summer, it was the first federally approved research on psilocybin in humans to be reported in four decades and leads a vanguard of studies that mark a quiet revival of research on psychedelic drugs.
When scientists in the United States and Europe first learned of the mushrooms' strange effects in the 1950s, along with those of related hallucinogens like LSD, research on the topic exploded. More than a hundred published reports cataloged the effects of the drugs, some rigorously, others not so.
Most notorious of the researchers was Timothy Leary, a psychologist at Harvard University who abandoned standard research conventions from the start and relied instead on testimonials, encouraging his subjects to record their experiences in whatever way they felt appropriate. He also took the drug along with his student subjects and conducted his "research" in his home, where participants listened to music and looked at art. Harvard took a dim view of this and, in 1963, declined to renew his contract.
By then, hallucinogens had escaped from the laboratory, and Mr. Leary and others began promoting their use as paths toward spiritual enlightenment. Legislators swiftly made the drugs illegal following alarming reports of bad trips and people arriving at emergency rooms convinced they had gone mad. Public opinion turned against the work, making psychedelic research a bad career move for scientists and a public-relations minefield for research institutions.
"It was a crazy period where these compounds were irresponsibly promoted for recreational use, and their use was widespread," says Roland R. Griffiths, a psychiatrist who led the study at Hopkins. "We got into what appears to me to be a little bit of cultural hysteria about their risks. They were swept out of the research domain."
Dr. Griffiths agrees that the compounds should have been made illegal. "That was a wise and prudent thing to do, given what happened," he says. "But to eliminate them as research tools just doesn't make any sense to me from a scientific point of view, from understanding the nature of consciousness and cognitive and perceptual experience."
Now the inquiry is quietly resuming. Federal agencies have granted a handful of investigators the licenses they need to do the work. And ethics-review boards at universities are approving the studies, after careful (and sometimes lengthy) consideration. Four studies of psilocybin in humans are either in progress or have recently been completed.
The researchers want to learn how to safely induce transcendent states that could help patients make positive changes in their lives or, with lower doses, end intractable pain or halt intrusive thoughts. Advocates hope this is the beginning of a new era of carefully considered exploration of the possible benefits of psychedelic drugs.
Wall Street to Haight Ashbury
Nearly 50 years ago, a Wall Street banker and fungi enthusiast named R. Gordon Wasson first brought hallucinogenic mushrooms to widespread attention in the United States and Europe.
When he heard that traditional Mexican healers used mushrooms to summon their visions, he traveled to Oaxaca to try them himself and emerged from the experience awestruck. "I was seeing the archetypes, the Platonic ideas, that underlie the imperfect images of everyday life," Mr. Wasson later wrote. His article, published in Life in May 1957, gave the fungi their popular name: magic mushrooms.
Within a year, a Swiss chemist had isolated the active chemicals in the mushrooms by sampling the extracts himself to determine which altered his perceptions. He named the compounds psilocybin and psilocin, and his employer, Sandoz Pharmaceuticals, quickly patented the drugs.
In contrast to Mr. Wasson's vigil in a cave guided by a traditional healer, Mr. Leary's first experience with mushrooms was poolside at a Cuernavaca resort. He too was enchanted. Upon returning to Massachusetts, Mr. Leary joined a growing number of researchers who, intrigued by anecdotal accounts of the effects caused by the curious chemicals, began to study their mind-altering properties.
Some thought psychedelic drugs might help the troubled by making them more responsive to psychotherapy. Others hoped a spiritual experience might help alcoholics abstain from drink or convicts renounce crime. Still others thought psychedelics might open a window into the human mind, providing a telling glimpse of how our brains assemble the experience we call consciousness, or explaining how that shatters in mental illnesses like schizophrenia.
In one famous experiment, Walter Pahnke, a physician and minister working on a Ph.D. with Mr. Leary, assembled 20 theology graduate students in the basement of Marsh Chapel at Boston University for a worship service on Good Friday in 1962. The idea was simple: Would psilocybin enhance their spiritual experience, even induce a mystical state? Half were given psilocybin and half nothing at all.
The result was chaos. One participant had a psychotic reaction and needed to be restrained, and those who were disappointed not to receive the drug became bored and disruptive. Still, those who received psilocybin were reportedly transformed by the experience.
But the promise of mind-opening experience also led to widespread misuse, and the researchers' hopes were dashed in 1970 when Congress outlawed hallucinogenic drugs. Federal money and support for the work vanished and commercial supplies were recalled, making further research, even responsible studies, nearly impossible.
As memories of the excesses of that time have faded, a more tolerant public climate has emerged. In 1989 the Food and Drug Administration reorganized its division in charge of drug testing, and the officials in charge of psychedelics signaled they would approve well-designed studies that met established criteria for good clinical research. That shift made it possible for researchers to once again consider studying hallucinogenic compounds.
Among the first to venture forward was Dr. Griffiths of Hopkins. He wanted to see if psilocybin could induce a mystical experience, like those reported by some participants in Dr. Pahnke's Good Friday experiment, but in a safe environment, with careful experimental controls. It took him two years to get the approval of the FDA, a license from the Drug Enforcement Administration, and the permission of the university committee that oversees human research.
