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
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, appeared online July 11 in
the journal Psychopharmacology.
Cited as "landmark" in the commentary by Charles
Schuster, former director of the National Institute on Drug
Abuse, 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 said. "Understanding what mediates these
effects is clearly within the realm of neuroscience and
Study leader Roland Griffiths, a professor in the
Psychiatry and Behavioral Biology in the
Johns Hopkins School of Medicine, said, "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. 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 40 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,"
Griffiths said. "Under unmonitored conditions, it's not
hard to imagine those emotions escalating to panic and
The researchers' message isn't just that psilocybin
can produce mystical experiences. "I had a healthy
skepticism going into this," Griffiths said, "and that
finding alone was a surprise." But, as important, he said,
"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 the
realm of science. "But establishing the basic science here
is necessary," Griffiths said, "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 said. "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 that 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 said that subjects likened it to the importance
of the birth of their first child or the death of a
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
yearlong follow-up 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," said 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
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 said. All gave informed consent to the study
approved by Johns Hopkins' institutional review board.
Thirty of the subjects each attended two separate
eight-hour drug sessions, conducted at two-month intervals.
In one, they received psilocybin; in 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 the participants 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 nonlaboratory 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, and they also learned that
they might get other substances — weak or strong
— that could 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-later verified by
questionnaires-kept participants and monitors in the dark
at the first two sessions about each capsule's contents.
Nine established questionnaires and a new specially
created follow-up survey were used to rate experiences at
appropriate times in the study. They included those that
differentiate effects of psychoactive drugs, detect altered
states of consciousness, rate mystical experiences and
assess changes in outlook.
The study, Griffiths said, has advanced the
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
conducted several decades ago. They're also designing
studies to test a role for psilocybin in treating drug
The study was funded by grants from NIDA and the
Council on Spiritual Practices.
Una McCann and William Richards, both of Johns
Hopkins, and Robert Jesse, of the Council on Spiritual
Practices in San Francisco, were co-researchers.
The commentaries on this study that appear in this
issue of Psychopharmacology are available online
here and include
remarks by Solomon Snyder, Distinguished Service Professor
of Neuroscience, Pharmacology and Psychiatry at Johns
Hopkins; former NIDA head Schuster, now Distinguished
Professor of Psychiatry and Behavioral Neuroscience at the
Wayne State University School of Medicine; Herbert Kleber,
professor of psychiatry at Columbia University and a former
deputy director of the White House Office of National Drug
Control Policy; David Nichols, with the Purdue University
School of Pharmacy and Pharmaceutical Sciences; and
Psychopharmacology editor Harriet de Wit, of the
University of Chicago Department of Psychiatry.