Amnestic Mild Cognitive ImpairmentPhase 2NCT06041152
Does Psilocybin Change Synaptic Density in Amnestic Mild Cognitive Impairment
A Phase 2 study testing Psilocybin in people with Amnestic Mild Cognitive Impairment, run by Centre for Addiction and Mental Health at 1 site in Canada.
Trial summary
The goal of this pilot, exploratory, clinical trial is to investigate the effects of psilocybin on synaptic vesicular density (SVD) as measured by the positron emission tomography (PET) radiotracer, 18F-SynVesT-1, in participants with amnestic Mild Cognitive Impairment (aMCI) and healthy participants. Read more about this study
- Who is it for?
- Ages 60 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Amnestic Mild Cognitive Impairment
- What is being tested?
- Psilocybin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 10 participants
- Where
- 1 siteCanada
- Study dates
- 27 Nov 2023to 19 Feb 2026
- 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 60 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- The aMCI participant must meet all of the inclusion criteria to be eligible for this clinical trial:
- Male or female participants of any race or ethnicity
- Inpatients or outpatients 60 to 75 years of age (on day of randomization)
- Diagnosis of MCI based on DSM 5 diagnostic criteria of Minor Neurocognitive Disorder
- Categorization of episodic memory impairment based on scores ≥ 1.0 SD lower on any of the following measures in comparison to normative data i. Logical Memory Test, ii. California Verbal Learning Test, iii. Brief Visual Memory Test
- Non-smoker/Non-nicotine user
Show all 20Show fewer
- Montreal Cognitive Assessment (MoCA) score = < 26 and MMSE score > = 24
- Capable of consenting to participate in the research study
- On a stable dose of medication for at least 2 months [see section 5.6], and unlikely to undergo changes in dose during the study
- Availability of a study partner who has regular contact with the participant
- Ability to read and communicate in English (with corrected vision and hearing, if needed)
- The Healthy Control participant must meet all of the inclusion criteria to be eligible for this clinical trial:
- Male or female participants of any race or ethnicity
- 60 to 75 years of age (on day of randomization)
- Does not meet SCID-5 criteria for Mild Neurocognitive Disorder, Alzheimer's disease, or other major neurocognitive disorder
- Non-smoker/Non-nicotine user
- Capable of consenting to participate in the research study
- On a stable dose of medication for at least 2 months [see section 5.6], and unlikely to undergo changes in dose during the study
- Availability of a study partner who has regular contact with the participant
- Ability to read and communicate in English (with corrected vision and hearing, if needed)
Who cannot join
- An individual who meets any of the following criteria will be excluded from participation in this clinical trial:
- Unwilling or incapable to consent to the study
- Unstable medical or any concomitant major medical or neurological illness, including presence of a relative or absolute contraindication to psilocybin, i.e. 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.
- History of head trauma resulting in loss of consciousness > 30 minutes that required medical attention.
- DSM-5 diagnosis, with active symptoms in the last three months, of major depression; lifetime diagnosis of bipolar disorder; intellectual disability; Alzheimer's Disease; or a psychotic disorder
- DSM-5 substance dependence (except caffeine) within 12 months of entering the study
Show all 19Show fewer
- Anticonvulsant, antidepressant, antipsychotic, mood stabilizer, opioid, or benzodiazepine use
- Use of serotonergic psychedelic drugs within the past 10 years
- Positive urine drug screen at the screening visit
- Having taken a cognitive enhancer (acetylcholinesterase inhibitor or memantine) within the past 6 weeks
- Acute suicidal or homicidal ideation
- Receiving treatment with medications such as levetiracetam that blocks SV2a binding, and/or inability to discontinue the following medications before study drug dosing: inhibitors of uridine 5'-diphospho-glucuronosyltransferase (UGT)1A9 and (UGT)1A10, and ALDH inhibitors and alcohol dehydrogenase (ADH) inhibitors.
