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, recently appeared online in the journal Psychopharmacology.
Cited as "landmark" in the commentary by former National Institute on Drug Abuse 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," says Schuster. "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, 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 40 years."
Caution the Keyword
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," according to 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 outside science's realm.
"But establishing the basic science here is necessary," states 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. 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 that their mood, attitudes and behaviors had changed for the better.