RecruitingPHASE2INTERVENTIONAL

Imaging the Effects of Serotonin 2A Receptor Modulation on Synaptic Density in Treatment-resistant Depression (SYNVEST)

This research, called SYNVEST, is for people with depression that hasn't improved with standard treatments. It aims to understand how psilocybin, a substance from 'magic mushrooms', affects the brain. Previous studies suggest psilocybin, combined with therapy, can significantly lift depression. We will use a special type of brain scan (PET scan) to see if psilocybin changes the connections between brain cells. We also want to find out if taking another medication called risperidone might block the effects of psilocybin. This helps us learn more about how psilocybin works and if it could be a future treatment option.

At a glance

Status

Recruiting

Phase

PHASE2

Sponsor

Centre for Addiction and Mental Health

Enrolment target

Start

21 Apr 2025

Estimated completion

01 Sep 2027

Treatment Resistant Depression

What is this study about?

This study, called SYNVEST, is exploring a new way to help people who have depression that hasn't gotten better with usual treatments. This is often called 'treatment-resistant depression'. We're looking at a substance called psilocybin, which comes from 'magic mushrooms'. Some earlier studies have shown that psilocybin, when given alongside talking therapy, can really help improve depression over a longer period.

The main aim of this study is to understand how psilocybin works in the brain. We'll be using special brain scans, called PET scans, to look at the connections between brain cells. We want to see if psilocybin changes these connections and if these changes are linked to feeling less depressed. We're also checking if another medication, risperidone, can stop psilocybin from having its effects. This helps us learn more about the specific way psilocybin interacts with certain parts of the brain.

Ultimately, by learning more about how psilocybin works and how to use these special brain scans in studies, we hope to pave the way for psilocybin to become a new and effective treatment option for people struggling with severe depression.

Key takeaways

This study explores psilocybin for depression that hasn't responded to usual treatments.
It uses special brain scans (PET scans) to see how psilocybin affects brain connections.
Participants will receive either psilocybin or risperidone.
People aged 18 to 65 with treatment-resistant depression are being sought.
You'll need to safely stop current antidepressants under medical supervision.
The goal is to understand how psilocybin works and if it could become a new treatment.

Who may be eligible?

This study is looking for adults between 18 and 65 years old who have depression that hasn't responded to at least two different antidepressant treatments. You must be able to understand the study information and be willing to follow all the study steps. It's also important that you can read and communicate in English well enough to understand the paperwork.

To join, your doctor would need to confirm it's safe for you to gradually stop any current antidepressant or antipsychotic medications for at least two weeks before the main study starts. If you can get pregnant, you'll need to be using effective contraception for the entire study period. There are also some lifestyle choices you'd need to agree to follow throughout the study.

You wouldn't be able to join if you are pregnant, breastfeeding, or planning to become pregnant during the study. If you've recently started psychotherapy (talking therapy) in the last three months, or taken part in another research study with a new drug in the last month, you wouldn't be eligible.

Could this study suit you?

Answer these quick questions to see if you may be eligible. This is a guide only — the research team makes the final call.

Are you between 18 and 65 years old?
Do you have depression that hasn't improved with at least two different medications?
Can you read and understand information in English?
Are you willing and able to stop your current antidepressants for a period, with your doctor's approval?
If you can get pregnant, are you using effective birth control and willing to continue throughout the study?

Answer every question to see your result.

What does participation involve?

If you join this study, you'll have several appointments. It starts with a first screening visit to check if you're suitable. Then, if eligible, you'll have a baseline visit where we do an initial brain scan and other assessments. You’ll be asked to gradually stop any current antidepressant or antipsychotic medications beforehand, under your doctor’s guidance.

During the study, you'll receive either a single dose of psilocybin (25 mg) or risperidone (1 mg), as decided by the study design. You'll have another brain scan after receiving the study medication, along with follow-up appointments and questionnaires to track your mood and well-being. The total duration of your participation in the study will involve several weeks, including the gradual stopping of your current medications and the follow-up period.

Potential risks and benefits

Participating in this study might offer some potential benefits, such as contributing to new knowledge about how to treat depression that hasn't responded to other medicines. You might also experience an improvement in your symptoms, though this is not guaranteed for everyone. There are potential risks associated with taking psilocybin, including strong emotional or psychological experiences, and side effects from risperidone. Your doctor will discuss all possible risks with you in detail. Remember, you have the right to withdraw from the study at any time, for any reason, without it affecting your medical care.

Locations (1)

Centre for Addiction and Mental Health
Verified postcode
Toronto, Canada· Recruiting

Common questions

What is psilocybin?

Psilocybin is a natural compound found in certain types of mushrooms, sometimes called 'magic mushrooms'. It can affect how you think and feel.

What is treatment-resistant depression?

This is a type of depression that hasn't gotten better, even after trying at least two different antidepressant medications in the past.

Will I receive therapy during the study?

The summary mentions psilocybin has been given with psychotherapy in other trials, but this study focuses on the brain changes and effects of the medication itself, not specifically on providing psychotherapy.

What is a PET scan?

A PET scan is a special type of medical imaging test that lets doctors see how your organs and tissues are working at a cellular level, including your brain.

Why is risperidone mentioned?

Risperidone is another medication that, in healthy people, has been shown to block the effects of psilocybin. The study will look at both to understand more about how psilocybin works.

How to find out more

Muhammad Ishrat Husain, MBBS, MD

ishrat.husain@camh.ca 416-535-8501 Official trial record

Always speak to your GP or specialist before deciding to take part in a study.