On a ski trip in the spring of 2010, Dinah Bazer felt a fear-inducing lump in her abdomen.
“I knew what it was,” Bazer tells Inverse. “I felt doomed and I thought, ‘This is gonna kill me.'”
In 2012, two years after her first cancer treatment and tormented with anxiety over her cancer resurfacing, Bazer participated in a clinical trial at NYU Langone. She reclined on a couch in a room that looked more like a living room than a lab — a space complete with flowers, art, and coffee table books. She put on a sleep mask and headphones and pressed play on a preselected playlist of classical music. Then she swallowed a dose of psilocybin.
But scientists say it could one day be reclassified as medicine, able to transform the lives, and deaths, of hundreds of thousands of cancer patients. Studies suggest the compound, paired with psychotherapy, can be a fast-acting, long-lasting treatment for crushing mental health effects and existential dread.
That future has already begun in Canada, where, in August 2020, four terminally ill cancer patients won the “right to try” psilocybin-assisted therapy after pushing back against the country’s legal restrictions. The group’s victory offers a playbook for others to follow suit in the United States.
Stephen Ross is a psychiatrist and researcher at NYU Langone. He led one of the three randomized double-blind clinical trials — the gold standard of medical research — which found a single dose of psilocybin can help people with cancer-related psychological distress, leading to immediate and sustained improvements in anxiety and depression.
“It was very surprising and very moving to see somebody terminally ill with cancer feeling like their life is over, scared out of their mind, disconnected from family and friends and their spirituality, to suddenly just be out of that terrible place and feeling so much better,” Ross tells Inverse.
“To this day, it’s some of the most rewarding work I’ve been able to do.”
But it comes with limits. For now, psilocybin-assisted therapy is not something that people in the US can easily — or legally — access outside of a clinical trial. This hasn’t stopped individuals from requesting it, often hoping that a lab like Ross’s can help.
“I’ve had thousands of terminally ill cancer patients contact me since our publication in 2016 and it’s heartbreaking,” Ross says.
“It’s horrible to say ‘there’s nothing I can offer you right now.’ That is very disturbing to me.”
An existential crisis
Cancer also jeopardizes mental health. About 40 percent of people with cancer will experience anxiety or depression. Another 25 percent have existential distress — feeling like their life is meaningless, that they have no hope, or wish they could be dead already. These symptoms can lower their chances of survival and heighten the risk of suicide.
Matthew Johnson, a psychiatrist at Johns Hopkins University who co-authored a 2016 landmark psilocybin trial, says that while cancer-related psychological distress is devastating and common, it’s also poorly understood. Cancer-related distress is not in the DSM, the so-called “psychiatric Bible.” There’s a huge unmet clinical need, Johnson explains.
“The problem is it’s an existential crisis. It’s an issue of meaning; it’s an issue of the story of their life,” Johnson tells Inverse.
“It’s oftentimes a sense of betrayal from the universe, from God, or whatever their particular metaphysical orientation is.”
Few approved treatments help provide relief. Antidepressants and anti-anxiety medications often don’t work any better than placebo treatments for people with cancer in the throes of anxiety, depression, or existential dread, Johnson explains.
Michael Verbora is a physician who advocates for the Canadian group of patients who received access to psilocybin-assisted therapy. This group waited over 90 days for a response from Canada’s federal health minister who ultimately granted their request after public outcry. (None of these patients were available for an interview due to treatment schedules.)
“The way we look at dying is not healthy,” Verbora tells Inverse. “We really don’t have the right therapies or medications to allow a patient to view their personal conditions or issue through a different light.”
That’s where psilocybin comes in.
To date, three randomized controlled trials and a longitudinal follow-up show that, contrary to its dangerous street reputation, psilocybin is extremely safe in clinical settings. And unlike conventional therapies, it appears to radically and immediately shift people’s orientation to cancer. It helps them overcome the fear of death and give some of “their life back,” researchers say.
In 2011, UCLA led the charge in reviving psilocybin as a potential mental health treatment for cancer patients with anxiety, depression, and existential dread. Twelve people with advanced cancer experienced long-term reductions in anxiety and depression after taking psilocybin. Still, the findings were limited due to the small sample size.
Five years later, Johns Hopkins researchers found that a high dose of psilocybin produced major decreases in depression and anxiety, along with increases in quality of life, life meaning, and optimism. Overall, study participants were less frightened of death.
That same year, in the 2016 NYU Langone study, 80 percent of participants no longer met criteria for depression related to cancer just one day after receiving a dose of psilocybin alongside psychotherapy. These effects lasted for close to five years after the initial dose.
“If you had to design a disorder that is going to be most optimally treated by psychedelic therapy, dealing with life-threatening cancer is right up there,” Johnson says.
