Psilocybin therapy for patients with advanced cancer

Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) Therapy for Patients With Advanced Cancer: A Phase II Open-Label Trial

This study is testing whether a single high dose of psilocybin, along with therapy, can help improve the mental well-being of people with advanced cancer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 15 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University Health Network, Toronto (Academic / other)
• Locations: 1 site (Toronto, Ontario)
• Trial ID: NCT06416085 on ClinicalTrials.gov

What this trial studies

The PEARL Pilot is a phase II open-label trial that investigates the effects of a single high-dose (25 mg) psilocybin treatment combined with existential, attachment, and relational therapy for individuals suffering from advanced cancer. This approach aims to alleviate psychological and existential distress often experienced by patients facing terminal illness. The study will assess the feasibility, acceptability, and safety of this combined therapy, which includes preparatory sessions, the drug session, and integration sessions. By addressing both psychological and physical suffering, the trial seeks to improve the overall well-being of participants.

Who should consider this trial

Good fit: Ideal candidates include adults over 18 with stage IV solid tumor cancers, sarcoma, lymphoma, or melanoma, who are experiencing mild depressive symptoms.

Not a fit: Patients with cognitive impairments or those who do not meet the specific cancer stage and symptom criteria may not benefit from this study.

Why it matters

Potential benefit: If successful, this therapy could significantly reduce psychological distress and improve quality of life for patients with advanced cancer.

How similar studies have performed: Previous studies have shown promising results with psilocybin-assisted psychotherapy, indicating potential success for this novel approach.

Eligibility criteria

Inclusion Criteria:

1. \>18 years of age.
2. Ability to speak and read English (patient to provide written informed consent and participate in PEARL intervention, as determined by study personnel).
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 cancers, sarcoma, endocrine, melanoma cancers, or stage 4 lymphoma with expected survival of greater than 6 months as determined by their oncologist or palliative care physician.
6. At least mild depressive symptoms, defined as \>8 on the Patient Health Questionnaire-9 (PHQ-9) (Kroenke et la., 2001).
7. Interest in and ability to participate in and complete the PEARL intervention and protocol as outlined.
8. Participants who are sexually active and could become pregnant must be using effective birth control (per their physician), prior to study entry, during study participation, and for the duration of the study. Participants who are sexually active and could inseminate a partner must agree to use effective birth control after psilocybin administration until the end of study. For participants of child-bearing potential, a negative serum pregnancy test result is required at screening. A urine pregnancy test will be administered on the morning of psilocybin administration for applicable participants. Participants cannot be pregnant or nursing through the duration of the study.
9. If using prescribed medications or other substances, participants must agree to refrain from taking them if instructed by study investigators. These include:

   * not using any non-prescription medication, nutritional supplement, or herbal supplement except when approved by the treatment team (exceptions will be evaluated by the Investigator and will include acetaminophen, non-steroidal anti-inflammatory drugs, and common doses of vitamins and minerals),
   * not using nicotine for at least 2 hours before psilocybin administration, and not again until approximately 7 hours after psilocybin administration,
   * consuming approximately the same amount of caffeine-containing beverages (e.g., coffee, tea) that they consume on a usual morning before arriving at the treatment centre for the psilocybin session day,
   * not taking any as needed medications on the mornings of psilocybin sessions (with the exception of daily and as needed opioid pain medication),
   * refraining from using any psychoactive drugs, including alcoholic beverages, within 24 hours of the psilocybin administration.
10. Participants must have someone drive them after the session to where they are staying (home, hotel or another location), because psilocybin may affect their alertness and concentration on the evening of the dosing session.

Exclusion Criteria:

1. Primary cancer of the brain, or metastasis to the brain associated with clinically significant symptoms (e.g., affective, cognitive, personality-related, psychotic, or other symptoms, including seizures).
2. Symptoms consistent with delirium, psychosis, or other symptoms judged to be incompatible with establishment of rapport or safe exposure to psilocybin.
3. A history of past intolerability of psilocybin or other psychedelics.
4. Past/present psychiatric diagnoses including bipolar disorder, psychotic disorders, active substance use disorders or suicidality (as distinguished from desire for hastened death or readiness for death, per the discretion of the study team).
5. If participant is under 30 years of age and has first degree relative with a primary psychotic disorder.
6. Severe hypertension (defined as systolic blood pressure \>150/or diastolic pressure \>95) based on two readings on the same day. If the second reading remains over 150/95, the patient can be brought in for another reading on a different day. Patients can be re-screened for participation once blood pressure is adequately controlled.
7. Moderate or severe hepatic impairment, as defined by Child-Pugh class B or C, or elevations in AST or ALT greater than 3 times the upper limit of normal.
8. Severe renal impairment (defined as eGFR \< 30).
9. Known paraneoplastic syndrome or "ectopic" hormone production by the primary tumor if incompatible with psilocybin, determined in consultation with the study palliative care physician. Patients could be enrolled if it is determined that the patient's condition is compatible with psilocybin administration.
10. Cardiovascular conditions including uncontrolled hypertension, angina, a clinically significant ECG abnormality (e.g., atrial fibrillation without rate control), transient ischemic attack in the last six months, stroke, peripheral or pulmonary vascular disease (no active claudication).
11. Uncontrolled epilepsy or history of seizures in past 6 months.
12. Participants with diabetes who are unable to skip a meal (lunch), or whose diabetes requires administration of medication more than twice daily, or who have had symptomatic hypoglycemia within the prior 30 days.
13. GI bleed in last 6 months.
14. Use of other agents that would be inappropriate to take with psilocybin in the judgement of the investigator. These agents may include psychoactive prescription medications (e.g., benzodiazepines, lithium, Selective serotonin reuptake inhibitors), medications having a primary pharmacological effect on serotonin-2a (5-HT2A) receptors (e.g., olanzapine), or medications that are monoamine oxidase (MAO) inhibitors, any potent metabolic inducers (e.g. rifamycin, rifampin, rifabutin, rifapentine, carbamazepine, phenytoin, phenobarbital, nevirapine, efavirenz, taxol, dexamethasone, St John's wort) or inhibitors (e.g. HIV protease inhibitors, itraconazole, ketoconazole, erythromycin, clarithromycin, troleandomycin).

Of note, in suitable patients, these medications may be paused or tapered between study enrolment and prior to the start of the intervention when it is deemed safe to do so. A safe and appropriate tapering regimen will then be developed based on the particular medication, on a case-by-case basis. If taking an MAO inhibitor, the psilocybin session will not be conducted until at least 5 half-lives of the agent have elapsed after the last dose. Patients prescribed opioids will be allowed to take their usual dose regimen for analgesia, including the use of as needed analgesic medications on psilocybin session days.

Where this trial is running

Toronto, Ontario

• Princess Margaret Cancer Centre — Toronto, Ontario, Canada (Recruiting)

Study contacts

• Principal investigator: Sarah Hales, MD — University Health Network, Toronto
• Study coordinator: Sarah Hales, MD

Conditions Advanced Cancer; Stage IV Solid Tumor Cancer; Stage IV Sarcoma of Bone; Stage IV Lymphoma; Stage IV Melanoma; Endocrine Cancer