Major Depressive DisorderPhase 2NCT05259943
Microdosing Psychedelics to Improve Mood
A Phase 2 study testing Psilocybin first in people with Major Depressive Disorder, run by Rotem Petranker at 1 site in Canada.
Trial summary
This trial aims to examine the safety and efficacy of small (2mg) sub-hallucinogenic doses of psilocybin in people with Major Depressive Disorder. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Psilocybin first
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 39 participants
- Where
- 1 siteCanada
- Study dates
- 15 Jul 2023to 1 Feb 2025
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participants must:
- Have given written informed consent.
- Have a high school level of education.
- Be fluent in speaking and reading the study site's predominantly used or recognized language (i.e., English).
- Be 18 to 65 years old.
- If of childbearing potential, must have a negative pregnancy test at study entry and must agree to use adequate birth control 10 days after the last Experimental Session (refer to section 9.4.2 for contraceptive guidelines).
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- Have a preexisting diagnosis of MDD with dysthymic subtype or receive a diagnosis of MDD during screening.
- Agree that for one week preceding each psilocybin session, they will refrain from taking any nonprescription medication, nutritional supplements, or herbal supplement except when approved by the research team. Exceptions will be evaluated by the research team and will include acetaminophen, non-steroidal anti-inflammatory drugs, and common doses of vitamins and minerals with the exception of SAM-e, 5-HTP, L-tryptophan, and St. John's Wort.
- Agree to consume approximately the same amount of caffeine-containing beverage (i.e. coffee, tea) that they consume on a usual morning, before arriving at the research unit on the mornings of psilocybin session days. Caffeine consumption should not exceed more than ≥600mg/day. If the patient does not routinely consume caffeinated beverages, they must agree not to do so on psilocybin session days.
- Agree not to take any as needed (PRN) medications on the mornings of psilocybin sessions. Non-routine PRN medications for treating breakthrough pain that were taken in the 24 hours before the psilocybin session may result in rescheduling the treatment session, with the decision at the discretion of the investigators.
- Agree to refrain from using any psychoactive drugs, including alcoholic beverages, within 24 hours of each psilocybin administration. As described elsewhere, exceptions include daily use of caffeine.
Who cannot join
- The subject has participated in another investigational study within 60 days prior to the screening visit.
- Cardiovascular conditions: coronary artery disease, uncontrolled hypertension, angina, a clinically significant ECG abnormality (i.e. atrial fibrillation), TIA in the last 6 months, stroke, peripheral or pulmonary vascular disease (no active claudication).
- Blood pressure exceeding screening criteria described below:
- ○ Cardiovascular screening:
- At the screening and randomization visit, blood pressure will be assessed to qualify to proceed in the trial. Each assessment occasion will involve two or more blood pressure readings. To qualify for the study, the mean blood pressure (mmHg) of the two readings will not exceed 140 systolic and 90 diastolic.
- Blood pressure (BP) will be taken while subjects are at rest and have been seated or supine for at least 5 minutes. The assessment will involve the average of 2 or more readings separated by fifteen minutes. If the first 2 readings differ by more than 5 mmHg, additional readings will be obtained and averaged. During the BP assessment, the volunteer will be acclimated to the automated blood pressure monitoring equipment by repeatedly taking blood pressure (at least 3 readings) with the device.
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- Epilepsy with a history of seizures.
- The subject has a history of cerebral ischemia, transient ischemic attack, intracranial aneurysm, or arteriovenous malformation.
- The subject has a clinically significant history of head injury or head trauma per the judgement of the investigator.
- The subject has a history of cancer.
- Unstable medical condition, severe renal disease (creatinine clearance < 40 ml/min using the Cockcroft and Gault equation), hepatic disease (known history of liver disease, abnormal elevations in LFTs), or serious central nervous system pathology.
- Insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of hypoglycemia.
- Are pregnant (positive urine pregnancy test assessed at screening) or nursing, or are of childbearing potential and are not practicing an effective means of birth control (refer to section 9.4.2 for contraceptive guidelines).
