What Is Ketamine Therapy? A Plain-Language Guide for Canadians

Ketamine therapy is a medically supervised treatment that uses sub-anaesthetic doses of ketamine — a drug Health Canada approves as an anaesthetic — to help patients with conditions including treatment-resistant depression, PTSD, anxiety, OCD, and chronic pain. It works through a different brain pathway than antidepressants, can produce rapid effects within hours rather than weeks, and is delivered in supervised clinical settings as either ketamine infusion therapy (the medication alone) or ketamine-assisted psychotherapy (the medication paired with structured therapy sessions).

Key takeaways

• Ketamine therapy is a treatment, not a recreational experience. Sub-anaesthetic doses are administered by licensed clinicians in monitored settings.
• Health Canada approves ketamine as an anaesthetic. Use for depression, PTSD, anxiety, and other psychiatric or pain indications is off-label — legal and common in Canadian medicine.
• Spravato (intranasal esketamine) is the only ketamine-class drug with a Health Canada psychiatric indication (treatment-resistant MDD, approved May 2020).
• Ketamine acts on the brain's glutamate system, not the serotonin system targeted by SSRIs. Antidepressant effects can emerge within 2 to 72 hours of a single dose.
• When ketamine is paired with psychotherapy before, during, and after dosing, the treatment is called ketamine-assisted psychotherapy (KAP) or ketamine-assisted therapy (KAT).

Ketamine therapy in one paragraph

Ketamine is a dissociative anaesthetic synthesized in 1962 and approved as a human anaesthetic in 1970. At the much lower doses used in psychiatric and chronic-pain treatment, it produces a brief altered-state experience and rapid antidepressant effects. The first published psychiatric observation came from Khorramzadeh and Lotfy in 1973; the first placebo-controlled randomized trial in depressed patients was published by Berman et al. in 2000. Ketamine therapy in 2026 is delivered through one of five routes — IV infusion, intramuscular injection, sublingual lozenge, oral, or intranasal — by physicians, nurse practitioners, and clinical teams that include regulated mental-health professionals.

How does ketamine work in the brain?

Ketamine acts primarily as an antagonist at NMDA (N-methyl-D-aspartate) receptors on inhibitory interneurons in the brain. Blocking these receptors triggers a downstream surge of glutamate — the brain's principal excitatory neurotransmitter — which activates AMPA receptors and stimulates BDNF (brain-derived neurotrophic factor) along with mTOR signalling. The cumulative effect is rapid synaptogenesis: the formation of new neural connections within 24 to 72 hours of a single dose.

A 2022 systematic review of 141 studies concluded that "ketamine induces an increase in molecules involved in modulating neuroplasticity" paired with rapid mood improvements (Kang et al., 2022). Aleksandrova and Phillips (2021) frame the mechanism as a neural "reset" — ketamine counteracts synaptic deficits and restores connectivity between the prefrontal cortex and limbic structures that becomes disrupted in depression (Aleksandrova & Phillips, 2021).

The contrast with conventional antidepressants matters clinically. SSRIs and SNRIs slowly modulate serotonin and norepinephrine signalling; meaningful clinical benefit typically emerges over four to six weeks of daily dosing. Ketamine acts on glutamate directly — antidepressant effects can appear within 2 to 72 hours of a single IV dose and last days to weeks (Lullau et al., 2023).

Atomic answer. Ketamine blocks NMDA receptors in the brain, triggering a surge of glutamate that activates AMPA receptors and stimulates BDNF — a protein that promotes new synaptic connections. This rapid synaptogenesis may restore neural pathways disrupted by depression, producing antidepressant effects within hours rather than weeks.

What conditions can ketamine therapy help with?

The strongest evidence base is for treatment-resistant major depressive disorder. Other indications are supported by smaller randomized trials, meta-analyses, or open-label studies. Always frame ketamine within Canada's off-label prescribing rules: for everything except Spravato in TRD, use is based on accumulating clinical evidence rather than a specific Health Canada psychiatric approval.

• Treatment-resistant depression (TRD). Multiple RCTs; CANMAT 2021 lists IV racemic ketamine as a third-line treatment for adults with TRD (Swainson et al., 2021).
• Major depressive disorder (non-TRD). Smaller proof-of-concept RCTs (Berman et al., 2000).
• Acute suicidal ideation. Individual-participant meta-analysis showing rapid reduction within 24 hours (Wilkinson et al., 2018).
• PTSD. Two RCTs (single and repeated dosing) showing significant CAPS reductions versus active placebo (Feder et al., 2014; Feder et al., 2021).
• Anxiety disorders. RCT data supporting use in social and generalized anxiety, particularly when treatment-refractory (Glue et al., 2017).
• OCD. One small RCT plus open-label data (Rodriguez et al., 2013).
• Bipolar depression (with mood stabilizer coverage) and chronic pain conditions (CRPS, neuropathic pain) round out the indication set.

This article is an introduction. For condition-specific deep dives, see Ketamine Therapy for Depression and the main ketamine therapy hub.

What types of ketamine therapy are available in Canada?

Five delivery routes are used clinically. Each has a different bioavailability, evidence base, regulatory status, and typical session experience.

