Psilocybin for Caregiver Burnout

(PEARL-C1 Trial)

Overseen By Sarah Hales, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University Health Network, Toronto

Must not be taking: Psychoactive medications, MAO inhibitors

Disqualifiers: Bipolar, Psychotic disorders, Severe hypertension, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a high dose of psilocybin, combined with a special type of therapy, can alleviate burnout in caregivers of advanced cancer patients. Caregiver burnout is a state of physical, emotional, and mental exhaustion resulting from prolonged and intense caregiving. Participants will receive a single 25 mg dose of psilocybin, a psychedelic compound, while undergoing PEARL therapy, which emphasizes existential and relational support. The trial seeks caregivers of advanced cancer patients in Ontario who experience mild anxiety or depression and can attend the therapy sessions. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications for the trial?

You may need to stop taking some medications for the trial, especially those that interact with psilocybin. The study team will guide you on which medications to stop and may help you safely reduce them if needed. You can continue taking opioids for pain as usual.

Is there any evidence suggesting that psilocybin is likely to be safe for humans?

Research has shown that psilocybin is generally safe for humans. Studies have found it may help with mental health issues like depression and burnout. In these studies, most participants did not experience serious side effects. Some reported temporary changes in perception or mood, which are expected with psychedelic treatments.

Psilocybin has been tested on various groups and conditions, enhancing understanding of its safety. Its testing in a phase 2 trial indicates that earlier studies found it safe enough for further research. Overall, while some mild, short-lived side effects occur, evidence suggests psilocybin is a safe option for most people in controlled settings. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for caregiver burnout?

Psilocybin is unique because it offers a novel approach to managing caregiver burnout by potentially tapping into the brain's serotonin receptors. Unlike traditional treatments, which might include therapies like counseling or medications such as antidepressants, psilocybin has the potential to induce profound psychological experiences that could help caregivers reframe their stress and emotional burdens. Researchers are excited about psilocybin because it could provide rapid and lasting relief after just one or two doses, rather than the weeks or months typically required for other treatments to take effect.

What evidence suggests that psilocybin might be an effective treatment for caregiver burnout?

Research shows that psilocybin might help reduce feelings of burnout. Studies have found small-to-moderate improvements in easing stress and burden on caregivers. In group settings, combining psilocybin with mindfulness training has been linked to relief from depression and burnout. Specifically, nearly half of healthcare workers who used psilocybin with meditation were free from depression two weeks after the session. This trial will evaluate psilocybin in the context of PEARL Therapy to determine its effectiveness in addressing caregiver burnout. ^{1 5 6 7 8}

Who Is on the Research Team?

Sarah Hales, MD, PhD

Principal Investigator

Princess Margaret Cancer Centre

Are You a Good Fit for This Trial?

This trial is for caregivers experiencing burnout from looking after patients with advanced cancer. Participants must meet certain health and psychological criteria to be eligible, which are not specified here.

Inclusion Criteria

I am 18 years old or older.

I am willing and able to follow the PEARL study plan.

My liver functions are normal.

Exclusion Criteria

History of past intolerability to psilocybin or other psychedelics

Psychiatric diagnoses of bipolar disorder, any psychotic disorder, active substance use disorders, or dementia

Clinically significant suicidal ideation either currently or within the past 6 months

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Preparatory Therapy Sessions

Participants undergo preparatory therapy sessions as part of the PEARL therapy

2-4 weeks

Psilocybin Session

Participants receive a single high-dose (25 mg) of psilocybin in a monitored setting

1 day

1 visit (in-person)

Integration Sessions

Participants engage in integration sessions to process the psilocybin experience

2-4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

30 months

What Are the Treatments Tested in This Trial?

Interventions

• Psilocybin

Trial Overview The PEARL-C1 trial is testing the effects of a single high-dose (25 mg) of psilocybin given alongside specialized therapy designed to help with existential, attachment, and relational issues faced by caregivers.

How Is the Trial Designed?

Group I: PEARL Therapy Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Citations

1. capmh.biomedcentral.com capmh.biomedcentral.com/articles/10.1186/s13034-025-00930-4

Leveraging family and caregiver support in psychedelic ... This review provides recommendations and unique considerations for the incorporation of caregivers into PAT protocols for adolescents to maximize safety and ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11658675/

Examining the Rationale for Studying Psychedelic-Assisted ... The results of these studies have generally revealed small-to-moderate improvements in perceived caregiver burden and associated distress with effect sizes ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05163496

NCT05163496 | Frontline Clinician Psilocybin Study Hypothesis 2.1: Compared to active placebo, PAP will result in short term improvement in symptoms of burnout 1 day and 1 week after the psilocybin dose session.

4. journals.plos.org journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1004519

Psilocybin-assisted group psychotherapy and mindfulness ... These findings suggest that group psilocybin-assisted therapy, when combined with mindfulness training, may provide greater relief from depression and burnout ...

5. attheu.utah.edu attheu.utah.edu/health-medicine/psilocybin-shows-promise-for-health-care-worker-depression/

Psilocybin shows promise for health care worker depression Nearly half of health care workers who received psilocybin alongside meditation instruction were free of depression at two weeks in a ...

6. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2827553

Psilocybin Therapy for Clinicians With Symptoms of ... This randomized clinical trial examines the effect of psylocibin on the level of depression, burnout, and posttraumatic stress disorder ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11621983/

Psilocybin Therapy for Clinicians With Symptoms of ... This randomized clinical trial examines the effect of psylocibin on the level of depression, burnout, and posttraumatic stress disorder among US physicians.

8. harvardpublichealth.org harvardpublichealth.org/mental-health/can-mushrooms-beat-burnout-clinicians-sign-up-to-see/

Can psilocybin treat burnout? Clinicians sign up to see The study will show that psilocybin opens the clinicians up to thinking about new ways to cope with their memories and fear of the future.