The goal of this clinical trial is to evaluate whether a single dose of psilocybin is feasible and safe for adults with opioid use disorder (OUD) who are recovering from trauma surgery. The main questions it aims to answer are: 1. Is a single psilocybin dose feasible to administer during postoperative hospitalization? 2. Is psilocybin safe in this patient population? 3. How does psilocybin affect postoperative pain, opioid use, anxiety, and depression after hospital discharge? Participants will: Receive one oral dose of psilocybin during their postoperative inpatient stay Complete assessments of pain, mood, and opioid use during recovery
This is an open-label pilot feasibility trial conducted at a single academic medical center. Fourteen participants receive a single oral dose of psilocybin during inpatient hospitalization following trauma surgery. Outcomes in the psilocybin group are compared with a retrospectively identified standard-of-care cohort of 56 trauma surgery patients with opioid use disorder, identified through electronic medical record review. The standard-of-care cohort is selected using propensity score methods based on baseline characteristics, including age, sex, trauma diagnosis, psychiatric comorbidities, baseline medications, comorbid conditions, type of surgery, and baseline opioid consumption measured in morphine milligram equivalents. No interim efficacy analyses are planned. After the first three participants have received psilocybin and completed the one-week follow-up assessments, the Data and Safety Monitoring Board reviews safety data to assess ongoing risk and determine whether study procedures should continue unchanged.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
70
Single oral dose of psilocybin (10 mg) administered once during inpatient hospitalization to postoperative trauma surgery patients with opioid use disorder, followed by an 8-hour monitored observation period.
Standard postoperative pain management, including multimodal analgesia and medications for opioid use disorder, provided per institutional clinical practice.
UPMC Presbyterian
Pittsburgh, Pennsylvania, United States
Feasibility: Recruitment
Recruitment feasibility will be assessed by calculating the enrollment rate, defined as the number of participants enrolled and receiving psilocybin divided by the number of individuals determined eligible. Accrual rate will be calculated as total enrolled participants divided by the number of months recruitment occurred.
Time frame: From enrollment and receipt of psilocybin to 3 days post-treatment.
Feasibility: Retention
Retention will be calculated as the proportion of enrolled participants who receive treatment and complete required study assessments through follow-up day 5, divided by the number of individuals enrolled, treated, and not withdrawn. Feasibility target: ≥90% retention by day 5.
Time frame: Day 5 post-treatment
Feasibility: Completion of One-Month PROs
Feasibility will also be assessed by determining the completion rate of patient-reported outcome assessments 1 month after treatment, defined as the number of participants completing PROs divided by the number of enrolled participants who have not withdrawn. Feasibility target: ≥80% PRO completion at 1-month follow-up.
Time frame: at 1-month post-treatment
Inpatient post-psilocybin acute pain scores (Visual Analogue Scale)
Inpatient post-psilocybin acute pain scores assessed by visual analogue scale pain scores (VAS scores 0-10). Postoperative pain intensity assessed using a Visual Analogue Scale (VAS) ranging from 0 to 10, where 0 indicates no pain and 10 indicates the worst possible pain.
Time frame: at baseline and Days 1, 2, 3, 5, and 7 after psilocybin administration
Opioid consumption
Opioid consumption measured in morphine milligram equivalents (MME), collected from the electronic medical record during hospitalization and after discharge.
Time frame: at baseline, and days 1, 2, 3, 5, and 7 after psilocybin administration.
Psilocybin Adverse side effects
Incidence and severity of adverse events following psilocybin administration, assessed through continuous clinical observation during the monitored dosing period, vital sign monitoring, and electronic medical record review.
Time frame: measured at days 1, 2, 3, 5, 7 after psilocybin administration.
Generalized Anxiety Disorder (GAD)
Severity of anxiety symptoms assessed using the Generalized Anxiety Disorder-7 (GAD-7) scale. The GAD-7 consists of 7 items scored from 0 to 3, yielding a total score range of 0 to 21. Scores of 5, 10, and 15 represent mild, moderate, and severe anxiety, respectively. Higher scores indicate greater anxiety severity.
Time frame: at Baseline, and 1-month after psilocybin administration
Physical Function (PROMIS Physical Function)
Physical function assessed using the PROMIS Physical Function instrument. Scores are reported as standardized T-scores with a mean of 50 and a standard deviation of 10. Higher scores indicate better physical function.
Time frame: at Baseline and 1-month after psilocybin administration
Resilience (Connor-Davidson Resilience Scale 10-Item Version)
Resilience assessed using the 10-item Connor-Davidson Resilience Scale (CD-RISC-10). The CD-RISC-10 consists of 10 items evaluating an individual's ability to cope with stress and adversity. Each item is scored from 0 (not true at all) to 4 (true nearly all the time), yielding a total score range from 0 to 40. Higher total scores indicate greater resilience.
Time frame: Baseline and 1-month after psilocybin administration
Depressive Symptoms (PHQ-9)
Patient-reported depressive symptom severity assessed using the Patient Health Questionnaire-9 (PHQ-9). The PHQ-9 consists of 9 items scored from 0 to 3, yielding a total score range of 0 to 27. Higher scores indicate greater severity of depressive symptoms.
Time frame: Baseline, and 1-month after psilocybin administration
PROMIS Pain Interference
Pain interference assessed using the PROMIS Pain Interference Short Form 8a. The instrument includes 8 items rated on a 5-point Likert scale from 1 (not at all) to 5 (very much). Raw scores are summed and converted to standardized T-scores with a mean of 50 and a standard deviation of 10. Higher T-scores indicate greater pain interference.
Time frame: Baseline, and 1-month after psilocybin administration
Post-psilocybin opioid-related harms
Occurrence of opioid-related harms following psilocybin administration, including unintended hospital admissions related to opioid use, opioid overdose events (fatal or non-fatal), opioid use disorder relapse, and emergency department visits related to opioid adverse events. Assessed by participant self-report and/or medical record review.
Time frame: Measured at 1-month after psilocybin administration
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