Treatment Resistant DepressionPhase 2SYNVESTNCT06512220
Imaging the Effects of Serotonin 2A Receptor Modulation on Synaptic Density in Treatment-resistant Depression (SYNVEST)
A Phase 2 study testing Psilocybin 25 mg and Risperidone 1 MG in people with Treatment Resistant Depression, run by Centre for Addiction and Mental Health at 1 site in Canada.
Trial summary
Psilocybin, the chemical component of "magic mushrooms", has been administered with psychotherapy in several randomized clinical trials (RCTs) showing large and sustained antidepressant effects. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Treatment Resistant Depression
- What is being tested?
- Psilocybin 25 mg and Risperidone 1 MG
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteCanada
- Study dates
- 21 Apr 2025to Sep 2027
- 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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adults 18 to 65 years old;
- Must be deemed to have capacity to provide informed consent;
- Must sign and date the informed consent form;
- Stated willingness to comply with all study procedures;
- Ability to read and communicate in English, such that their literacy and comprehension is sufficient for understanding the consent form and study questionnaires, as evaluated by study staff obtaining consent;
- Primary DSM-5 diagnosis of non-psychotic MDD, single or recurrent, based on the Structured Clinical Interview for DSM-5 (SCID-5) administered at the first screening visit;
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- Participants diagnosed with treatment-resistant depression defined as individuals with a baseline HamD-17 score > 14 and that have not responded to two or more separate trials of antidepressants at an adequate dosage and duration based on the Antidepressant Treatment History Form Short Form (ATHF-SF) (Sackeim et al., 2019); there is no upper limit on the number of treatment failures;
- Ability to take oral medication;
- Individuals who are capable of becoming pregnant: use of highly effective contraception for at least 3 months prior to screening and agreement to use such a method during study participation;
- Individuals who are willing to taper off current antidepressant and antipsychotic medications for a minimum of 2-weeks (or more depending on the medication) prior to Baseline (V2) and whose physician confirms that it is safe for them to do so; and
- Agreement to adhere to Lifestyle Considerations (section 4.5) throughout study duration.
Who cannot join
- Pregnant as assessed by a urine pregnancy test at Screening (V1) or individual's that intend to become pregnant during the study or are breastfeeding;
- Treatment with another investigational drug or other intervention within 30 days of Screening (V1);
- Have initiated psychotherapy in the preceding 12 weeks prior to Screening (V1);
- Have a DSM-5 diagnosis of substance use disorder (use of tobacco is permitted) within the preceding 6 months;
- Have active suicidal ideation with intent and plan as determined by item 3 of the HamD-17;
- Any DSM-5 lifetime diagnosis of a schizophrenia-spectrum disorder; obsessive-compulsive disorder, psychotic disorder (unless substance induced or due to a medical condition), bipolar I or II disorder, paranoid personality disorder, borderline personality disorder, or neurocognitive disorder as determined by medical history and the SCID-5 clinical interview;
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- Any first-degree relative with a diagnosis of schizophrenia-spectrum disorder; psychotic disorder (unless substance-induced or due to a medical condition); or bipolar I disorder as determined by the family medical history form and discussions with the participant;
- Presence of a relative or absolute contraindication to psilocybin, including a drug allergy, recent stroke history, uncontrolled hypertension, low or labile blood pressure, recent myocardial infarction, cardiac arrhythmic, severe coronary artery disease, or moderate to severe renal or hepatic impairment.
- Presence of baseline prolonged QTc or Torsade de Pointes as measured by the ECG or a history of long QTc syndrome or related risk factors;
- History of allergy or contraindication to risperidone
- Current or past traumatic brain injury or other neurological/neurodegenerative disorder
- Unable or unwilling to undergo PET or MRI scanning (e.g. claustrophobia, pacemaker);
- Blood disorders, disorders of coagulation, or ongoing use of anticoagulant medication
- Any disability that may prevent the participant from completing study requirements (e.g., non-correctable clinically significant sensory impairment such as not hearing well enough to communicate with study personnel during scans, or physical disability that does not allow them to lie still on the scanner bed for 1-2 hours);
- Participant exceeds the annual or lifetime amount of radiation
- Any other clinically significant physical illness including chronic infectious diseases or any other major concurrent illness that, in the opinion of the investigator, may interfere with the interpretation of the study results or constitute a health risk for the participant if they take part in the study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Psychedelics Research contact
Canada1 site, 1 recruiting
- Recruiting
Centre for Addiction and Mental Health
Toronto, Ontario, M6J1H4
Emily Gilbert, MSc, 416-535-8501 ext. 39570, emily.gilbert@camh.ca
Psychedelics Research, psychedelics.research@camh.ca
About this study
Psilocybin, the chemical component of "magic mushrooms", has been administered with psychotherapy in several randomized clinical trials (RCTs) showing large and sustained antidepressant effects. In healthy volunteers, the psychedelic effects of psilocybin have been shown to be blocked by administration of certain medications such as risperidone.
