Ways to Take Ketamine: IV, Sublingual, Nasal, IM, and More (2026)

Ketamine's versatility is one of the reasons it has become such an important therapy for mood and pain conditions. Different ways of giving ketamine, known as routes of administration, affect how quickly it works, how long it lasts, and what safety measures are needed. Below you'll find a clear, patient-friendly overview of all major options, from intravenous infusions to emerging transdermal systems.

Routes of Administration

1. Intravenous (IV)

How it works: Direct infusion into a vein.

Bioavailability: ~100%.

Benefits: Precise control of dose; fastest onset; used in most clinical studies and settings.

Risks: Requires IV setup and monitoring; IV site complications, bruises.

2. Intramuscular (IM)

How it works: One-time injection into a large muscle.

Bioavailability: ~93%.

Benefits: Simple and fast; no IV line needed.

Risks: Once injected, cannot adjust dose mid-session; muscle pain or swelling; site reactions.

3. Subcutaneous (SQ)

How it works: Injection under the skin's fatty layer.

Bioavailability: Slightly lower than IM ~90%.

Benefits: Less invasive; used occasionally for pain management.

Risks: Slower onset and more variable absorption.

4. Intranasal (IN)

FDA-approved form: Spravato (esketamine).

Bioavailability: ~45-50%.

Benefits: Needle-free; reliable onset; supervised use in certified clinics; sometimes covered by insurance (Spravato has a formal indication, but coverage usually requires prior authorization and copays of $150-$300 per session are common).

Risks: Transient nasal irritation; requires post-dose observation when prescribed as Spravato.

More on this route: The 2026 ketamine nasal spray guide covers Spravato versus compounded nasal sprays, REMS logistics, and insurance reality.

5. Oral (Swallowed)

Bioavailability: ~16-29% (commonly cited around 17%). The drop is driven by extensive hepatic first-pass metabolism through CYP3A4 and CYP2B6, which converts most of the ingested dose into the metabolite norketamine before it reaches systemic circulation.

Benefits: Convenient and cost-effective; suitable for structured at-home program when taste is an issue. Norketamine (the primary first-pass metabolite) is itself pharmacologically active and accumulates to higher levels with oral dosing than with other routes, partially offsetting the lower parent-drug bioavailability.

Risks: Unpredictable absorption; may cause nausea.

6. Sublingual / Buccal (Under Tongue or Cheek)

Bioavailability: ~25-32%.

Benefits: Better absorption than swallowed tablets; favored for telehealth programs for ease of use.

Risks: Bitter taste, oral numbness, variable absorption.

7. Rectal

Bioavailability: ~25-30%.

Benefits: Useful when oral or nasal routes are not possible.

Risks: Limited acceptance, irritation, variable results; mainly pediatric or procedural use.

8. Dermal / Transdermal (Creams or Patches)

Status: Experimental for chronic pain; not used for mood disorders yet.

Benefits: Non-invasive and steady absorption potential.

Risks: Skin reactions; unproven dosing consistency.

Comparison at a Glance

What's FDA-Approved and What's Off-Label?

FDA-approved: Esketamine nasal spray (Spravato), for treatment-resistant depression, administered in certified clinics under supervision.

Off-label but well-established: IV, IM, and oral/sublingual racemic ketamine, widely used under physician care for depression, PTSD, chronic pain, and anxiety.

Investigational / limited data: Pure R-ketamine, rectal, and transdermal applications.

Safety Considerations Across All Routes

Cardiovascular: Temporary increases in blood pressure or heart rate.

Neuropsychiatric: Dissociation or perceptual changes during treatment.

Other: Nausea, fatigue, rare bladder irritation with long-term heavy use.

Misuse prevention: Only take ketamine prescribed and monitored by a licensed clinician. Integration therapy enhances long-term benefit and safety.

How Discreet Ketamine Approaches Treatment

At Discreet Ketamine, we combine clinical precision with patient comfort. We use racemic ketamine through sublingual, oral, and occasionally intranasal or IM routes depending on your individualized plan. All treatments include screening, ongoing monitoring, and therapeutic integration, ensuring privacy and safety every step of the way.

Frequently Asked Questions

What's the most effective way to take ketamine for depression?

For acute crisis (severe TRD with suicidal ideation), IV ketamine in a clinic is generally preferred: 100% bioavailability, fastest onset, and direct medical supervision. For ongoing maintenance, anxiety, and chronic pain, sublingual ketamine at home delivers comparable real-world outcomes at a fraction of the cost. Spravato (intranasal esketamine) is the FDA-approved pathway with a chance at insurance coverage. The "best" route depends on severity, cost constraints, and whether ongoing maintenance or acute relief is the goal.

What's the difference between IV, IM, and sublingual ketamine bioavailability?