“The thing that our patients often came to was that they weren’t engaging with life — but they still could. So much of the suffering was through their own creation.”
What it’s like to receive psilocybin-assisted therapy?
In the 2016 NYU Langone trial, three out of four participants said psilocybin-assisted therapy was the singular or top five most spiritual and most meaningful experiences of their lives. One of these patients was Estalyn Walcoff. She had been diagnosed with a rare form of incurable lymphoma.
“The whole experience opened me in a way — I wish I could put it into words,” Walcoff tells Inverse.
“It was life-changing and one of the most beautiful experiences of my life.”
During her psychedelic experience, she was neither cognizant of her cancer, her fear, or, really, herself. She was connected to broad dimensions of suffering across humanity like slavery and environmental destruction. Since her treatment, Walcoff has carried this feeling of connectedness forward by embracing meditation and a deep spiritual practice.
“Even had I not survived the cancer diagnosis, the psilocybin dosing would’ve given me the courage and faith to know that, in some way, I would have ‘gone on,’” Walcoff says. “I didn’t know this before the dosing.”
Bazer’s experience, although the same to Walcoff’s in dose and setting, was quite different; initially rooted in what brought her there — her anxiety and fear.
“The psilocybin dose took effect very suddenly, and it was terrifying for me,” Bazer recalls.”I was really, really scared and I was thrown into an incomprehensible space.”
Bazer reached out to her therapists who took her hand and encouraged her to “just go with it.” So she did.
“I saw my fear as a big black lump in my abdomen under my rib cage. It was not the cancer — that’s not where the cancer was, to begin with. But it was the fear itself. And it infuriated me to see it. I was so angry, and I screamed, ‘Who do you think you are? Get the fuck out.'”
“Once I did that, it was gone,” Bazer says. “It just disappeared. And it has never come back.”
It’s been eight years and Bazer’s cancer-related anxiety never returned.
At times, Johnson questions if psilocybin’s therapeutic effects are as breathtaking as they seem.
Then a session like Walcoff’s happens — a breakthrough moment that reminds him, “Holy cow, that’s why we’re doing this.”
“It radically puts their mind in this place of the big picture and has this Gestalt-like quality of allowing them to get out of their own way,” Johnson says.
People report radical self-acceptance and an awareness that they are simply one part of a larger, more meaningful story. They are brought to joyful tears when describing this experience to the research teams responsible, and they are affected long after they leave the lab. These are the kind of breakthroughs, Johnson says, that psychologists hope for but often take years or never happen at all.
“It is indescribable how it makes you feel,” Johnson says. “You’re just lucky to be a part of it.”
“Resetting” the brain
Psilocybin works dramatically different than other common mental health medications. It’s not a daily pill or a series of treatments that mask symptoms but a single dose therapy that appears to make psychological turmoil disappear.
The process isn’t necessarily euphoric or even easy. Instead, it enables people to confront their fears and “pass through them,” Ross says.
How, exactly, psilocybin produces these seemingly magical effects is still a mystery to scientists. They do know that psilocybin activates the brain’s serotonin 2A receptors, which sets off a chain of neural effects.
After this initial activation, some researchers hypothesize psilocybin acts as a brain “reset,” temporarily reducing blood flow to the amygdala — a part of the brain involved in emotional processing, including stress and fear. Psilocybin also seems to connect areas of the brain that typically don’t communicate.
Others theorize psilocybin disrupts the brain’s default mode network. This network is active when people are at rest, daydreaming, planning for the future, and constructing their sense of self. It can be overly active in people with mental illness, causing people to ruminate and worry.
Importantly, using psilocybin and other psychedelics don’t come without any risks. The main harm with these drugs is that in unstructured settings, they can create enormous anxiety and panic, Ross explains. This acute emotional overload can lead to dangerous accidents like falling off great heights or accidentally injuring oneself.
People with a history of psychosis can also have psychotic reactions to the drug. That’s why researchers take care to screen for people with these medical histories and create a calming, comfortable setting to help people safely process the drug and its acute effects.
“Psilocybin is very intoxicating,” Johnson says. “At these high dose levels that we’re talking about, the way this therapy is done, it’s never been, ‘Take two and call me in the morning.’ It’s done like outpatient surgery and the FDA has mechanisms to mandate this.”
Legal barriers, “needless suffering”
Currently, psilocybin is regulated in the most restrictive drug category and patient availability is limited to the confines of clinical trials. The FDA considers psilocybin a Schedule I drug that has a high potential for abuse and serves no legitimate medical purpose in the United States.
