Something was gnawing at Manish Agrawal, MD. Every day, the oncologist treated patients with standard cancer therapies, but his care could never touch their deepest pains: their despair about death.
"In 20 years, I've had close to 100,000 patient encounters," Agrawal says, "and the one thing I know we don't do well is dying."
Hospitalist Shoshana Ungerleider, MD, was also troubled by the care her dying patients received.
"We don't have the tools in medicine to adequately care for people who have that deep-seated existential distress and fear when they're diagnosed with a terminal illness," says Ungerleider, who founded the nonprofit End Well to improve end-of-life care. "The medicines we have really tend to blunt our senses and do not allow us to live fully until we die."
The question of how to die better unexpectedly led both physicians to an interest in psilocybin, the psychoactive compound in "magic" mushrooms. A growing body of evidence shows that psilocybin is safe and can relieve symptoms of depression and end-of-life demoralization in people with cancer and other life-threatening conditions.
In fact, Agrawal recently conducted a trial at the Aquilino Cancer Center in Maryland, where he is the clinical director. In the trial, 30 patients with advanced cancer received a single dose of psilocybin along with group therapy. Eight weeks later, 80% experienced a 50-plus percentage drop in their depression.
But psilocybin-based therapies are hard to come by because most psychedelics are illegal. With few exceptions, the only ways patients can take psilocybin are by entering a clinical trial, finding an underground practitioner, or traveling to the few places, such as the Netherlands or Jamaica, where it's possible to access psilocybin-based substances.
The psilocybin landscape, however, is starting to shift. An increasing number of cities, states, and countries are considering decriminalizing or legalizing psychedelics. "I think this could be potentially game-changing for an inherently broken system," Ungerleider says.
A Mystical Experience
When facing death, people often feel robbed of choice, destined to a singular fate filled with fear. But with psilocybin-assisted therapy, people may regain a sense of agency.
"I'm dying, but I can choose how I respond." That's how Agrawal characterizes the new sense of control many express following a psilocybin experience.
Psychologist Bill Richards, PhD, the lead therapist in Agrawal's study and a psychologist at Johns Hopkins University School of Medicine in Baltimore, has witnessed this type of realization many times.
"Psychedelics open up this inner door, and you discover there are resources in you that you never expected to find: the ability to love, to forgive, to perceive beauty, to live in the present moment and feel gratitude," explains Richards, who has been researching psychedelic therapy since 1963 after earning a degree in divinity. "When these transcendental experiences occur, cancer patients often claim to have lost fear of death. They live more fully."
Others may begin to see their own life as part of a larger web. A young father in Agrawal's study had a vision of what his family's life would be like after he died. He saw his children as part of a tree, and he was nestled in the earth below, still nourishing them like soil and fungi feed a forest. Afterwards, he felt better able to prepare himself and his kids for his death.
"In a mystical experience, many people realize that we're all part of one whole, that there's no separation between you and the tree and the sky," says Dingle Spence, MD, an oncologist and palliative care physician at Hope Institute Hospital in Kingston, Jamaica.
In fact, a single psilocybin journey can shift your mindset in a way that a decade of talk therapy just never will, Spence notes.
But, Agrawal cautions, "this is not a magic-bullet cure. It doesn't take away your problems. It's meant to shift the lens on your thinking, and that causes growth and an opportunity to be with your feelings."
A Journey Toward Healing
In 2015, Lauren Macdonald, MD, was diagnosed with stage 4 melanoma.
At that time, Macdonald, a psychiatrist in the UK, did not have access to immunotherapy and available treatments did little to help. Tumors filled her lungs and adrenal gland; another protruded from her right breast.
At 31, Macdonald was told that without further therapy, she had approximately 1 year to live.
But just 3 months later, in January 2016, the immunotherapy pembrolizumab (Keytruda) became available to patients through the National Health Service, and Macdonald became one of the first patients in the UK to receive the drug outside of a trial.
Soon after, she went into remission.
Despite the incredible turn of events, each quarterly scan or random ache gripped Macdonald with terror. What if her cancer was back?
Then she got hit by a car. During her recovery, she tried to process the trauma of two life-threatening events. She underwent talk therapy, meditation, but still felt half alive.
That's when she watched a TED Talk on psilocybin therapy by Johns Hopkins researcher Roland Griffiths, PhD. Intrigued, she began digging into the scientific literature, and found Michael Pollan's bestseller How to Change Your Mind, which explored his own revelatory experience with magic mushrooms.
Macdonald decided to travel to the Netherlands where she could experience this for herself. Although it's illegal to take psilocybin mushrooms under medically therapeutic conditions, because of a loophole in the law, it's legal to take magic truffles, made from the mycelium of psilocybin fungi, at retreat centers focused on "inner healing."
During her psilocybin session, Macdonald had a vision of people with cancer she'd met in the chemotherapy unit who had since died. She saw herself and peers as an energetic form, having a voiceless conversation.
In that moment, she understood that, although they don't exist in human form anymore, "they're all around me and always with me, and when I die, I will exist as an essence of spirit," she says.
For Macdonald, the finality of death had petrified her. But now, "it was really comforting to have the sense that something else goes on," she says.
Three years after her retreat, Macdonald is still cancer-free. And inspired by her journey, she now works as a therapist guide at the Centre for Psychedelic Research at Imperial College London and as a psilocybin retreat facilitator in the Netherlands.
"I couldn't believe that that one experience enabled such a huge shift in me," she says. "I had been in 'survival mode' for so many years. And it just opened me up again to love and joy and the beauty of life."
