Clinical TrialPalliative & End-of-Life DistressPsilocybinPsilocybinCompleted

Psychopharmacology of Psilocybin in Cancer Patients

Randomised, quadruple-blind, crossover trial (n=56) in adults with cancer-related anxiety/depressive symptoms testing two oral psilocybin sessions (low vs high dose) as supportive care.

Target Enrollment
56 participants
Study Type
Phase II interventional
Design
Randomized, quadruple Blind

Detailed Description

This supportive-care study evaluates whether psilocybin can produce personally and spiritually meaningful experiences and reduce anxiety/depressive symptoms in patients with life-threatening cancer diagnoses.

Participants (21–80 years; ECOG 0–2) complete two monitored oral psilocybin sessions in a randomised, quadruple-blind, crossover sequence comparing low and high doses; outcomes include mood, anxiety, and coping.

Key exclusions include major cardiovascular, hepatic, renal, or neurological disease; contraindicated medications; severe psychiatric comorbidity; and family history of psychosis or bipolar disorder.

Study Protocol

Preparation

sessions

Dosing

2 sessions

Integration

sessions

Study Arms & Interventions

Low then high

experimental

Low dose first session, high dose second session (crossover).

Interventions

  • Psilocybin
    via Oral• two sessions• 2 doses total

    Sequence: low-dose then high-dose; exact dose values per protocol.

High then low

experimental

High dose first session, low dose second session (crossover).

Interventions

  • Psilocybin
    via Oral• two sessions• 2 doses total

    Sequence: high-dose then low-dose; exact dose values per protocol.

Participants

Ages
21 – 80
Sexes
Male & Female

Inclusion Criteria

  • Inclusion criteria
  • Volunteers must:
  • Have given written informed consent
  • Have a high school level of education
  • Be 21 to 80 years old
  • Has or has had a cancer diagnosis that is potentially life-threatening. Patients with an active cancer (e.g., stage III or IV with a poor prognosis) or disease progression or recurrence are eligible. Patients who do not have an active cancer or disease progression or disease recurrence are only eligible if at least 1 year has elapsed since their diagnosis.
  • Have an ECOG performance status of 0, 1, or 2.
  • Have a DSM-IV psychiatric diagnosis, as determined by the SCID, of one or more of the following Axis I psychiatric disorders that is either precipitated by or exacerbated by the psychological stress of the cancer diagnosis: Generalized Anxiety Disorder; Acute Stress Disorder; Posttraumatic Stress Disorder; Major Depressive Disorder (mild or moderate severity); Dysthymic Disorder; Adjustment Disorder with Anxiety; Adjustment Disorder with Depressed Mood; Adjustment Disorder with Mixed Anxiety and Depressed Mood; Adjustment Disorder with Disturbance of Conduct; Adjustment Disorder with Disturbance of Emotions and Conduct.
  • Patients receiving chemotherapy, hormonal therapy, radiation therapy, or biologic therapies may participate while receiving those therapies. Continuing hormonal therapy, chemotherapy, or radiation treatment is acceptable if the patient is tolerating the therapy sufficiently to allow oral psilocybin.
  • Agree that for one week preceding each psilocybin session, they will refrain from taking any nonprescription medication, nutritional supplement, or herbal supplement except when approved by the research team (exceptions may include acetaminophen, NSAIDs, common-dose vitamins/minerals).
  • Agree not to use nicotine for at least 2 hours before psilocybin administration, and not again until questionnaires are completed approximately 7 hours after administration.
  • Agree to consume approximately their usual amount of morning caffeine on psilocybin session days (or none if they do not routinely consume caffeine).
  • Agree not to take any PRN medications on psilocybin session mornings, except daily opioid analgesics; non-routine breakthrough pain PRNs within 24 h may lead to rescheduling at investigators' discretion.
  • Agree to refrain from using any psychoactive drugs, including alcohol, within 24 hours of each psilocybin administration (exceptions: daily caffeine, nicotine, and opioid pain medication).

Exclusion Criteria

  • Exclusion criteria
  • General Medical Exclusion Criteria
  • Cancer with known CNS involvement, or other major CNS disease; neurological exam with focal deficit leads to exclusion.
  • Hepatic dysfunction: GGT > 3× ULN; AST > 3× ULN; ALT > 3× ULN; total bilirubin > 3.0 mg/dL.
  • Known paraneoplastic syndrome or ectopic hormone production by the primary tumour (e.g., risk for hypercalcaemia, Cushing's syndrome, hypoglycaemia, SIADH, or carcinoid syndrome).
  • Cardiovascular conditions: uncontrolled hypertension, angina, clinically significant ECG abnormality (e.g., atrial fibrillation), TIA in last 6 months, stroke, peripheral or pulmonary vascular disease (no active claudication).
  • Blood pressure exceeding screening criteria.
  • Epilepsy with history of seizures.
  • Renal disease (creatinine clearance < 40 mL/min, Cockcroft–Gault).
  • Insulin-dependent diabetes; if on oral hypoglycaemic agents, then no history of hypoglycaemia.
  • Females who are pregnant or nursing, or not practising effective contraception.
  • Regular (e.g., daily) use of investigational agents, psychoactive prescription medications (e.g., benzodiazepines), drugs with primary serotonergic effects (e.g., ondansetron), or MAO inhibitors. Long-acting opioid analgesics allowed if last dose ≥6 h before psilocybin and not taken again until ≥6 h after.
  • Intermittent/PRN use of the above agents within 5 half-lives before a session.
  • Potent enzyme inducers or inhibitors that meaningfully alter psilocybin/psilocin metabolism (e.g., inducers: rifamycins, carbamazepine, phenytoin, phenobarbital, nevirapine, efavirenz, paclitaxel, dexamethasone, St John's wort; inhibitors: HIV protease inhibitors, itraconazole, ketoconazole, erythromycin, clarithromycin, troleandomycin).
  • Required co-administration within 12 h after psilocybin of drugs with low therapeutic index (e.g., ergot alkaloids, pimozide, midazolam, triazolam, lovastatin, simvastatin, fentanyl).
  • Psychiatric Exclusion Criteria
  • Depression or anxiety of severity warranting immediate treatment (e.g., suicidal ideation).
  • Current or past DSM-IV diagnosis of Schizophrenia, Psychotic Disorder (unless substance-induced or due to a medical condition), or Bipolar I/II Disorder.
  • Current or past (within 5 years) DSM-IV alcohol or drug dependence (excluding caffeine and nicotine).
  • First- or second-degree relative with schizophrenia, psychotic disorder (unless substance-induced/medical), or bipolar I/II disorder.
  • Current DSM-IV Dissociative Disorder, Anorexia Nervosa, Bulimia Nervosa, or other psychiatric conditions judged incompatible with rapport or safe psilocybin exposure.
  • Cardiovascular screening
  • At least four blood pressure assessment occasions over ≥2 days; within-day occasions separated by ≥15 minutes; each occasion uses ≥2 readings. Mean BP across occasions must not exceed 140/90 mmHg.
  • BP measured after ≥5 minutes rest; average of ≥2 readings separated by 2 minutes; if first two differ by >5 mmHg, obtain and average additional readings; acclimation to automated monitor permitted.

Study Details

Locations

Behavioral Pharmacology Research Unit, Johns Hopkins Bayview Campus — Baltimore, Maryland, United States

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