Psilocybin After Trauma Surgery for Pain

NCT07406828 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: STUDY24040071
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

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. 1.Is a single psilocybin dose feasible to administer during postoperative hospitalization?
2. 2.Is psilocybin safe in this patient population?
3. 3.How does psilocybin affect postoperative pain, opioid use, anxiety, and depression after hospital discharge?

Conditions

Pain Management; Postoperative Pain

Keywords

psilocybin; postoperative trauma; opioid; opioid use prevention; surgery; mushrooms; opioid adverse events

Outcome Measures

Primary Outcomes (3)

• 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.

  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required study assessments through follow-up day 5, divided by the number of individuals enrolled, treated, and not withdrawn.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.

  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defined as the number of participants completing PROs divided by the number of enrolled participants who have not withdrawn.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.

  at 1-month post-treatment

Secondary Outcomes (9)

• Inpatient post-psilocybin acute pain scores (Visual Analogue Scale)

  at baseline and Days 1, 2, 3, 5, and 7 after psilocybin administration

• Opioid consumption

  at baseline, and days 1, 2, 3, 5, and 7 after psilocybin administration.

• Psilocybin Adverse side effects

  measured at days 1, 2, 3, 5, 7 after psilocybin administration.

• Generalized Anxiety Disorder (GAD)

  at Baseline, and 1-month after psilocybin administration

• Physical Function (PROMIS Physical Function)

  at Baseline and 1-month after psilocybin administration

Study Arms (2)

Postoperative Standard of Care

ACTIVE COMPARATOR

Participants receive standard postoperative pain management following trauma surgery, including multimodal analgesia and medications for opioid use disorder, as determined by the clinical care team. No psilocybin is administered.

Drug: Postoperative analgesia

Single Dose Psilocybin

EXPERIMENTAL

Participants receive a single oral dose of psilocybin (10 mg) administered during inpatient hospitalization within 72 hours after trauma surgery, along with the standard postoperative care.

Drug: Psilocybin (Usona Institute); Drug: Postoperative analgesia

Interventions

Psilocybin (Usona Institute) DRUG

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.

Single Dose Psilocybin

Postoperative analgesia DRUG

Standard postoperative pain management, including multimodal analgesia and medications for opioid use disorder, provided per institutional clinical practice.

Postoperative Standard of Care; Single Dose Psilocybin

Eligibility Criteria

• Age: 25 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• ≥ 25 years old and ≤65 years old
• Inpatient
• English-speaking
• History of opioid use disorder as diagnosed by DSM-V
• Able to swallow capsules.
• Patients are able to be enrolled and receive psilocybin within 3 days (72 hours) of surgery (time point 0 for this three-day window begins after patient arrival in the ICU) after a trauma surgery. Psilocybin will be administered in the morning to allow for the 8-hour monitoring period.

You may not qualify if:

• Pregnancy. Women of child-bearing potential need to have a negative pregnancy test result at screening and baseline.
• Sexually active male participants and/or their female partners and female participants of child-bearing potential need to be on adequate and effective method of contraception (diaphragm, male condom, combined pill, copper IUD, levonorgestrel IUS, etonogestrel implant).for one week following study drug administration.
• Breastfeeding
• Patients receiving concurrent ketamine therapy or who have received ketamine therapy during the trauma admission.
• UDS screen on admission (if obtained) positive for alcohol, opioids other than prescribed for pain or maintenance opioids for OUD, or other substances of abuse
• History of psychedelic substance use in the preceding 5 years
• History (or active) cardiovascular disease (non-optimized coronary vascular disease, stable or unstable angina, new onset EKG abnormalities, congenital long QT syndrome, cardiac trauma involving surgical repair or CABG within 1 year)
• Screening blood pressure SBP \>140 mmHg or DBP \> 90 mmHg on three separate occasions
• Head trauma, traumatic brain injury, or concussion.
• Tachycardia defined as HR \> 100, averaged over the previous 12 hours, excluding intra-operative care)
• History of dementia
• History of pre-existing neurological conditions (including TIA, stroke, epilepsy, MS, ALS, Guillain-Barre, Parkinson's)
• Patients on SSRIs, TCAs, MAO-Is, lithium, or other serotonergic medications, antipsychotics. Prohibited medications need to be discontinued at least 30 days prior to psilocybin dosing.
• Patients that received intra-operative intravenous methadone dosing \> 20 mg.
• On vasopressors

Sponsors & Collaborators

• Trent Emerick: lead
• The Beckwith Institute: collaborator

Study Sites (1)

UPMC Presbyterian

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

Agnosia; Pain, Postoperative

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Postoperative Complications; Pathologic Processes; Pain

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Study Officials

• Trent D. Emerick

  University of Pittsburgh / UPMC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alisha Maslanka, BS, CCRC

CONTACT

4128646779; maslankaaa@upmc.edu

Dayana Alsamsam, BSPS, MSc

CONTACT

alsamsamd@upmc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: January 31, 2026
• First Posted: February 12, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2027
• Last Updated: February 12, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)