Roland Griffiths first tried meditation as a grad student in the early 1970s. He lasted only a few weeks. He wanted to follow the directions, to quiet his mind and stop thinking, but every time the voice in his mind piped up again. Two decades passed before Griffiths gave meditation another shot. Since that first try, he had finished his doctorate in psychology and pharmacology, become a professor at Johns Hopkins, and established himself as one of the foremost researchers on effects of caffeine on the brain. This time, he tried Siddha Yoga, a practice that builds on millennia of Hindu traditions. As Griffiths became accustomed to sitting in silent meditation, he explored the "fantastically interesting" process by which thoughts arise.

We tend to believe, says Griffiths, a tall, skinny man with a mop of wavy white hair, that we are the voice in our heads—the voice that reminds us to floss, that nurses grudges and holds spirited debates on whether to eat the cheesecake: "There's an ongoing dialogue, and very often we think that that dialogue is the mind. But if you sit with the mind, you realize the voice is saying all kinds of stuff and you may or may not agree with everything that it says." Beyond that voice lies something else, Griffiths believes. He describes it as "a sense of clarity and wonder and observational power." That something else—call it consciousness or awareness—is what most fascinates Griffiths. It hovers just beyond the bounds of modern science, not observable on any brain scan.

Roland Griffiths "I'm trained as a scientist and I think science is really powerful. But I also sit with the absolute wonder of not knowing exactly what's going on and wanting to explore that."

Mystics and meditators have probed consciousness for millennia. For the last 17 years, scores of research volunteers in Griffiths' lab have fallen into these states after taking psilocybin—the compound that gives certain mushrooms their magic. His experiments have shown startling results. Participants shake off persistent depression, quit smoking after decades of failed attempts, and even, in the case of people facing life-threatening cancers, transcend the fear of death—raising hopes that psilocybin might receive FDA approval as a treatment for some mental health conditions.

Ultimately, Griffiths believes, these experiments provide insight into the nature of consciousness. "We get so lost in the stories of our lives that we sometimes forget what an incredible thing it is to be aware," says Griffiths, his pale blue eyes intense behind wire-rimmed glasses. He's sitting in his office in the Behavioral Biology Research Center, a bland brick structure on the Johns Hopkins Bayview campus. The walls are decorated with vintage Coca-Cola ads, an old art poster of hands balancing coffee cups, and yellowed paintings that his children created decades ago. On a filing cabinet sits a model of a clump of hallucinogenic psilocybe mushrooms—slim, dun-colored stalks with pointed caps.

Down the hall, in a section of Griffiths' lab outfitted with comfy couches and embroidered pillows, scores of people have spent some of the most profound hours of their lives. Participants swallow a capsule of psilocybin and plunge into hours of singular intensity, accompanied by specially trained guides who monitor them and help them feel safe and nurtured, Griffiths says. The volunteers report visions of lofty cathedrals and dense jungles and loved ones long dead. They have relived moments from their past, as if unscrewing a series of jars containing forgotten days. The experience ripples through them in the months and years to come. They report feeling more open and creative, more caring toward others, and aware of the interconnectedness of all life.

These are also the gifts of meditation, says Griffiths, who continues to meditate for as long as two hours each day. Meditation enables you to shift your identity, he says, to reshape your sense of self. For him, that has meant letting go of focusing on material accomplishments and professional recognition. A former confirmation class dropout, he has developed a sense of spirituality. After decades spent examining the effects of various substances such as caffeine on the brain, now he wants to delve into the questions of consciousness that most interest him.

Psilocybin offers a sort of "crash course" in the nature of the mind, Griffiths says. "Literally a crash course, because it can go off the rails." Without the proper preparation, environment, or companions, a person is at more risk to have a bad trip and be overwhelmed by fear or negative emotions. But under the right conditions, psilocybin has the power to change lives. "I'm trained as a scientist and I think science is really powerful," says Griffiths. "But I also sit with the absolute wonder of not knowing exactly what's going on and wanting to explore that."

In his encyclopedic book, Shroom: A Cultural History of the Magic Mushroom (Ecco, 2007), Andy Letcher describes how mind-altering mushrooms first captured the imagination of Europeans in the 18th century, when explorers described encounters with Siberian tribespeople who became intoxicated after eating fly agaric mushrooms. With their cheery red caps and white spots, this particular fungus became an enduring cultural trope—the preferred seat of garden gnomes and children's book fairies. If asked to draw a mushroom, many of us would likely draw a fly agaric, although few have seen a real one.

