USC Initiates Clinical Trial Combining Psilocybin Therapy and Mindfulness for Depression

The clinical trial will involve 80 participants and aims to determine if an eight-week mindfulness training program can enhance the effects of psilocybin therapy, a psychedelic compound found in certain mushrooms. This compound has shown potential in treating mental health conditions like depression and substance use disorder. In 2019, the U.S. Food and Drug Administration designated psilocybin as a “breakthrough therapy” for major depressive disorder, paving the way for further clinical research.

Rael Cahn, MD, PhD, a clinical associate professor at the Keck School of Medicine of USC, is leading the development of a mindfulness intervention designed to amplify and sustain the benefits of psychedelic therapy. The hypothesis is that mindfulness may help individuals integrate insights gained during treatment and maintain improvements in their symptoms.

Cahn noted, “Psychedelics appear to ignite something in the brain and behavior that allows people to adopt new perspectives... they need tools to help maintain that mindset of self-exploration and discovery.”

The trial, titled Evaluation of Integrated Digital, Biomarker and Neurophysiological Tracking in Mindfulness-Assisted Psilocybin Therapy (EVIDENT-MAP), will recruit adults in Los Angeles diagnosed with depression who have no prior experience with psychedelics or meditation. Participants will be divided into two groups: one receiving psilocybin therapy alone and the other receiving both psilocybin therapy and mindfulness training.

Researchers will collect extensive data to assess the therapy's effects, including EEG and MRI brain recordings, biological samples, psychological evaluations, and information from wearable devices. Each participant will undergo two psilocybin sessions, spaced about a month apart, following preparatory therapy and several integration sessions designed to help them process their experiences.

Cahn explained that the approach to therapy during the psilocybin sessions will differ from standard psychotherapy, emphasizing the therapist's supportive role rather than direct intervention. Participants in the mindfulness training group will complete a program focusing on cultivating awareness, compassion, and daily meditation practice.

The study has also incorporated musical elements, as previous research suggests that a person’s environment can affect their psychedelic experience. Assal Habibi, PhD, is leading the effort to design a playlist of lyric-free music, timed to complement the psilocybin experience. MRI scans will be conducted post-treatment to explore any brain signals linked to therapeutic outcomes.

In addition to Cahn and Habibi, Shrikanth Narayanan, PhD, a University Professor at USC, is a principal investigator on the project.

The research is part of ARPA-H’s initiative aimed at accelerating behavioral health research through detailed clinical data collection, contributing to a secure national repository to identify patterns in mental health changes.

This study is partially funded by ARPA-H, an entity within the U.S. Department of Health and Human Services dedicated to advancing high-impact health research.