- Currently taking on a regular (i.e. daily) basis any psychotropic medications including: investigational agents, psychoactive prescription medications (i.e. benzodiazepines), antidepressants, medications having a primary pharmacological effect on serotonin neurons (i.e. ondansetron), medications that are MAO inhibitors, opioid medications. If previously on antidepressants a minimum of five half lives must have passed from the last dose of medication plus an additional seven days of stabilization before first administration of the drug.
- Current use of any the following of potent metabolic inducers or inhibitors: Inducers - Rifamycin (rifampin, rifabutin, rifapentine), anticonvulsants (carbamazepine, phenytoin, Phenobarbital), Nevirapine, Efavirenz, Taxol, Dexamethasone), St John's Wort; All cytochrome P450 Inhibitors - including all HIV protease inhibitors, verapamil, diltiazem, itraconazole, ketoconazole, erythromycin, clarithromycin, azithromycin, and troleandomycin.
- Use of steroids within the past two weeks.
- Current use of the following drugs will also meet exclusion criteria: ergot alkaloids, pimozide, midazolam, triazolam, lovastatin, simvastatin, fentanyl.
- Agree to refrain from using any psychoactive drugs, including alcoholic beverages within 24 hours of each drug administration. The exception is caffeine.
- Must not be a habitual smoker.
- Refrain from starting any new medications.
- Refrain from starting any new complementary or alternative medicine practices (i.e. nutrition/diet modifications, supplements, meditation practice, etc.).
- Are willing to comply with medication requirements per the protocol (refer to Section 6.2).
- Lifestyle Criteria; Refrain from working night shifts.
- Psychiatric Exclusion Criteria:
- Current or past history of meeting DSM-V criteria for Schizophrenia, Psychotic Disorder, or Bipolar I or II Disorder.
- Active Major Depressive Disorder Episode.
- Having a first or second-degree relative with schizophrenia, psychotic disorder (unless substance-induced or due to a medical condition), or bipolar I or II disorder.
- Currently meets DSM-V criteria for Dissociative Disorder, Anorexia Nervosa, Bulimia Nervosa, or other psychiatric conditions judged to be incompatible with the establishment of rapport or safe exposure to psilocybin.
- Current or past history within the last 5 years of meeting DSM-V criteria for a moderate or severe alcohol or drug use disorder (excluding caffeine and nicotine).
- Use within 6 months of psychedelic substances.
Trial locations and contacts
1 site in 1 country.
About this study
This trial aims to examine the safety and efficacy of small (2mg) sub-hallucinogenic doses of psilocybin in people with Major Depressive Disorder.
Read the detailed description
This protocol is for a University of Toronto - sponsored, randomized, placebo-controlled crossover phase 2 study of the safety and efficacy of low doses of psilocybin in subjects with depressive symptoms who meet Diagnostic and Statistical Manual 5 (DSM-5) criteria for diagnosis of a major depressive disorder (MDD) and who are either unwilling to pursue standard treatment (psychotherapy and/or pharmacotherapy) or have previously been non-responsive to standard treatment. This feasibility study will assess whether microdosing has a short-term impact on participant ratings of depressive symptoms. Participants will be administered one dose of either placebo or psilocybin once weekly for four weeks, and then all participants will be administered a dose of psilocybin once weekly for four additional weeks. Short surveys will be collected once weekly three days after the administration of psilocybin/placebo, and follow-ups will occur for up to two years following the beginning of the trial. Using this design will maximize the experimental power to detect an effect if one exists and would inform future research on microdosing in terms of duration, effect size, and expectancy bias.
- Conditions
- Major Depressive Disorder
- Being tested
- Psilocybin first, Placebo first
- Keywords
- Psilocybin, Psychedelics, Creativity, Mindfulness, Depression
- Medical subject headings
- Depressive Disorder, Major, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Psilocybin firstDrug
Participants will receive 8 doses of 2mg psilocybin.
