Abstract C001: A pilot study of palliadelic treatment with psilocybin to reduce psychological distress and improve quality of life in patients with advanced pancreatic adenocarcinoma
Authors: Klute Kelsey A. , Lukas Lou , Hwang Soonjo , Gwon Yeongjin , Krishnan Mridula , Grem Jean , Hingorani Sunil , Kellas Jody Koenig 
Published: January 2024

Abstract
Background: Psychological distress is a common reaction to a cancer diagnosis and its treatment. Distress impacts quality of life, adherence to treatment, decision making and survival. Patients with pancreatic adenocarcinoma (PDAC) experience exceptionally high rates of psychological distress, most commonly depression, anxiety and suicidality. Psilocybin, a serotonergic psychedelic which is the active component in “magic mushrooms,” is a promising treatment for several mental health disorders. Prior studies in patients with cancer have combined a single dose of psilocybin with preparation and integration counseling and have shown significant, rapid and sustained improvement in depression, anxiety and quality of life. These studies have primarily been conducted in psychiatry or neuroscience clinics in heterogenous groups of patients, many of whom had completed cancer treatment. This study will evaluate the feasibility and safety of psilocybin-assisted therapy delivered in the outpatient palliative care clinic in patients with advanced PDAC who are receiving chemotherapy. Methods: This is a single center, open label pilot study of a psilocybin-assisted therapy integrated with palliative care in patients with advanced PDAC. The primary endpoints are the feasibility and safety of this strategy when integrated into routine palliative care. Secondary endpoints include short term changes in depression, anxiety and demoralization and changes in neuronal activity by functional MRI (fMRI). After 2-4 outpatient preparation sessions with a palliative medicine physician (PMP), the subject will take psilocybin (25mg capsule) at an individual session supported by a PMP and a trained mental health professional. Up to 3 integration sessions with a PMP will follow. Patient-reported measures of psychological distress and quality of life will be assessed at baseline, after the psilocybin dose and periodically during follow-up. Neuronal changes will be measured using fMRI before and after the psilocybin dose. Eligible patients are adults (ECOG 0-3) with advanced PDAC with adequate organ function. Patients with psychiatric conditions which preclude safe cessation of psychotropic drugs or requires hospitalization, a personal or family history of schizophrenia, psychotic disorder or bipolar disorder, who have a high risk of suicide or have serious or uncontrolled hypertension or cardiovascular disease are ineligible. Given the exploratory nature of the study, a formal statistical assessment of the sample size was not conducted. Twelve evaluable subjects will provide sufficient power to detect large effect sizes (Cohen’s d1.0) in the secondary endpoints. Wilcoxon signed rank test will determine the reduction in distress scores before and after the psilocybin session. Enrollment began in June 2023; two subjects have enrolled. The study is funded by the Jim Young Pancreatic Cancer Research Memorial Fund. Psilocybin is provided by Usona. ClinicalTrials.gov Identifier: NCT05220046
Citation Format: Kelsey A. Klute, Lou Lukas, Soonjo Hwang, Yeongjin Gwon, Mridula Krishnan, Jean Grem, Sunil Hingorani, Jody Koenig Kellas. A pilot study of palliadelic treatment with psilocybin to reduce psychological distress and improve quality of life in patients with advanced pancreatic adenocarcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr C001.