The purpose of this study is to use an established SV2A radiotracer produced at our Centre to determine the feasibility of integrating PET imaging in to psilocybin trials. The preliminary imaging data will assess whether psilocybin's antidepressant effects are related to changes in synaptic density in adults with TRD, and whether any changes in synaptic density are associated with psilocybin's actions on the 5-HT2AR.
- Conditions
- Treatment Resistant Depression
- Being tested
- Psilocybin 25 mg, Risperidone 1 MG
- Keywords
- Psilocybin, Psychedelics, Clinical Trial, Positron-Emission Tomography, Treatment Resistant Depression, Neurophysiology Testing, Magnetic Resonance Imaging
- Medical subject headings
- Depressive Disorder, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Psilocybin 25 mgDrug
Also called PEX010
The psilocybin used in this study meets quality specifications suitable for human research use. The active drug is encapsulated using a hydroxypropyl methylcellulose (HPMC) capsule and contains 25 mg of psilocybin. The psilocybin will be administered once during the trial in combination with or without risperidone 1 mg. It will also be administered in conjunction with supportive therapy.
Risperidone 1 MGDrug
Also called MAR-Risperidone
The risperidone is encapsulated using a cellulose capsule and contains 1 mg of risperidone. The risperidone will be administered once during the trial in combination with psilocybin 25 mg. It will also be administered with supportive therapy.
| Study group | Role | What they receive |
|---|---|---|
| Risperidone (1 mg) + Psilocybin (25 mg) | Experimental | o One capsule of risperidone 1 mg will be taken first followed 60 minutes later by one capsule of psilocybin 25 mg. Both capsules will be taken orally with a glass of water. Receives: Drug: Psilocybin 25 mg; Drug: Risperidone 1 MG |
| Psilocybin (25 mg) | Experimental | One capsule of psilocybin 25 mg will be taken orally with a glass of water. Receives: Drug: Psilocybin 25 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Feasibility of obtaining PET imaging scans before and after administration of psilocybin (25 mg) with and without risperidone (1 mg) in adults with TRD.
Percentage of participants recruited, enrolled, and retained.
Measured: Screening to end of follow up (Day 28)
Secondary outcomes (1)
Obtain preliminary data on synaptic density (as measured by [18F] SynVesT-1 volume distribution, VT) in brain regions relevant to MDD (i.e., hippocampus, prefrontal cortex)
as measured by [18F] SynVesT-1 volume distribution, VT
Measured: Before and 4 weeks after administration of psilocybin 25 mg with and without risperidone 1 mg
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2024
- Study start21 Apr 2025
- Primary completionApr 2027 (estimated)
- Study completionSep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Treatment Resistant DepressionStudies 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
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 12 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Centre for Addiction and Mental Health
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ishrat Husain, Centre for Addiction and Mental Health
- Investigators
- Ishrat Husain, MBBS, MD, Principal investigator, Centre for Addiction and Mental Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06512220
- Sponsor's protocol ID
- 052-2022
- Acronym
- SYNVEST
- Status last verified
- Oct 2026
- First submitted
- 16 Jul 2024
- Last updated
- 19 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Imaging the Effects of Serotonin 2A Receptor Modulation on Synaptic Density in Treatment-resistant Depression (SYNVEST)
- ClinicalTrials.gov ID
- NCT06512220
- Acronym / sponsor ID
- SYNVEST / 052-2022
- Conditions
- Treatment Resistant Depression
- Keywords
- Psilocybin, Psychedelics, Clinical Trial, Positron-Emission Tomography, Treatment Resistant Depression, Neurophysiology Testing, Magnetic Resonance Imaging
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 12 participants (estimated)
- Lead sponsor
- Centre for Addiction and Mental HealthUniversity, hospital or other
- Study start
- 21 Apr 2025 (actual)
- Primary completion
- Apr 2027 (estimated)
- Study completion
- Sep 2027 (estimated)
- First posted
- 22 Jul 2024 (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.