- Exceeding allowed annual radiation exposure levels (20 mSv), as outlined by our PET Centre guidelines
- Having completed multiple PET scans in the past, such that participation in this study would cause participant to exceed lifetime limit (8 PET scans)
- Metal implants or pacemaker precluding an MRI scan or other contraindications to MRI (e.g., claustrophobia)
- Female with childbearing potential*, pregnancy (as confirmed by a negative pregnancy test) or breastfeeding
- Active gender affirming hormonal treatment
- 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 or II disorder as determined by the family medical history form and discussions with the participant.
- Allergies to hydroxypropyl methylcellulose *A woman/female or person who is not of childbearing potential is considered to be postmenopausal after at least 12 months without menstruation. Postmenopausal is defined as 12 consecutive months with no menses without an alternative medical cause. Females/people of childbearing potential are those who have experienced menarche and do not meet the criteria for women not of childbearing potential.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Does Psilocybin Change Synaptic Density in the Brains of Patients With Amnestic Mild Cognitive Impairment
The goal of this pilot, exploratory, clinical trial is to investigate the effects of psilocybin on synaptic vesicular density (SVD) as measured by the positron emission tomography (PET) radiotracer, 18F-SynVesT-1, in participants with amnestic Mild Cognitive Impairment (aMCI) and healthy participants. The investigators hypothesize that SVD levels in the brain will be higher following the ingestion of psilocybin in comparison to placebo, and that increases in SVD will be associated with improvements in cognition.
10 participants (6 with aMCI, and 4 sex and age matched healthy volunteers) will:
Read more
- Be randomized to receive either:
- Two 25 mg macrodoses of psilocybin separated by 1 week.
- Two placebo doses separated by 1 week.
- Receive a baseline 18F-SynVesT-1 PET scan, clinical, and neuropsychological assessments.
- Receive a 18F-SynVesT-1 PET scan one week after the last dose of treatment.
- Depending on available funds, receive a third PET scan at any time within 4 weeks of the screening visit to quantify tauopathy with the [18F]T807 radiotracer.
- Receive clinical and neuropsychological testing 1, 4, and 12 weeks after the last treatment.
Researchers will compare placebo vs. experimental groups to see if psilocybin will increase SVD, and if increases in SVD are associated with cognitive improvements.
Read the detailed description
The proposed study will investigate the effects of on synaptic vesicular density (SVD) levels as measured by the positron emission tomography (PET) radiotracer, 18F-SynVesT-1, and cognition (i.e., global cognition, executive function, and memory domains) in amnestic Mild Cognitive Impairment (aMCI) and healthy participants. Participants will be randomized to receive either two 25mg doses of psilocybin separated by one week, or two placebo doses separated by one week. Brain scans, clinical, and cognitive assessments will be conducted one week before, and one week, four weeks, and 12 weeks post dosing.
- Conditions
- Amnestic Mild Cognitive Impairment
- Being tested
- Psilocybin, Placebo
- Keywords
- amnestic mild cognitive impairment, psilocybin, SV2A, positron emission tomography, synaptic vesicular density
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PsilocybinDrug
2 macrodoses of 25mg separated by one week.
PlaceboDrug
2 doses of placebo separated by one week.
| Study group | Role | What they receive |
|---|---|---|
| Amnestic Mild Cognitive Impairment Participants Receiving Psilocybin | Experimental | Receiving 2 doses of 25mg of psilocybin separated by 1 week. Receives: Drug: Psilocybin |
| Healthy Participants Receiving Psilocybin | Experimental | Receiving 2 doses of 25mg of psilocybin separated by 1 week. Receives: Drug: Psilocybin |
| Amnestic Mild Cognitive Impairment Participants Receiving Placebo | Placebo comparator | Receiving 2 doses of placebo separated by 1 week. Receives: Drug: Placebo |
| Healthy Participants Receiving Placebo | Placebo comparator | Receiving 2 doses of placebo separated by 1 week. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Synaptic Vesicular Density
Synaptic vesicular density will be assessed with PET imaging by measuring the volume of distribution (i.e., defined as the ratio of the radioligand concentration in tissue target region (CT, kBq·cm-3) to that in plasma (CP, kBq·mL-1) at equilibrium) of the [18F]SynVesT-1 radioligand in the cortical and subcortical gray matter regions in the whole brain and more specifically, the hippocampus and dorsolateral prefrontal cortex.
