Psilocybin, a naturally occurring psychedelic compound, has shown potential to enhance emotional processing and facilitate profound shifts in perspective. Psilocybin-assisted cognitive processing therapy offers a promising approach for individuals suffering from chronic Post-Traumatic Stress Disorder (PTSD). By integrating the therapeutic benefits of cognitive processing therapy with the potential healing properties of psilocybin, this innovative treatment aims to provide a comprehensive and holistic path to recovery. When combined with the structured framework of cognitive processing therapy, which focuses on addressing maladaptive thought patterns and processing traumatic experiences, individuals may experience a more effective and transformative healing journey. This study aims to establish the feasibility,  tolerability, safety and efficacy of using psilocybin assisted-CPT in individuals with chronic PTSD. In this pilot study, 15 individuals will be recruited to receive a single dose of psilocybin with cognitive processing therapy.

Interested in participating in our study? Please email psilocybin@unityhealth.to to find out if you are eligible.

Inclusion Criteria: 1) Meet Diagnostic and Statistical Manual-5th edition (DSM-5) criteria for current PTSD with a duration of 6 months or longer. 2) Between the ages of 18 and 65 (inclusive). 3) Able to understand and comply with the requirements of the study, as judged by the investigator(s). 4) Willing to stop prohibited medications such as antidepressants, psychostimulants, and antipsychotics. 5) Ownership of a smartphone. 6) Agree to video and audio recording of all study visits including therapy sessions and clinical assessments.

Exclusion Criteria: 1) Have a history of or a current primary diagnosis of psychotic disorder, schizophrenia, delusional disorder, borderline personality disorder, schizoaffective disorder, bipolar disorder or, dissociative identity disorder. 2) Pregnant, lactating or of childbearing potential and not willing to use an approved method of contraception during the study. 3) Have any other condition that, in the opinion of the investigator(s), would adversely affect the subject’s ability to complete the study or its measures. 4) Do not own a smartphone. 5) Non-English-speaking individuals are excluded because the ability to communicate study information, answer questions accurately and completely about the study, and obtain consent are necessary

*Inclusion/exclusion criteria is not exhaustive. Lifestyle modifications such as alcohol consumption may be required as part of this study.

Treatment description:

• All participants in this study will receive a 25 mg dose of psilocybin as well as 12 cognitive processing therapy sessions and preparatory and integration sessions.
• Participants will be followed up with for 12 weeks after the intervention week.
• All participants will receive an Oura Ring which will collect passive physiological data (e.g. sleep, activity and readiness) throughout the course of the study. 
• On a daily or weekly basis, participants will complete self-report questionnaires relevant to mental health and quality of life.

We are conducting a clinical trial testing temporal interference (TI) stimulation to help people living with major depressive disorder (MDD). This study focuses on a brain region called the subgenual anterior cingulate cortex (sgACC), which plays an important role in mood and emotional regulation. Participants will receive non-invasive TI stimulation while completing simple mood-related activities, such as watching short emotional video clips, across 10 sessions. By studying how this stimulation affects brain activity and mood, we hope to develop new, more targeted treatment options for depression in the future.

If you’re interested in contributing to this innovative research, please get in touch with TIStimulation@unityhealth.to or call the study coordinator, Ilya, at 416-360-4000 (ext. 77062).

Eligibility: 

Inclusion Criteria: 1) Any sex or gender, aged 18 to 65 years, 2) Diagnosis of Major Depressive Disorder, 3) Able to speak and understand English

Exclusion Criteria: 1) History of bipolar disorder or psychosis, 2) Current substance use or history of substance use during the past year (excluding nicotine and caffeine use disorder), 3) Certain medical illnesses and blood test results, 4) Recent change in treatment regimen for depression that happened less than 1 month ago.

Treatment description:

• You will receive 10 sessions of TI stimulation or placebo over 2 weeks (weekdays only). Each session lasts 30–45 minutes and involves watching film clips during the session.  
• On select days, we will record brain activity using electroencephalography (EEG), a safe and non-invasive procedure.  
• You will complete two MRI scans — one before you start and one after you finish 10 days of treatment — each lasting about 1 hour.  
• We will follow up with you for 1 month after completing treatment to monitor longer-term effects. 

Approximately one-third of individuals with major depressive disorder (MDD) do not respond to standard antidepressant treatments and are considered to have treatment-resistant depression (TRD). The Interventional Psychiatry Program offers several outpatient treatments for TRD, including repetitive transcranial magnetic stimulation (rTMS), intravenous ketamine (IVK), and electroconvulsive therapy (ECT).
This study examines whether wearable devices and digital monitoring tools can help track mental health symptoms and treatment response during care. Participants will complete daily and weekly mood assessments through the REDCap platform and wear a smart ring (Oura Ring) that records physiological measures such as sleep, activity, heart rate, and temperature. The data collected will help researchers better understand treatment outcomes, predict who may benefit from specific therapies, and identify early signs of symptom improvement or relapse in individuals with TRD.

If you’re interested in contributing to this innovative research, please contact the study coordinator, Dr. Reinhard Janssen Aguilar, at IAMGOLD@unityhealth.to.

