Clinical TrialChronic PainPsilocybinNot yet recruiting

Psilocybin With Psychotherapy for Improving Chronic Pain in Cancer Patients Requiring Opioids

Phase II, single-group supportive-care study (n=20) of low-dose oral psilocybin (source: Psilocybe mexicana) given twice weekly for 4 weeks (8 doses) with preparatory and integration psychotherapy in cancer patients with chronic opioid-treated pain.

Target Enrollment
20 participants
Study Type
Phase II interventional
Design
Non-randomized

Detailed Description

This single-group Phase II study evaluates safety, tolerability, and feasibility of low-dose psilocybin combined with psychotherapy for chronic cancer-related pain in patients requiring opioids.

Participants attend two preparatory psychotherapy sessions, receive oral psilocybin twice weekly for four weeks (8 doses total) with integration therapy at sessions 2, 4, and 6 (three 90-minute sessions), and may have optional additional therapy during follow-up.

Exploratory assessments include fMRI, blood and urine biomarkers, and patient-reported measures to probe mechanisms (resting brain network activity, inflammation, psychological processes) and preliminary efficacy on pain and opioid use; follow-up visits at days 28–34, 56, and 84.

Study Protocol

Preparation

2 sessions

Dosing

8 sessions

Integration

3 sessions
90 min each

Therapeutic Protocol

Manualized psychotherapy included

Study Arms & Interventions

Psilocybin + psychotherapy

experimental

Single-group supportive-care intervention combining low-dose oral psilocybin with preparatory and integration psychotherapy, plus fMRI and biospecimen collection.

Interventions

  • Psilocybin
    via Oral• twice weekly• 8 doses total

    Psilocybin source: Psilocybe mexicana; dose not specified in registry text.

  • Compound
    • per protocol

    Psychotherapy: 2 preparatory sessions; integration sessions at dosing sessions 2,4,6 (3 × 90 min); optional additional sessions during follow-up.

  • Compound
    • per protocol

    Functional MRI (fMRI) assessments during study.

  • Compound
    • per protocol

    Biospecimen collection (blood and urine) and questionnaire administration.

Participants

Ages
18 – 75
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • Age ≥ 18 and ≤ 75 years old
  • Diagnosis of active cancer, any stage
  • Participants must have an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
  • Estimated prognosis of ≥ 3 months at the time of enrollment, determined by participant's primary oncologist or palliative physician
  • Diagnosis of moderate to severe pain (reported average pain score ≥ 4 on the 11-point Numerical Rating Scale) that is chronic (≥ 3 months) and secondary to cancer or cancer treatment
  • Pain regimen has been escalated to opioid therapy
  • Participants must be on stable pain regimen for at least one month prior, with no intention to adjust pain regimen during the study period
  • Participants must be ≥ 4 weeks beyond treatments/procedures that, in the opinion of the study physician, would significantly affect outcomes related to pain and physical function (e.g., surgery or radiation). Participants may otherwise receive cancer-directed treatment throughout the study period
  • Have no known procedures/treatments scheduled in advance that would prohibit patient from completing or significantly delaying completion of the study
  • The participant has no vacations or plans to be out of town during their study enrollment
  • Participants must not plan for additional treatments/procedures that, in the opinion of the study physician, would significantly affect outcomes related to pain and physical function (e.g., surgery or radiation) for ≥ 4 weeks following psilocybin treatment initiation. Participants may otherwise receive cancer-directed treatment throughout the study period
  • No use of other illicit substances (excluding cannabis) within the past year based on self-report at screening and routine urine toxicology screen
  • Participants must be able to read, write, and speak English
  • Participants must be able to swallow pills
  • Agree to refrain from using any unprescribed psychoactive drugs, including alcoholic beverages, ≤ 24 hours of before each psilocybin administration. Exceptions include daily caffeine or nicotine and certain stable prescribed sedative/hypnotic medications as described in protocol
  • Participants using cannabis must agree to refrainencing beginning two weeks before dosing and one week following completion of dosing; positive cannabis at second drug test (visit 10) will lead to withdrawal
  • Participants must agree to be driven home after each experimental session and not drive or operate heavy machinery ≤ 16 hours of ingesting psilocybin
  • Participants must provide an emergency contact and agree to participate in all study procedures and sign informed consent

Exclusion Criteria

  • Exclusion Criteria:
  • Participants who are pregnant or breast-feeding
  • Participants of childbearing potential who decline to use a highly effective dual contraceptive method for the duration of the study
  • Participants with a condition impairing oral intake or digestive absorption
  • Cognitive impairment as defined by Montreal Cognitive Assessment (MOCA) score < 23
  • Medical conditions or serious abnormalities of complete blood count, chemistries, or electrocardiography (ECG) that in the opinion of the study physician would preclude safe participation (examples include CHF, valvular disease, recent MI, clinically significant arrhythmias, QTcF > 450 ms males or > 470 ms females, uncontrolled hypertension, CrCl < 40 mL/min, significant hepatic dysfunction, paraneoplastic syndrome, respiratory failure, dementia, known cerebral aneurysm, seizure disorder, recent stroke/TIA, cancer with known CNS involvement, previously treated brain metastasis, or other major CNS disease)
  • Personal history of, or a current diagnosis of: primary psychotic disorder, major depressive disorder with psychotic features, bipolar I disorder, or dissociative identity disorder
  • Ongoing substance use disorder (active in the past year)
  • First-degree relatives with schizophrenia or bipolar disorder may be eligible depending on age and history; decision by PI and study psychiatrist
  • Any contraindications to undergoing an fMRI scan (e.g., metal implants/fragments)
  • Hypersensitivity to ingredients of the IMP (including psilocybin/psilocin, constituents of Psilocybe species, or capsule excipients)
  • Medications with significant interaction potential that cannot be tapered (SSRIs, SNRIs, TCAs, efavirenz, serotonin supplements, MAO inhibitors, antipsychotics for psychiatric disorder, mood stabilizers like lithium/valproate, disulfiram, significant UGT1A9/1A10 inhibitors)
  • Use of serotonergic hallucinogens within the past 12 months or significant lifetime use (> 25 uses)
  • History of violent and/or drug-related felonies or current incarceration
  • Unwilling or unable to follow protocol requirements or any social circumstance rendering participant unsuitable by investigator judgment

Study Details

  • Status
    Not yet recruiting
  • Phase
    Phase II
  • Type
    interventional
  • Design
    Non-randomized
  • Target Enrollment20 participants
  • Timeline
    Start: 2025-03-03
    End: 2027-03-05
  • Compound
    Psilocybin
  • Topic
    Chronic Pain

Locations

Roswell Park Cancer Institute — Buffalo, New York, United States

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