Hopkins scientists show hallucinogen in mushrooms creates universal 'mystical' experience

Using unusually rigorous scientific conditions and measures, Johns Hopkins researchers have shown that the active agent in "sacred mushrooms" can induce mystical/spiritual experiences descriptively identical to spontaneous ones people have reported for centuries.

The resulting experiences apparently prompt positive changes in behavior and attitude that last several months, at least.

The agent, a plant alkaloid called psilocybin, mimics the effect of serotonin on brain receptors-as do some other hallucinogens-but precisely where in the brain and in what manner are unknown.

An account of the study, accompanied by an editorial and four experts' commentaries, appears online today in the journal Psychopharmacology.

Cited as "landmark" in the commentary by former National Institute on Drug Abuse (NIDA) director, Charles Schuster, the research marks a new systematic approach to studying certain hallucinogenic compounds that, in the 1950s, showed signs of therapeutic potential or value in research into the nature of consciousness and sensory perception. "Human consciousness…is a function of the ebb and flow of neural impulses in various regions of the brain-the very substrate that drugs such as psilocybin act upon," Schuster says. "Understanding what mediates these effects is clearly within the realm of neuroscience and deserves investigation."

"A vast gap exists between what we know of these drugs-mostly from descriptive anthropology-and what we believe we can understand using modern clinical pharmacology techniques," says study leader Roland Griffiths, Ph.D., a professor with Hopkins' departments of Neuroscience and Psychiatry and Behavioral Biology. "That gap is large because, as a reaction to the excesses of the 1960s, human research with hallucinogens has been basically frozen in time these last forty years."

All of the study's authors caution about substantial risks of taking psilocybin under conditions not appropriately supervised. "Even in this study, where we greatly controlled conditions to minimize adverse effects, about a third of subjects reported significant fear, with some also reporting transient feelings of paranoia," says Griffiths. "Under unmonitored conditions, it's not hard to imagine those emotions escalating to panic and dangerous behavior."

The researchers' message isn't just that psilocybin can produce mystical experiences. "I had a healthy skepticism going into this," says Griffiths, "and that finding alone was a surprise." But, as important, he says, "is that, under very defined conditions, with careful preparation, you can safely and fairly reliably occasion what's called a primary mystical experience that may lead to positive changes in a person. It's an early step in what we hope will be a large body of scientific work that will ultimately help people."

The authors acknowledge the unusual nature of the work, treading, as it does, a fine line between neuroscience and areas most would consider outside science's realm. "But establishing the basic science here is necessary," says Griffiths, "to take advantage of the possible benefits psilocybin can bring to our understanding of how thought, emotion, and ultimately behavior are grounded in biology."

Griffiths is quick to emphasize the scientific intent of the study. "We're just measuring what can be observed," he says; "We're not entering into 'Does God exist or not exist.' This work can't and won't go there."

In the study, more than 60 percent of subjects described the effects of psilocybin in ways that met criteria for a "full mystical experience" as measured by established psychological scales. One third said the experience was the single most spiritually significant of their lifetimes; and more than two-thirds rated it among their five most meaningful and spiritually significant. Griffiths says subjects liken it to the importance of the birth of their first child or the death of a parent.

Two months later, 79 percent of subjects reported moderately or greatly increased well-being or life satisfaction compared with those given a placebo at the same test session. A majority said their mood, attitudes and behaviors had changed for the better. Structured interviews with family members, friends and co-workers generally confirmed the subjects' remarks. Results of a year-long followup are being readied for publication.

Psychological tests and subjects' own reports showed no harm to study participants, though some admitted extreme anxiety or other unpleasant effects in the hours following the psilocybin capsule. The drug has not been observed to be addictive or physically toxic in animal studies or human populations. "In this regard," says Griffiths, a psychopharmacologist, "it contrasts with MDMA (ecstasy), amphetamines or alcohol."

The study isn't the first with psilocybin, the researchers say, though some of the earlier ones, done elsewhere, had notably less rigorous design, were less thorough in measuring outcomes or lacked longer-term follow-up.