Eligibility

• Primary diagnosis of major depressive disorder (MDD) without psychotic symptoms
• Failure to respond to 2+ antidepressant therapies (i.e., treatment-resistant depression)
• Referred to the Interventional Psychiatry Program at St. Michael’s Hospital, Unity Health Toronto for outpatient treatment (rTMS, IVK, or ECT)
• 18+ years of age
• Ownership of a smartphone 

Exclusion criteria: 1) Participants involved in experimental interventions (e.g., take-home neurostimulation, nitrous oxide, stellate ganglion block, psilocybin), 2) Poor/unreliable access to Internet/Wifi

Treatment description:

• The wearable device will unobstrusively passively is digital suite will collect active and passive digital data continuously,physiological biomarkers (e.g., heart rate variability, respiration, temperature, activity, sleep) as patient-users go about their lives in the real world, while patients are enrolled in the Interventional Psychiatry Program.
• The clinical care team will enter responses to self-report (PHQ-9 and/or GAD-7) and clinician-administered (MADRS) assessments of depression and anxiety completed as part of clinical care, into the REDCap system at the end of each treatment sessionParticipants will complete daily/weekly web-based surveys related to mental health using REDCap.
• Participants will be offered a wearable device (Oura Ring or Empatica watch), which will monitor physiological features (e.g., body temperature, heart rate, respiratory rate, sleep, physical activity)

Physical activity (PA) has been associated with improvements in mood and mental health in both clinical and non-clinical populations. Recent research suggests that low doses and enjoyability of PA underlie its protective effect on mental health and well-being. As a result, in this study, we seek to explore the impact of a 4-week remotely delivered individualized one-on-one PA programme in addition to treatment as usual (TAU) on depressive symptoms of participants with treatment-resistant depression (TRD). At this time, we aim to conduct a pilot study with 30 participants, wherein 20 will be randomized to the PA group, and 10 will be in the control group. 

We have recently reached the target enrollment for this study and are no longer recruiting. If you’re interested in contributing to similar innovative research, please get in touch with the study team at PA.TRD@unityhealth.to.

Eligibility:

• Sedentary adults (engage in less than 60 minutes of moderate-to-vigorous physical activity per week) between the ages of 18 and 65 years, inclusive, capable of giving informed consent.
• Participants meeting diagnostic criteria for major depressive disorder (MDD) without psychotic symptoms according to the Diagnostic and Statistical Manual of Mental Disorders – 5th Ed. (DSM-5) and currently experiencing a major depressive episode (MDE) as confirmed by the Mini International Neuropsychiatric Interview (MINI).
• A Montgomery-Åsberg Depression Rating Scale (MADRS) total score of ≥ 7 at screening (mild to severe MDE).
• Failure of at least two trials of antidepressant therapy of adequate dose and duration during the current episode as established by the Antidepressant Treatment History Form (ATHF) and self-report.
• Receiving treatments congruent with Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines, with no medication changes or no introduction of psychotherapy allowed one month before screening (28 days), during the randomized intervention phase (28 days), and during the follow-up phase (42 days).

Exclusion Criteria:

• Current symptoms of mania, hypomania, mixed episodes, or psychosis.
• Have received a diagnosis of alcohol or a substance use disorder within the past 3 months or as confirmed by the MINI. Other secondary psychiatric comorbidities (e.g., anxiety disorders, trauma-related disorders, etc.) will not be excluded.
• Pregnant females.
• Acute risk for a cardiovascular event (i.e., cardiovascular event within the past 12 months). 
• Have any medical contraindications to exercise according to the Physical Activity Readiness Questionnaire (PAR-Q).
• Self-reported balance, gait, or locomotion difficulties that would preclude participation in a physical activity programme. 
• Have any other condition that, in the opinion of the investigator(s), would adversely affect the subject’s ability to complete the study or its measures.
• Have exercise-induced asthma. 
• Taking medication that interferes with heart rate response to exercise, such as beta blockers.
• Do not own a smartphone. 
• Do not have reliable access to the Internet.
• Have previously received intravenous ketamine treatment in the last 2 months.
• Non-English-speaking individuals are excluded because the ability to communicate study information, answer questions accurately and completely about the study, and obtain consent is necessary.

Treatment Description:

At the end of their participation in the study, participants who were randomized to the control group will have access to at least one session with a program trainer. Upon confirming eligibility in the study, participants will be randomized to the PA group (PA programme plus TAU) or the control group (no PA programme, only TAU). All participants will receive an Oura Ring which will collect passive physiological data (e.g. sleep, activity and readiness) throughout the course of the study. On a daily and weekly basis, participants will complete self-report questionnaires relevant to mental health and quality of life. Participants in the PA group will meet with their program trainer once a week for 4 weeks for a supervised PA session and engage in PA outside of the supervised session. Participants will be followed up with for 6 weeks after the intervention period.

Bilateral functional electrical stimulation (FES) of the facial muscles involves stimulating specific facial muscles with an FES device. It is being investigated as a potential novel intervention for major depressive disorder (MDD). Applying FES to specific facial muscles associated with smile patterns may result in better emotional control and mood elevation. FES is a low-risk, non-invasive technique that causes muscles to contract using electrical current. The purpose of this study is to learn whether FES of the facial muscles is effective in treating MDD. This study aims to assess the effectiveness, tolerability, and safety of FES in patients with MDD. 

We are currently recruiting participants for this innovative study. If you’re interested in contributing to this innovative research, please get in touch with the study team at FES&MDD@unityhealth.to or call 416-360-4000 (ext. 40675).

Eligibility

Inclusion Criteria: 1) Diagnosis of Major Depressive Disorder, 2) Male or non-pregnant female, aged 18 to 70 years old

Exclusion Criteria: 1) Have a history of epilepsy or seizures, 2) Have any damage or dysfunction of facial nerves

Treatment description:

In this study, we will be applying FES to specific facial muscles. This electrical current may cause gradual, long-lasting changes in brain activity levels due to the physiological connection existing between facial muscles and the brain. Depressive symptoms will be assessed pre-treatment, at the end of each treatment week, and during the post-stimulation visits. Participants will be randomized to receive either 20 sessions (45 minutes- once per day) of  FES or sham stimulation over 4 weeks.