Major Depressive Disorder MedDRA version: 20.0 Level: LLT Classification code 10025462 Term: Major depressive disorder, recurrent episode, unspecified degree System Organ Class: 100000004873
Conditions
Interventions
Product Name: Psilocybin
Product Code: Psilocybin
Pharmaceutical Form: Capsule
INN or Proposed INN: PSILOCYBINE
CAS Number: 520-52-5
Current Sponsor code: Psilocybin
Concentration unit: mg milligram(s
Sponsors
SLSO
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria Individuals eligible to be randomized in this protocol are those who meet all of the following criteria: 1. Are 20 to 65 years old at the time of written informed consent at the In-Person Screening visit 2. Are able to read, speak, and understand Swedish 3. Are able and willing to adhere to study requirements, including attending all study visits, preparatory and follow-up sessions, and completing all study evaluations 4. Are able to swallow capsules 5. Women of childbearing potential (WOCBP) must agree to practice an effective means of birth control throughout the duration of the study, from Screening through the Day 42 assessment 6. Meet ICD-10 criteria for a diagnosis of remitting major depressive disorder and are currently experiencing a major depressive episode of a) at least a 30-day duration at the time of the Screening b) less than 5 years at time of Screening 7. Have sustained moderate-severe depression symptoms at Screening and Baseline, as defined by a Screening MADRS total score = 22 and =30% and =7 point improvement (i.e. decrease) in MADRS total score from web-screening to screening visit (assuming 3 points on item 1 at web screening). 9. Have an identified support person a. Agree to be driven/accompanied home (or to an otherwise safe destination) by the support person, or another responsible party, following dosing Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Exclusion Criteria Individuals not eligible to be randomized in this protocol are those who meet any of the following criteria: 1. 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. 2. Current depressive episode lasting >5 years 2. Unwilling or unable to discontinue formal psychotherapy 3. Ongoing antidepressant drug treatment 4. Have previously during the current episode received the following non-medication treatments: a. deep brain stimulation (DBS) b. vagus nerve stimulation (VNS) 5. Currently receiving electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) 6. Unable or unwilling to discontinue any current medications that are known uridine diphosphate (UDP) or glucuronosyltransferase (UGT) enzyme modulators (eg valproate) o Note: Any prohibited agents must have been stopped at least 5x the elimination half-life of the specific drug at the time of Baseline. See Appendix A for a full list of prohibited medications. 7. 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, 2C compounds, 3,4-methylenedioxy- methamphetamine (MDMA), methylone or other psychedelics. 8. Have the following cardiovascular conditions: a. coronary artery disease, congenital long QT syndrome (prior diagnosis), cardiac hypertrophy, cardiac ischemia, congestive heart failure, myocardial infarction (prior diagnosis); b. tachycardia (defined as heart rate > 100 beats per minute); c. a clinically significant Screening ECG abnormality (e.g., atrial fibrillation); oNote: A QTcF interval > 450 milliseconds is considered a clinically significant ECG abnormality d. artificial heart valve; or e. any other significant current or history of cardiovascular condition, based on the clinical judgment of study physician, that would make a participant unsuitable for the study 9. At Screening or Baseline have elevated blood pressure as defined as: a. Screening blood pressure SBP >135 mmHg or DBP > 85 mmHg on three separate readings; or b. Baseline blood pressure SBP >140 mmHg or DBP > 90 mmHg on three separate readings 10. Have a history of stroke or Transient Ischemic Attack (TIA) 11. Have moderate to severe hepatic impairment, as indexed by a Child-Pugh score = 7 12. Have epilepsy 13. Have insulin-dependent diabetes o Note: Participants who are taking oral hypoglycemic agent and have a history of