In the present work, 36 healthy, well-educated volunteers-most of them middle-aged-with no family history of psychosis or bipolar disorder were selected. All had active spiritual practices. "We thought a familiarity with spiritual practice would give them a framework for interpreting their experiences and that they'd be less likely to be confused or troubled by them," Griffiths says. All gave informed consent to the study approved by Hopkins' institutional review board.

Each of thirty of the subjects attended two separate 8-hour drug sessions, at two month intervals. On one they received psilocybin, on another, methylphenidate (Ritalin), the active placebo.

In designing the study, researchers had to overcome or at least, greatly minimize two hurdles: the risk of adverse side-effects and the likelihood that the expectations of getting the test drug or the placebo would influence subjects' perceptions.

To lessen the former, each subject met several times, before drug sessions began, with a reassuring "monitor," a medical professional experienced in observing drug study participants. Monitors stayed with them during the capsule-taking sessions. Actual trials took place in a room outfitted like a comfortable, slightly upscale living room, with soft music and indirect, non-laboratory lighting. Heart rate and blood pressure were measured throughout.

The researchers countered "expectancy" by having both monitors and subjects "blinded" to what substance would be given. For ethical reasons, subjects were told about hallucinogens' possible effects, butalso learned they could, instead, get other substances-weak or strong-that might change perception or consciousness. Most important, a third "red herring" group of six subjects had two blinded placebo sessions, then were told they'd receive psilocybin at a third. This tactic-questionnaires later verified-kept participants and monitors in the dark at the first two sessions about each capsule's contents.

Nine established questionnaires and a new, specially createdfollowup survey were used to rate experiences at appropriate times in the study. They included those that differentiate effects of psychoactive drugs, that detect altered states of consciousness, that rate mystical experiences and assess changes in outlook.

The study, Griffiths adds, has advanced understanding of hallucinogen abuse.

As for where the work could lead, the team is planning a trial of patients suffering from advanced cancer-related depression or anxiety, following up suggestive research several decades ago. They're also designing studies to test a role for psilocybin in treating drug dependence.

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The study was funded by grants from NIDA and the Council on Spiritual Practices.

Una McCann, M.D., William Richards, Ph.D., of the Johns Hopkins Medical Institutions and Robert Jesse of the Council on Spiritual Practices, San Francisco, were co-researchers.

The commentaries on this study that appear in this issue of Psychopharmacology are available at: http://www.hopkinsmedicine.org/Press_releases/2006/Griffithspsilocybin.html

and include remarks by:

Hopkins neuroscientist and Professor of Neuroscience, Solomon Snyder, M.D.

Former NIDA head Charles Schuster, Ph.D., now Distinguished Professor of Psychiatry and Behavioral Neuroscience at the Wayne State University School of Medicine

Herbert Kleber, M.D., a professor of psychiatry at Columbia University and a former deputy director of the White House Office of National Drug Control Policy (ONDCP)

David Nichols, Ph.D., with the Purdue University School of Pharmacy and Pharmaceutical Sciences

Harriet de Wit, Ph.D., at the University of Chicago Department of Psychiatry. DeWit is the editor of Psychopharmacology.

The following Q&A is with Roland Griffiths, the study's lead researcher.

  • Q 1: Why did you undertake this research?

In the 1950s and 1960s, basic science and applied research studies were taking place with hallucinogens, offering hints that they might be of value in psychotherapy, addiction treatment, and creativity enhancement, and suggestions that the hallucinogens can occasion mystical-type experiences. Laws enacted in response to excesses of the "psychedelic 1960s" stopped almost all that work, leaving some promising threads dangling. Despite ongoing illicit and licit use, remarkably little is known, from the standpoint of modern psychopharmacology research, about the acute and long-term effects of the hallucinogens. Our study is among the first to re-open this field. Since the Hopkins psilocybin work began, researchers at other major universities, such as UCLA, the University of Arizona, and Harvard, have begun planning or are carrying out hallucinogen research.

  • Q 2: Do you have any sign that the same brain "machinery" affected by psilocybin is identical to what people experience in spiritual epiphanies that occur without drugs?

