Advanced CancerPhase 2PEARL RCTNCT07820033

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

A Phase 2 study testing Psilocybin (high dose), Psilocybin (low dose) and PEARL Therapy in people with Advanced Cancer and Stage IV Solid Tumor Cancer, run by University Health Network, Toronto at 1 site in Canada.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Advanced Cancer, Stage IV Solid Tumor Cancer, Stage IV Sarcoma of Bone
What is being tested?: Psilocybin (high dose), Psilocybin (low dose) and PEARL Therapy
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 46 participants
Where: 1 siteCanada
Study dates: 14 Sep 2026to 30 Jul 2029
Phase: Phase 2
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

>/= 18 years of age
Ability to speak and read English fluently (participant to provide written informed consent and participate in PEARL intervention, as determined by study personnel)
Resident of Ontario;
No cognitive impairment indicated in medical record or by attending oncologist or palliative care physician;
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
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.

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Interest in and ability to participate in and complete the PEARL intervention and protocol as outlined
Participants who are sexually active and could become pregnant or inseminate a partner must be using one method of highly effective contraception (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.
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
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
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.
Participants must agree not to drive or operate machinery for at least 24 hours after dose administration

Who cannot join

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)
Symptoms consistent with delirium, psychosis, or other symptoms judged to be incompatible with establishment of rapport or safe exposure to psilocybin;
A history of past intolerability of psilocybin or other psychedelics;
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);
If participant is under 30 years of age, has first degree relative with a primary psychotic disorder
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;

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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;
Severe renal impairment (defined as eGFR < 30)
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.
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)
Uncontrolled epilepsy or history of seizures in past 6 months
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
Gastrointestinal bleed in the 6 months prior to screening
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. HIV protease inhibitors, itraconazole, ketoconazole, erythromycin, clarithromycin, troleandomycin)
Any other medication condition or lab abnormality judged to be incompatible with safe exposure to psilocybin.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Sarah Hales, MD contact

416-340-4800 ext. 8051

UHNPPRG@uhn.ca

Canada1 site

University Health Network
Toronto, Ontario
Sarah Hales, MD, 416-340-4800 ext. 8051, UHNPPRG@uhn.ca

Other trials in Canada

About this study

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.

Conditions: Advanced Cancer, Stage IV Solid Tumor Cancer, Stage IV Sarcoma of Bone, Stage IV Lymphoma, Stage IV Melanoma, Endocrine Cancer
Being tested: Psilocybin (high dose), Psilocybin (low dose), PEARL Therapy
Medical subject headings: Osteosarcoma, Lymphoma, Melanoma, Endocrine Gland Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT07820033
Study group	Role	What they receive
high-dose group	Experimental	Single high dose of psilocybin taken orally in the context of Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy. Receives: Drug: Psilocybin (high dose); Other: PEARL Therapy
low-dose group	Placebo comparator	Single low dose of psilocybin taken orally in the context of Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy. Receives: Drug: Psilocybin (low dose); Other: PEARL Therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: At T2 (2 weeks after the last follow up)

Secondary outcomes (10)

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.
Measured: T3 (6 weeks after last follow up)
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.
Measured: T3 (6 weeks after last follow up)
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.
Measured: T3 (6 weeks after last follow up)
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.
Measured: T3 (6 weeks after last follow up)
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.
Measured: T3 (6 weeks after last follow up)
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.
Measured: T3 (6 weeks after last follow up)
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.
Measured: T3 (6 weeks after last follow up)
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
Measured: T3 (6 weeks after last follow up)
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
Measured: T3 (6 weeks after last follow up)
Adherence feasibility as assessed by the number of participants completing all PEARL sessions.
Used to assess the feasibility of a larger PEARL therapy RCT
Measured: T3 (6 weeks after last follow up)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

14 Sep 202630 Jul 2029

First posted15 Sep 2026
Study start14 Sep 2026 (estimated)
Primary completion30 Dec 2028 (estimated)
Study completion30 Jul 2029 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (58)Papers the sponsor has linked to this study.
Other trials for Advanced CancerStudies of the same condition, open and under way.
More trials run by University Health Network, TorontoThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 2
Primary purpose: Supportive care
Allocation: Randomised
Intervention model: Parallel groups
Model description: Single high-dose capsules of psilocybin or low-dose comparator capsule of psilocybin-control arm) taken orally in the context of Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy.
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 46 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07820033
Sponsor's protocol ID: PEARL RCT
Acronym: PEARL RCT
Status last verified: Oct 2026
First submitted: 17 Aug 2026
Last updated: 15 Oct 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Publications

