SALT LAKE CITY — On an early morning in July 2013, Octavian Mihai walked into a room in the New York University School of Medicine. Soft music was playing. He was greeted by two trained therapists who, after several prior sessions with him, had said his anxiety was “off the charts.”
Mihai was there to take “magic mushrooms.”
He was part of a clinical trial testing whether psilocybin, the psychedelic compound produced by a group of mushrooms, might be an effective treatment for cancer patients with severe anxiety and depression.
The therapists brought Mihai a synthetic psilocybin pill. Before taking it, Mihai joined hands with the therapists and set an intention for the eight-hour “trip” he was about to embark on: Eradicate his anxiety.
He swallowed the pill, laid down on the couch, slipped on a pair of headphones to listen to music. He flipped through a book containing images of mountains and peaceful landscapes. Eventually, he put eyeshades over his eyes. He didn’t feel much of anything for the first 45 minutes.
And then he felt like he was floating above his own body.
He saw himself lying prone on a stretcher in the entrance of the New York hospital where he had recently undergone chemotherapy. Diagnosed with stage three Hodgkin’s lymphoma cancer at age 21, the disease had invaded every part of his body except for his bone marrow. As he watched, black smoke suddenly began to pour out of him.
Mihai understood that the black smoke represented the cancer leaving his body. Technically, he had been cured of the disease in May 2013, within six months of his diagnosis, but he had been plagued ever since by debilitating anxiety that the cancer would return. This resulted in him obsessively touching his lymph nodes, trying to detect cancerous lumps. Now, two months after his remission, Mihai swooped in closer to his body and examined his lymph nodes. The fluid within them was clear.
“I realized that I had been cured physically in the hospital, but not yet psychologically,” Mihai, 28, said. “And I understood, ‘This is a moment where I’m going to cure myself psychologically so I’m completely done.’”
Will this become a new and effective treatment for anxiety and depression?
Some academics and health professionals argue that caution is needed. Keith Humphreys, a professor of psychiatry and behavioral sciences at Stanford University, said it’s possible that the medicinal properties of psychedelics have been “oversold,” because so far they’ve only been tested in “highly controlled trials” and administered by “highly trained” professionals who are enthusiastic about the drugs’ potential.
Other experts point out that much remains unknown about psychedelic drugs, including their safety and effectiveness in large, diverse groups of people; their optimal dosage size; and the risk of having a bad trip or incurring psychosis.
With a few cities and states already moving to decriminalize “magic mushrooms,” psilocybin is emerging as the next drug battleground — medically, politically and culturally. And with the potential for big money to influence the process, can the country learn from its experience with marijuana to find a good result?
‘Psychedelic renaissance’
Long associated with the “Summer of Love” and 1960s and 70s fringe culture, psilocybin and other psychedelic drugs — when paired with psychotherapy, and when taken in the company of trained therapists — are now emerging as potential treatments for afflictions ranging from depression to alcohol dependence to obsessive-compulsive disorder. Researchers are conducting clinical trials of psychedelic therapy at some of the United States’ most prestigious universities, including Johns Hopkins University, Yale University, New York University and the University of California, Los Angeles.
Results have been promising. The randomized controlled study in which Mihai participated found that after just one psilocybin treatment paired with psychotherapy, 80 percent of the 29 patients experienced significant relief from previously crushing anxiety and depression. The relief was both immediate — setting in soon after the psilocybin trip — and enduring, lasting longer than six months for many of the patients. Various other studies, including a study of 51 patients at Johns Hopkins, have corroborated these results.
This is a big change when compared to antidepressants and anti-anxiety medication, which generally have to be taken every day and whose effects don’t kick in for around six to eight weeks, according to medical literature.
With the caution to go slowly and learn more about “bad trips,” key institutions are moving forward. The Food and Drug Administration has granted “breakthrough therapy” status to psilocybin-assisted psychotherapy for treatment-resistant depression and to MDMA-assisted psychotherapy for post-traumatic stress disorder. (MDMA, often referred to as “ecstasy,” is a synthetic drug with psychoactive properties, but is not technically considered a psychedelic drug.) This means the FDA will expedite the drugs’ development and review process because clinical evidence has shown they may be a substantial improvement over existing therapies.
