A woman being treated for cancer enters a quiet, comfortable room. She pulls a mask over her eyes, lies back on a couch and begins listening to soothing instrumental music. A psychologist sits nearby, but this isn't your typical psychotherapy session. The woman has just swallowed a pill containing psilocybin, the hallucinogenic compound in so-called magic mushrooms. The drug is intended to induce a mystical experience: a sense of profound interconnectedness with people and the world, and feelings of the sacredness of the experience. If all goes as planned, that experience will help her move beyond the existential distress associated with her cancer diagnosis.
It might sound like an underground experiment, but sessions like this are being conducted at institutions such as New York University (NYU) and the Johns Hopkins University School of Medicine. They're part of a series of rigorous, double-blind clinical trials to explore the therapeutic value of this once-maligned drug. The research is still in its early stages, but so far the results suggest that even a single session with psilocybin can generate meaningful, spiritual experiences that ease the anxiety and distress that often accompany a cancer diagnosis.
"We don't deal well with death and dying in this culture," says Roland Griffiths, PhD, a professor of behavioral biology and neuroscience at the Johns Hopkins University School of Medicine. Being diagnosed with a potentially fatal disease often leads to a kind of chronic syndrome of anxiety, depression and emotional distress. "But under appropriate conditions in well-prepared participants, psilocybin can produce these really quite profound and abrupt shifts in mood and attitude and behavior, even after a single session," he says. "It's unlike anything available within psychiatry."
A fresh look
Though the current wave of research began only about a decade ago, psilocybin is anything but new. For centuries, indigenous groups in the Americas have used the compound, which naturally occurs in many species of mushrooms, for ceremonial and healing purposes. Nor is its use in Western medicine new. In the 1950s and 1960s, scientists explored the use of psilocybin and other hallucinogens, including mescaline and LSD, to treat clinical conditions such as addiction, post-traumatic stress and end-of-life distress.
But after Congress passed the Controlled Substances Act in 1970, psilocybin research in the United States came to a halt until the early 2000s, when the Food and Drug Administration (FDA) cautiously began allowing a new wave of research into the drug.
In 2006, Griffiths and colleagues published the results of their first psilocybin study. The team recruited 36 healthy volunteers who had never before taken a hallucinogenic drug. The double-blind protocol involved two sessions, one with psilocybin and another with an active placebo (methylphenidate, or Ritalin). Following psilocybin trials, most volunteers reported having had mystical-type experiences that, two months later, continued to have significant personal meaning. Participants also reported positive changes in attitudes and behaviors. And those beneficial changes were confirmed by ratings from the participants' friends, family and work colleagues (Psychopharmacologyopens in new window, 2006).
In a follow-up study 14 months after participants took psilocybin, 58 percent of the participants rated the experience as one of the five most personally meaningful experiences of their lives. Nearly two-thirds said the psilocybin session had increased their well-being or life satisfaction (Journal of Psychopharmacologyopens in new window, 2008). The team has since conducted several additional studies confirming and extending the findings in healthy volunteers.
That initial research at Johns Hopkins opened the doors for scientists to begin testing psilocybin's therapeutic value. In 2011, Charles Grob, MD, and colleagues at Harbor-UCLA Medical Center published the result of a small pilot study demonstrating the drug's potential for reducing anxiety in cancer patients (JAMA Psychiatry, 2011).
Larger studies, using higher doses of the drug, have recently been completed at NYU and Johns Hopkins and the results are being prepared for publication. Those studies investigated the drug's effect on anxiety and depression, as well as measures such as spirituality, quality of life and existential distress.
Patients grappling with a potentially fatal cancer diagnosis often suffer such distress, says Anthony Bossis, PhD, a psychologist specializing in palliative care and one of the lead investigators of the NYU trial. "We've gotten better at targeted chemotherapies and pain control, but there's really a paucity of approaches to address end-of-life distress and existential suffering," he says.
Such distress can affect treatment adherence, decrease quality of life and increase suicidal thinking, adds Griffiths. Cancer patients experiencing anxiety, depression and distress are "an at-risk population for which we don't have good treatments, either pharmacological or psychological," he says.
Existential wonder
Griffiths, Bossis and their colleagues hope psilocybin could address that treatment gap. To test that possibility, they've designed their studies in cancer patients to be double-blind and methodologically rigorous. Volunteers in the trials each participated in two blinded sessions, receiving an active placebo in one and psilocybin in the other. In several meetings before and after the trials, volunteers met with a therapist who helped them establish expectations and discuss the feelings and emotions stirred up by the psychedelic session. That therapist was also present to guide and help volunteers, if necessary, during the drug sessions.
The researchers say patients have described impressive transformations.
"As soon as [the psilocybin] started working, I knew I had nothing to be afraid of," one volunteer said after a session. "I thought about being involved with people I loved, things I would do with people I knew, things I would tell them. … It reconnected me to the universe."