IV ketamine has ~100% bioavailability (drug enters bloodstream directly). IM (intramuscular injection) reaches ~93%. Sublingual (under-the-tongue troches or ODTs) lands at 25-32% because much of the medication is swallowed and lost to first-pass liver metabolism. Intranasal ranges from 8-50% depending on formulation; Spravato lands around 45-50%. Sublingual doses are adjusted upward to compensate for the lower bioavailability.

Why is sublingual ketamine bioavailability lower than IV?

Two reasons. First, only the medication that absorbs through the sublingual mucosa enters the bloodstream directly; saliva that gets swallowed loses ~80% of the drug to first-pass liver metabolism. Second, individual oral mucosa absorption varies based on technique (how long you hold the troche, whether you swallow saliva early). The 25-32% bioavailability range reflects this variability, which is why sublingual programs typically titrate dose based on response.

Can ketamine be given as an injection at home?

IM (intramuscular) ketamine is generally administered in clinical settings, not at home. The bioavailability is ~93% and onset is fast (5-15 minutes), but once injected the dose can't be adjusted mid-session. Most at-home ketamine programs use sublingual troches or ODTs precisely because they don't require injection equipment or training, and any complications can be managed by spitting out residue or aborting the session before peak effect.

Is intranasal ketamine the same as Spravato?

Not exactly. Spravato is the FDA-approved esketamine (S-enantiomer only) nasal spray made by Janssen, restricted to certified clinics under a REMS program. "Intranasal ketamine" can also refer to compounded racemic or S-ketamine nasal preparations made by compounding pharmacies for off-label use, typically for chronic pain. Both are nasal sprays containing ketamine-class molecules, but they differ in formulation, regulation, and how they're prescribed.

Which form of ketamine has the fastest onset?

IV ketamine wins on speed: 2-5 minutes from infusion start to onset of effects. IM injection comes next at roughly 5-15 minutes. Intranasal Spravato lands at 10-15 minutes. Sublingual ketamine takes the longest to onset at 10-20 minutes, with peak at 40-60 minutes. Faster isn't necessarily better; the slower sublingual onset is often easier for first-time patients to manage at home.

Is oral ketamine effective?

Less so than sublingual at the parent-drug level, but the picture is more nuanced than a single number suggests. Swallowed ketamine has roughly 16-29% bioavailability (most studies cluster around 17%), substantially lower than sublingual's 25-32%. The reason is hepatic first-pass metabolism: most of the swallowed dose is converted by liver enzymes (primarily CYP3A4 and CYP2B6) into norketamine before reaching systemic circulation. Norketamine is itself an active metabolite with antidepressant and analgesic effects of its own, and oral dosing produces higher norketamine levels than other routes; some pharmacokinetic analyses estimate the combined ketamine + norketamine "effective bioavailability" of oral dosing reaches ~59%. In practice, sublingual remains the standard for at-home psychiatric use because it's more predictable and produces faster onset, but oral dosing is a legitimate option when sublingual isn't tolerable.

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References

1. Peltoniemi MA, Hagelberg NM, Olkkola KT, Saari TI. Ketamine: A Review of Clinical Pharmacokinetics and Pharmacodynamics in Anesthesia and Pain Therapy. Clin Pharmacokinet. 2016;55(9):1059-1077. PubMed: 27028535 The standard pharmacokinetics review across routes of administration. Source for the bioavailability ranges (IV ~100%, IM ~93%, intranasal ~45-50%, sublingual ~25-32%, oral ~20-25%) referenced throughout the body and the comparison table.

2. Daly EJ, Trivedi MH, Janik A, et al. Efficacy of Esketamine Nasal Spray Plus Oral Antidepressant Treatment for Relapse Prevention in Patients With Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2019;76(9):893-903. PubMed: 31166571 Establishes the FDA-approval and clinical-context basis for Spravato (esketamine nasal spray) as administered in certified clinics under the REMS program.

3. Sanacora G, Frye MA, McDonald W, et al. A Consensus Statement on the Use of Ketamine in the Treatment of Mood Disorders. JAMA Psychiatry. 2017;74(4):399-405. PubMed: 28249076 APA-task-force consensus on screening, dosing, and monitoring across routes of clinical ketamine use, including off-label IV, IM, and sublingual considerations.

4. Dutton M, Can AT, Lagopoulos J, Hermens DF. Oral ketamine may offer a solution to the ketamine conundrum. Psychopharmacology (Berl). 2023;240(12):2483-2497. PubMed: 37882811 · Free full text Recent review establishing the oral-ketamine bioavailability range (16-29%, commonly ~17%) and the role of the active metabolite norketamine in driving clinical effects despite low parent-drug bioavailability. Supports the FAQ's "effective bioavailability ~59%" figure when norketamine is included.