Psilocybin-assisted Existential, Attachment and... — Clinical Trial Details

The PEARL pilot is a phase II, single-group, open-label study evaluating feasibility, acceptability and safety of a single high-dose (25 mg) oral psilocybin session delivered within Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy for patients with advanced cancer.

Participants receive preparatory psychotherapy sessions, one supervised dosing session, and post-session integration. Outcomes include feasibility, adverse events, and changes in depressive and end-of-life distress measures (e.g., PHQ-9).

The study recruits from Princess Margaret Cancer Centre (Toronto) and is sponsored by University Health Network; eligibility requires English proficiency, expected survival >6 months, and excludes those with uncontrolled medical or psychiatric conditions that increase risk.

Participants

Ages

18 – 99

Sexes

Male & Female

BMI

Psychosis History

Excluded

Inclusion Criteria

Inclusion Criteria:
1. >18 years of age.
2. Ability to speak and read English and provide written informed consent.
3. Resident of Ontario.
4. No cognitive impairment indicated in medical record or by attending oncologist or palliative care physician.
5. Confirmed diagnosis of stage IV solid tumour, sarcoma, endocrine, melanoma cancers, or stage IV lymphoma with expected survival >6 months as determined by oncologist or palliative care physician.
6. At least mild depressive symptoms (PHQ-9 >8).
7. Interest in and ability to participate in and complete the PEARL intervention and protocol.
8. Effective birth control for participants of child-bearing potential; negative serum pregnancy test at screening and urine pregnancy test on morning of psilocybin administration for applicable participants; not pregnant or nursing for duration of study.
9. Agreement to refrain from certain prescribed or non-prescription medications/supplements as instructed (exceptions evaluated by investigator), refrain from nicotine for 2 hours before and ~7 hours after dosing, maintain usual caffeine intake before arrival, not take as-needed medications on dosing mornings (except daily and as-needed opioid analgesics), and refrain from psychoactive drugs including alcohol within 24 hours of psilocybin administration.
10. Have someone to drive them after the session.

Exclusion Criteria

Exclusion Criteria:
1. Primary brain cancer or clinically significant symptomatic brain metastasis (e.g., affective, cognitive, personality-related, psychotic symptoms, seizures).
2. Symptoms consistent with delirium, psychosis, or other symptoms judged incompatible with safe exposure to psilocybin.
3. History of past intolerability to psilocybin or other psychedelics.
4. Past or present psychiatric diagnoses including bipolar disorder, psychotic disorders, active substance use disorders, or active suicidality (distinguished from desire for hastened death or readiness for death, per study team discretion).
5. Participants under 30 with a first-degree relative with a primary psychotic disorder.
6. Severe hypertension (systolic >150 or diastolic >95) on two readings; may be re-screened once controlled.
7. Moderate or severe hepatic impairment (Child-Pugh B or C) or AST/ALT >3x ULN.
8. Severe renal impairment (eGFR <30).
9. Known paraneoplastic syndrome or ectopic hormone production incompatible with psilocybin without clinician agreement.
10. Cardiovascular conditions including uncontrolled hypertension, angina, clinically significant ECG abnormality (e.g., uncontrolled atrial fibrillation), recent TIA (<6 months), stroke, peripheral or pulmonary vascular disease with active claudication.
11. Uncontrolled epilepsy or seizure in past 6 months.
12. Diabetes requiring >2 daily medication administrations or inability to skip a meal, or recent symptomatic hypoglycaemia (30 days).
13. GI bleed in last 6 months.
14. Use of agents inappropriate with psilocybin (e.g., certain psychoactive meds including benzodiazepines, lithium, SSRIs; potent metabolic inducers/inhibitors; MAO inhibitors) unless safely paused/tapered per investigator guidance.

Company

Product

Legal

Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) Therapy for Patients With Advanced Cancer

Detailed Description

Study Protocol

Preparation

Locations

Dosing

Integration

Therapeutic Protocol

Study Arms & Interventions

Psilocybin

Interventions

Participants

Inclusion Criteria

Exclusion Criteria

Study Details

Study Team

Sponsors & Collaborators