Another said, "I emerged from that first session … having an extremely strong sense of self and the importance of me, and my relationship to everything around me. I came out of this feeling assured. … I just knew everything was going to be OK. The study has changed everything in my life. I am more patient. I am more thoughtful. … I am present."
Although psilocybin is technically a hallucinogen, visual hallucinations are not necessarily a hallmark of the experience, Bossis says. Some volunteers reported seeing images such as landscapes, celestial scenes or childhood memories — but the transformative nature of the experience seems to have more to do with insight than with eyesight.
While there is variety in people's individual experiences with the drug, volunteers often walk away having similar changes in outlook. Anxiety surrounding death is decreased, while spirituality, altruism and a sense of meaning tend to increase.
"My sense is that these experiences open people up to a sense of existential wonder. The fear starts dissolving," Griffiths says.
And encouragingly, he says, those positive changes appear to last for months — after just a single session.
Other research groups have begun exploring the effects of psilocybin in the brain using fMRI. A team at Oxford University, for instance, found the drug decreased activity and connectivity in hub regions of the brain such as the anterior cingulate cortex and the medial prefrontal cortex, thus allowing "unconstrained" cognition (PNAS, 2011).
But one unique aspect of psilocybin is that it doesn't appear to create lasting changes in brain structure or function. Unlike medications such as antidepressants, psilocybin doesn't remain in the body, and it has no lasting neurochemical effects.
"It's the experience that changes the person, not the drug," says Jeffrey Guss, MD, another lead investigator of the NYU psilocybin project.
Still, the drugs are not risk-free. So far, volunteers have been carefully screened to exclude anyone with a vulnerability to psychiatric illness. Griffiths says he has not witnessed lasting adverse effects in any of the almost 250 volunteers his team has studied over the last decade. But in a survey of recreational psilocybin users, some respondents reported persistent anxiety or other negative psychiatric effects, he says. Of course, it's impossible to verify what dose survey respondents swallowed — or even if they actually took psilocybin versus another substance. Yet the findings underscore the need for more research to determine whether some people might be at increased risk of such negative reactions.
While the long-term benefits of psilocybin seem to be positive, the sessions themselves are not always pleasant. "There can be anxiety during the experience. Like any therapy session, it can bring up a lot," Bossis says. But the therapists in the room can help volunteers deal with — and learn from — those unpleasant feelings.
"Sometimes anxiety and fear experiences open up into experiences of insight and transformation," Griffiths adds.
Indeed, the researchers say that having a trained therapist present is key to the protocol. It can be unwise to try the drug without guidance, says Guss. While the drug itself is not dangerous to the body, he says, it can certainly alter perception in ways that could be risky — if, for example, someone is so inwardly focused that he or she wanders into oncoming traffic.
Therapists also help volunteers frame the experience in a therapeutic way. "If a person took the drug and went to a rave and danced all night, they might have a fun, intense and even meaningful experience, but not necessarily a therapeutic or transformative experience," says Guss. "In my opinion, the best and safest way to use psychedelics is to take wisdom from the shamanic model used around the world, where an experienced guide and valued healer in the community administers the drug to a person who is suffering, stays with them and helps them interpret its effects afterward."
Out of the deep freeze
If the results of the recently completed trials are as positive as the investigators anticipate, they hope to follow them up with a Phase 3 trial to demonstrate psilocybin's efficacy in a much larger number of patients, says Griffiths. Ultimately, he and his colleagues hope that if the evidence supports its safety and effectiveness, the FDA will consider removing psilocybin from Schedule 1, making it available for medical purposes.
Elsewhere, scientists are beginning to explore the therapeutic role of other psychedelics, such as LSD and ayahuasca. The researchers at Johns Hopkins and NYU have chosen to focus on psilocybin for now because it has "less cultural baggage than LSD," says Bossis. "It's shorter acting, easier to manage in a lab setting and is a natural compound that has been used a long time in indigenous cultures." He hopes those characteristics — combined with positive results from rigorous studies — will be enough to earn public support for psilocybin-assisted therapy.
Meanwhile, researchers are beginning to consider how psilocybin-assisted therapy might be used to treat a range of other conditions. "There's no reason this should be restricted to cancer in the end," Griffiths says.
In a small pilot study, Matthew W. Johnson, PhD, at Johns Hopkins, along with Griffiths and colleagues, demonstrated that the drug has promise for tobacco smoking cessation (Journal of Psychopharmacologyopens in new window, 2014). Meanwhile, researchers at NYU and the University of New Mexico are exploring whether psilocybin-assisted therapy could be used as treatment for alcoholism.
Though the research still needs to be done, cautions Griffiths, the list of possible therapeutic uses for the drug is long. "These drugs have been unavailable for clinical research for decades — put in the deep freeze while science kept moving on," he says. "Now all of a sudden we can use them again, and use them safely. There are so many different directions in which to go."