Psychedelic-assisted therapy in Canada uses several distinct substances, each with its own pharmacology, route of administration, dose range, duration of effect, monitoring requirements, and maintenance schedule. This article is a Canadian cross-substance guide to dosing protocols for ketamine (IV, IM, sublingual, oral), esketamine (Spravato), psilocybin, and MDMA-assisted therapy — what doses are used, why those doses, how long the experience lasts, what monitoring looks like, and how dosing decisions are made. The summary is intended for patients evaluating treatment and for clinicians comparing options. Dosing decisions are clinical decisions made by the prescribing physician; nothing in this article is a recommendation for any specific patient.

Key takeaways

Ketamine IV for psychiatric indications: ~0.5 mg/kg over 40 minutes (Berman 1999, Zarate 2006); 0.5–1.0 mg/kg ranges in chronic-pain protocols (Cohen 2018 consensus, PMID 29870457).

Ketamine IM: ~0.5–1.0 mg/kg, ~30–45 minutes of subjective effect.

Ketamine sublingual (SL): 150–300 mg lozenge typical; 60–90 minute experience window; less standardized than IV / IM.

Ketamine oral: lower bioavailability; sometimes combined with sublingual to extend exposure.

Spravato (esketamine): 56 mg or 84 mg intranasal; induction twice weekly × 4 weeks; maintenance once weekly weeks 5–8, then every 1–2 weeks (Health Canada product monograph).

Psilocybin (investigational, SAP): 25 mg single dose in Goodwin 2022 COMP001 (PMID 36322843); some protocols include 1 mg or 10 mg dose-finding arms; 6–8 hour experience window.

MDMA-AT (investigational, SAP): 80–120 mg initial + supplemental 40–60 mg ~90 min later per Mitchell 2021/2023 MAPP1/MAPP2 (PMID 33972795, 37709999); 6–8 hour experience window; 3 dosing sessions over 12+ weeks.

More is not better: set, setting, patient context, and clinical preparation modulate effect substantially. Dose-response curves are not linear into higher doses.

Why dose-response matters in psychedelic-assisted therapy

Across psychedelic-assisted therapy substances, dose-response is non-linear and is modulated by set and setting. Higher doses are not uniformly more therapeutic; they are more intense, more demanding of clinical preparation, and more associated with acute adverse events (transient hypertension, anxiety, dissociation, vomiting). Dosing decisions therefore balance pharmacology, the patient's clinical situation, the indication, the route of administration, the monitoring environment, and the integration capacity of the program.

Three dose-response patterns recur across the substances:

Sub-threshold doses produce mild subjective effects without the experiential or neurobiological events most commonly associated with therapeutic outcomes (the "mystical-type experience" in psilocybin literature; the dissociative window in ketamine literature).
Therapeutic-window doses are where current RCT evidence is concentrated — 0.5 mg/kg ketamine IV, 56–84 mg Spravato intranasal, 25 mg psilocybin, 80–180 mg total MDMA.
Supratherapeutic doses produce diminishing additional clinical benefit and increasing acute-event risk.

This article walks substance-by-substance, then closes with a comparison table, monitoring considerations, and the boundary between clinical-dose protocols and microdosing.

Ketamine — IV, IM, SL, oral

Ketamine is a Health Canada-approved anaesthetic. Psychiatric and chronic-pain use is off-label but well-established within Canadian off-label prescribing principles. Routes of administration differ in bioavailability, onset, duration, and dose range.

Intravenous (IV) ketamine

The pivotal psychiatric ketamine RCTs used a standardized 0.5 mg/kg infusion over 40 minutes. Berman et al. (1999, PMID 10686270) was the first published RCT; Zarate et al. (2006, PMID 16894061) replicated rapid antidepressant effect within 24 hours. This 0.5 mg/kg / 40-minute regimen has remained the dominant psychiatric IV ketamine protocol for two decades, and the Anand 2023 ELEKT-D non-inferiority-vs-ECT trial (PMID 37224135) used a comparable infusion regimen.

For chronic pain, the Cohen et al. 2018 consensus guidelines (PMID 29870457) describe a wider range of 0.5–1.0 mg/kg infusions, often longer than 40 minutes, with somewhat different infusion-rate strategies. Pain protocols are clinically distinct from psychiatric protocols even though the drug and route are the same.