Sixteenth-century Spanish conquistadors and missionaries described Aztecs consuming the other main category of hallucinogenic mushrooms, psilocybes, at coronations, dances, and feasts. Aztec priests ate them to divine the outcome of battles. But the Roman Catholic church saw the use of mushrooms as a form of idolatry, so for the following four centuries the use of psilocybes in Mexico was driven underground.

That changed in the mid-1950s when American banker and amateur mushroom expert R. Gordon Wasson, his pediatrician wife, and a photographer traveled to the tiny village of Huautla de Jiménez in Oaxaca. There they met a Mazatec Indian healer named María Sabina who invited them to take part in a ceremony involving psilocybe mushrooms. Like other Mazatec curanderos, María Sabina used mushrooms to produce visions in which she would determine the nature of a person's illness and a cure. Wasson described the experience in a breathless 1957 Life magazine article. "There I was, poised in space, a disembodied eye, invisible, incorporeal, seeing but not seen," Wasson wrote. The visions were "sharply focused, the lines and colors being so sharp that they seemed more real to me than anything I had ever seen with my own eyes. I felt that I was now seeing plain, whereas ordinary vision gives us an imperfect view; I was seeing the archetypes, the Platonic ideas, that underlie the imperfect images of everyday life."

Wasson's article sparked intense interest. Beatniks and curiosity seekers traveled to Oaxaca to swallow mushrooms. The psilocybin craze fed into the burgeoning field of psychedelics research. Between 1953 and 1973, more than 1,000 studies on psychedelics were launched, many funded by the federal government. The results were intriguing, though, in hindsight, the experiments lacked the rigor of modern standards, says David Nichols, a Purdue University psychopharmacology professor emeritus. One of the first researchers to study psilocybin was Harvard psychologist Timothy Leary, later known for his flamboyant use of LSD and for exhorting a generation to "turn on, tune in, and drop out." Psychedelics soon became associated with—and blamed for—much of the '60s youth culture: free love, anti-war protests, even the Charles Manson murders. Politicians, members of the clergy, and worried parents considered them a threat to traditional values. In October 1970, Richard Nixon curtailed research on hallucinogens for two decades when he signed the Comprehensive Drug Abuse Prevention and Control Act, outlawing psilocybin, LSD, and other hallucinogens.

That did not deter some prominent scholars, including Nichols, from their interest in the compounds. In 1993, Nichols founded the Heffter Research Institute to advocate and provide funding for psilocybin research. "I thought it would really be useful to go back and study this class of drugs and see if they had any value or not," Nichols says. "Of course scientists had always been interested because these drugs had such fundamental effects on the human mind, but the problem was the funding and some of the institutions."

Video credit: TEDMed

Meanwhile, in California, software engineer Robert Jesse, Engr '81, organized a separate push to expand the understanding of what he calls entheogens, or chemicals that help people experience the divine. Jesse had moved to the Bay Area after graduating from Johns Hopkins. There he discovered that many in the tech industry used hallucinogens, believing they spurred creativity and deepened self-awareness and empathy. Jesse became convinced that making these drugs more widely available could improve the lives of not only those who took them but, by extension, their neighbors, relatives, and co-workers. He formed an organization called the Council on Spiritual Practices and convened a gathering of "experts and elders" in the field at Esalen, the retreat center in Big Sur, California. On a whim, he invited Robert Schuster, who headed the National Institute on Drug Abuse under two Republican presidents. To his surprise, Schuster came, and even had a profound experience of his own—not through hallucinogens but a shamanic drumming workshop.

A couple of weeks later, Schuster, who died in 2011, introduced Jesse to an old friend of his—Roland Griffiths. He was "a scientist's scientist," Schuster said, and had a storied career researching drug effects as well as an interest in meditation and altered states of mind. Jesse struck up a correspondence with Griffiths and flew to meet with him in early 1997. Over a lengthy lunch at a cafeteria at Bayview, they discussed meditation, states of consciousness, and psilocybin.

Griffiths was skeptical. Although he had come of age in San Francisco in the late 1960s, he had never identified with the hippie movement or had much interest in using drugs himself. He knew that many people thought they had profound experiences while tripping, but he doubted the lasting impact. "I was suspicious about some of the claims people were making," he says. Yet he was intrigued by the possibility of using the drugs to study spiritual experiences. He had been reading books on comparative religion and the psychology of religion, trying to comprehend his own experiences while meditating. Perhaps these drugs could provide some insight in the lab.

