The Montreal Model: Ketamine Therapy for Alcohol + Depression

Alcohol use disorder and treatment-resistant depression are two of the most difficult conditions in psychiatry, and they frequently occur together. An estimated 30 to 40 percent of people with AUD also meet criteria for major depressive disorder, and among those whose depression has failed to respond to standard antidepressants, alcohol misuse rates are even higher. Each condition worsens the other: depression drives drinking as a form of self-medication, while chronic alcohol use disrupts the very neurochemistry that antidepressants rely on to work. A 2026 feasibility trial protocol published in BMJ Open by McAnulty and colleagues proposes a structured approach — what they call the Montreal Model — designed to treat both conditions simultaneously with psychedelic ketamine therapy.

What is the Montreal Model?

The Montreal Model is an integrative psychedelic ketamine therapy protocol originally developed at a Canadian research center for patients with severe treatment-resistant depression. It combines ketamine administration with structured psychotherapy, carefully curated music during infusion sessions, and a defined follow-up framework. The key insight behind the model is that ketamine's acute psychoactive effects — the altered state of consciousness, the temporary dissolution of rigid thought patterns — are not merely side effects to be tolerated. They are therapeutic opportunities that, when paired with psychological support, may produce deeper and more lasting change.

In the McAnulty et al. protocol, the Montreal Model is being adapted specifically for patients who carry both AUD and TRD diagnoses. The trial is designed as a feasibility study, meaning its primary goal is to determine whether this combined approach can be safely and practically delivered, with preliminary data on effectiveness guiding future larger trials.

Key protocol elements

The protocol includes several distinctive features that set it apart from standard ketamine infusion clinics:

• Music during infusions: Patients listen to a curated playlist during ketamine sessions. Research on psychedelic-assisted therapy has consistently found that music can guide the emotional trajectory of the experience and may deepen therapeutic engagement.

• Psychotherapy integration: Each ketamine session is bookended by preparatory and integration psychotherapy. Preparation sessions help patients set intentions and address anxiety about the experience. Integration sessions afterward help patients process what emerged during the ketamine state and connect it to their recovery goals for both depression and alcohol use.

• Structured follow-up: The protocol defines specific timepoints for follow-up assessment, monitoring both depressive symptoms and drinking behavior over time. This structured approach allows researchers to track whether initial improvements are sustained.

Why treating both conditions matters

Most addiction treatment programs do not adequately address underlying depression, and most depression treatments are not designed with alcohol use in mind. This disconnect has real consequences. A patient whose depression is treated with an SSRI but who continues drinking heavily may see limited antidepressant benefit — alcohol is a central nervous system depressant that can directly counteract the effects of serotonergic medications. Conversely, a patient who achieves sobriety through an addiction program but whose depression remains untreated faces a high risk of relapse, because the emotional pain that drove the drinking has not been addressed.

Ketamine is pharmacologically interesting in this context because its mechanism of action — NMDA receptor antagonism, enhanced glutamate signaling, and promotion of synaptic plasticity through BDNF — targets neural circuits implicated in both depression and addictive behavior. Early evidence suggests ketamine may reduce the reinforcing properties of alcohol while simultaneously improving mood, potentially breaking the cycle in which the two conditions sustain each other.

What patients have experienced

While clinical trial results from the Montreal Model are still forthcoming, the connection between ketamine therapy and reduced alcohol use is something clinicians have observed in practice. At Isha Health, some patients who began ketamine therapy primarily for depression have reported meaningful reductions in their alcohol consumption as a secondary benefit. As one patient described it: "I started ketamine therapy for my depression. It ended up also helping me stop drinking."

These individual experiences are not a substitute for controlled trial data, but they are consistent with the hypothesis that treating the underlying mood disorder can have downstream effects on addictive behavior — and that ketamine's unique mechanism may facilitate this in ways that conventional antidepressants do not. You can read more patient experiences on our outcomes page.

Important context

It is essential to note that the McAnulty et al. publication is a feasibility trial protocol, not a report of clinical results. The study is designed to establish whether the Montreal Model can be delivered safely and consistently for the AUD plus TRD population. Efficacy data will follow in subsequent publications. Clinicians and patients should not interpret this protocol paper as evidence that the approach works — rather, it represents a carefully designed framework for finding out.

Additionally, patients with active severe alcohol dependence require medical management of withdrawal before any ketamine therapy can be safely considered. Ketamine is not a replacement for medically supervised detoxification when indicated.

Further reading

For more on the relationship between ketamine and alcohol use disorder, see our earlier post on navigating alcohol withdrawal and the potential of ketamine in AUD treatment. For information about Isha Health's approach to alcohol addiction treatment, including how ketamine therapy may complement recovery, visit our conditions page.

Reference: McAnulty C, et al. "The Montreal Model: an integrative psychedelic ketamine therapy for alcohol use disorder and treatment-resistant depression — a feasibility trial protocol." BMJ Open. 2026.

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