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Not yet recruitingNCT07820033PEARL RCTUpdated Oct 15, 2026

Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) Therapy for Patients With Advanced Cancer: A Randomized Controlled Trial

A Phase 2 interventional study of Psilocybin (high dose) and Psilocybin (low dose) in Advanced Cancer, Stage IV Solid Tumor Cancer and Stage IV Sarcoma of Bone, sponsored by University Health Network, Toronto. Not yet recruiting at 1 site in Canada. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-15.

Sponsored by University Health Network, Toronto · Phase 2, Interventional, and Supportive care

Updated Oct 15, 2026Primary outcomes revisedInterventions changedGo to Updates ↓
Phase
Phase 2
Study type
Interventional
Enrollment
46
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

Phase II randomized controlled trial, followed by an open-label extension phase. In the main study, participants will receive either a single high or low dose of psilocybin in the context of Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy. Upon completion of main study, participants who received the low dose will be offered a single high dose of psilocybin in the context of PEARL therapy (Open label extension study).

Read the detailed description

Individuals with advanced cancer often experience high levels of distress due to physical suffering, difficult treatment decisions, social isolation, and fear of death. While there are many treatment options for the management of physical symptoms associated with cancer, there are relatively few standard treatment approaches to help patients deal with psychological and existential suffering. Over the past decade, research has shown that psychotherapies incorporating existential, attachment and relational approaches can address the specific needs and challenges of the advanced cancer population and thus help to reduce distress. Simultaneously, recent research has shown that psilocybin-assisted psychotherapy, in which, an individual ingests the psychoactive drug within the carefully monitored therapeutic setting, can reduce end-of-life distress and greatly benefit those with advanced disease. The multidisciplinary team has combined these two evidence-based approaches into what the team calls Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy. PEARL therapy combines elements from psilocybin-assisted psychotherapy, including preparatory therapy sessions, a high-dose drug session, and integration sessions, with important elements from manualized individual psychotherapies designed for patients with advanced cancer. This study will determine if PEARL therapy with high-dose psilocybin is associated with greater improvement in depressive symptoms when compared to control 2 weeks after treatment completion. Participants will receive either a single high or low dose of psilocybin in the context of Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy. Upon completion of main study, participants who received the low dose will be offered the high dose of psilocybin in the context of PEARL therapy (Open label extension study). This type of therapy has the potential to improve quality of life among those with advanced disease and careful research is needed to build upon previous findings to outline the necessary components of therapy and guide public policy, legislation, and clinical guidelines.

02

Conditions studied

  • Advanced Cancer
  • Stage IV Solid Tumor Cancer
  • Stage IV Sarcoma of Bone
  • Stage IV Lymphoma
  • Stage IV Melanoma
  • Endocrine Cancer
03

In context

Osteosarcoma

488 studies on the registry are indexed under Osteosarcoma; 124 are open to participants now.

This study's planned enrollment of 46 is above the median of 40 across 354 interventional studies indexed under Osteosarcoma.

Browse Osteosarcoma studies →

Lead sponsor

University Health Network, Toronto is the lead sponsor of 1,438 studies on the registry; 297 are open to participants now.

Of its 17 completed or terminated interventional studies of FDA-regulated products, 3 (18%) have results posted.

Browse University Health Network, Toronto studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  1. >/= 18 years of age
  2. Ability to speak and read English fluently (participant to provide written 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 cancer, 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 at the time of screening, defined as a score >/= 10 on the Montgomery-Asperg Depression Rating Scale (MADRS) Note: Participants may be asked to retake the MADRS if they initially score under 10.
  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 or inseminate a partner must be using one method of highly effective (hormonal contraceptives (e.g. combined oral contraceptives, patch, vaginal ring, injectables, and implants); intrauterine device (IUD) or intrauterine system (IUS); vasectomy or tubal ligation). Alternatively, they may use a combination of two or more effective methods of contraception which include male condom, female condom, cervical cap, diaphragm, or contraceptive sponge. These acceptable methods of contraception must be used from the time of informed consent until 28 days after psilocybin administration.
  9. For participants of , 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