The committee at Johns Hopkins reviewed Dr. Griffiths's proposal with unusual caution. "The concern that went into the approval process was unlike anything I've ever experienced in my 30-plus years of doing human research," he says.
The review board wondered if people given psilocybin during the study might go on to abuse the drug. But people have been taking psilocybin for decades, and that history has shown that it is not addictive. Reviewers also worried that a vulnerable subject could be tipped into psychosis by taking psilocybin. Dr. Griffiths and his colleagues ruled out potential participants who had previous mental troubles or even a family member with psychiatric illness.
That screening left them with 36 adult participants who had never used hallucinogens before. All the participants followed some sort of spiritual practice, whether it was participation in organized worship or individual meditation. Curiosity led them to join the experiment: They wished to try psilocybin in a context of self-reflection.
Transcendence and Fear
Each subject took the drug in one of two sessions. During the other, they were given methylphenidate, commonly known as Ritalin, which changed their physiology ? their heart rate, for example ? in a way similar to psilocybin but possessed no hallucinogenic properties.
Participants spent each daylong session in a room furnished with an Oriental carpet, pictures, and a sofa on which they were encouraged to lie down. Their monitors gave them eye masks and earphones with a playlist of classical music and encouraged them to focus inward. At the end of each session, after the drug wore off, they answered questionnaires designed to assess their spiritual and perceptual experiences.
After taking psilocybin, participants reported intense emotions ? grief, joy, anxiety ? and feelings of transcendence, a reprieve from the normal constraints of space and time. Colors brightened, and some people reported a confusion of senses called synesthesia ? musical tones that take on hues, for example. In contrast, the methylphenidate improved self-control and concentration.
But nearly a third of the participants felt fearful after taking psilocybin, and four of the 36 spent their entire session in unpleasant psychological struggles. Two compared the experience to being in a war, and three said they would never wish to repeat the experience, the research team reports.
"It really underscores the risks of using these kinds of compounds in a nonsupervised, nonresearch setting," Dr. Griffiths says. "It's really not difficult at all to imagine that under uncontrolled conditions these kinds of things could escalate into panic and engaging in risk-taking behaviors."
Yet two months later, none of the subjects, not even those who reported an unpleasant encounter with the drug, said that the experience had decreased their sense of well-being or satisfaction with life.
Rachel Yehuda, a psychologist who specializes in post-traumatic stress at Mount Sinai School of Medicine and the Bronx Veterans Affairs Medical Center and who was not involved in the study, says she is not concerned by the anxiety experienced by some of the participants in the experiment. "What people don't realize about trauma is that it often ends up being a meaningful experience," she says. "It's a watershed event."
Other researchers hope Dr. Griffiths's article will stand as a benchmark for a new era of psychedelic research. "It sailed through the review process because it was a well-done study by a very recognized researcher," says Harriet de Wit, a behavioral pharmacologist at the University of Chicago who, as a principal editor of Psychopharmacology, shepherded the paper through review.
Dr. Griffiths hopes his work with healthy, well-functioning adults might eventually help those who struggle with addiction. The most effective interventions in use now are 12-step programs. But they rely heavily on a belief in a "higher power," and people who lack faith have trouble embracing them.
"It's possible that if you could occasion a single primary transcendent experience of the type that was seen in our study," he says, "that that single experience alone would allow somebody subsequently to engage in a 12-step process with renewed interest, vigor, and excitement in a way that they couldn't otherwise."
Charles S. Grob, a psychiatrist at Harbor-UCLA Medical Center, agrees that this line of inquiry is worth pursuing again. Some of the most impressive work in the 1960s was done with alcoholics, he says. More support comes from Dr. Grob's own work 10 years ago with a native church in Brazil. He found that former alcoholics who drank a hallucinogenic herbal brew twice a month as part of a religious ceremony stayed sober.
Dr. Grob is in the midst of a study that asks whether psilocybin might ease the anxiety of people who are dying. In an experiment similar in design to Dr. Griffiths's, he is giving the drug to patients with end-stage cancer. So far, seven patients have received psilocybin, and Dr. Grob has approval to treat five more.
The Harbor-UCLA study follows up on research done by Stanislav Grof and Dr. Pahnke, who worked at the Maryland Psychiatric Research Center, in Baltimore, in the late 1960s, the very end of the psychedelic era. They gave the more powerful hallucinogen LSD to patients with terminal cancer. About two-thirds of their subjects got by with less pain medication as a result. They feared death less or not at all, and their anxiety abated, which is known to help ease pain.
"Their outcomes were best with people who had what they described as a mystical experience, or a full-on, spiritual, transpersonal epiphany," Dr. Grob says.
Because the review board at his institution required a lower dose of psilocybin than he had wanted to use, about half of that used in the Hopkins experiment, his patients' experiences are not as intense. "We're hoping to get approval, when we're done with this group, for a higher dose," says Dr. Grob.