There were risks to his career. Griffiths recalls mentioning the possibility of launching such a study to a working group of other professors in the department. Some nodded with interest, but others looked aghast. Still, Griffiths drew up a protocol and sent it off for review, wondering if there was any chance it would be approved. It was. And then there was the question of funding, which remains a struggle for research in hallucinogens. Griffiths secured some support from NIDA, but Jesse's nonprofit, the Council on Spiritual Practices, covered much of the expense.

Griffiths launched that first study in 2000, after teaming up with Bill Richards, a Baltimore therapist who had been on the vanguard of hallucinogen research in the 1980s. They used funds from the Council on Spiritual Practices to transform a section of Griffiths' lab into what looks rather like a hip therapist's office. The focal point is a long white couch, where participants recline during the sessions. The guides sit in a pair of leather chairs. Relics from various cultures and faith traditions decorate the room—a blue-and-gold mandala, a statue of the Buddha, a brightly beaded mask. On one table sits an earthenware chalice that Jesse brought back from Huautla de Jiménez, the town where Wasson first took psilocybin. Participants pluck a capsule of psilocybin from this chalice and the session begins.

Many psilocybin study participants report the classic hallmarks of a mystical experience, including a feeling of sacredness, interconnectedness, and a sense that the drug trip is more real than everyday life.

In that first study, 36 healthy normal volunteers who had never taken a hallucinogen before ingested either psilocybin or Ritalin in a series of three sessions (each participant took psilocybin at least once). It was a double-blind experiment, so neither the volunteers nor their guides knew which drug they had taken. Since Ritalin produces psychological effects—a sense of well-being and a rush of energy—it is useful for masking who were the control subjects. The results of the study were striking. Two months after the sessions, the majority of those who had taken psilocybin reported feeling better about themselves and about life, being more altruistic, and having an overall improved mood. Nearly two-thirds said that the session was one of the most meaningful experiences of their lives, ranking with the birth of a child or the death of a parent, and a third said it was the single most spiritually significant thing that had ever happened to them. "That was hugely impressive to me," says Griffiths. "What was going on here?"

So he pursued answers. Since that first study, Griffiths has launched more than a dozen studies on psilocybin and seven more on other hallucinogens. One found that 80 percent of chronic smokers managed to kick the habit after a combination of psilocybin and cognitive behavioral therapy. Another showed that taking psilocybin correlated with increased openness—a psychological trait associated with creativity and appreciating the arts—for at least a year.

Late last year, Griffiths and a team from the New York University School of Medicine published the data from two similar but independent studies on people facing life-threatening cancer. After receiving a single dose of psilocybin in tandem with counseling, 80 percent of patients reported feeling their depression and anxiety recede. The results were not fleeting: Six months later, the majority still had improved moods despite their health problems. Many reported feeling as if the psilocybin session had erased their fear of death. "To see a person have an incredibly meaningful, meaning-making, and spiritual experience that changes how they view death, that recalibrates how they die—it's hard to describe," says Anthony Bossis, a psychologist who worked on the NYU study.

Clark Martin, a retired psychologist from Portland, Oregon, enrolled in Griffiths' cancer study in 2010, two decades after he was first diagnosed with renal cell cancer. Since his diagnosis, he has undergone numerous rounds of surgery, chemotherapy, radiation, and immunotherapy as metastases have recurred again and again.

The years of fear and pain took a toll, Martin says. He became "myopically focused" on the cancer, closed off to the pleasures of everyday life. In his first session, he received a low dose of psilocybin, which he says had little effect. But at his second session, he felt reality dissolve. He lost all sense of time. He could sense his guides talking but couldn't tell what they were saying. It all felt, he says, too much like how he imagined death, and it was terrifying.

Then, one of his guides sat down next to Martin and wordlessly put an arm around him. Martin's fear melted away and he felt himself in a "formless void kind of space." It was familiar and comfortable, and Martin felt like a child exploring a new place, full of curiosity and wonder. Unlike many people who take psilocybin, Martin did not see visions or hear voices talking to him. But the experience fundamentally changed him. "My approach to life used to be very cerebral," he says. "Now I come from a place of mindfulness."

A few years after taking part in the experiment, Martin had a profound experience of nature. He was visiting Hawaii, hiking in the mountains early one morning when he was struck by the sound of leaves rustling in the wind. It occurred to him that the air pushing the leaves is no different from the air moving across the human larynx. He felt a deep sense of kinship with the trees and with nature. A couple of years later, he had a similar experience while hiking the Oregon coast. Now this sense of unity with nature sweeps over him more frequently. He also swims laps several times a week—the repetitive motion helps him dip into the deeply meditative state he first experienced through psilocybin.