That work hasn't been done yet, though there is good reason to believe that similar mechanisms are at work during profound religious experiences, however they might be occasioned (for example, by fasting, meditation, controlled breathing, sleep deprivation, near death experiences, infectious disease states, or psychoactive substances such as psilocybin). The neurology of religious experience, newly termed neurotheology, is drawing interest as a new frontier of study.

  • Q 3: Is this God in a pill? Does it render God or "revelation" irrelevant?

The scientific method works with what can be observed in the physical realm, using tools such as atomic particle detectors, medical imaging devices, people's responses to psychological tests, interviews, and behavioral observations. We are attempting neither to validate nor to invalidate the truth of claims that some people have made about metaphysical realities as a consequence of their psilocybin experiences (or as a consequence of their meditation, fasting, or prayer experiences) - that's beyond our purview as scientists. It is within the purview of science to study the changes in mood, values, view of self, and behaviors that may follow such experiences.

Of course it would be a profound mistake to confuse the experience of something for the thing itself. We are not aware of study participants who felt their psilocybin experience devalued their own religious traditions; interviews suggested the opposite was more usually the case.

  • Q 4: Are you trying to find a short cut to the spiritual journey that some people pursue for years?

Our focus in this research was to study the effects of psilocybin using the methods of modern psychopharmacology. It's true that "transformative" changes in values, self-perception, and behaviors have been reported across cultures and eras as a consequence of mystical-type experience. This bears investigation.

  • Q 5: Should religions feel threatened by this work?

I can't see why.

The psychologist Walter Clark, in his 1958 book The Psychology of Religion, had this to say: "There is no more difficult word to define than 'religion'…With full recognition that we are on ground where the experts disagree…we will venture our own definition. It is our feeling that religion can be most characteristically described as the inner experience of the individual when he senses a Beyond, especially as evidenced by the effect of this experience on his behavior when he actively attempts to harmonize his life with the Beyond."

Many of the volunteers in our study reported, in one way or another, a direct, personal experience of the "Beyond." Far from being threatened, the only thing we can imagine being of greater interest to religions is whether people live more wholesome, compassionate, and equanimous lives in consequence of such experiences.

  • Q 6: Why did you use volunteers who have active spiritual practices? Didn't that help assure the results you got?

Psilocybin and similar compounds have been reported to sometimes bring about experiences called spiritual, religious, mystical, visionary, revelatory, etc. Such experiences may be difficult psychologically and emotionally. We felt that volunteers who had some engagement with prayer, meditation, churchgoing, or similar activities would be better equipped to understand and consolidate any mystical-type experiences they might have in the study.

  • Q 7: Aren't hallucinogens dangerous? How can you give them to human volunteers?

No mind-affecting drug is absolutely safe. But the risks of the hallucinogens can be managed in appropriate research settings.

Unlike drugs of abuse such as alcohol and cocaine, the classic hallucinogens are not known to be physically toxic and they are virtually non-addictive, so those are not concerns.

The primary effect of psilocybin, in medium to large doses, is strong alteration of consciousness. It is possible that such experiences can trigger latent schizophrenia in susceptible individuals. Thus in our study we disqualified potential volunteers whose personal or family psychiatric histories indicate that they may be at increased risk of that disorder.

Our study confirms that some individuals, during some or all of the hours of the drug's action, may experience paranoia, extreme anxiety, or other unpleasant psychological effects. It is not difficult to imagine such stresses leading to dangerous or inappropriate behaviors, which may constitute the substance's most prominent risk. We managed that in our study through a short course of psychological preparation and through careful and interpersonally sensitive monitoring of each drug session. The monitors were trained to provide reassurance (e.g., supportive words or gentle touch to a hand) if needed.

  • Q 8: What kind of substance is psilocybin?

Psilocybin is one of a class of compounds whose primary activity is known to be on 5-HT-2a/c serotonin receptors. Their effects include changes in perception and cognition. In the pharmacology literature, this class of drugs is called "hallucinogens, " though they rarely cause "hallucinations" in the sense of seeing or hearing things that are not there. Within other academic fields, the term 'entheogen,' roughly meaning "spirit-facilitating," is coming into prominence for this class of substances.