Inside a Psilocybin Session
How people receive psilocybin varies, depending on the setting — if it's at a retreat or in a clinical trial, for instance.
Macdonald's Netherland's retreat, run by an organization now called Alalaho, did not include psychotherapy. However, facilitators offer sessions, including sharing circles and activities in nature, that allow people to share their experiences and encourage healing.
This differs somewhat from the psilocybin-assisted therapy that's offered in clinical trials, which puts more focus on the therapist-patient interaction. Depending on the trial, patients may attend an individual or communal session to prepare themselves for the experience. In these sessions, patients share stories, expectations, and concerns, and a therapist coaches them through the process of navigating the psilocybin journey.
In Agrawal's Aquilino Cancer Center trial, participants received psilocybin simultaneously (though each person had their own room and therapist). This gave patients privacy, plus the reassurance that their group was journeying alongside them.
During the psilocybin dosing session, which can last 6-8 hours, the therapist typically doesn't converse much with the patient but can provide support if difficult emotions arise, and it's not unusual for a patient to hold the therapist's hand if they need comfort.
It's impossible to predict what a person will encounter. A patient in Agrawal's trial encountered his cancer manifested as a Ferris wheel full of giant clacking crabs bearing down on him. Another relived a previous miscarriage, except in her psychedelic vision, she was birthing herself into a new life.
The visions want to teach you something, says Richards. "What comes into the field of consciousness during a psilocybin session, if a person is well prepared, is intrinsically meaningful. It might not be what you expect. People often say, 'I didn't experience what I wanted, but I experienced what I needed.' "
In fact, these dreamlike — and sometimes nightmarish — visions seem to be key to the healing process.
The highly publicized 2016 Johns Hopkins University trial, for instance, found patients with cancer who had a "mystical experience" during their psilocybin session were more likely to undergo significant and sustained decreases in depression and anxiety as well as enhanced feelings of life satisfaction, meaningfulness, and an acceptance of death.
"If something comes into your field of consciousness that looks scary, dark, or threatening, try not to run away from it, but go toward it," Richards tells patients. "And as you go toward it, what was scary one minute is almost funny the next. People start laughing sometimes, [like] 'How could I ever have been so scared of living?' "
In the weeks following the dosing session, patients can attend individual or group sessions to discuss how to incorporate their epiphanies into everyday life. This could mean resolving a fractured relationship or having heart-to-heart talks with their loved ones.
"One of the most inspiring things about [psilocybin therapy] is the way many cancer patients kind of become the social workers in their families instead of being the passive, hopeless victim," Richards says. "The patient almost says, 'Watch me; I'll show you how to die well.' "
A Place for Psychedelics in Medicine?
Based on the promising research to date, the US Food and Drug Administration designated psilocybin as a "breakthrough therapy."
But the psychedelic is still classified as a Schedule 1 substance, leaving most who hope psilocybin can ease their trauma with their hands tied.
What should doctors advise patients who want to experience this therapy?
"I recommend [participating in] clinical trials because people being able to access it in a safe way is essential, and there are an increasing number of clinical trials available now," Agrawal says.
Some patients may be able to travel to places where it's legal. That will include Oregon in 2023. The state will allow adults to consume psilocybin at licensed facilities under the watchful eye of trained facilitators. Anyone, including people suffering from depression or a life-threatening condition as well as those seeking spiritual growth, will have access without needing a prescription. Many other cities have decriminalized psilocybin, meaning prosecution for possession is discouraged or deprioritized, but the substance remains illegal.
Despite the paucity of legal avenues for use, Ungerleider says, "it's really important for providers to be somewhat knowledgeable about this space. I think we owe it to our patients to educate them."
And as psychedelics research rapidly advances, many physicians are contemplating how these therapies could change healthcare.
However, patients with certain medical and psychological conditions, including a family history of psychosis, are screened out of psilocybin clinical trials. And while psilocybin clinical trials usually require participants to taper off SSRI antidepressants, there's a deficit of data on drug interactions with psychedelics. In addition, existing trials have been criticized for their lack of racial and ethnic diversity.
In short, there's not enough research yet to be able to predict how people with various neurodiversities, mental health issues, histories of trauma, and different racial backgrounds might react to psilocybin-assisted therapy.
"Psychedelic therapy isn't going to be for everyone," Macdonald says. "But it should be one of the tools in the toolkit."
When it comes to oncology, Agrawal believes psychedelic-assisted therapy should be an element of cancer care. "I think about [cancer care] like an iceberg. Above the water is chemotherapy, radiation, and surgery. Underneath it, are psycho-spiritual or psychological issues. Cancer care is all of that," he says.
However, both Agrawal and Ungerleider recognize that psilocybin-assisted therapy is too time-consuming to be offered as inpatient care in most hospitals. Instead, they say it could be incorporated into cancer centers, regional hospitals, and outpatient settings.
Spence says she would like palliative care physicians to be trained to facilitate psilocybin therapy as a standard modality. And Macdonald would like psilocybin therapy to be available for patients earlier, given the existential dread she experienced from the time of her cancer diagnosis.
Ultimately, the hope is to "change how we approach death in this culture — with more openness, curiosity, and living fully in the present," Richards says.
Ungerleider agrees. "Dying is part of the human experience, and so many of us have a very normal fear around that," she says. "If this can be a tool to help alleviate that, my goodness, we have such a huge opportunity here to get this right."
Keridwen Cornelius is a freelance journalist and editor based in Berlin, Germany. Follow her on Twitter @keridwen77.
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Cite this: 'Magic' of Psychedelics: Easing the Trauma of Terminal Illness - Medscape - Sep 12, 2022.