Typical psychiatric IV ketamine clinical features:

Dose: 0.5 mg/kg over 40 minutes (most common starting protocol)
Subjective onset: 5–10 minutes from start of infusion
Peak effect: ~20–30 minutes in
Resolution: most subjective effect is gone within 60–90 minutes of infusion end
Antidepressant effect: detectable within 4–24 hours; cumulative across induction sessions
Induction series: typically 4–6 sessions over 2–4 weeks
Maintenance: variable; some patients move to monthly or as-needed sessions

Intramuscular (IM) ketamine

IM ketamine is dosed at approximately 0.5–1.0 mg/kg, with onset in 5–10 minutes and a subjective duration of approximately 30–45 minutes. IM is sometimes preferred when IV access is impractical or where the program's clinical model favours a single bolus rather than infusion. IM produces a shorter, sharper effect than IV at equivalent total dose.

Sublingual (SL) ketamine

SL (lozenge / troche / "rapidly dissolving tablet") ketamine is dosed in the range of ~150–300 mg per lozenge, with a typical subjective experience window of 60–90 minutes and lower, more variable bioavailability than IV or IM. SL protocols are less standardized across Canadian clinics than IV protocols; doses depend on patient weight, compounding pharmacy, and program design. SL ketamine is often used in at-home protocols under telehealth supervision; quality of supervision varies and is a meaningful clinical consideration.

Oral ketamine

Oral ketamine has lower bioavailability than IV, IM, or SL ketamine, in part because of substantial first-pass hepatic metabolism. Some programs combine an oral dose with a sublingual dose to extend the duration of exposure or to flatten the experience curve. Oral-only protocols are less common in Canadian psychiatric ketamine practice and are typically reserved for specific clinical situations.

Spravato (esketamine intranasal)

Spravato is the (S)-enantiomer of ketamine, formulated as an intranasal spray, and is Health Canada-approved for treatment-resistant depression (Notice of Compliance May 2020). Dosing is on-label and is set by the Health Canada product monograph.

Spravato dosing per Health Canada product monograph:

Strength: 56 mg or 84 mg per session, delivered as 28-mg device sprays
Induction phase: twice weekly for 4 weeks (8 sessions)
Maintenance phase 1: once weekly for weeks 5–8
Maintenance phase 2: every 1–2 weeks ongoing, decided clinically
Monitoring: 2-hour in-clinic post-dose monitoring at every session; trained healthcare professional present; blood-pressure monitoring before, during, and after dosing
Co-administration: Spravato is administered with an oral antidepressant per the label

Spravato's two-phase induction-then-maintenance structure is the most defined ongoing-dosing schedule across psychedelic-assisted therapy options in Canada and is one reason it is the most predictable option for insurance prior-authorization pathways. For Spravato deep-dive: Spravato Coverage — PSHCP and Canada Life, Private Insurance Prior Authorization for Spravato, Intranasal Ketamine (Spravato).

Psilocybin — investigational, SAP-only

Psilocybin is a Schedule III controlled substance in Canada; clinical access is via Health Canada's Special Access Program on a case-by-case basis. The pivotal phase 2 evidence for treatment-resistant depression is Goodwin et al. 2022 COMP001 (NEJM, PMID 36322843), which used a single 25 mg oral dose of synthetic psilocybin (COMP360) with structured preparation and integration. Goodwin 2022 also included 1 mg and 10 mg comparator arms; the 25 mg dose produced a 37% response rate and 29% remission rate at week 3 for a TRD population. The MAGNUS phase 3 program (COMP005, COMP006) is ongoing in TRD.

Typical psilocybin clinical-dose features:

Dose: 25 mg synthetic psilocybin (COMP360 standard); SAP supply via Filament Health no-charge program also available
Onset: 30–60 minutes after oral administration
Peak effect: ~2–3 hours in
Experience window: 6–8 hours total
Sessions: most RCT and SAP-pathway protocols use 1–2 dosing sessions rather than ongoing maintenance
Preparation and integration: always required (per Goodwin 2022 protocol structure and per SAP clinical practice)

Some research and SAP protocols use a dose-finding approach with a 1-mg or 10-mg lower-arm dose preceding a higher dose. Psilocybin 5HT2A receptor tolerance develops rapidly, which is one reason daily or near-daily psilocybin re-dosing is not used clinically: subjective and likely therapeutic effects are blunted with insufficient inter-dose spacing. Re-dosing intervals in research protocols are typically days to weeks, not days.

For psilocybin pathway detail: Psilocybin Therapy in Canada.

