Easing End-of-Life Care With Shrooms

It's been 60-plus years since the Harvard Psilocybin Project, the rise of hippie communes, and the psychedelic era. Now some baby boomers are returning to the drugs of their youth — to confront aging. Whether a person has terminal cancer or another life-ending illness, future end-of-life care may include psilocybin, the hallucinogenic substance in “magic mushrooms” or “shrooms.”

Patients with cancer or other life-threatening/life-limiting illnesses are often emotionally and spiritually distressed, and sleeplessness, dread, fear, and major depression are common. But psilocybin may help ease their path. A recent study found only one or two doses of psilocybin may markedly improve the mental health of cancer patients when accompanied by psychotherapy. It’s important to note, however, that psilocybin is classified as a Schedule I substance under the Controlled Substances Act, and consequently, research on psilocybin requires Drug Enforcement Administration (DEA) oversight.

Although the drug is illegal, about 8 million adults used psilocybin in the past year, making it the most popular hallucinogen. When asked why they used psilocybin, the top three reasons given by respondents to the RAND survey were: fun and social enjoyment, mental health, and personal development and existential exploration.

Psilocybin in Palliative Care

The work of the late Roland Griffiths of Johns Hopkins has been pivotal in advancing psilocybin’s potential in palliative/end-of-life care. Research provides strong evidence supporting psilocybin for alleviating anxiety, depression, and existential distress in patients facing terminal illnesses.

Griffiths's pioneering study in patients with life-threatening cancer was reported in 2016. It was a randomized trial double-blind study of 51 patients with cancer and clinically significant anxiety or depressive symptoms. The study used a moderate and high dose of psilocybin compared to a very low placebo-like dose. Results showed 80% of the high-dose participants experienced significant reductions in depression and anxiety, with improvements lasting six months or longer. Psilocybin apparently helped patients reframe individual perspectives on death/dying, and they reported increased life satisfaction, greater sense of meaning, and improved overall psychological well-being.

Before his own passing, Griffiths publicly shared he used psychedelics as part of his journey facing terminal illness. He described profound spiritual insights providing peace and acceptance, echoing benefits observed in his research participants.

In a newer survey of 3,000+ adults, Johns Hopkins Medicine researchers compared patients’ psychedelic experiences with near-death experiences not drug-related and found notable similarities in attitudes toward death. For example, survey participants in both groups reported a lowered fear of death and dying after the psychedelic experience. The researchers also reported the experience was enduringly positive, providing personal meaning, spiritual significance, and psychological insight to subjects.

In a recently published study from NYU Langone Health, researchers found psilocybin accompanied by psychotherapy significantly reduced anxiety, depression, obsessive thoughts, anger toward others, and physical symptoms associated with psychological distress, with improvements lasting up to six months. The study analyzed data from two previous clinical trials using psilocybin-assisted psychotherapy to address anxiety and depression in 79 men and women with cancer. "Our findings suggest that the mental health benefits of psilocybin therapy for cancer patients may reach far beyond what we have previously understood," said study lead author Petros Petridis, clinical assistant professor in the Department of Psychiatry at NYU Grossman School of Medicine. Their analysis adds to the evidence that psilocybin can be safely administered under close medical supervision to produce improvements in psychological distress associated with terminal illness.

Steve Levine, psychiatrist and Chief Patient Officer at Compass Pathways, a biotechnology company accelerating the study of novel treatments like psychedelics and evidence-based innovations in general, told me, “Across the spectrum of mental health diagnoses, patients continue to suffer with treatment options that are modestly effective and often intolerable, unacceptable, or inaccessible. Pilot studies of psychedelic treatments in palliative care settings show promise, and the overall evidence base across indications is growing towards that need to fulfill this hope.”

A pilot survey published in Frontiers in Psychiatry explored the openness of patients with incurable illnesses toward psilocybin-assisted psychotherapy (PAT). The pilot study provides insights into support for and concerns toward PAT among patients with incurable illnesses.

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When Psychedelics Work Therapeutically

A recent study found that psilocybin changes functional connectivity across various brain regions in humans. This disruption desynchronizes neural activity, particularly within the default mode network (DMN) and connected to the anterior hippocampus, to create a sense of space, time, and self.

Psilocybin influences the brain’s default mode network, reducing rumination and fear of death. “When psilocybin works, it works because it occasions a cathartic experience that refreshes the mind in a fundamental way. There isn’t anything specific to depression or anxiety about that. It is a tool to loosen the grip of hardwired habits and perspectives that can keep people stuck,” said Joshua Siegel, an assistant professor at NYU Langone. The drug should only be administered in a structured therapeutic environment to maximize benefits and minimize risks.

Psilocybin has been shown to have a favorable safety profile in controlled settings, with minimal risk of addiction or lasting negative effects. Common side effects (transient) may include nausea, mild increases in heart rate, and feelings of unease during the experience.

The FDA and Psilocybin

The FDA pathway for psilocybin to be approved for anxiety, depression, and existential distress in palliative/end-of-life care involves a series of rigorous regulatory steps. Luckily, psilocybin has already received Breakthrough Therapy status from the FDA for depression-related conditions. This designation accelerates development and review.

Data from cancer-related anxiety and depression trials may support a secondary indication for psilocybin in palliative care. Companies like COMPASS Pathways and Usona Institute are conducting Phase 3 trials to establish psilocybin’s safety and efficacy for treatment-resistant depression, which may pave the way for expanded indications. Avextra, a European pharmaceutical company, has announced financial support for a pioneering randomized controlled trial to examine psilocybin’s potential to alleviate psychological distress in palliative care patients, marking a significant step toward integrating psychedelic-assisted therapies into mainstream medical practice.

Recent Developments

Recent developments have highlighted the potential of psilocybin-assisted therapy in palliative care, particularly for patients with terminal illnesses.

• A December 17, 2024, article in the New York Times describes the experience of Barry Blechman, one of thousands of Americans with serious medical conditions who turned to psychedelic medicine to address the anxiety and existential distress often accompanying a terminal diagnosis.
• A study last year in Cancer found 80 percent of patients taking a single dose of psilocybin had a sustained, positive response, and 50 percent reported full remission in depressive symptoms two months later. A 2020 study in Psychopharmacology found similar results for patients more than four years after their initial treatment.
• UCSF is conducting a multi-center triple-blind phase 2 randomized controlled trial evaluating the safety and efficacy of psilocybin therapy in treating demoralization in adults near the end of life. https://clinicaltrials.ucsf.edu/trial/NCT05403086
• May of 2026 -Led by Dr. Moran Amit, MD Anderson is spearheading a pioneering clinical trial that combines the active ingredient found in so-called "magic mushrooms" with a rigorous psychotherapy framework. This initiative is part of a broader Cancer Neuroscience Program designed to help patients not only survive their diagnosis but truly thrive.

Conclusion

Psychedelics have entered the mainstream, with investors supporting startups with capital, hopeful these investments will lead to FDA approval. Recent scientific findings and anecdotal reporting in the media suggest psilocybin-assisted therapy holds promise in promoting long-term relief from cancer-related psychiatric distress. But psychedelic-assisted treatment is not for everyone. Psilocybin can be harmful to some with panic or those in whom it could precipitate psychosis, such as people with schizophrenia or bipolar disorders. Although experts in the field are bullish on psychedelic therapy for palliative care, they acknowledge the need for larger and more rigorous studies. Outside of an approved research protocol with a DEA waiver, there is no current federally legal pathway for licensed medical providers to provide a patient with psilocybin-containing mushrooms.