Placebo firstDrug
Participants will receive 4 doses of placebo followed by 4 doses of 2mg psilocybin
| Study group | Role | What they receive |
|---|---|---|
| Blinded Placebo | Placebo comparator | In this condition participants will receive an inert placebo once weekly for 4 weeks, but they will not know whether they receive placebo or psilocybin. Receives: Drug: Placebo first |
| Blinded Psilocybin | Experimental | In this condition participants will receive psilocybin once weekly for 4 weeks, but they will not know whether they receive placebo or psilocybin. Receives: Drug: Psilocybin first |
| Open Label | Experimental | In this condition participants will receive psilocybin once weekly for 4 weeks, and will be told that they are receiving psilocybin. Receives: Drug: Psilocybin first; Drug: Placebo first |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Patient Health Questionnaire Somatic-Anxiety-Depression
The PHQ-SADS is a 32-item self-report subset of the full PHQ designed to detect the co-occurrence of somatic, anxiety, and depressive symptoms (the SAD triad). Responses are measured using a likert scale between 0 (not bothered) and 2 (bothered a lot). Higher scores suggest more severe depressive symptoms.
Measured: This measure will be used at every lab visit: at baseline, and then once a week for eight weeks or until participants exit the study.
SCID-5 (Structured Clinical Interview for DSM-5)
The Structured Clinical Interview for DSM-5 (SCID) was designed as a brief structured diagnostic interview for the major psychiatric disorders in the DSM-5 (First \& Williams, 2020). Validation and reliability studies have shown that the psychometric indicators of this version of the instrument is in accordance with the quality parameters of the health status instruments (Osório et al., 2019).
Measured: This study will use the SCID screening module, and the mood disorders module for screening purposes at baseline, and administer the mood disorders module again on visit 5 (four weeks after baseline) and visit 9 (eight weeks after baseline).
Secondary outcomes (2)
DAS-A-17 (Dysfunctional Attitudes Scale, 17 item)
The DAS-A-17 is a short-version of the Dysfunctional Attitude Scale, a 40-item self-report scale designed to measure the presence and intensity of dysfunctional beliefs (de Graaf, Roelofs, \& Huibers, 2009). Participants rate statements of beliefs (e.g., "If I fail at my work, then I am a failure as a person.") on a 7-point Likert scale and the total score is the sum of the 17-items (range: 17-119) with higher scores indicating more dysfunctional attitudes (Weissman \& Beck, 1978). The DAS-A-17 includes a total score and two subscales: perfectionism/performance evaluation (11 items) and dependency (6 items). Reliability for total score was excellent (α = 0.91) and good for the subscales (perf: α = 0.87, dep: α = 0.85) (Anderson et al., 2019).
Measured: This measure will used at every physical lab visit: at baseline, and then once a week for eight weeks or until participants exit the study. It will also be administered 3 days after each physical lab visit.
Quick Inventory Of Depressive Symptomatology (QIDS)
The Quick Inventory of Depressive Symptomatology (QIDS) is a widely used clinical assessment tool designed to measure the severity of depressive symptoms in individuals. Developed by Rush et al. in 2003, the QIDS is a self-report questionnaire consisting of 16 items that assess various domains of depression, including mood, sleep disturbance, energy level, concentration, and suicidal ideation. The QIDS has demonstrated excellent psychometric properties, displaying high internal consistency (Cronbach's α = 0.86) and test-retest reliability (intraclass correlation coefficient = 0.84) (Rush et al., 2003). Furthermore, it has shown strong concurrent validity when compared to other established depression rating scales, such as the Hamilton Rating Scale for Depression (r = 0.84) and the Montgomery-Asberg Depression Rating Scale (r = 0.87) (Rush et al., 2003). Due to its brevity, ease of administration, and sound psychometric properties, the QIDS has become a valuable tool for clinicians and
Measured: This measure will used at every physical lab visit: at baseline, and then once a week for eight weeks or until participants exit the study. It will also be administered 3 days after each physical lab visit.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2022
- Study start15 Jul 2023
- Primary completion21 Dec 2024
- Study completion1 Feb 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- This trial starts as a placebo-control for 4 weeks and then becomes Open Label for 4 additional weeks. Follow-up assessments will be performed weekly for the first 4 weeks following the last Open Label week.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 39 participants (actual)
Sponsor and investigators
- Lead sponsor
- Rotem Petranker
- Sponsor type
- University, hospital or other
- Collaborators
- Nikean Foundation
- Responsible party
- Sponsor-investigator, Rotem Petranker, University of Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05259943
- Sponsor's protocol ID
- ABC123DRM
- Status last verified
- Oct 2026
- First submitted
- 15 Feb 2022
- Last updated
- 20 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: We will pre-register our study and we will make our data available. Whether IPD will be available is TBD.