The heightened sense of altruism and interconnectedness one experiences after taking psilocybin in the right conditions could help our society and the world, Griffiths says.

Martin says he has grown to be more emotionally available to his family. He ruminates on the moment when his counselor put his arm around him on the couch, reassuring him simply with his presence. He has reached the conclusion that presence—just being there for someone—is even more important than empathy, and this guides his interactions with relatives and friends. He talks to his adult daughter in Texas frequently and visits her with no particular goal other than sharing time together. His father died from Alzheimer's a few years ago, but, before that, Martin learned to let all expectations fall away from their interactions. When his dad didn't respond to him, Martin wouldn't be sad or angry. Instead, he would drive his father through the countryside, stopping to gaze at deer or eat ice cream. With the pressure gone, his dad "brightened up and became more animated," he says. "In a paradoxical way, our relationship in the final years was deeper and more meaningful that it had ever been."

So how does psilocybin produce these powerful transformations? "We know quite a bit, but there's a lot we don't know," says Griffiths. Like other classic hallucinogens, psilocybin acts on receptors for the neurotransmitter serotonin. It appears to reduce activity in certain neural networks, most notably one that is responsible for the sense of self. Psilocybin also appears to accelerate the speed with which the brain makes connections, Griffiths says.

Many psilocybin study participants report the classic hallmarks of a mystical experience, including a feeling of sacredness, interconnectedness, and a sense that the drug trip is more real than everyday life, Griffiths says. He believes the brain is wired to have such experiences. From the poet Rumi to St. Thérèse, people across time and cultures have experienced these flashes of the divine. In most cases, the experiences occur spontaneously, say when a person is walking in the woods or praying. "Humans are wired for meaning, and I think that is at the core of religions and philosophies and traditions," says Bossis. The two are also working on a pair of studies looking at the effects of psilocybin on clergy, a group of people who have trained their brains to be open to such experiences.

The big question—and perhaps this is beyond the realm of science—is what do these experiences mean? Are people really tapping into a deeper reality? "There's no question they feel like they are," Griffiths says. "It goes beyond anything I have a ready explanation for, philosophically or scientifically." So—does he believe in God? Griffiths stammers. "I don't even know how to answer that question," he says. "I've become comfortable with God as a placeholder for the benevolent mystery for which there are no words, and I think that's what people must mean by God."

And has he taken psilocybin himself? Griffiths won't say. There's a group of people who feel that it would be unethical for a researcher in hallucinogens to dose volunteers with a substance he had never tried, he says. And yet there are others who feel that he would lose his impartiality if he experimented with the drug on himself. "What I can say is I'm familiar with different states of consciousness," he says. "I have a deep empathy for people in different states of consciousness."

In addition to the studies on meditators and clergy, Griffiths' lab has launched larger studies with smokers and people with depression. Griffiths is also gearing up for a new project that will involve taking brain scans of healthy, normal people before and after psilocybin, to help better understand the drug's effects.

Griffiths is hopeful that his work will eventually pave the way for people with life-threatening cancer to receive psilocybin as a treatment for anxiety or depression. Perhaps one day the drug could be prescribed to healthy patients with mood disorders as well. In either case, Griffiths believes the drug is most effective when administered in a clinical setting, under the guidance of a counselor, much as it is in his lab. Yet it's hard to imagine the drug making it to market. How would a pharmaceutical company make money from something that people take one dose of, once, but that has life-changing effects?

Ultimately, Griffiths says he feels a great sense of fulfillment in leading research that is "a remarkable integration of what I'm most interested in personally and professionally." He believes, too, that his work can improve humanity. The heightened sense of altruism and interconnectedness one experiences after taking psilocybin in the right conditions could help our society and the world, he says. "There's an argument to be made that we need to act on that immediately," he says.

In a drawer of his desk, Griffiths keeps a stash of medallions he had made to give to volunteers and visitors. One side, marked "Meditation," is emblazoned with these words by the mystic poet William Blake: "The true method of knowledge is experiment." The other side shows a cluster of psilocybe mushrooms—a symbol, he says, that meditation and the psilocybin represent two sides of the same coin. Under the mushrooms is printed Griffiths' own blessing: "May you remain aware of awareness."