Summary: A single psilocybin dose, administered once with psychotherapy, produced sustained reductions in depression, anxiety, hopelessness and existential distress for cancer patients, with benefits observed up to 4.5 years after treatment.
Source: NYU
Overview
Researchers at NYU Grossman School of Medicine followed up on a landmark randomized trial and report that a single administration of psilocybin, given in a controlled therapeutic setting alongside psychotherapy, was associated with long-lasting improvements in emotional and existential distress among patients with life-threatening cancer. This long-term follow-up assessed a subset of the original participants roughly three years and 4.5 years after the psilocybin dose and found sustained reductions in anxiety, depression, hopelessness, demoralization, and death anxiety.
In the initial 2016 study published in the Journal of Psychopharmacology, a single dose of psilocybin produced rapid and durable reductions in anxiety and depression, improved spiritual well-being, reduced cancer-related demoralization, and enhanced overall quality of life. At the 6.5-month follow-up of the parent trial, about 60–80 percent of participants continued to show clinically meaningful antidepressant or anxiolytic responses and sustained gains in existential well-being and attitudes about death.
The new long-term follow-up, published online on Jan. 28 in the same journal, evaluated the same group over a much longer interval. Of the original trial participants, 16 were alive at the time of recontact and 15 agreed to participate in the follow-up assessments. These assessments, conducted an average of 3.2 years and again at 4.5 years after psilocybin administration, showed that many participants maintained the clinical benefits observed earlier.
Key findings
- Reductions in anxiety, depression, hopelessness, demoralization, and death anxiety were sustained at both long-term follow-ups.
- At the 4.5-year follow-up, roughly 60–80 percent of participants still met criteria for clinically significant antidepressant or anxiolytic responses.
- Between 71 and 100 percent of participants attributed positive, lasting life changes to the psilocybin-assisted therapy and rated the experience among the most personally meaningful and spiritually significant in their lives.
These outcomes add to a growing body of evidence suggesting that psilocybin-assisted psychotherapy can produce prolonged improvements in psychological and existential distress for people facing life-threatening illness.
Why this matters
According to the investigators, conventional pharmacologic treatments for cancer-related anxiety and depression are often insufficient: antidepressants work for less than half of patients in this population and typically have limited or no effect on existential concerns and death anxiety. Those forms of distress are linked to lower quality of life, greater suicidal ideation, and poorer overall outcomes. The NYU team argues that psilocybin, when combined with psychotherapy in a controlled setting, may provide a much-needed alternative or adjunct treatment for this form of suffering.
Possible mechanisms
While the exact neurobiological mechanisms remain under study, psilocybin is thought to increase brain plasticity and cognitive flexibility, making individuals more receptive to therapeutic insights and new patterns of thought. Prior research points to effects on the brain’s default mode network — a system involved in self-reflection and narrative identity that can become hyperactive in depression and anxiety, contributing to rumination and rigid thinking. Psilocybin appears to transiently alter activity in that network, enabling people to adopt broader perspectives on their lives and behaviors.
How the original trial and follow-up were conducted
The parent randomized controlled trial enrolled 29 cancer patients who each received nine psychotherapy sessions and a single dose of either psilocybin or an active placebo (niacin, which can produce a flushing sensation and mimic some physical aspects of a psychedelic experience). After seven weeks, participants crossed over to the alternate treatment. Clinical outcome measures tracked anxiety, depression, demoralization, quality of life, and related variables.
The long-term follow-up contacted all 16 participants who remained alive from the parent trial; 15 agreed to be assessed at the two long-term time points. The follow-up is the longest assessment to date of psilocybin’s effects on cancer-related psychiatric and existential distress.
Lead investigator Stephen Ross, MD, an associate professor of psychiatry at NYU Langone Health and principal author of the original study, emphasized that these findings, along with earlier research dating back to the 1950s, suggest psilocybin-assisted therapy could change how clinicians address psychological and spiritual suffering in patients with terminal illness.
Gabrielle Agin-Liebes, the lead author of the long-term follow-up and a PhD candidate in clinical psychology, cautioned that positive outcomes depend on the controlled therapeutic setting. She noted that psilocybin does not guarantee benefit when used alone in uncontrolled or recreational contexts and stressed the importance of trained psychological support during treatment.
Next steps
The investigators plan larger, more diverse trials to evaluate psilocybin-assisted psychotherapy in broader patient populations with advanced cancer and significant psychiatric or existential distress. They say this approach could ultimately be applied in psycho-oncology and hospice care to help patients approach death with improved emotional and spiritual well-being.
Funding: The long-term follow-up study received funding from the Source Research Foundation.
Source:
NYU
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Original research: Closed access. Title: “Long-term follow-up of psilocybin-assisted psychotherapy for psychiatric and existential distress in patients with life-threatening cancer.” Authors: Gabrielle I Agin-Liebes et al. Journal of Psychopharmacology. DOI: 10.1177/0269881119897615.
Abstract (summary)
The randomized controlled parent trial compared single-dose psilocybin to single-dose niacin alongside psychotherapy in participants with cancer-related psychiatric distress. Early results showed psilocybin-assisted psychotherapy improved psychiatric and existential distress, quality of life, and spiritual well-being up to the crossover point. At 6.5 months, 60–80% of participants still met criteria for clinically significant antidepressant or anxiolytic responses. The present long-term follow-up assessed a subset of the original cohort at approximately 3.2 and 4.5 years after psilocybin administration, with 15 participants completing assessments. Large within-group effect sizes were observed for sustained reductions in anxiety, depression, hopelessness, demoralization, and death anxiety. Most participants attributed positive life changes to the psilocybin-assisted therapy and described the experience as highly meaningful. Although the crossover design of the parent trial limits definitive efficacy conclusions, these findings support further study of psilocybin-facilitated psychotherapy as a potential long-term treatment for cancer-related psychiatric and existential distress.