Measured: 3 years
Secondary outcomes (3)
Global Cognition
The results of the neuropsychological battery will be combined to a global cognition composite score as a Z-score, the change of which will be a secondary outcome measure. Z-scores will be comprised of the Mini-Mental State Examination, Montreal Cognitive Assessment, Boston Naming Test, Category Fluency Test, Letter Fluency Test, Trail Making Test Parts A and B, Wisconsin Card Sorting Test, Stroop Neuropsychological Test, Executive Interview, Block Design Test, Clock Drawing Test, Grooved Pegboard, Digit Symbol Test, Logical Memory Test, California Verbal Learning Test, and Modified Rey-Osterrieth Complex Figure, and will be calculated based on the performance of the equated comparison group. Each domain will contribute equally to the global cognition composite score.
Measured: 3 years
Memory
A memory composite Z-score will be generated using the performance on the following individual tests: Logical Memory Test, California Verbal Learning Test, and Modified Rey-Osterrieth Complex Figure. Z-scores will be calculated based on the performance of the equated comparison group, and each domain will contribute equally to the global cognition composite score.
Measured: 3 years
Executive Function
An executive function composite Z-score will be generated using the performance on the following individual tests: Trail Making Test Part B, Wisconsin Card Sorting Test, Stroop Neuropsychological Screening, and the Executive Interview. Z-scores will be calculated based on the performance of the equated comparison group, and each domain will contribute equally to the global cognition composite score.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Sep 2023
- Study start27 Nov 2023
- Primary completion19 Feb 2026
- Study completion19 Feb 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Amnestic Mild Cognitive ImpairmentStudies of the same condition, open and under way.
- More trials run by Centre for Addiction and Mental HealthThe sponsor's other registered studies.
- 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
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre for Addiction and Mental Health
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Philip Gerretsen, Centre for Addiction and Mental Health
- Investigators
- Philip Gerretsen, MD, PhD, Principal investigator, Centre for Addiction and Mental Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06041152
- Sponsor's protocol ID
- 101-2021
- Status last verified
- Sep 2026
- First submitted
- 1 Aug 2023
- Last updated
- 5 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- 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 5 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Does Psilocybin Change Synaptic Density in the Brains of Patients With Amnestic Mild Cognitive Impairment
- ClinicalTrials.gov ID
- NCT06041152
- Acronym / sponsor ID
- 101-2021
- Conditions
- Amnestic Mild Cognitive Impairment
- Keywords
- amnestic mild cognitive impairment, psilocybin, SV2A, positron emission tomography, synaptic vesicular density
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Centre for Addiction and Mental HealthUniversity, hospital or other
- Study start
- 27 Nov 2023 (actual)
- Primary completion
- 19 Feb 2026 (actual)
- Study completion
- 19 Feb 2026 (actual)
- First posted
- 18 Sep 2023 (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.
The goal of this pilot, exploratory, clinical trial is to investigate the effects of psilocybin on synaptic vesicular density (SVD) as measured by the positron emission tomography (PET) radiotracer, 18F-SynVesT-1, in participants with amnestic Mild Cognitive Impairment (aMCI) and healthy participants. The investigators hypothesize that SVD levels in the brain will be higher following the ingestion of psilocybin in comparison to placebo, and that increases in SVD will be associated with improvements in cognition.
10 participants (6 with aMCI, and 4 sex and age matched healthy volunteers) will:
- Be randomized to receive either:
- Two 25 mg macrodoses of psilocybin separated by 1 week.
- Two placebo doses separated by 1 week.
- Receive a baseline 18F-SynVesT-1 PET scan, clinical, and neuropsychological assessments.
- Receive a 18F-SynVesT-1 PET scan one week after the last dose of treatment.
- Depending on available funds, receive a third PET scan at any time within 4 weeks of the screening visit to quantify tauopathy with the [18F]T807 radiotracer.