But psilocybin is “completely misclassified” when it comes to harm of addiction, Ross says. That’s because psilocybin and psychedelics are not addictive in any way that you measure them, he explains. You can’t get animals to self-reinforce them; they don’t light up the nucleus accumbens, the reward center of the brain. Epidemiological studies fail to show that people use them daily and get addicted to them.
They’re also not the scary drugs described by urban legends that Americans have absorbed for the past 50 years. That they’re dangerous, create schizophrenia, chromosomal damage, fry the brain — these are “misconceptions [that] are far from reality,” says Ross.
Some of these associations are rooted in the infamous “war on drugs,” which kicked off in 1971 and criminalized a laundry list of drugs including psychedelics. The current boom in psychedelic research is a reputational return to before psychedelics were vilified.
Between 1964 and 1980, six clinical trials including 341 cancer patients suggested LSD-assisted therapy can improve cancer-related depression, anxiety, and fear of death. Overcoming field-wide stigma and trouble securing funding, Ross, Johnson, and the team at UCLA built their work off these initial findings.
“The older era of [psychedelic] research for a number of disorders was extremely promising,” Johnson agrees. “The drug was just pulled out from underneath the researchers because of the countercultural use and recreational use.”
“I feel like there’s needless suffering going on right now where people could be helped.”
Moving forward, it’s unclear what steps Americans who want to replicate what happened in Canada could take. It’s possible the FDA’s Expanded Access program could be an option. Historically, it’s been a potential pathway for a person with a serious or life-threatening disease or condition to try an investigational medical product (drug, biologic, or medical device) for treatment outside of clinical trials when there are no comparable or satisfactory therapies available.
The FDA declined to give comment on whether psilocybin is available through this program or answer any specific psilocybin-related questions via email. Neither Ross nor Johnson, two of the world’s leading psychedelic researchers, know of anyone within the United States who has requested or accessed psilocybin therapy through the FDA’s Expanded Access program.
Johnson appreciates the FDA’s rigorous drug approval process.
“It’s largely not a smoke-filled room of folks that want to stamp out this hippie woo-woo sounding area of science,” Johnson says. “It’s really institutional, and part of it is very understandable. It’s a good thing we have an FDA that says, ‘You have to show safety and efficacy for treatment.’ But if someone is dying, the risk-benefit calculation is different.”
Ross has considered administering psilocybin assisted therapy to patients through Expanded Access but worries the FDA may say he can’t be doing research and “compassionate care” simultaneously because “they interfere with each other,” he says.
“I’m a researcher — I’d rather do the research and make it available, but I feel tugged in this other direction as well to try to help patients,” Ross says.
“It really worked dramatically for these people. If that is true on a population level, then I feel like there’s needless suffering going on right now where people could be helped.”
What’s next for psilocybin?
As of August 2020, there is one active clinical trial testing psilocybin for cancer patients in the United States, but it is not yet recruiting participants. There are two active trials studying psilocybin and depression, which some, not all, cancer patients with mental distress would qualify for, Johnson explains.
To convince the FDA of psilocybin’s safety and efficacy, and overturn some of the drug’s restrictions, scientists in the field need to conduct phase 3 clinical trials. But these trials, which include hundreds of people and take an enormous amount of money, time, and energy, and are hard to get off the ground. Despite the hurdles, Ross and his team are applying for FDA approval to conduct phase 3 trials at NYU Langone.
If future outcomes mirror these early positive results, these trials could lead the FDA to reclassify psilocybin as medicine for cancer patients in the next three to five years, he says.
“It’s not 10 years away; it’s on the near horizon,” Ross adds.
But while this therapy may be accessible in the near future, what many people with cancer do not have is time.
“It’s not 10 years away; it’s on the near horizon.”
Verbora emphasizes that many terminally ill patients have months, not years, to wait. He also notes that by Canadian law, terminally ill patients can request a consultation to see if you are approved to end your life with medicine through medical-assisted dying. (Physician-assistant suicide is legal in nine US states.)
“It seems really odd that we’ve legalized the ability to end your life for pain and suffering, but we won’t let people access other therapies that are obviously far less invasive than ending one’s life for pain and suffering,” Verbora tells Inverse.
“There are hundreds, if not thousands, of patients that would immediately benefit.”
Time is a recurring theme in the conversation surrounding terminal illness and psilocybin-assisted therapy. Johnson recalls a woman calling to ask if his lab offered psilocybin-assisted therapy. Her husband had stage four pancreatic cancer. In tears, she told Johnson that her husband didn’t have time to wait for clinical trials — he simply wouldn’t be around.
All Johnson could do was cite the FDA regulations, explain how clinical trials and funding work, and show empathy.
“You try to be as compassionate as possible and sometimes that can be really difficult to deal with,” Johnson says. “It’s tragic because you know what’s possible.”