A “psychedelic renaissance” is also taking place in the public imagination. On May 7, residents of Denver, Colorado, voted to decriminalize the personal use and possession of “magic mushrooms.” The city of Oakland, California, followed suit on June 5 with a unanimous vote to decriminalize psychedelic mushrooms and other psychoactive plants and fungi. Republican Rep. Jeff Shipley recently introduced two bills to decriminalize psychedelic drugs in Iowa. And in 2020, residents of Oregon will vote on a ballot measure that would legalize a psilocybin therapist industry, while also lowering criminal penalties for growing or consuming mushrooms.
On June 7, Rep. Alexandria Ocasio-Cortez, D-New York, filed a legislative amendment to make it easier for scientists to use federal funds to study the medical properties of psychedelic drugs. (Under current law, federal funds can’t be used to research Schedule 1 drugs.) The amendment was soundly defeated, but the following week the heads of the FDA and the National Institutes of Health released a letter stating that psychotropic substances such as psilocybin, LSD, MDMA, ketamine and ibogaine have the potential to shed light on “mechanisms of illness and possible interventions, ultimately leading to novel treatments with fewer side effects and lower abuse potential.”
Before taking psilocybin, Mihai had used Xanax to treat his anxiety, but found it ineffective.
“It was just silencing the symptoms temporarily, not actually curing my anxiety or addressing the cause,” he said.
But Mihai said his psilocybin trip changed everything.
“I no longer have anxiety about cancer, or more generally death,” Mihai said. “I’m more concerned with life and living my life.”
Treating depression
Psilocybin’s potential to treat anxiety and depression comes at a time when Americans are beginning to view antidepressants and anti-anxiety medications in a drastically different light.
Recent publications, including the 2018 book “Blue Dreams: The Science and the Story of the Drugs That Changed Our Minds” by psychologist and writer Lauren Slater, have shown that current antidepressants are not very effective and little is known about their long-term side effects.
Slater points out that in the 47 clinical trials of America’s six major antidepressants — Celexa, Effexor, Paxil, Prozac, Serzone, and Zoloft — the drugs only outperformed the placebo in 20 cases, or less than half the time. The average patient improved by only two points more on the drugs than on the placebo, and the drugs didn’t work at all for 30 percent of patients.
“We have no idea what anti-anxiety medications or antidepressants do to people over (the course of) 30 to 40 years,” said Jonathan Moreno, a professor of medical ethics and health policy at the University of Pennsylvania’s Perelman School of Medicine. “It’s a massive public health experiment.”
Depression has proven a difficult disease to tamp down — let alone cure — even when attacked from numerous angles. The World Health Organization estimates there are more than 300 million people with depression worldwide, and studies have shown about one-third experience treatment-resistant depression. Depression is also the most costly of mental health and substance abuse disorders — in 2013, the U.S. spent $71 billion on depression-related treatments, according to the American Psychological Association.
Slater and a slew of other mental health professionals, doctors, and academics, argue that psychedelic drugs could change the status quo.
It’s revolutionary that depressed and anxious cancer patients only took one dose of psilocybin in conjunction with psychotherapy and felt better for months afterward, said George Greer, medical director of the Heffter Research Institute, a nonprofit that has supported and reviewed seminal psilocybin research.
The FDA has taken note. On March 5, the agency approved esketamine — a drug derived from the psychedelic substance ketamine — to be used with an oral antidepressant for patients who experience treatment-resistant depression.
Like psilocybin, esketamine has been celebrated for its ability to provide depressed patients with relief merely hours after ingestion. However, it’s not entirely clear how effective the drug is. As The New York Times reported, the results of the esketamine clinical trials — which were paid for and run by Janssen Pharmaceuticals Inc., the drug’s developer — were “mixed.” Patients who took esketamine statistically performed better than those who took the placebo in only one of three short-term trials. Typically, the FDA requires that a drug outperform placebo in two out of three trials in order to be approved.
This raises the question: Are Americans, in their desire and desperation to find more effective treatments for depression and other afflictions, jumping on the psychedelics train before knowing quite where it’s headed? Will this result in its own bad trip?
How does psychedelic therapy work?