- Receive clinical and neuropsychological testing 1, 4, and 12 weeks after the last treatment.
Researchers will compare placebo vs. experimental groups to see if psilocybin will increase SVD, and if increases in SVD are associated with cognitive improvements.
Detailed description
The proposed study will investigate the effects of on synaptic vesicular density (SVD) levels as measured by the positron emission tomography (PET) radiotracer, 18F-SynVesT-1, and cognition (i.e., global cognition, executive function, and memory domains) in amnestic Mild Cognitive Impairment (aMCI) and healthy participants. Participants will be randomized to receive either two 25mg doses of psilocybin separated by one week, or two placebo doses separated by one week. Brain scans, clinical, and cognitive assessments will be conducted one week before, and one week, four weeks, and 12 weeks post dosing.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Amnestic Mild Cognitive Impairment Participants Receiving Psilocybin | Experimental | Drug: PsilocybinReceiving 2 doses of 25mg of psilocybin separated by 1 week. |
| Healthy Participants Receiving Psilocybin | Experimental | Drug: PsilocybinReceiving 2 doses of 25mg of psilocybin separated by 1 week. |
| Amnestic Mild Cognitive Impairment Participants Receiving Placebo | Placebo comparator | Drug: PlaceboReceiving 2 doses of placebo separated by 1 week. |
| Healthy Participants Receiving Placebo | Placebo comparator | Drug: PlaceboReceiving 2 doses of placebo separated by 1 week. |
Who may qualify
- Ages
- 60 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- The aMCI participant must meet all of the inclusion criteria to be eligible for this clinical trial:
- Male or female participants of any race or ethnicity
- Inpatients or outpatients 60 to 75 years of age (on day of randomization)
- Diagnosis of MCI based on DSM 5 diagnostic criteria of Minor Neurocognitive Disorder
- Categorization of episodic memory impairment based on scores ≥ 1.0 SD lower on any of the following measures in comparison to normative data i. Logical Memory Test, ii. California Verbal Learning Test, iii. Brief Visual Memory Test
Key exclusion criteria (19 listed)
- An individual who meets any of the following criteria will be excluded from participation in this clinical trial:
- Unwilling or incapable to consent to the study
- Unstable medical or any concomitant major medical or neurological illness, including presence of a relative or absolute contraindication to psilocybin, i.e. 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.
- History of head trauma resulting in loss of consciousness > 30 minutes that required medical attention.
- DSM-5 diagnosis, with active symptoms in the last three months, of major depression; lifetime diagnosis of bipolar disorder; intellectual disability; Alzheimer's Disease; or a psychotic disorder
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 |
|---|---|---|
| Psilocybin2 macrodoses of 25mg separated by one week. | Drug | Amnestic Mild Cognitive Impairment Participants Receiving Psilocybin, Healthy Participants Receiving Psilocybin |
| Placebo2 doses of placebo separated by one week. | Drug | Amnestic Mild Cognitive Impairment Participants Receiving Placebo, Healthy Participants Receiving Placebo |
Primary outcome
Synaptic Vesicular Density
Time frame: 3 years
Synaptic vesicular density will be assessed with PET imaging by measuring the volume of distribution (i.e., defined as the ratio of the radioligand concentration in tissue target region (CT, kBq·cm-3) to that in plasma (CP, kBq·mL-1) at equilibrium) of the [18F]SynVesT-1 radioligand in the cortical and subcortical gray matter regions in the whole brain and more specifically, the hippocampus and dorsolateral prefrontal cortex.
3 secondary outcomes
Global Cognition
Time frame: 3 years
Memory
Time frame: 3 years
Executive Function
Time frame: 3 years
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 5 Oct 2026.
- The Centre for Addiction and Mental Health (CAMH) is the leading mental health and addictions research facility in Canada, and one of the largest in the world.Link provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Philip Gerretsen, MD, PhD 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 in people with Amnestic Mild Cognitive Impairment, 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 20 inclusion and 19 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 5 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?
Synaptic Vesicular Density (time frame: 3 years). 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 5 Oct 2026.