What is Psilocybin Doing for Cancer Patients and People with Major Depression?

New research published in JAMA Oncology suggests that psilocybin therapy may help alleviate symptoms of major depressive disorder in patients with cancer. It has been reported that around 15% of individuals with cancer experience major depression, associated with decreased treatment adherence and poorer quality of life. Despite the high prevalence of major depression among cancer patients, many oncologists feel inadequately prepared to address mental health concerns. Current treatment options have also demonstrated limited effectiveness in treating depression.

Psilocybin, a 5-HT2A receptor agonist, may present a novel alternative for treating depression. Prior studies have demonstrated the efficacy of psilocybin in reducing various psychiatric symptoms when administered with a ratio of 2 therapists per patient. The recent study sought to establish a scalable and rapidly adequate treatment for depression using psilocybin with a therapist-to-patient ratio of 1-to-1.

To their knowledge, the researchers also highlighted that this is the first study on psilocybin therapy conducted in a community cancer setting instead of an academic institution or psychiatric hospital.

The Study

Lead investigator Manish Agrawal, MD, who is part of the Center for Psychedelic Therapy and Research, co-founder and CEO of Sunstone Therapies, and co-director of Clinical Research at Aquilino Cancer Center, noted in an interview with Pharmacy Times® that this study was distinctive in two ways.

Firstly, it employed a group approach, different from previous studies on psychedelic-assisted therapy in cancer patients conducted in specialized academic hospitals or large psychiatric facilities. Additionally, the study was conducted in a Community Cancer Center, which was a new setting for such research.

For the phase 2 study, which was open-label and had a fixed dose, 30 participants were enrolled at Aquilino Cancer Center or referred from specialized oncology and psychiatric services. The patients were divided into groups of 3 to 4 individuals based on the time of recruitment, and all of them were adults diagnosed with cancer and major depressive disorder.

On average, the participants' age was 56 years, and the group consisted of 70% women and 30% men. Of the 30 individuals, 14 (47%) had cancer that was deemed curable, while 16 (53%) had non-curable cancer. Half of the participants also reported having received previous treatment with antidepressant medication.

Administration, Preparation, and Integration

In this study, each cohort of participants was given a 25-mg dose of COMP360 in separate rooms connected to a shared space, and the therapist-to-patient ratio was 1-to-1. The groups received group therapy consisting of one preparation session, two integration sessions, and individual therapy. The outcomes of interest included safety and improvement in depression, which was primarily evaluated using the Montgomery-Asberg Depression Rating Scale (MADRS), where higher scores indicated more severe depression.

According to Agrawal, the patients underwent a group preparation session before receiving psilocybin, administered simultaneously in adjacent rooms. This process was referred to as simultaneous administration. The day after the psilocybin session, the patients returned for a discussion of their experiences.

This was followed by another session a week later, where they continued to discuss their experiences, which was called integration. As Agrawal explained, this approach of simultaneous administration, group preparation, and group integration has not been previously studied in patients with cancer or any other population.

Remission was defined as a MADRS score of less than 10 following treatment, and prolonged response to therapy was defined as a reduction in MADRS score of at least 50% from baseline to weeks 3 and 8. The Maudsley Visual Analogue Scale and the Quick Inventory of Depressive Symptomatology-Self-Report were two more tests for depression.

According to the Columbia Suicide Severity Rating Scale, no major adverse events (AEs) were associated with the treatment during the research, and there was also no suicidality. Hallucinations (n=1), anxiety (n=7), altered mood (n=8), nausea (n=12), and headache (n=24) were minor or expected adverse events.

Results Of The Experiment

The significant decrease in MADRS scores from baseline to post-treatment suggested the effectiveness of psilocybin treatment. Results showed a reduction of 19.1 points by week 8, with 80% of patients showing a sustained response. Notably, 15 (50%) patients achieved complete remission of their depressive symptoms.

Self-reported measures of depressive symptoms reinforced the reduction in MADRS scores. The Quick Inventory of Depressive Symptomatology–Self-Report indicated an average decrease of 5.9 points, a 48% reduction from baseline to week 8. Similarly, the Maudsley Visual Analogue Scale showed a 53% decrease in self-rated depression severity, reducing 46.2 points.

The investigators concluded that the participants demonstrated clinically significant improvement in depression symptoms, which was rapid and sustained over 8 weeks after a single psilocybin therapy treatment. This improvement was observed in patients with both curable and incurable cancers.

The absence of a control group was one of the constraints mentioned by the investigators. The researchers concluded that their findings support a randomized clinical trial, but more study is required to evaluate placebo and different antidepressant medications for cancer patients.

Agrawal remarked that with only 30 patients, the trial had some restrictions, such as the absence of a placebo group. Nevertheless, the effectiveness was significant and fascinating. But the most thrilling part was that people genuinely connected in the group and wanted to share their experiences and stories for mutual benefit. Due to the benefits, they observed in the studies, [which] showed fairly spectacular results, individuals are still meeting once a month. This is two years after the trials were ended, and participants were only followed up for 8 weeks.

Conclusion

New avenues for treating depression in a community cancer environment have been made possible by the landmark study on psilocybin therapy in cancer patients. In patients with both curable and incurable malignancies, the study's findings revealed considerable reductions in depressive symptoms, including persistent response and complete remission. No significant adverse effects have been recorded following the unique methodology of simultaneous delivery, group preparation, and group integration.

Despite the study's limitations, the results lay a solid groundwork for future research. It is impossible to deny the potential advantages of psilocybin therapy for cancer patients, and the researchers have recommended conducting additional randomized clinical trials in the future.