Psilocybin After Trauma Surgery for Pain

This Phase I, non-randomised trial (n=70) will evaluate the feasibility and safety of a single oral dose of psilocybin (10 mg) in adults with opioid use disorder (OUD) recovering from trauma surgery. The study aims to determine whether administering psilocybin during inpatient hospitalisation is practical and safe, while also assessing its effects on postoperative pain, opioid use, anxiety, and depression following discharge. Participants will receive either the experimental intervention of psilocybin alongside standard postoperative pain management or standard care alone, which includes multimodal analgesia and medications for opioid use disorder. The trial will involve a monitored observation period of 8 hours post-administration. A total of 14 participants will be enrolled in the psilocybin group, with outcomes compared to a retrospective cohort of 56 patients receiving standard care. Key measures of feasibility include recruitment and retention rates, as well as the completion of patient-reported outcomes one month post-treatment. The study is set to commence in July 2026 and conclude by August 2027.

Detailed Description

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

Study Arms & Interventions

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.

Interventions

Placebo
Unmatched intervention: Postoperative analgesia

Single Dose Psilocybin

experimental

Participants

Ages

25 – 65

Sexes

All

BMI

Psychosis History

Inclusion Criteria

1. ≥ 25 years old and ≤65 years old
2. Inpatient
3. English-speaking
4. History of opioid use disorder as diagnosed by DSM-V
5. Able to swallow capsules.
6. 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.

Exclusion Criteria

1. Pregnancy. Women of child-bearing potential need to have a negative pregnancy test result at screening and baseline.
2. 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.
3. Breastfeeding
4. Patients receiving concurrent ketamine therapy or who have received ketamine therapy during the trauma admission.
5. 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
6. History of psychedelic substance use in the preceding 5 years
7. 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)
8. Screening blood pressure SBP \>140 mmHg or DBP \> 90 mmHg on three separate occasions
9. Head trauma, traumatic brain injury, or concussion.
10. Tachycardia defined as HR \> 100, averaged over the previous 12 hours, excluding intra-operative care)
11. History of dementia
12. History of pre-existing neurological conditions (including TIA, stroke, epilepsy, MS, ALS, Guillain-Barre, Parkinson's)
13. 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.
14. Patients that received intra-operative intravenous methadone dosing \> 20 mg.
15. On vasopressors
16. Hepatic impairment, mild to moderate, with Child-Pugh score ≥ 7
17. Nicotine dependence, which would prevent the patient from staying in their room for the duration of the 8-hour psilocybin study period.
18. On sedating IV infusions (propofol, ketamine, fentanyl, benzodiazepine, dexmedetomidine)
19. History of suicidal or homicidal ideations within the last year
20. History of seizure disorder
21. Requiring restraints or active sitter
22. Patients with a history of poorly controlled anxiety (GAD7 score of 10 or more), poorly controlled depression (PHQ9 score of 15 or more), panic disorder, paranoia, PTSD, bipolar disorder, any primary psychotic disorder like schizophrenia, schizoaffective disorder, or antisocial personality disorder; personal or first- or second-degree relative history of psychotic or bipolar I or II disorder
23. History of Hallucinogen Use Disorder or Hallucinogen Persisting Perception Disorder (per DSM-V)
24. Unable to consent (intubated/sedated)
25. Intellectual disability
26. Additional or anticipated surgeries within 7248 hrs of psilocybin administration
27. Discharge from hospital pending within 24 hrs of psilocybin administration
28. Any allergy to psilocybin or other inert substances in the product

Company

Product

Legal

Psilocybin After Trauma Surgery for Pain

Detailed Description

Study Arms & Interventions

Postoperative Standard of Care

Interventions

Single Dose Psilocybin

Locations

Interventions

Participants

Inclusion Criteria

Exclusion Criteria

Study Details