A Target in the Brain
Advances in neuroscience over the past four decades have helped pave the path toward acceptance of this revived line of research. "At one time, when people were just exploring consciousness, it was hard to justify," says John H. Krystal, a psychiatrist at Yale University School of Medicine who was an editor of Psychopharmacology when Dr. Griffiths's paper was submitted.
But once researchers had worked out the molecular basis of the drugs, he says, "then a whole new opportunity to study important aspects of the neurobiology of consciousness opened up."
David E. Nichols, a medicinal chemist at Purdue University who synthesized the psilocybin used in two of the recent studies, agrees. "We know quite a bit more about the brain now than we did then, and human experimental methods are certainly much better," he wrote in a commentary that appeared in the same issue of Psychopharmacology as Dr. Griffiths's paper.
Psilocybin closely resembles serotonin, a neural signaling molecule or neurotransmitter. Calm, happy states coincide with the release of serotonin in the brain. Psilocybin fits serotonin receptors that are especially abundant in a kind of cell in the cerebral cortex that gathers and sorts signals coming in from other parts of the brain.
Psilocybin's effect is to make these "computational" cells more likely to register an incoming signal, Mr. Nichols explains, "potentially amplifying processes that are normally running, but which are not generally apparent in everyday awareness."
Psilocybin could have medical uses if the way it latches onto brain cells remedies an imbalance or malfunction in the serotonin system. In fact, a few patients have found relief from their maladies in magic mushrooms, and those reports of self-medication have led to two recent clinical reports.
The first was spurred by an online discussion group on cluster headaches. The pain from such headaches repeats in regularly timed bouts that typically continue for two to four months, and it strikes quickly, without warning, and rapidly becomes excruciating. Some of the people posting on the site reported relief from LSD or magic mushrooms.
That those drugs would help is not particularly surprising: LSD was initially created as a potential treatment for migraine, and psilocybin is chemically related to sumatriptan, the most commonly prescribed drug for heading off cluster headaches.
One member of the group, a 34-year-old man, had suffered cluster headaches since he was 16, except for a period of two years in early adulthood when he was experimenting with LSD. Later he found he could prevent his attacks altogether if he drank mushroom tea every three months. When that patient contacted a group of psychiatrists at Harvard University's McLean Hospital, R. Andrew Sewell, then a postdoctoral fellow, and John H. Halpern, an assistant professor of psychiatry, decided to follow up.
The team found 53 people who had been treating their headaches with psilocybin or LSD and were willing to release their medical records. When they questioned their subjects by telephone or e-mail about their drug use, they found that for many, the drugs could end the paroxysms of pain in the midst of a headache and extend the pain-free period between attacks, something no other treatment could do.
"Research on the effects of psilocybin and LSD on cluster headache may be warranted," the researchers conclude in their case reports, which were published in the journal Neurology this summer.
No serious opposition to this new work has yet emerged. The Chronicle contacted more than a dozen psychiatrists and psychologists ? including specialists on anxiety and post-traumatic stress ? and none expressed concern about this round of research, in part because the experimenters closely supervised each subject.
Mindful of the past, though, all of the scientists said they did not advocate illegal or indiscriminate use of mushrooms or other hallucinogens. And most said further work should be pursued if the initial results of carefully designed studies showed promise, particularly if they helped patients for whom standard treatments failed.
Quieting Intrusive Thoughts
That is exactly the kind of patient that Francisco A. Moreno hoped to help. Last month Dr. Moreno, a psychiatrist at the University of Arizona, reported success in treating particularly difficult cases of obsessive-compulsive disorder with psilocybin.
Dr. Moreno was inspired to try the drug when a patient reported that the only time his symptoms had ever abated was when he was using magic mushrooms as a young adult. Prozac and similar drugs, which extend the working period of serotonin, sometimes help people with OCD. Others find no relief. Dr. Moreno thought psilocybin might help patients for whom approved drugs and psychotherapy had failed. He gave the drug to nine patients with OCD.
The patients he treats are seriously impaired. They have intrusive thoughts of harming themselves or others, he says, such as "the urge to pinch or bite little babies." But they are not suicidal or homicidal. "They are horrified by their thoughts," he says.
In this small and preliminary study, psilocybin ended the obsessive thoughts and compulsive actions ? such as hand washing ? of some patients completely, and for the first time in their adult lives, for at least the brief follow-up period of 24 hours. The symptoms of all nine subjects markedly improved.
That the drug worked so soon was surprising: Other medications can take weeks to kick in. "Nothing works as quickly and as drastically as these hallucinogens do," Dr. Moreno says.
Despite his promising results, Dr. Moreno is not an advocate for the drug. He published his report quietly in the Journal of Clinical Psychiatry last month. Neither the journal nor the university has alerted the media as they usually do when a promising new treatment is found.
Dr. Moreno hopes his work might lead to the discovery of a safer drug that treats OCD more effectively. He does plan, however, to continue his work with psilocybin, following his patients for longer periods next time, he says. "If this, if any drug, could help people with OCD, with mental illness," he says, "then we should explore it."
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