hypoglycemia requiring medical intervention will be excluded 14. Are unable or unwilling to adhere to the following medication requirements: a. Agree to suspend sildenafil (Viagra®), tadalafil, or similar medications at least 72 hours prior to dosing b. If taking any supplement containing >20 mg of niacin, agrees to suspend use for the duration of the study 15. Have a positive urine drug test including Amphetamines, Barbiturates, Buprenorphine, Benzodiazepines, Cocaine, Cannabis, Methamphetamine, MDMA, Methadone, Opiates (Morphine, Oxycodone), Phencyclidine (PCP), and Tetrahydrocannabinol (THC). Exceptions are made for prescribed Benzodiazepines (stable dose for sleep or anxiety). o Note: Benzodiazepine
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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 (niacin) in otherwise medically-healthy participants between the ages of 20 and 65, assessed as the difference between groups in changes in depressive symptoms.;Secondary Objective: One secondary objective is to evaluate the effect of psilocybin on synaptic density in prefrontal cortex and hippocampus, by comparing the change in [11C]UCB-J binding after psilocybin and placebo dosing. The other exploratory objective is to study the clinical effect on depressive symptoms, clinical global impression, perceived disability and of post treatment use of antidepressants. Exploratory objectives: is to evaluate the effect of psilocybin on biological markers of synaptogenesis, neuroinflammation, serotonergic activity and on self-rated depressive symptoms, reversal fear learning, clinical global functioning, anxiety symptoms, functional disability, health-related meaning of/satisfaction with life and psychological flexibility, subjective psychedelic experiences, participants’ expectations prior to the/experience of the intervention, and facilitator and participants’ in-session behaviors.;Primary end point(s): Primary Outcome Measure Change in blinded rater MADRS total score from Baseline to Day 8. ;Timepoint(s) of evaluation of this end point: Day 8 after dosing | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary Outcome Measures • Relative increase (ratio) in [11C]UCB-J binding from Baseline to Day 15 post dose • Change in MADRS total score from Baseline to Day 15, 42, 180 and 365 (end of study) respectively • Change in MADRS total score from Baseline to the treatment period (mean of Day 8-365) • Change in MADRS-S score from Baseline to Day 365 (end of study) • Change in MADRS-S score from Baseline to the treatment period (mean of Day 8-365) • Response rate at all time points post dose (MADRS and MADRS-S) • Remission rate at all time points post dose (MADRS and MADRS-S) • Change in Sheehan Disability Scale (SDS) score from Baseline to Day 365 (end of study) • Change in SDS score from Baseline to the treatment period (mean of Day 8-365) • Change in Clinical Global Impression (CGI) score from Baseline to Day 8, 42, 180 and 365 (end of study) respectively • Change in CGI score from Baseline to the treatment period (mean of Day 8-365) • Time to initiation of antidepressant treatment in follow up phase (day 43-365) Exploratory Outcome Measures 1. Biomarkers 1.1. fMRI BOLD signal 1.2. fMRI activation paradigms post dosing 1.3. p11 (blood) 1.4. BDNF and VEGF (plasma) 1.5. monoamines and monoamine metabolites (CSF) 1.6. cytokines (CSF) 1.7. kynurenic acid and metabolites (CSF) 2. Scales 2.1. General Anxiety Disorder 7 (GAD-7) 2.2. Euroqol five dimension five level (E-5D-5L) 2.3. Euroqol visual analogue scale (EQ-VAS) 2.4. Mystical Experience Questionnaire (MEQ) 2.5. Emotional Breakthrough Inventory (EBI) 2.6. Challenging Experience Questionnaire (CEQ) 2.7. Lasting Effects Questionnaire (LEQ) 2.8. Treatment Expectation and Evaluation questionnaires 2.9. Meaning of Life Questionnaire (MLQ) 2.10. Satisfaction with Life Scale (SWLS) 2.11. Acceptance in Action Questionnaire (AAQ-II) 2.12. The Actively Living and Interconnecting Vitally in one’s Embedded-world (ALIVE) Questionnaire 2.13. Working Alliance Inventory-Short (WAI-S) 2.14. Motivational I | — |
Countries
Sweden
Contacts
Public ContactPSIPET information
SLSO
Outcome results
None listed