  10. 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 number 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
  11. Participants must have someone drive them after the session to where they are staying (home, hotel or another location), since psilocybin may affect their alertness and concentration on the evening of the dosing session.
  12. Participants must agree not to drive or operate machinery for at least 24 hours after dose administration

Exclusion criteria

Exclusion Criteria:

  1. Primary cancer of the brain, or 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 I 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, 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 (measured during the screening period); if the second reading remains over 150/95, the participant can be brought in for another reading on a different day. Participants can be re-screened for participation once blood pressure is adequately controlled;
  7. Moderate or severe hepatic impairment, as defined by class B or C, or elevations in or ALT greater than 3 times the ;
  8. Severe renal impairment (defined as \< 30)
  9. Known paraneoplastic syndrome or "ectopic" hormone production by the primary tumor if incompatible with psilocybin, as determined in consultation with the study palliative care physician; participants could be enrolled if it is determined that their condition is compatible with psilocybin administration.
  10. Cardiovascular conditions including uncontrolled hypertension, angina, a abnormality (e.g., atrial fibrillation without rate control), 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. If participant has diabetes, inability to skip a meal (lunch), or required administration of medication more than twice daily, or symptomatic hypoglycemia within 30 days prior to screening
  13. Gastrointestinal bleed in the 6 months prior to screening
  14. Use of other agents that would be inappropriate to take with psilocybin in the judgment of the investigator. These agents may include psychoactive prescription medications (e.g., benzodiazepines, lithium, SSRIs), medications having a primary pharmacological effect on serotonin-2a (5-HT2A) receptors (e.g., olanzapine), 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. protease inhibitors, itraconazole, ketoconazole, erythromycin, clarithromycin, troleandomycin)
  15. Any other medication condition or lab abnormality judged to be incompatible with safe exposure to psilocybin.
Terms in these criteria, in plain language(12)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Metastases

Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.

Child-Pugh class

A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

GFR and eGFR (kidney filtering)

GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².

Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.

Clinically significant

Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.

ECG (electrocardiogram)

A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.

TIA (transient ischaemic attack)

A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.

Stroke symptoms need emergency care at once, even if they go away.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

05

Study design

Phase
Phase 2
Primary purpose
Supportive care
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Triple (Participant, Care provider, Investigator)
Enrollment
46 participants (estimated)

Study arms

  • Experimental
    high-dose group

    Single high dose of psilocybin taken orally in the context of Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy.

    Drug: Psilocybin (high dose) · Other: PEARL Therapy

  • Placebo comparator
    low-dose group

    Single low dose of psilocybin taken orally in the context of Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy.

    Drug: Psilocybin (low dose) · Other: PEARL Therapy

Interventions

  • DrugPsilocybin (high dose)

    Single high dose of psilocybin taken orally in the context of Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy

  • DrugPsilocybin (low dose)

    Single low dose of psilocybin taken orally in the context of Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy

  • OtherPEARL Therapy

    Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy

06

What researchers measure

Primary outcomes

  1. Change in mean severity of depressive symptoms as assessed by the Montgomery-Asperg Depression Rating Scale (MADRS) score from baseline to 2 weeks after completion of PEARL therapy, comparing the high-dose with the low-dose psilocybin group.

    The MADRS is a 10-item rater-administered scale measuring depressive symptoms. Total score range is 0 to 60, with higher scores indicating greater severity of depressive symptoms.

    Time frame: At T2 (2 weeks after the last follow up)

Secondary outcomes

  1. Number of participants with treatment-related adverse events after PEARL as assessed by the Swiss Psychedelic Side Effects Inventory (SPSI).

    The SPSI is a 32-item self-report measure designed to systematically assess adverse effects experienced by participants in studies involving psychedelic drugs and MDMA. The inventory contains 32 clinically relevant side effects and assesses severity, impact, duration, treatment-relatedness and timing.

    Time frame: T3 (6 weeks after last follow up)

  2. Change in mean anxiety symptoms from baseline to T3 as assessed by the Generalized Anxiety Disorder (GAD-7) scale.

    The GAD-7 is a 7-item self-report scale used to screen for and measure anxiety symptoms. Total score range is 0 to 21. Higher scores indicate higher levels of anxiety.