Publications
Beidas Z, Ragnhildstveit A, Blackman A, Anderson T, Fewster E, Syed OA, Sobolenko V, Kanca IK, Jaglinska M, Son T, Farb N, Petranker R. Microdosing psilocybin for major depressive disorder: study protocol for a phase II double-blind placebo-controlled randomised partial crossover trial. BJPsych Open. 2026 Feb 16;12(2):e65. doi: 10.1192/bjo.2025.10968.
PubMed 41693474
Study at a glance
From the registry record, last updated by the sponsor on 20 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Microdosing Psychedelics to Improve Mood
- ClinicalTrials.gov ID
- NCT05259943
- Acronym / sponsor ID
- ABC123DRM
- Conditions
- Major Depressive Disorder
- Keywords
- Psilocybin, Psychedelics, Creativity, Mindfulness, Depression
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 39 participants (actual)
- Lead sponsor
- Rotem PetrankerUniversity, hospital or other
- Collaborators
- Nikean Foundation
- Study start
- 15 Jul 2023 (actual)
- Primary completion
- 21 Dec 2024 (actual)
- Study completion
- 1 Feb 2025 (actual)
- First posted
- 2 Mar 2022 (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.
This trial aims to examine the safety and efficacy of small (2mg) sub-hallucinogenic doses of psilocybin in people with Major Depressive Disorder.
Detailed description
This protocol is for a University of Toronto - sponsored, randomized, placebo-controlled crossover phase 2 study of the safety and efficacy of low doses of psilocybin in subjects with depressive symptoms who meet Diagnostic and Statistical Manual 5 (DSM-5) criteria for diagnosis of a major depressive disorder (MDD) and who are either unwilling to pursue standard treatment (psychotherapy and/or pharmacotherapy) or have previously been non-responsive to standard treatment. This feasibility study will assess whether microdosing has a short-term impact on participant ratings of depressive symptoms. Participants will be administered one dose of either placebo or psilocybin once weekly for four weeks, and then all participants will be administered a dose of psilocybin once weekly for four additional weeks. Short surveys will be collected once weekly three days after the administration of psilocybin/placebo, and follow-ups will occur for up to two years following the beginning of the trial. Using this design will maximize the experimental power to detect an effect if one exists and would inform future research on microdosing in terms of duration, effect size, and expectancy bias.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
- Model description
- This trial starts as a placebo-control for 4 weeks and then becomes Open Label for 4 additional weeks. Follow-up assessments will be performed weekly for the first 4 weeks following the last Open Label week.
| Arm | Type | Receives |
|---|---|---|
| Blinded Placebo | Placebo comparator | Drug: Placebo firstIn this condition participants will receive an inert placebo once weekly for 4 weeks, but they will not know whether they receive placebo or psilocybin. |
| Blinded Psilocybin | Experimental | Drug: Psilocybin firstIn this condition participants will receive psilocybin once weekly for 4 weeks, but they will not know whether they receive placebo or psilocybin. |
| Open Label | Experimental | Drug: Psilocybin first, Drug: Placebo firstIn this condition participants will receive psilocybin once weekly for 4 weeks, and will be told that they are receiving psilocybin. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Have given written informed consent.