Psilocybin, the chemical component of "magic mushrooms", has been administered with psychotherapy in several randomized clinical trials (RCTs) showing large and sustained antidepressant effects. In healthy volunteers, the psychedelic effects of psilocybin have been shown to be blocked by administration of certain medications such as risperidone.
The purpose of this study is to use an established SV2A radiotracer produced at our Centre to determine the feasibility of integrating PET imaging in to psilocybin trials. The preliminary imaging data will assess whether psilocybin's antidepressant effects are related to changes in synaptic density in adults with TRD, and whether any changes in synaptic density are associated with psilocybin's actions on the 5-HT2AR.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Risperidone (1 mg) + Psilocybin (25 mg) | Experimental | Drug: Psilocybin 25 mg, Drug: Risperidone 1 MGo One capsule of risperidone 1 mg will be taken first followed 60 minutes later by one capsule of psilocybin 25 mg. Both capsules will be taken orally with a glass of water. |
| Psilocybin (25 mg) | Experimental | Drug: Psilocybin 25 mgOne capsule of psilocybin 25 mg will be taken orally with a glass of water. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Adults 18 to 65 years old;
- Must be deemed to have capacity to provide informed consent;
- Must sign and date the informed consent form;
- Stated willingness to comply with all study procedures;
- Ability to read and communicate in English, such that their literacy and comprehension is sufficient for understanding the consent form and study questionnaires, as evaluated by study staff obtaining consent;
Key exclusion criteria (16 listed)
- Pregnant as assessed by a urine pregnancy test at Screening (V1) or individual's that intend to become pregnant during the study or are breastfeeding;
- Treatment with another investigational drug or other intervention within 30 days of Screening (V1);
- Have initiated psychotherapy in the preceding 12 weeks prior to Screening (V1);
- Have a DSM-5 diagnosis of substance use disorder (use of tobacco is permitted) within the preceding 6 months;
- Have active suicidal ideation with intent and plan as determined by item 3 of the HamD-17;
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 25 mgAlso: PEX010The psilocybin used in this study meets quality specifications suitable for human research use. The active drug is encapsulated using a hydroxypropyl methylcellulose (HPMC) capsule and contains 25 mg of psilocybin. The psilocybin will be administered once during the trial in combination with or without risperidone 1 mg. It will also be administered in conjunction with supportive therapy. | Drug | Psilocybin (25 mg), Risperidone (1 mg) + Psilocybin (25 mg) |
| Risperidone 1 MGAlso: MAR-RisperidoneThe risperidone is encapsulated using a cellulose capsule and contains 1 mg of risperidone. The risperidone will be administered once during the trial in combination with psilocybin 25 mg. It will also be administered with supportive therapy. | Drug | Risperidone (1 mg) + Psilocybin (25 mg) |
Primary outcome
Feasibility of obtaining PET imaging scans before and after administration of psilocybin (25 mg) with and without risperidone (1 mg) in adults with TRD.
Time frame: Screening to end of follow up (Day 28)
Percentage of participants recruited, enrolled, and retained.
1 secondary outcome
Obtain preliminary data on synaptic density (as measured by [18F] SynVesT-1 volume distribution, VT) in brain regions relevant to MDD (i.e., hippocampus, prefrontal cortex)
Time frame: Before and 4 weeks after administration of psilocybin 25 mg with and without risperidone 1 mg
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 19 Oct 2026.
- Individual participant dataSharing planned: No
Related trials for Treatment Resistant Depression
Active, not recruitingPhase 1
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ALTO-207 in Adults With Treatment-resistant Depression (TRD)
Treatment-resistant Depression (TRD)
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Psilocybin Intervention for Veterans Overcoming Treatment-Resistant Depression
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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.
Psychedelics Research contact
Ishrat Husain, MBBS, MD principal investigator
Centre for Addiction and Mental Health
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 25 mg and Risperidone 1 MG in people with Treatment Resistant Depression, run by Centre for Addiction and Mental Health 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 16 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: looking for participants now, as of the sponsor's last update on 19 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. 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 Emily Gilbert, MSc (416-535-8501 ext. 39570, emily.gilbert@camh.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Feasibility of obtaining PET imaging scans before and after administration of psilocybin (25 mg) with and without risperidone (1 mg) in adults with TRD. (time frame: Screening to end of follow up (Day 28)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 Oct 2026.