  • Q 9: Studies at Hopkins have shown the potential for brain damage from MDMA ( "ecstasy"). How do you know psilocybin doesn't have the same risk?

Some studies have shown that MDMA can damage certain nerve cells. There is no experimental or clinical evidence in animals or humans that psilocybin, even in very high doses, is similarly neurotoxic. Enough research has been done with psilocybin, starting in the 1950s, that we can be reasonably confident that it is not physically toxic in doses humans ordinarily use. This is consistent with the fact that psilocybin-containing mushrooms have not, in millennia of use, acquired a reputation of being physically harmful. Traditions that use psilocybin mushrooms do, however, caution about psychological and spiritual risks of using them haphazardly.

  • Q 10: Isn't your work similar to what Timothy Leary did?

We are conducting rigorous, systematic research with psilocybin under carefully monitored conditions, a route which Dr. Leary abandoned in the early 1960s.

  • Q 11: Isn't there a risk that a study like this could encourage abuse of psilocybin or similar substances?

Our report explains the substantial risks that could easily follow from use without the psychiatric screening, preparation, and monitoring we provided in this study.

Herbert D. Kleber, M.D., addressed this question in a commentary published concurrently with our paper. Dr. Kleber is Professor of Psychiatry at the Columbia University College of Physicians & Surgeons and the Director of Division on Substance Abuse of the New York State Psychiatric Institute. He previously served as a deputy director of the White House Office of National Drug Control Policy (ONDCP).

Dr. Kleber wrote, "The positive findings of the study cannot help but raise concern in some that it will lead to increased experimenting with these substances by youth in the kind of uncontrolled and unmonitored fashion that produced casualties over the past three decades…

"Any study reporting a positive or useful effect of a drug of abuse raises these same concerns. In this Internet age, however, where youth are deluged with glowing personal reports in chat rooms and web sites as well as detailed information about the various agents and how to use them, it is less likely that a scientific study would move the needle much.

"Psychedelic drug use has remained in a relatively constant range over the past three decades as various fads have come and gone and enthusiastic personal accounts are balanced by negative reports about casualties.

Discovering how these mystical and altered consciousness states arise in the brain could have major therapeutic possibilities, e.g., treatment of intolerable pain, treatment of refractory depression, amelioration of the pain and suffering of the terminally ill, to name but a few, as well as the…needed improvement in treatment of substance abuse…so that it would be scientifically shortsighted not to pursue them."

Huston Smith comments

Huston Smith, holder of 12 honorary degrees, is one of the great authorities on comparative religion. His book The World's Religions has for forty years been the most widely used textbook on its subject, and in 1996 he was the focus of a five part Bill Moyers PBS program, "The Wisdom of Faith with Huston Smith." See hustonsmith.net for more.

Commenting on the Griffiths et al. study, Smith said:

"Mystical experience seems to be as old as humankind, forming the core of many if not all of the great religious traditions. Some ancient cultures, such as classical Greece, and some contemporary small-scale cultures, have made use of psychoactive plants and chemicals to occasion such experiences. But this is the first scientific demonstration in 40 years, and the most rigorous ever, that profound mystical states can be produced safely in the laboratory. The potential is great."

Smith also issued a caution and suggested that further research on the topic include social as well as neurological variables: "In the end, it's altered traits, not altered states, that matter. 'By their fruits shall ye know them.' It's good to learn that volunteers having even this limited experience had lasting benefits. But human history suggests that without a social vessel to hold the wine of revelation, it tends to dribble away. In most cases, even the most extraordinary experiences provide lasting benefits to those who undergo them and people around them only if they become the basis of ongoing work. That's the next research question, it seems to me: What conditions of community and practice best help people to hold on to what comes to them in those moments of revelation, converting it into abiding light in their own lives?"


Last reviewed: By John M. Grohol, Psy.D. on 21 Feb 2009
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Men are not prisoners of fate, but only prisoners of their own minds.
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