Freidel N, Kreuder L, Rabinovitch BS, Chen FY, Huang RST, Lewis EC. Psychedelics, epilepsy, and seizures: a review. Front Pharmacol. 2024 Jan 12;14:1326815. doi: 10.3389/fphar.2023.1326815. eCollection 2023.
PubMed 38283836
Kelly DF, Heinzerling K, Sharma A, Gowrinathan S, Sergi K, Mallari RJ. Psychedelic-Assisted Therapy and Psychedelic Science: A Review and Perspective on Opportunities in Neurosurgery and Neuro-Oncology. Neurosurgery. 2023 Apr 1;92(4):680-694. doi: 10.1227/neu.0000000000002275. Epub 2022 Dec 8.
PubMed 36512813
Simonsson O, Goldberg SB, Chambers R, Osika W, Long DM, Hendricks PS. Prevalence and associations of classic psychedelic-related seizures in a population-based sample. Drug Alcohol Depend. 2022 Oct 1;239:109586. doi: 10.1016/j.drugalcdep.2022.109586. Epub 2022 Aug 11.
PubMed 35981469
Doyle MA, Ling S, Lui LMW, Fragnelli P, Teopiz KM, Ho R, Di Vincenzo JD, Rosenblat JD, Gillissie ES, Nogo D, Ceban F, Jawad MY, McIntyre RS. Hallucinogen persisting perceptual disorder: a scoping review covering frequency, risk factors, prevention, and treatment. Expert Opin Drug Saf. 2022 Jun;21(6):733-743. doi: 10.1080/14740338.2022.2063273. Epub 2022 May 3.
PubMed 35426769
Rosenblat JD, Meshkat S, Doyle Z, Kaczmarek E, Brudner RM, Kratiuk K, Mansur RB, Schulz-Quach C, Sethi R, Abate A, Ali S, Bawks J, Blainey MG, Brietzke E, Cronin V, Danilewitz J, Dhawan S, Di Fonzo A, Di Fonzo M, Drzadzewski P, Dunlop W, Fiszter H, Gomes FA, Grewal S, Leon-Carlyle M, McCallum M, Mofidi N, Offman H, Riva-Cambrin J, Schmidt J, Smolkin M, Quinn JM, Zumrova A, Marlborough M, McIntyre RS. Psilocybin-assisted psychotherapy for treatment resistant depression: A randomized clinical trial evaluating repeated doses of psilocybin. Med. 2024 Mar 8;5(3):190-200.e5. doi: 10.1016/j.medj.2024.01.005. Epub 2024 Feb 14.
PubMed 38359838
Harris G, Jones S, Pinkham MB, Lion KM, Ownsworth T. Reliability and validity of the telephone-based version of the Montgomery-Asberg depression rating scale for assessing depression in individuals with primary brain tumour. Disabil Rehabil. 2024 Mar;46(6):1158-1166. doi: 10.1080/09638288.2023.2191015. Epub 2023 Apr 5.
PubMed 37021336
Eskelinen M, Selander T, Ollonen P, Korhonen R. Moderate/severe Depression (MADRS) Can Affect the Quality of Life and Outcome Among Patients Admitted to Breast Cancer Diagnosis Unit. Anticancer Res. 2017 May;37(5):2641-2647. doi: 10.21873/anticanres.11611.
PubMed 28476839
Li M, Fitzgerald P, Rodin G. Evidence-based treatment of depression in patients with cancer. J Clin Oncol. 2012 Apr 10;30(11):1187-96. doi: 10.1200/JCO.2011.39.7372. Epub 2012 Mar 12.
PubMed 22412144
Evans J, Robinson OC, Argyri EK, Suseelan S, Murphy-Beiner A, McAlpine R, Luke D, Michelle K, Prideaux E. Extended difficulties following the use of psychedelic drugs: A mixed methods study. PLoS One. 2023 Oct 24;18(10):e0293349. doi: 10.1371/journal.pone.0293349. eCollection 2023.
PubMed 37874826
Barrett FS, Bradstreet MP, Leoutsakos JS, Johnson MW, Griffiths RR. The Challenging Experience Questionnaire: Characterization of challenging experiences with psilocybin mushrooms. J Psychopharmacol. 2016 Dec;30(12):1279-1295. doi: 10.1177/0269881116678781. Epub 2016 Nov 17.
PubMed 27856683
Rosenblat JD, Li M. Is ketamine a litmus test for capacity in assisted dying with depression? Psychooncology. 2021 Mar;30(3):417-420. doi: 10.1002/pon.5586. Epub 2020 Nov 15. No abstract available.
PubMed 33140440
Lowe B, Unutzer J, Callahan CM, Perkins AJ, Kroenke K. Monitoring depression treatment outcomes with the patient health questionnaire-9. Med Care. 2004 Dec;42(12):1194-201. doi: 10.1097/00005650-200412000-00006.
PubMed 15550799
Borm GF, Fransen J, Lemmens WA. A simple sample size formula for analysis of covariance in randomized clinical trials. J Clin Epidemiol. 2007 Dec;60(12):1234-8. doi: 10.1016/j.jclinepi.2007.02.006. Epub 2007 Jun 6.
PubMed 17998077
O'Cathain A, Murphy E, Nicholl J. Three techniques for integrating data in mixed methods studies. BMJ. 2010 Sep 17;341:c4587. doi: 10.1136/bmj.c4587. No abstract available.
PubMed 20851841
Bowleg L. The problem with the phrase women and minorities: intersectionality-an important theoretical framework for public health. Am J Public Health. 2012 Jul;102(7):1267-73. doi: 10.2105/AJPH.2012.300750. Epub 2012 May 17.
PubMed 22594719

Interested in taking part?