IV ketamine has the largest psychiatric evidence base because most randomized trials used it. KAP-style protocols using IM and sublingual ketamine are also widely used in Canadian clinics, often paired with structured psychotherapy. Spravato is the only ketamine-class drug Health Canada has approved for a psychiatric indication; administration must occur in a certified clinical setting with mandatory post-dose monitoring under the Janssen Journey program.

A separate compounded racemic ketamine nasal spray exists at some clinics. It is off-label, distinct from Spravato, and the FDA has issued safety alerts about compounded intranasal ketamine specifically. Spravato is the only intranasal product with regulatory approval.

What's the difference between ketamine infusion and ketamine-assisted psychotherapy?

Ketamine infusion (or ketamine alone) is the medical model: a clinician administers a dose, monitors the patient through the dosing window, and discharges the patient with follow-up medical visits. There is no structured therapy session attached.

Ketamine-assisted psychotherapy (KAP) is the integrative model: a regulated mental-health professional provides preparation sessions before dosing, supports the patient during the active session, and conducts integration sessions in the days and weeks after each dose. The therapy component is what the "assisted" in KAP refers to.

A 2022 systematic review of 17 KAP studies (n=603) concluded that "psychotherapy, provided before, during, and following ketamine sessions, can maximize and prolong benefits" (Drozdz et al., 2022). A 2017 trial demonstrated that adding 12 weeks of cognitive-behavioural therapy after a 4-session IV ketamine course extended antidepressant durability — relapse occurred in only 25% of responders by week 8 (Wilkinson et al., 2017).

ATMA CENA's ketamine programs use the KAP model. Two dosing modes are offered: psychedelic (higher dose, altered-state experience) and psycholytic (lower dose with the patient engaged in talk therapy).

What happens during a ketamine therapy session?

A typical ketamine therapy program includes preparation, dosing, and integration.

Preparation. One to three sessions before the first dose, typically with a regulated mental-health professional. The team reviews medical history, screens for contraindications, sets intentions, and discusses what to expect. For KAP programs, the preparation phase establishes the therapeutic relationship that supports the dosing experience.

The dosing session. Patients arrive at a clinical setting having fasted (typical for IV protocols) or eaten lightly per program instructions. Vitals are checked. The dose is administered — IV over 40 minutes, IM as a single injection, sublingually held under the tongue for ~10 minutes, or Spravato self-administered as a nasal spray under direct healthcare supervision. The acute experience typically lasts 45 to 90 minutes. Patients commonly describe altered time perception, mild visual or auditory shifts, an emotional softening, and a sense of distance from habitual thought patterns. The therapist or nurse stays with the patient throughout. Hartogsohn (2016) frames this in the language of set and setting — the psychological state and environment shape the response to the substance, alongside the pharmacology itself (Hartogsohn, 2016).

After the dosing window, patients rest in a recovery setting for another 30 to 60 minutes (longer for Spravato — Health Canada requires a minimum 2-hour observation). Patients cannot drive for at least 24 hours and need an escort home.

Integration. Sessions in the days and weeks after each dose where the patient and therapist process material that surfaced during the experience. Integration is where KAP differs most from infusion-only models — it translates the acute experience into sustained behavioural change.

How does ketamine therapy compare to traditional antidepressants?

Conventional antidepressants — SSRIs, SNRIs, atypicals, MAOIs — work primarily on the serotonin and norepinephrine systems. They produce clinical benefit over 4 to 6 weeks of daily dosing, work for roughly 50–60% of patients on a first trial, and require ongoing daily medication.

Ketamine acts on the glutamate system, can produce antidepressant effects within 24 to 72 hours, and is delivered as a course of sessions rather than as daily medication. CANMAT 2021 places IV racemic ketamine as a third-line treatment for adults with treatment-resistant depression — meaning after failure of multiple first-line antidepressants and at least one adjunctive agent (Swainson et al., 2021).

Most patients in Canadian ketamine programs continue their existing antidepressants alongside ketamine treatment. Discuss any medication adjustments with the prescribing physician at intake. Some medications interact pharmacodynamically — benzodiazepines may attenuate ketamine's antidepressant effect (Andrashko et al., 2021) — and the screening process addresses these interactions case-by-case.

Is ketamine therapy legal in Canada?

Yes. Ketamine is a Schedule I controlled substance under the Controlled Drugs and Substances Act, legally permitted for medical use when prescribed by a licensed physician or nurse practitioner. Health Canada has approved ketamine as an anaesthetic. Use for depression, PTSD, anxiety, OCD, and chronic pain is off-label — a legal and common practice in Canadian medicine where physicians prescribe an approved drug for indications beyond its original approval based on clinical judgment.

Spravato (intranasal esketamine) is the only ketamine-class drug Health Canada has approved for a psychiatric indication: treatment-resistant major depressive disorder in adults who have not responded adequately to at least two antidepressant courses (Health Canada DPD).

