Cancer Related Major Depression Treated With a Single Dose of Psilocybin

NCT06319378 | Recruiting Phase 2

• 2 other identifiers: CAPSI no 2 date 2310242023-505532-35-00
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 4

Brief Summary

The goal of this randomized placebo controlled trial is to compare the antidepressant effect of a single oral dose of psilocybin 25 mg compared to 1 mg in 100 patients with cancer related major depressive disorder. The main question it aims to answer is: The primary objective of this study is to evaluate the efficacy of a single 25 mg oral dose of psilocybin for major depressive disorder (MDD) compared to an active placebo (psilocybin 1 mg) assessed as the difference between groups in changes in depressive symptoms, in the following Population: 20-80 (inclusive) years old, current depressive episode (according to Patient Health Questionnaire (PHQ-9) ≥10), \>1 month after cancer diagnosis, with at least 12 months of life expectancy, willingness to abstain from other psychotherapeutic or antidepressant treatments during the study (wash out time 5 half-lives).

Conditions

MDD

Keywords

malignant neoplasm

Outcome Measures

Primary Outcomes (1)

• MADRS at day 42

  Montgomery Asberg Depression Rating Scale (MADRS) total score (0-60, smaller equals better)

  day 42

Secondary Outcomes (16)

• MADRS day 8

  day 8

• MADRS-S at all evaluations between Day 0 and Day 42 (Mixed Models for Repeated Measures (MMRM) x1)

  Day 42

• SDS at Day 42

  Day 42

• CGI at Day 8 and Day 42 (analysis of covariance (ANCOVA) x6)

  Day 8 and 42

• EQ-5D-5L at Day 8 and Day 42 (ANCOVA x6)

  Day 8 and 42

Study Arms (2)

psilocybin 25 mg (active)

EXPERIMENTAL

Drug: psilocybin 25 mg sod

psilocybin 1 mg

ACTIVE COMPARATOR

Drug: psilocybin 1 mg sod

Interventions

psilocybin 25 mg sod DRUG

psilocybin 25 mg sod

psilocybin 25 mg (active)

psilocybin 1 mg sod DRUG

active placebo

psilocybin 1 mg

Eligibility Criteria

• Age: 20 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• signed informed consent via minavårdkontakter.se
• Are 20 to 80 (inclusive) years old at the time of signed informed consent
• Are able to read, speak, and understand Swedish
• Are able and willing to adhere to study requirements, including attending all study visits, preparatory and follow-up sessions, and completing all study evaluations
• Are able to swallow capsules
• Women of childbearing potential (WOCBP) must agree to practice an effective means of birth control throughout the duration of exposure to the Investigational Product, from Screening through the Day 8.
• A diagnosis of a malignant neoplasm with a diagnostic code from C00 to C97 according to the International Classification of Diseases and Related Health Problems, 10th Revision (ICD-10)
• physical functioning performance status 0-2 (World Health Organisation/Eastern Cooperative Oncology Group (WHO/ECOG))
• Meet ICD-10 criteria for a diagnosis of major depressive disorder and are currently experiencing a major depressive episode of at least a 30-day duration at the time of the Screening less than 1 year at time of Screening
• Have moderate-severe depression symptoms at Screening, as defined by a Screening PHQ-9 total score ≥ 10.
• Are willing to abstain from other psychotherapeutic or antidepressant treatments during the study period (180 days; wash out time 5 half-lives). Note, if antidepressant treatment becomes needed as determined by the study physician this will be supported by the study personnel.
• Have an identified support person.
• Agree to be driven/accompanied home (or to an otherwise safe destination) by the support person, or another responsible party, following dosing

You may not qualify if:

• Individuals not eligible to be randomized in this protocol are those who meet any of the following criteria:
• Last contact with health care due to cancer monitoring or treatment \>1 year ago.
• Women who are pregnant, as indicated by a positive urine pregnancy test at Screening or Baseline. Women who intend to become pregnant during the study or who are currently nursing.
• Unwilling or unable to discontinue formal psychotherapy
• Ongoing antidepressant drug treatment. No interruption of ongoing antidepressant treatment will be done on the initiation of the study personnel. Patients will be encouraged to discuss any interruption with their responsible clinical physician.
• Have previously during the current episode received the following non-medication treatments: deep brain stimulation (DBS); vagus nerve stimulation (VNS)
• Currently receiving electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS)
• Unable or unwilling to discontinue any current medications that are known uridine diphosphate (UDP) or glucuronosyltransferase (UGT) enzyme modulators (eg valproate) Note: Any prohibited agents must have been stopped at least 5x the elimination half-life of the specific drug plus one week at the time of Baseline. See Appendix A for a full list of prohibited medications.
• Report psychedelic substances use ever
• o Note: Psychedelic substances include psilocybin, Lysergic acid diethylamide (LSD), mescaline (and natural products containing mescaline including peyote and San Pedro cactus), N,N-Dimethyltryptamine (DMT), natural products containing DMT including ayahuasca and 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT), ibogaine, 3,4-methylenedioxy- methamphetamine (MDMA) or other psychedelics.
• Cancer treatment/follow up regime determined to be incompatible with the CAPSI protocol (eg due to time lines, interaction between cancer treatment and psilocybin 25 mg or 1 mg exposure).
• Have any of the following cardiovascular conditions:
• congenital long QT syndrome (prior diagnosis),
• any of the following if disabling physical exercise similar to walking two stairs without pause: coronary artery disease, cardiac hypertrophy, cardiac ischemia, congestive heart failure
• a clinically significant Screening Electro Cardio-Graphy (ECG) abnormality (e.g., atrial fibrillation);

Sponsors & Collaborators

• Section for Affective Disorders; Northern Stockholm Psychiatry: lead
• Uppsala University Hospital: collaborator
• Region Örebro County: collaborator
• Vastra Gotaland Region: collaborator
• Karolinska Institutet: collaborator

Study Sites (4)

region Västra Götaland

Gothenburg, Göteborg, Sweden

RECRUITING

Norra Stockholms Psykiatri

Stockholm, Stockholm County, Sweden

RECRUITING

Psykiatriska Kliniken, Akademiska Sjukhuset

Uppsala, Uppsala County, Sweden

RECRUITING

Örebro sjukhus

Örebro, Örebro County, Sweden

RECRUITING

Related Publications (1)

• Morel NS, Stenbaek DS, Lundberg J, Beckman M. Evaluation of a facilitator training program in a randomized controlled trial of psilocybin treatment for depression. BMC Med Educ. 2026 Apr 9. doi: 10.1186/s12909-026-09124-8. Online ahead of print.

  PMID: 41952163 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Neoplasms

Interventions

Psilocybin; Superoxide Dismutase

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines; Oxidoreductases; Enzymes; Enzymes and Coenzymes

Study Officials

• Johan Lundberg, MD PhD

  Norra Stockholms Psykiatri and Karolinska Institutet

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Johan Lundberg

CONTACT

0812340000; johan.lundberg@ki.se

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized Controlled Trial, active placebo, randomization ratio 2:1

Study Record Dates

• First Submitted: November 8, 2023
• First Posted: March 20, 2024
• Study Start: April 19, 2024
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: April 13, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

SE (4)