    Time frame: T3 (6 weeks after last follow up)

  3. Change in death-related distress from baseline to T3 as assessed by the Death and Dying Distress Scale (DADDS).

    The DADDS is a 15-item self-report measure designed for populations facing imminent death and addresses fears about the dying process, and about lost opportunities and self-perceived burden placed on others as a result of impending mortality. Total score range is 0 to 75. Higher scores indicate greater death-related distress.

    Time frame: T3 (6 weeks after last follow up)

  4. Change in demoralization symptoms from baseline to T3 as assessed by the Demoralization Scale (DS).

    The DS is a 24-item self-report measure that assesses loss of meaning and purpose, disheartenment, and helplessness. Total score range is 0 to 96. Higher scores indicate higher levels of demoralization.

    Time frame: T3 (6 weeks after last follow up)

  5. Change in spiritual well-being from baseline to T3 as assessed by the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being Scale (FACIT-Sp).

    The FACIT-Sp is a 12-item scale designed to measure important aspects of spirituality including sense of meaning in one's life, harmony, peacefulness and a sense of comfort and strength from one's faith. Total score range is 0 to 48. Higher scores indicate higher spiritual well-being.

    Time frame: T3 (6 weeks after last follow up)

  6. Change in quality of life from baseline to T3 as assessed by the Quality of Life at the End of Life-Cancer Scale (QUAL-EC).

    The Quality of Life at the End of Life-Cancer (QUAL-EC) is a 17-item measure that includes subscales which assess symptom impact, preparation for end of life (i.e., the extent to which the family is prepared and financial plans have been made), relationship with healthcare providers (i.e., the extent to which patients feel informed and are able to participate in decisions about their care) and sense of life completion (i.e., being able to share important things and feel connected to others). For Symptom Control, score range is 3 to 15, with higher scores reflecting greater symptom control; for the Relationship with Healthcare Provider, score range is 5 to 25, with higher scores reflecting a better relationship with healthcare providers; for the Preparation for End-of-Life, score range is 4 to 20, with higher scores reflecting greater preparation for end-of-life; and the for Life Completion, score range is 5 to 25, with higher scores reflecting a greater sense of life completion.

    Time frame: T3 (6 weeks after last follow up)

  7. Number of participants with treatment-related adverse events as assessed by CTCAE v6 and the Monitor Rating Questionnaire (MRQ).

    The MRQ is clinician-rated and administered during the dosing session. It is adapted from the measure used by Griffiths et al. to monitor elevated heart rate and blood pressure, confusion, headache, nausea/vomiting, anxiety, and paranoia. Adverse events will be tracked until study completion.

    Time frame: T3 (6 weeks after last follow up)

  8. Recruitment feasibility as assessed by the number of participants referred and screened, the number that meet eligibility criteria, and the number of these participants who consent to participate.

    Used to assess the feasibility of a larger PEARL therapy RCT

    Time frame: T3 (6 weeks after last follow up)

  9. Retention feasibility as assessed by the number of participants completing study measures across all time points.

    Used to assess the feasibility of a larger PEARL therapy RCT

    Time frame: T3 (6 weeks after last follow up)

  10. Adherence feasibility as assessed by the number of participants completing all PEARL sessions.

    Used to assess the feasibility of a larger PEARL therapy RCT

    Time frame: T3 (6 weeks after last follow up)

Other outcomes

  1. Quality of Acute Drug Experience in response to PEARL as assessed with Mystical Experiences Questionnaire (MEQ30) and the Persisting Effects Questionnaire (PEQ).

    Quality of Acute Drug Experience will be measured with the Mystical Experiences Questionnaire (MEQ30). Any persisting effects of the drug will be assessed using the following three questions from the Persisting Effects Questionnaire (PEQ): 1) how personally meaningful was the experience; 2) how spiritually significant was the experience; and 3) did the experience change your sense of well-being or life satisfaction?

    Time frame: T1 (day after dosing visit)

  2. Assess the nature of the PEARL therapy experience and what factors are associated with positive or negative outcomes via qualitative study of participants

    All participants from both study arms will be invited to take part in a semi-structured interview to explore the PEARL experience and factors that influenced it (i.e., aspects of identity including gender, race, ethnicity, the gender(s) of therapist dyads and perceived psilocybin dose). Throughout the study, the guide will be modified to focus attention on areas of particular importance to the emerging qualitative interpretations.