Provincial physician colleges have published ketamine guidance:

• Alberta — CPSA (March 2026)
• Manitoba — CPSM (January 2026)
• Ontario — CPSO Out-of-Hospital Premises Inspection Program
• British Columbia — CPSBC (August 2025 interim guidance)

These rules govern where and how ketamine can be administered, who can prescribe and supervise, and what facility accreditation is required for IV administration. Ketamine does not require Health Canada's Special Access Program (which governs psilocybin and MDMA) because it has existing medical licensure.

Is ketamine therapy safe?

At sub-anaesthetic doses with proper screening and supervised administration, ketamine has a well-established short-term safety profile. Common side effects:

• Dissociation or perceptual changes during the dosing window (resolves within 1–3 hours)
• Mild nausea
• Transient increase in blood pressure (typically 10–30 mmHg) and heart rate
• Dizziness or unsteadiness
• Headache
• Mild dysphoria in a minority of sessions

Sessions are conducted with vital-sign monitoring throughout. Patients cannot drive for 24 hours after a session. Dependency risk is low at therapeutic doses in supervised contexts; it is higher with frequent unsupervised recreational use, which is why active ketamine use disorder is a contraindication for ketamine therapy.

Long-term safety considerations from heavier or unsupervised use — bladder toxicity (cystitis), hepatic and biliary effects, dependency — are linked to high-frequency, high-dose, unsupervised exposure rather than the controlled clinical dosing used in therapy. Health Canada has issued a safety review noting hepatotoxicity and cholangiopathy risk with extended ketamine exposure; baseline and ongoing liver-function monitoring is appropriate for patients receiving maintenance infusions.

For a full breakdown of contraindications and screening criteria, see How to Qualify for Ketamine Therapy in Canada.

Is ketamine therapy right for you?

The clearest indication is treatment-resistant depression — typically defined as failure of at least two adequate antidepressant trials at therapeutic dose for 6+ weeks each. Other indications (PTSD, anxiety, OCD, chronic pain) are evaluated individually by the clinical team based on diagnosis, severity, prior treatment history, and absence of contraindications.

Conditions that disqualify ketamine therapy include active psychosis, uncontrolled severe hypertension, severe cardiovascular disease, increased intracranial pressure, current pregnancy, anaphylactic reaction to ketamine, and active manic episode. Conditions that require careful evaluation include history of substance use disorder, severe personality disorder with marked instability, recent stroke, untreated severe sleep apnea, and concurrent use of MAOIs or high-dose benzodiazepines.

Frequently asked questions

What is ketamine therapy in simple terms? Ketamine therapy uses sub-anaesthetic doses of ketamine — a Health Canada-approved anaesthetic — to treat conditions such as treatment-resistant depression, PTSD, anxiety, and chronic pain. It works through a different brain pathway than antidepressants and can produce effects within hours rather than weeks.

Is ketamine therapy legal in Canada? Yes. Ketamine is legally prescribed by physicians and nurse practitioners for medical purposes. Off-label use for psychiatric indications is permitted under Canadian off-label prescribing rules. Spravato (intranasal esketamine) is Health Canada-approved for treatment-resistant MDD.

Does ketamine therapy get you high? The dissociative experience at therapeutic doses differs from recreational drug use. Patients describe altered time perception, mild visual or auditory shifts, and an emotional softening. The experience occurs in a clinical setting, peaks during the 45–90 minute dosing window, and resolves within hours.

How quickly does ketamine therapy work? Antidepressant effects can emerge within 2 to 72 hours of a single IV dose. The 4-to-6-week onset typical of SSRIs does not apply to ketamine.

What's the difference between IV ketamine and Spravato? Spravato is the S-enantiomer of ketamine, delivered as a Health Canada-approved nasal spray for treatment-resistant MDD. IV ketamine is racemic (50/50 R and S), prescribed off-label for a wider range of indications, with a deeper psychiatric evidence base. Spravato has clearer insurance coverage pathways; IV ketamine is typically self-pay.

Do I need a doctor's referral? Most private Canadian ketamine clinics accept self-referrals. Some publicly funded programs require physician referral. Verify with the specific clinic.

Is ketamine addictive? Ketamine has a low dependency risk at therapeutic doses in supervised clinical contexts. Higher dependency risk is associated with frequent unsupervised recreational use. Active ketamine use disorder is a contraindication for ketamine therapy.

Can I drive after a ketamine session? No. Patients cannot drive for at least 24 hours after a session. An escort home is required.

How long does the antidepressant effect last? A single dose typically produces antidepressant effects lasting days to a few weeks. Repeated sessions during the acute phase (4–8 sessions over 2–4 weeks) extend durability. Adding integration psychotherapy after the acute phase appears to extend the effect (Wilkinson et al., 2017).

How much does ketamine therapy cost in Canada? Most Canadian patients pay out-of-pocket. IV ketamine sessions typically cost CAD $375–$1,000; KAP programs CAD $685–$1,400 per session. See Ketamine Therapy Cost in Canada for the full breakdown.

Sources

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Related articles

• Ketamine Therapy in Canada
• Ketamine Therapy Cost in Canada
• How to Qualify for Ketamine Therapy in Canada
• Ketamine Therapy for Depression
• Ketamine Therapy in Calgary
• Ketamine Therapy in Edmonton

Last updated: 2026-05-05