MDMA-assisted therapy — investigational, SAP-only

MDMA is a Schedule I controlled substance in Canada; clinical access is via Health Canada SAP on a case-by-case basis. The pivotal phase 3 evidence is Mitchell et al. 2021 MAPP1 (PMID 33972795) and Mitchell et al. 2023 MAPP2 (PMID 37709999), which used a structured 3-session dosing protocol for severe and moderate-to-severe PTSD respectively.

MAPP-style MDMA-AT dosing per Mitchell 2021/2023:

Initial dose: 80–120 mg MDMA (typically 120 mg in MAPP1; 80–120 mg titrated in MAPP2)
Supplemental dose: 40–60 mg approximately 90 minutes after initial dose
Total dose per session: approximately 120–180 mg
Experience window: 6–8 hours total; some patients are kept onsite overnight
Number of dosing sessions: 3 sessions over approximately 12+ weeks, with preparation sessions before and integration sessions between and after

MDMA-AT is investigated for PTSD specifically, not depression. Patients should be cautious of providers conflating MDMA-AT with depression treatment. The FDA issued a Complete Response Letter on the MAPS / Lykos Therapeutics MDMA-AT new drug application in August 2024; Canadian SAP access remains the only domestic clinical pathway. For MDMA-AT pathway detail: MDMA-Assisted Therapy in Canada.

Maintenance considerations across substances

The maintenance question — once you respond, what comes next — is answered differently by substance:

Ketamine (off-label): typical induction 4–6 sessions over 2–4 weeks; maintenance is variable and individualized (every 2 weeks; monthly; as-needed; tapered to no maintenance). The KETOL multi-site Canadian program and observational cohorts continue to develop the maintenance evidence base.
Spravato (on-label): maintenance is per the two-phase Health Canada label — once weekly weeks 5–8, then every 1–2 weeks ongoing. This is the most defined maintenance schedule across psychedelic-assisted therapy in Canada.
Psilocybin (investigational): most SAP-pathway and RCT protocols use 1–2 dosing sessions rather than ongoing maintenance. Long-term re-dosing schedules are not yet established by phase 3 evidence.
MDMA-AT (investigational): a 3-session protocol per the MAPP1/MAPP2 RCTs. MDMA-AT is not delivered as ongoing maintenance.

Why "more is not better"

Across substances, dose-response is non-linear and is heavily modulated by set (the patient's preparation, intentions, mindset, current state) and setting (the physical and relational environment of dosing). The set-and-setting framework is one of the best-evidenced predictors of psychedelic experience quality (Hartogsohn 2017). Higher doses without commensurate preparation, alliance, and integration capacity tend to produce more difficult subjective experiences and weaker therapeutic outcomes, not better ones.

Practical consequences:

Increasing a psilocybin dose beyond 25 mg has not been shown in current phase 2 RCTs to increase therapeutic effect proportionally; it does increase acute-event likelihood.
Increasing a Spravato dose beyond 84 mg is outside the Health Canada label and is not supported by the pivotal trial program.
IV ketamine doses substantially above 0.5 mg/kg are sometimes used in chronic-pain settings (per Cohen 2018) but are not the standard starting psychiatric dose.
A larger MDMA dose than the MAPP1/MAPP2 80–120 mg + 40–60 mg supplemental schedule has not been shown to produce better outcomes in the phase 3 RCT base.

For pathway detail see Set and Setting in Psychedelic-Assisted Therapy.

Microdosing vs clinical-dose protocols

Microdosing — sub-perceptual doses of psilocybin (~1–3 mg dried mushroom or equivalent), or low-dose ketamine, or low-dose LSD — is a categorically different intervention from the clinical-dose protocols discussed in this article. Microdosing:

Is generally not delivered under clinical supervision
Does not use the preparation–dosing–integration model
Does not produce the subjective experiences associated with the clinical-dose RCT evidence base
Does not have phase 3 RCT evidence supporting psychiatric efficacy at this time

Patients researching psychedelic-assisted therapy frequently encounter microdosing content; it is important to distinguish microdosing from the clinical-dose protocols described above. For ATMA CENA's microdosing-specific framing see Microdosing Psilocybin.