Sarah Hales, MD

416-340-4800 ext. 8051

UHNPPRG@uhn.ca

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 15 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) Therapy for Patients With Advanced Cancer: A Randomized Controlled Trial
ClinicalTrials.gov ID: NCT07820033
Acronym / sponsor ID: PEARL RCT / PEARL RCT
Conditions: Advanced Cancer, Stage IV Solid Tumor Cancer, Stage IV Sarcoma of Bone, Stage IV Lymphoma, Stage IV Melanoma, Endocrine Cancer
Phase: Phase 2
Study type: Interventional
Recruitment status: Not yet recruiting
Enrolment: 46 participants (estimated)
Lead sponsor: University Health Network, TorontoUniversity, hospital or other
Study start: 14 Sep 2026 (estimated)
Primary completion: 30 Dec 2028 (estimated)
Study completion: 30 Jul 2029 (estimated)
First posted: 15 Sep 2026 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Supportive care
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2
Model description: Single high-dose capsules of psilocybin or low-dose comparator capsule of psilocybin-control arm) taken orally in the context of Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy.

Arm	Type	Receives
high-dose group	Experimental	Drug: Psilocybin (high dose), Other: PEARL TherapySingle high dose of psilocybin taken orally in the context of Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy.
low-dose group	Placebo comparator	Drug: Psilocybin (low dose), Other: PEARL TherapySingle low dose of psilocybin taken orally in the context of Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (17 listed)

>/= 18 years of age
Ability to speak and read English fluently (participant to provide written informed consent and participate in PEARL intervention, as determined by study personnel)
Resident of Ontario;
No cognitive impairment indicated in medical record or by attending oncologist or palliative care physician;
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

Key exclusion criteria (15 listed)

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)
Symptoms consistent with delirium, psychosis, or other symptoms judged to be incompatible with establishment of rapport or safe exposure to psilocybin;
A history of past intolerability of psilocybin or other psychedelics;
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);
If participant is under 30 years of age, has first degree relative with a primary psychotic disorder

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Psilocybin (high dose)Single high dose of psilocybin taken orally in the context of Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy	Drug	high-dose group
Psilocybin (low dose)Single low dose of psilocybin taken orally in the context of Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy	Drug	low-dose group
PEARL TherapyPsilocybin-assisted Existential, Attachment and RelationaL (PEARL) therapy	Other	high-dose group, low-dose group

Primary outcome

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

10 secondary outcomes

Number of participants with treatment-related adverse events after PEARL as assessed by the Swiss Psychedelic Side Effects Inventory (SPSI).
Time frame: T3 (6 weeks after last follow up)
Change in mean anxiety symptoms from baseline to T3 as assessed by the Generalized Anxiety Disorder (GAD-7) scale.
Time frame: T3 (6 weeks after last follow up)
Change in death-related distress from baseline to T3 as assessed by the Death and Dying Distress Scale (DADDS).
Time frame: T3 (6 weeks after last follow up)
Change in demoralization symptoms from baseline to T3 as assessed by the Demoralization Scale (DS).
Time frame: T3 (6 weeks after last follow up)
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).
Time frame: T3 (6 weeks after last follow up)
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).
Time frame: T3 (6 weeks after last follow up)
Number of participants with treatment-related adverse events as assessed by CTCAE v6 and the Monitor Rating Questionnaire (MRQ).
Time frame: T3 (6 weeks after last follow up)
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.
Time frame: T3 (6 weeks after last follow up)
Retention feasibility as assessed by the number of participants completing study measures across all time points.
Time frame: T3 (6 weeks after last follow up)
Adherence feasibility as assessed by the number of participants completing all PEARL sessions.
Time frame: T3 (6 weeks after last follow up)

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2026.
Background: PubMed 38283836Freidel N, Kreuder L, Rabinovitch BS, Chen FY, Huang RST, Lewis EC. Psychedelics, epilepsy, and seizures: a review. Front Pharmacol. 2024 Jan 12;14:1326815. doi: 10.3389/fphar.2023.1326815. eCollection 2023.
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Psilocybin-assisted Existential, Attachment and RelationaL (PEARL) Therapy for Patients With Advanced Cancer (NCT06416085)Link provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

Sarah Hales, MD contact

416-340-4800 ext. 8051

UHNPPRG@uhn.ca

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 17 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: opening soon, as of the sponsor's last update on 15 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Sarah Hales, MD (416-340-4800 ext. 8051, UHNPPRG@uhn.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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. (time frame: At T2 (2 weeks after the last follow up)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07820033, which also lists 58 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2026.