Not Yet RecruitingPhase 1

Oral and Sublingual Ketamine

10 participantsStarted 2026-10-01

Plain-language summary

Major Depressive Disorder (MDD) is one of the most common and severe mental illnesses in the world. Ketamine treatment, especially intravenous ketamine (IVK) and intranasal esketamine (INE), is becoming more popular and is being used more. But these ways of administering aren't perfect. They mostly have problems with cost, accessibility, and the issues of administering. The oral and sublingual routes of ketamine are cheaper alternatives, but they haven't been looked into as much in the medical and academic circles. This is a small pilot feasibility study, involving ten patient participants who will be randomly assigned to take ketamine by oral and sublingual routes as part of a single-blind, crossover design. A local London pharmacy-Ultimate Care Compounding will provide the ketamine formulations. Ten patients between 18 and 65 years old with Major Depressive Disorder will be recruited from the Mental Health Care Programs at LHSC, Victoria Hospital and SJHC, Parkwood Institute, (that has treatment resistant depression treatment focus). After a screening baseline visit, which will include clinical interviews with medication reconciliation, psychiatric evaluations, routine standard laboratory tests, and an electrocardiogram (ECG). Due to capacity limitations at the Centre for Clinical Investigation and Therapeutics (CCIT), a maximum of 5 participants will undergo pharmacokinetic sampling simultaneously, enrolment will proceed in two sequential groups with treatment order assigned by group. Group A (n=5): The first 5 eligible participants will receive oral ketamine in Treatment Period 1 and sublingual ketamine in Treatment Period 2. Group B (n=5): The next 5 eligible participants will receive sublingual ketamine in Treatment Period 1 and oral ketamine in Treatment Period 2. Recruitment for Group B will commence once Group A has completed the clinical intervention phase. During Monday and Thursday of each of Weeks 1 and 2, Group A will receive oral ketamine, while Group B will receive sublingual ketamine. Weeks 3 and 4 are a washout period. In Weeks 5 and 6, on Mondays and Thursdays, groups will switch to the other form of administration \[See flowchart of study procedure\]. Weeks 7 and 8 are washout periods to ensure consistency with the first half of the study and provide a similar framework for clinical assessments. Blood samples will be collected at 2 time points at the Center for Clinical Investigation and Therapeutics at University Hospital. The study goal is to help define safe and effective oral/SL ketamine doses based on Pharmacokinetic profiles.

Who can participate

Age range

18 Years – 65 Years

Sex

ALL

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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.

Exclusion criteria

. Age: Between 18 and 65 years (inclusive) at the time of screening.
. Weight: Equal to or greater than 50 kg (110 lbs).
. Diagnosis: A current diagnosis of Major Depressive Disorder (MDD), moderate to severe in intensity, as defined by the DSM-5 criteria.
. Current Episode: Experiencing a moderate to severe Major Depressive Episode (MDE) at screening.
. Ongoing Treatment: Actively receiving pharmacological treatment for MDD at the time of enrollment.
. Treatment Resistance: Documented history of inadequate response to at least two antidepressant medications, each from a different pharmacological class, administered at an adequate dose and duration.

Questions worth asking your doctor

Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.

1Since this is a Phase 1 trial primarily measuring how the body absorbs and processes oral and sublingual ketamine — not yet focused on whether it relieves depression — what does that mean for my chances of actually seeing a benefit versus just contributing to early safety data?
2Ketamine already has an intravenous form used in some clinics — can you help me understand why this oral and sublingual version is still being studied at such an early phase, and whether an existing approved option like esketamine nasal spray might be a more appropriate path for me right now?
3The trial isn't recruiting yet, so there's no clear timeline for when it will start — given how serious my depression is, is it worth waiting to see if I qualify, or should we be pursuing active treatment options in the meantime?
4Because this is a Phase 1 study, the main goal is understanding ketamine's pharmacokinetics — things like how it's absorbed and how long it stays in the body — so what safety risks are still unknown at this stage, and how does that factor into whether this would be right for me?
5If I were eventually considered for this trial, what would participation actually involve day-to-day — like how often I'd need to come in, whether doses would be monitored in a clinical setting, and how that would fit alongside any current treatments I'm already taking?

Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.

Questions for the trial coordinator

The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.

1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?

A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.

What they're measuring

Pharmacokinetic measures

Timeframe: Plasma samples will be collected at 0, 0.25, 0.5, 0.75, 1, 2, 3, 4, 6, and 8 hours of the first day of weeks 1 and 5.

Trial details

NCT IDNCT07683988

SponsorWestern University, Canada

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2027-08-01

Contact for this trial

Rohit Lodhi, MD

+1-519-646-6100 rlodhi2@uwo.ca

View on ClinicalTrials.gov More Major Depression Severe trials