Mihai took psilocybin in the company of two trained therapists from the NYU School of Medicine with whom he had worked in prior sessions. The therapists gave him “flight instructions” to help him prepare for the trip, helped him set an intention for the trip, and sat by his side and monitored him for its duration. Afterward, they helped him process the experience in what’s called an integration session.
Psilocybin-assisted psychotherapy differs from the recreational use of psilocybin in several key ways, Greer said. First, at-risk patients — those with heart problems, high blood pressure, schizophrenia, psychosis, or a predilection to manic episodes — are screened out. Second, patients are accompanied by therapists, both for their own safety and to reap the psychological benefits of the experience by talking about it in a series of therapy sessions.
“Nobody says the drug by itself does it. It’s the drug combined with a very specific protocol: therapist accompaniment and integration,” said Michael Pollan, a professor of journalism at Harvard and the University of California, Berkeley, and author of the 2018 book “How to Change Your Mind: What the New Science of Psychedelics Teaches Us About Consciousness, Dying, Addiction, Depression, and Transcendence.”
The precise mechanism by which psilocybin affects the brain is still unclear, but studies have shown that it leaves a long-lasting impression on patients.
In a landmark 2006 psilocybin study led by Roland Griffiths, a professor of psychiatry and neurosciences at Johns Hopkins University, two-thirds of participants said the psilocybin session was one of the top five “most spiritually significant experiences” of their lives, and the remaining one-third said it was the most spiritually significant experience of their lives. Similar results have since been found in more recent studies, including one published April 23 in the scientific journal PLOS One.
After taking the drug, Mihai said he “realized that people have debilitating psychological problems — they are trapped within themselves because their mind is terrorizing them. And then I had an epiphany: Why would I let my mind terrorize me? I can choose to get away from it, move away from it. I don’t have to be under this crazy pressure and anxiety. All of a sudden, something changed.”
The unique psychological experience occasioned by psilocybin, experts say, can help the mind escape negative feedback loops, giving patients new perspectives on life and creating healthier paths and frameworks for thinking.
“What is striking about this whole line of clinical research is the premise that it is not the pharmacological effect of the drug itself but the kind of mental experience it occasions — involving the temporary dissolution of one’s ego — that may be the key to changing one’s mind,” Pollan writes.
Can society handle the drug?
As psychedelics progress toward medicalization, questions have been raised about what role these drugs would play in society and how accessible they would be.
If the FDA were to approve psilocybin and MDMA, they would likely be reclassified as Schedule 2 substances, or drugs “that are approved for therapeutic use but have a high potential for abuse,” said Alan Kirschenbaum, an attorney at Washington, D.C.-based FDA law firm Hyman, Phelps & McNamara, P.C.
Kirschenbaum added that the FDA would also likely impose a Risk Evaluation and Mitigation Strategy on psychedelics that might involve restricting distribution to a certain pharmacy, requiring prescribing physicians and patients to enroll in the program, and requiring the patient to attend therapy sessions. (This strategy was implemented for esketamine.)
Access has also been a point of contention. Psilocybin- and MDMA-assisted psychotherapy are expected to be high-cost treatments, largely because of the amount of psychotherapy involved.
“Eventually,” said Greer of the Heffter Research Institute, “insurance companies will realize that when people with depression go the hospital, it costs them tens of thousands of dollars and it’s worth it for them to pay for psilocybin treatments because it saves money in the long run. But it will take time for that to happen.”
Tracy Cheung, director of communications for Compass Pathways, a British company conducting the largest clinical trial of psilocybin to date in a phase 2B study, said that Compass is already in talks with payers, insurers, and regulators to figure out a realistic insurance model for psilocybin-assisted psychotherapy.
For some in the medical and academic communities, however, wider access to psychedelics, even when regulated, poses concerns.
Once a drug is approved and “it goes out into the wild, risk goes up enormously,” Humphreys, of Stanford University, said. He added that he doubts all therapists who would supervise patients during their trips would have the same level of training as those currently supervising patients at universities like Johns Hopkins, which could result in “a lot of harm.”
In addition, the movement to medicalize psychedelics isn’t just about treating illness, Humphreys said: “Don’t forget the role of money.”
