Psilocybin May Help Ease Depression in Cancer Patients

In small trial, half had early remission of depressive symptoms after psilocybin-assisted therapy

By Diana Swift

Psilocybin-assisted therapy in a group setting was safe and appeared effective in patients with cancer and depression, according to a small, phase II, open‐label trial.

After one dose of psilocybin among 30 patients, depression severity scores dropped by an average of 19.1 points by week 8, with half of patients showing full remission of depressive symptoms at 1 week and 80% experiencing a sustained response, reported Manish Agrawal, MD, of Sunstone Therapies in Rockville, Maryland, and colleagues.

Treatment-related adverse events such as nausea and headache were generally mild, and there was no indication of suicidality, the authors noted in Cancer.

A qualitative analysis of the study showed that adding peer group support before and after psilocybin therapy alleviated patients’ apprehension about the unknown and generally improved their experience of psychedelic treatment, said Yvan Beaussant, MD, MSc, of Dana-Farber Cancer Institute and Harvard Medical School in Boston, and colleagues.

Interviewed participants said the simultaneous group model fostered a sense of connectedness, meaning, and transcendence through the shared psilocybin experience and group integration. The supportive framework eased their fears of the unknown and increased their sense of safety and preparedness. In addition, the connection with fellow patients enriched their experience and contributed to their sense of self-transcendence and compassion for one another.

Some 25% to 33% of patients with cancer meet criteria for clinically significant depressive symptoms. These symptoms are associated with lower treatment adherence, reduced quality of life, and higher rates of mortality — not to mention higher healthcare costs.

“These studies provide more evidence that psilocybin is safe and efficacious for treating psychiatric symptoms in individuals with cancer, especially if a group component is added to the typical model,” said Nehal P. Vadhan, PhD, of the Feinstein Institutes for Medical Research at Northwell Health in Manhasset, New York, in an interview with MedPage Today. “But there’s still a long road ahead to having it as a legal, accepted, and accessible treatment for this and other purposes.”

Agrawal and team explained that psilocybin is a serotonergic agonist that interacts with 5‐HT2A receptors and modulates neural networks to alter perception, affect, and ego function. Serotonin deficits are thought to be instrumental in triggering depression.

“Antidepressants also work through this system, but long-term use is required, and they don’t cause a psychedelic experience,” said Vadhan, who was not involved in the studies. “The psychedelic experience is thought to be critical to psilocybin’s ability, with a single dose, to attenuate depression, potentially by increasing senses of connectedness to the world and meaning in one’s life, as well as increasing psychological flexibility.”

The hallucinogen is currently classified as a Schedule I drug with no accepted medical use and a high potential for misuse.

The currently accepted model for clinical psilocybin treatment of major depressive symptoms includes psychological support from trained therapists (but not peer group support), which helps patients deal with the adverse aspects of the psychedelic experience. “Of course many people use psilocybin on their own without clinical support, but the effects of this type of use on depression are unknown,” said Vadhan.

The psilocybin-plus-psychotherapy approach is under study for other mental health conditions such as anxiety, addiction, and post-traumatic stress disorder, with a recent multicenter study finding the hallucinogen to be effective for treating major depressive symptoms. In a small trial synthetic psilocybin was seen as an effective adjunct to psychotherapy for treatment-resistant depression in bipolar disorder.

From November 2020 to May 2021, the phase II trial recruited 30 adult cancer patients with major depression at a single community oncology center. Mean age was 56 years, 70% were women, and 80% were white. Participants received a single 25-mg dose of synthesized psilocybin plus a one-on-one session with a trained therapist. The cohort also received before-and-after peer group support.

Further studies of this promising agent appear to be in order, but its designation as a controlled substance at the strictest level is impeding investigation, said Vadhan. “More research, formal guidelines, and training are needed before it can be released for general clinical use. However, regulatory barriers make research on psilocybin and other psychedelics difficult to conduct.”

According to Agrawal’s group, future studies should include larger samples with control arms to compare effects with other treatments or placebo. They might also explore variations in group preparation, administration, and integration, as well as care for the “whole person.”

On the patient satisfaction front, the peer support approach was positive, according to Beaussant and colleagues. It gauged 28 of the original 30 patients’ reactions in exit interviews.

“As a hematologist and palliative care physician and researcher, it was profoundly moving and encouraging to witness the magnitude of participants’ improvement and the depth of their healing journey following their participation in the trial,” Beaussant said in a press release. “Many described an ongoing transformative impact on their lives and well-being more than 2 months after having received psilocybin, feeling better-equipped to cope with cancer and, for some, end of life.”

This article was published by: MedPage Today