Tolerance, contraindications, and monitoring

Tolerance considerations

Psilocybin produces rapid 5HT2A receptor tolerance; daily or near-daily redosing produces blunted effect. Inter-dose spacing of days to weeks is required for subjective effect to recover.
Ketamine tolerance considerations are clinically meaningful in repeat-dose protocols and are part of why maintenance schedules are individualized rather than fixed.
MDMA tolerance and the 1–2 month inter-session spacing in MAPP-style protocols reflect both pharmacodynamic considerations and the integration window.

Contraindications by substance

Contraindications are clinical decisions and overlap meaningfully across substances. Common screens:

Psilocybin and MDMA: personal history of psychotic disorder is generally an absolute contraindication; first-degree-relative family history is a strong relative contraindication. Lithium co-administration with psilocybin is associated with seizure risk and is contraindicated in most protocols. SSRIs / SNRIs are generally tapered before MDMA-AT and high-dose psilocybin under medical supervision; MAOIs are an absolute contraindication to MDMA.
Ketamine and Spravato: uncontrolled hypertension is a relative contraindication; recent cardiovascular event, structural heart disease, and pregnancy are typically absolute contraindications. Active substance-use disorder involving ketamine is a clinical exclusion.
All substances: pregnancy and lactation are contraindications across all current Canadian psychedelic-assisted therapy protocols.

Vital signs and cardiovascular load

Monitoring during dosing is non-negotiable across substances and varies in intensity:

IV / IM / SL ketamine and Spravato: blood pressure baseline, periodic measurement during dosing, post-dose monitoring (2 hours for Spravato; ~60–90 minutes for IV ketamine post-infusion). Transient hypertension is common and expected; sustained elevation prompts clinical review.
MDMA-AT: blood pressure and heart rate monitoring throughout the session; MDMA produces sympathomimetic load (modest blood-pressure and heart-rate elevation) that requires baseline cardiovascular screening.
Psilocybin: cardiovascular load is comparatively modest; monitoring still includes blood pressure and overall observation; psychiatric monitoring is the dominant component.

For first-session detail: What to Expect at Your First Psychedelic-Assisted Therapy Session.

Comparison table — dosing protocols across substances

Substance / route	Typical dose	Duration of subjective effect	Sessions per protocol	Maintenance	Health Canada status
Ketamine IV (psychiatric)	0.5 mg/kg over 40 min	60–90 min total	4–6 induction	Variable / individualized	Off-label (anaesthetic approved)
Ketamine IV (chronic pain)	0.5–1.0 mg/kg	Variable	Variable	Variable	Off-label
Ketamine IM	0.5–1.0 mg/kg	30–45 min	4–6 induction	Variable	Off-label
Ketamine SL	150–300 mg lozenge	60–90 min	4–6 induction	Variable	Off-label; less standardized
Ketamine oral	Lower bioavailability; sometimes adjunctive to SL	Variable	Variable	Variable	Off-label
Spravato (esketamine)	56 mg or 84 mg intranasal	~40 min + 2 h monitoring	8 induction (4 wks twice weekly)	1×/wk wks 5–8, then q1–2 wks	On-label TRD (May 2020)
Psilocybin (SAP)	25 mg single dose (Goodwin 2022)	6–8 hours	1–2 dosing sessions	Generally none	Investigational; SAP only
MDMA-AT (SAP)	80–120 mg + 40–60 mg supplemental	6–8 hours	3 sessions over 12+ weeks	Not maintenance-based	Investigational; SAP only

How ATMA CENA works with dosing decisions

ATMA CENA's pathway is the three-phase model — preparation + dosing + integration — adapted to substance and patient. Dosing decisions are made by the prescribing physician, in collaboration with the patient, the clinical team, and (under coordinated care) the patient's existing therapist or psychiatrist.

Substance choice: ketamine (route per clinic capability and patient situation); Spravato per Health Canada label; psilocybin or MDMA via SAP application
Dose selection: per substance protocol, with weight-based titration for ketamine and per-label dose selection for Spravato
Monitoring: blood pressure, heart rate, and psychiatric monitoring across all protocols; intensity scales with substance
Maintenance planning: built into the integration phase, decided across the clinical team rather than at the end of a single dosing session

For pathway depth: The Preparation Phase of Psychedelic-Assisted Therapy, The Integration Phase of Psychedelic-Assisted Therapy.