He drew a comparison with marijuana, pointing out that “People are making millions and millions of dollars selling cannabis. Some genuinely believe in the medical effects and are sincere, and some want to make a lot of money. But it’s definitely the case that the very wealthy people who supported marijuana legislation did it because they wanted to make money. I’m sure it’s true in the (psychedelic medicine) space too.”
However, psychedelic mushrooms were decriminalized in Denver and Oakland, not legalized. In other words, the ballot initiatives didn’t legalize the selling or manufacturing of mushrooms — rather, they made possession of mushrooms the lowest law enforcement priority, citing their therapeutic benefits.
But even proponents of psychedelic drugs’ medical properties are wary about people self-medicating — taking them outside of a clinical setting and without the company of trained therapists.
“We don’t encourage anyone to take (psilocybin) on their own,” Greer said. “I don’t think any of us feel people should go to jail if they possess such a drug, but that’s different from saying that it could be risky for your health to take this without supervision.”
In this way, psychedelics might have something to learn from marijuana’s roller coaster journey. Cannabis gained medical, then cultural acceptance, only to have concerns raised about its properties and side effects after it became increasingly accessible and its use was legalized in many states.
Humphreys pointed out that although marijuana was originally marketed as a drug that had the potential to “cure cancer and diabetes and end opioid addiction,” it ultimately “couldn’t live up to that promise. ... What happened in reality was that consumption went up, and people are being harmed. Reality started to batter the fantasy,” he said.
Indeed, recent articles in the New Yorker, the Atlantic, and The New York Times highlight some of the risks and unintended consequences resulting from more widespread marijuana use. The articles suggest that the country may have been too quick to accept marijuana as safe for both medical and recreational use, without truly understanding its long-term or side effects.
Will this be an approved medical treatment?
In order for psychedelic therapy to become an approved medical treatment for a specific indication, like depression, it will need to be found “safe and effective” by the FDA after passing three stages of clinical trials and FDA reviews.
MDMA-assisted psychotherapy could be approved by the FDA as a treatment for post-traumatic stress disorder as early as 2021, said Brad Burge, director of strategic communications for the nonprofit Multidisciplinary Association for Psychedelic Studies, which is currently conducting phase 3 clinical trials of MDMA.
And psilocybin-assisted psychotherapy could be approved by the FDA for treatment-resistant depression as early as 2023, said Cheung.
“But there’s a long way between now” and FDA approval, Cheung said. “We’re just focused on doing the work we need to do, gathering the evidence, and seeing what the science tells us.”
Although studies have established that psychedelics are “safe physiologically compared to a lot of other drugs” in that “they’re non-toxic and they don’t lead to addiction,” research has yet to prove that psychedelics are “safe and effective in larger groups,” Pollan said.
So far, psychedelics have only been tested in relatively homogenous groups made up of people who are mostly white and well-educated, said Albert Garcia, an instructor in the Behavioral Pharmacology Research Unit at Johns Hopkins University School of Medicine.
Garcia added that drugs have different effects and risks for different groups of people, which can’t be known until the drug is tested in larger, more diverse groups.
And although methods have been developed to screen out patients for whom psychedelics might be dangerous or in whom they might “trigger permanent psychosis,” there still needs to be “more refined research into how we can prevent people from having bad trips” in general, said Manoj Doss, a postdoctoral research fellow at the Johns Hopkins Psychedelic Research Unit.
In addition, it’s still unclear what the optimal dosage would be and how often it should be given to patients, Cheung said.
Some experts in the field, including Doss, have called for more research into how the environment in which a patient takes a psychedelic drug might affect their trip.
Right now, Doss said, when patients are tripping, it’s customary for them to lie on their backs while wearing eyeshades and listening to a curated playlist of music through headphones.
But this method is “not empirical,” Doss said, adding that none of its different aspects “have been validated. Therapists recommend that patients lie down and relax. That may be one way to do it, but there may be other things we should be considering that could lead to an improved experience.”
Pollan summed up the situation: “I don’t think the research has proven (the effectiveness of psychedelics) to the standard they need to prove it. There’s still a lot we don’t know, and we have to be careful to not put the cart before the horse.”