- Have a high school level of education.
- Be fluent in speaking and reading the study site's predominantly used or recognized language (i.e., English).
- Be 18 to 65 years old.
- If of childbearing potential, must have a negative pregnancy test at study entry and must agree to use adequate birth control 10 days after the last Experimental Session (refer to section 9.4.2 for contraceptive guidelines).
Key exclusion criteria (30 listed)
- The subject has participated in another investigational study within 60 days prior to the screening visit.
- Cardiovascular conditions: coronary artery disease, uncontrolled hypertension, angina, a clinically significant ECG abnormality (i.e. atrial fibrillation), TIA in the last 6 months, stroke, peripheral or pulmonary vascular disease (no active claudication).
- Blood pressure exceeding screening criteria described below:
- Epilepsy with a history of seizures.
- The subject has a history of cerebral ischemia, transient ischemic attack, intracranial aneurysm, or arteriovenous malformation.
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 firstParticipants will receive 8 doses of 2mg psilocybin. | Drug | Blinded Psilocybin, Open Label |
| Placebo firstParticipants will receive 4 doses of placebo followed by 4 doses of 2mg psilocybin | Drug | Blinded Placebo, Open Label |
Primary outcome
Change in Patient Health Questionnaire Somatic-Anxiety-Depression
Time frame: This measure will be used at every lab visit: at baseline, and then once a week for eight weeks or until participants exit the study.
The PHQ-SADS is a 32-item self-report subset of the full PHQ designed to detect the co-occurrence of somatic, anxiety, and depressive symptoms (the SAD triad). Responses are measured using a likert scale between 0 (not bothered) and 2 (bothered a lot). Higher scores suggest more severe depressive symptoms.
SCID-5 (Structured Clinical Interview for DSM-5)
Time frame: This study will use the SCID screening module, and the mood disorders module for screening purposes at baseline, and administer the mood disorders module again on visit 5 (four weeks after baseline) and visit 9 (eight weeks after baseline).
The Structured Clinical Interview for DSM-5 (SCID) was designed as a brief structured diagnostic interview for the major psychiatric disorders in the DSM-5 (First \& Williams, 2020). Validation and reliability studies have shown that the psychometric indicators of this version of the instrument is in accordance with the quality parameters of the health status instruments (Osório et al., 2019).
2 secondary outcomes
DAS-A-17 (Dysfunctional Attitudes Scale, 17 item)
Time frame: This measure will used at every physical lab visit: at baseline, and then once a week for eight weeks or until participants exit the study. It will also be administered 3 days after each physical lab visit.
Quick Inventory Of Depressive Symptomatology (QIDS)
Time frame: This measure will used at every physical lab visit: at baseline, and then once a week for eight weeks or until participants exit the study. It will also be administered 3 days after each physical lab visit.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Oct 2026.
- Derived from this study: PubMed 41693474Beidas Z, Ragnhildstveit A, Blackman A, Anderson T, Fewster E, Syed OA, Sobolenko V, Kanca IK, Jaglinska M, Son T, Farb N, Petranker R. Microdosing psilocybin for major depressive disorder: study protocol for a phase II double-blind placebo-controlled randomised partial crossover trial. BJPsych Open. 2026 Feb 16;12(2):e65. doi: 10.1192/bjo.2025.10968.
- Individual participant dataSharing planned: Undecided. We will pre-register our study and we will make our data available. Whether IPD will be available is TBD.
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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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Psilocybin first in people with Major Depressive Disorder, run by Rotem Petranker at 1 site in Canada.
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 11 inclusion and 30 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: finished, as of the sponsor's last update on 20 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Patient Health Questionnaire Somatic-Anxiety-Depression (time frame: This measure will be used at every lab visit: at baseline, and then once a week for eight weeks or until participants exit the study.). The study lists 2 primary outcomes in all. 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 NCT05259943, which also lists 1 linked publication.
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 20 Oct 2026.