What dosing protocols do NOT do

Dosing protocols are not patient-determined. Dose selection, route of administration, frequency, and maintenance schedule are clinical decisions made by the prescribing physician.
Higher doses are not uniformly better. Across substances, dose-response is non-linear and heavily modulated by set, setting, and integration capacity.
A single dosing session is rarely the entire intervention. Ketamine and Spravato use induction and maintenance. Psilocybin uses 1–2 sessions plus structured preparation and integration. MDMA-AT uses 3 sessions plus preparation and integration.
Dosing protocols do not guarantee response. Goodwin 2022 COMP001 25-mg psilocybin produced 37% response and 29% remission at week 3 — meaningful, but not universal. Spravato, off-label ketamine, and MDMA-AT response rates similarly fall short of 100%.
Off-label is not unapproved. Ketamine for psychiatric and chronic-pain indications is off-label; the medication is Health Canada-approved as an anaesthetic, and off-label psychiatric use is within Canadian off-label prescribing principles.

Frequently asked questions

What dose of IV ketamine is used for depression? The standard psychiatric IV ketamine protocol is 0.5 mg/kg over 40 minutes, originally established by Berman 1999 and Zarate 2006 and used through the Anand 2023 ELEKT-D non-inferiority trial vs ECT. Chronic-pain protocols use a wider 0.5–1.0 mg/kg range per the Cohen 2018 consensus.

What dose of Spravato is used? 56 mg or 84 mg intranasal per session, delivered as 28-mg device sprays. The induction phase is twice weekly for 4 weeks; maintenance is once weekly weeks 5–8, then every 1–2 weeks ongoing. This is the Health Canada product monograph schedule.

What dose of psilocybin is in the COMP001 trial? Goodwin 2022 COMP001 used a 25-mg single oral dose of synthetic psilocybin (COMP360) as the principal therapeutic arm, with 1-mg and 10-mg comparator arms. The 25-mg dose produced 37% response and 29% remission at week 3 in TRD.

What dose of MDMA is used in MAPP1/MAPP2? 80–120 mg initial dose plus 40–60 mg supplemental dose approximately 90 minutes later, for a total of approximately 120–180 mg per session. Three dosing sessions are delivered over approximately 12+ weeks with preparation and integration sessions structured around dosing.

Is sublingual ketamine as effective as IV? Sublingual ketamine has lower and more variable bioavailability than IV ketamine and is less standardized in clinical practice. Comparative-effectiveness evidence is more limited than for IV ketamine. SL is often used in at-home telehealth protocols; quality of supervision is a meaningful clinical consideration.

Why does psilocybin only require 1–2 sessions? Goodwin 2022 COMP001 and most current psilocybin RCTs use 1–2 dosing sessions because the antidepressant signal in TRD has been observed after a single 25-mg dose and because rapid 5HT2A receptor tolerance makes daily or near-daily redosing pharmacodynamically impractical. Long-term re-dosing schedules are still being established by phase 3 evidence (MAGNUS).

Is microdosing the same as clinical-dose psilocybin? No. Microdosing is a categorically different intervention — sub-perceptual doses, generally not delivered under clinical supervision, without the preparation–dosing–integration model, and without phase 3 RCT support for psychiatric indications at this time. See Microdosing Psilocybin.

Why isn't MDMA-AT given as ongoing maintenance? MDMA-AT is investigated as a 3-session protocol per the MAPP1/MAPP2 RCTs. It is not delivered as ongoing maintenance because the trial-level evidence base is built on a finite-session structure with structured preparation and integration around the dosing sessions.

Can my dose be adjusted if it's too intense? Dose adjustment between sessions is a clinical decision made by the prescribing physician. Patient feedback about subjective intensity, tolerability, and integration capacity is part of the clinical record and is one of the inputs the team uses to calibrate subsequent sessions.

Who decides what substance and dose? The prescribing physician, in consultation with the patient and the clinical team. Substance choice is shaped by indication, contraindications, prior treatments, insurance pathway, and clinic capability. Dose selection is per substance protocol with patient-specific titration where applicable.

Compliance disclaimer

This article is educational and is not a clinical recommendation for any specific individual. Ketamine is a Health Canada-approved anaesthetic; psychiatric and chronic-pain use is off-label and within Canadian off-label prescribing principles. Esketamine (Spravato) is Health Canada-approved for treatment-resistant depression. Psilocybin and MDMA are Schedule III and Schedule I controlled substances respectively; clinical access in Canada is via Health Canada's Special Access Program on a case-by-case basis. Dosing decisions belong with a qualified prescribing physician. No outcome is promised by this article for any patient.

Sources

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Last updated: 2026-05-06

Dosing Protocols Across Psychedelic-Assisted Therapy Substances