    Time frame: T3 (6 weeks after last follow up)

  3. Integrity of masking of PEARL.

    Integrity of Trial Masking will be assessed the day after the psilocybin dosing session by asking both participants and study therapists to guess treatment condition assignment.

    Time frame: T1 (day after dosing visit)

  4. Assess the predictors of response to PEARL as assessed by demographics, cancer type, medical and psychiatric comorbidities and depression diagnosis.

    As measured by: * demographic information (self-report including age, sex, gender, race, ethnicity, sexual orientation, level of education, marital status, household income, and housing status) * Medical and Background Information (cancer type and stage, length of illness, previous psychiatric and medical diagnoses, current medications, and past use of psychedelic medicines) * The Structured Clinical Interview for DSM-5 Disorders Research Version (SCID-5-RV)

    Time frame: Screening

  5. Assess the predictors of response to PEARL as assessed by physical symptoms.

    As measured by Physical Symptoms assessed with The Edmonton Symptom Assessment Scale (ESAS)

    Time frame: at baseline, T2 (2 weeks after the last follow up) and T3 (6 weeks after last follow up)

  6. Emotional Breakthrough in response to PEARL with the Emotional Breakthrough Inventory (EBI).

    Emotional Breakthrough will be measured with the Emotional Breakthrough Inventory (EBI), a 6-item self-report questionnaire designed to capture the phenomenon of overcoming challenging emotions or memories during or after a psychedelic experience.

    Time frame: T1 (day after dosing visit)

  7. Treatment Expectancy in response to PEARL as assessed by Stanford Expectation of Treatment Scale (SETS).

    Treatment Expectancy will be assessed with the Stanford Expectation of Treatment Scale (SETS), a 6-item self-report measure of positive and negative treatment expectancies.

    Time frame: Baseline and T1 (day after dosing visit)

  8. Assess the predictors of response to PEARL as assessed by attachment style.

    As measured by Relationship (Attachment) Style assessed with the Experiences in Close Relationships Inventory (ECR).

    Time frame: at baseline, T2 (2 weeks after the last follow up) and T3 (6 weeks after last follow up)

07

Study locations

1 site
08

References and documents

Publications

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09

Updates

1 registry update since Sep 25, 2026
Interventions
Added Drug: Psilocybin (high dose)·Drug: Psilocybin (low dose); removed Drug: Psilocybin (25mg)·Drug: Psilocybin (1mg)
Oct 15, 2026
Primary outcomes
1 edited
What changed in the outcomes
  • EditedChange in mean severity of depressive symptoms as assessed by the Montgomery-Asperg Depression Rating Scale (MADRS) score from baseline to 2 weeks after completion of PEARL therapy, comparing the 25mg psilocybin grouphigh-dose with the 1mglow-dose psilocybin group.Time frame: At T2 (2 weeks after the last follow up)
Oct 15, 2026
Show all 1 update
  1. Oct 15, 2026
    Primary outcomes 1 edited
    What changed in the outcomes
    • EditedChange in mean severity of depressive symptoms as assessed by the Montgomery-Asperg Depression Rating Scale (MADRS) score from baseline to 2 weeks after completion of PEARL therapy, comparing the 25mg psilocybin grouphigh-dose with the 1mglow-dose psilocybin group.Time frame: At T2 (2 weeks after the last follow up)
    Interventions Added Drug: Psilocybin (high dose)·Drug: Psilocybin (low dose); removed Drug: Psilocybin (25mg)·Drug: Psilocybin (1mg)
    + 3 other changes: verification date, description and design details

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

10

Registry details

Key details

Study ID
NCT07820033
Lead sponsor
University Health Network, Toronto
Responsible party
Sponsor
First posted
Sep 15, 2026
Start date
Sep 14, 2026 (estimated)
Primary completion
Dec 30, 2028 (estimated)
Completion
Jul 30, 2029 (estimated)
Last update
Oct 15, 2026

Study contacts

Sarah Hales, MD
Contact
UHNPPRG@uhn.ca
416-340-4800 ext. 8051

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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