Ketamine is taken in several different ways depending on the medical purpose, and the route of administration changes how quickly it works, how much of the drug your body absorbs, and where you receive treatment. The most common methods are intravenous (IV) infusion, nasal spray, intramuscular injection, and oral lozenges or tablets. Each has a distinct profile, and understanding the differences can help you know what to expect if ketamine treatment is recommended for you.
IV Infusion
Intravenous infusion is the most studied method for treating depression with ketamine. The standard protocol starts at 0.5 mg per kilogram of body weight, delivered slowly over 40 minutes. Clinicians often cap the first infusion at 50 mg and may gradually increase the dose in later sessions up to about 1.0 mg per kilogram, with 100 mg as a typical upper limit per infusion.
Because IV delivery puts the drug directly into your bloodstream, it has 100% bioavailability, meaning none of the dose is lost to digestion or absorption. Effects begin within minutes. For depression treatment, the dose is kept well below anesthetic levels. Sub-anesthetic doses for mood disorders range from 0.1 to 0.5 mg/kg, while full anesthesia requires 1 to 4.5 mg/kg delivered more rapidly.
IV infusions take place in a clinical setting equipped for resuscitation, with a nurse monitoring your blood pressure, heart rate, and oxygen levels throughout the session and for at least one hour afterward. You’ll need someone to drive you home, and you shouldn’t operate a vehicle or heavy machinery for the rest of the day.
Nasal Spray (Esketamine)
The FDA-approved nasal spray, sold under the brand name Spravato, uses esketamine, a slightly different molecular form of ketamine. Each spray device delivers 28 mg, and a typical dose session involves two devices (56 mg) or three devices (84 mg), with a five-minute rest between each one. You tilt your head back about 45 degrees, spray once into each nostril per device, and sniff gently to keep the medication in place.
For treatment-resistant depression, the schedule starts with twice-weekly sessions for the first four weeks, drops to once weekly for the next four weeks, then shifts to every one or two weeks for ongoing maintenance. For depression with acute suicidal thoughts, the recommended dose is 84 mg twice weekly for four weeks.
Spravato is only available through a restricted program called REMS. That means you cannot take it home. Every dose is self-administered under direct supervision at a certified healthcare facility, and you must be monitored for at least two hours afterward so staff can check for sedation, dissociation, and changes in vital signs. A healthcare provider confirms the spray device is empty before you finish each session. Pharmacies are prohibited from dispensing Spravato for use outside a certified setting.
Compounded Nasal Ketamine
Some clinics prescribe compounded racemic ketamine as a nasal spray, which is a different product from Spravato. Compounded versions are not FDA-approved for depression and are used off-label. They’re typically administered under medical supervision in a clinic as well, though the regulatory requirements are less rigid than the REMS program that governs Spravato.
Intramuscular Injection
Intramuscular (IM) injection delivers ketamine into a large muscle, usually the thigh or upper arm. It has a bioavailability of roughly 41%, meaning less than half the dose reaches your bloodstream compared to IV. Effects begin within about 5 minutes and reach full intensity in 10 to 15 minutes.
IM injection is commonly used in emergency and surgical settings for sedation and pain control, where doses range from 6.5 to 13 mg/kg for full anesthesia lasting 12 to 30 minutes. For mental health treatment, much lower doses are used. The IM route is simpler to set up than an IV line, making it a practical option in some outpatient clinics.
Oral Tablets and Sublingual Lozenges
Oral ketamine comes in capsules, tablets, or sublingual lozenges (sometimes called troches). This is the route most commonly used for at-home ketamine therapy, typically prescribed through telehealth platforms with remote monitoring and psychosocial support.
Sublingual lozenges are held under the tongue or against the cheek for 10 to 15 minutes to allow absorption through the mouth’s lining. Swallowing the medication reduces how much reaches your bloodstream because the liver breaks down a significant portion before it can take effect. Sublingual wafers have a bioavailability of about 29%, lozenges around 24%, and oral tablets roughly 32%. All of these are substantially lower than IV or even IM routes, so oral doses are adjusted higher to compensate.
Peak blood levels from sublingual administration occur around 45 minutes after the dose, with a range of 15 minutes to an hour depending on the formulation. Effects come on more gradually and feel less intense than IV or IM ketamine, which is part of why this route is considered more manageable for home use. Screening by a clinician and remote monitoring during sessions help keep adverse events low, though some patients do discontinue treatment due to side effects.
How Bioavailability Shapes the Experience
The route you use determines how much of the drug actually enters your system and how fast. IV delivery is the benchmark at 100%. Intramuscular injection drops to about 41%. Sublingual formulations land between 24% and 32%, depending on the specific product. This is why a 200 mg oral lozenge and a 35 mg IV infusion might produce comparable effects in the same person.
Faster routes (IV, IM) produce more pronounced dissociative and perceptual effects during the session. Slower routes (oral, sublingual) tend to create a gentler, more gradual experience. The tradeoff is that faster routes require more intensive medical monitoring, while oral forms are practical enough for supervised home use.
Therapeutic Doses vs. Anesthetic Doses
The gap between a mental health dose and an anesthesia dose is large. For depression, IV ketamine is given at 0.1 to 0.5 mg/kg. For surgical anesthesia, the IV dose jumps to 1 to 4.5 mg/kg, delivered much faster. Similarly, IM doses for anesthesia range from 6.5 to 13 mg/kg, while IM doses for mood treatment stay far below that threshold. At sub-anesthetic levels, you may feel floaty, detached, or mildly altered in perception, but you remain conscious and breathing on your own. Full anesthetic doses produce complete dissociation and loss of awareness.
This distinction matters because it shapes what your treatment session feels like. A 40-minute IV infusion for depression is not the same experience as ketamine used in an operating room. Most people describe the sub-anesthetic experience as dreamlike, with mild visual or sensory changes that resolve within an hour or two after the session ends.