Ketamine can be ingested through several routes, each with different absorption rates, onset times, and medical uses. The most common methods in clinical settings are intravenous infusion, intramuscular injection, nasal spray, and oral formulations like lozenges and liquid solutions. The route matters because it dramatically affects how much of the drug actually reaches your bloodstream, ranging from 100% with an IV down to as little as 15% when swallowed as a liquid.
Intravenous Infusion
IV infusion is the most direct and precisely controlled method. The drug enters the bloodstream immediately, producing 100% bioavailability and a peak effect within about one minute. For depression treatment, the standard protocol involves a dose of 0.5 mg per kilogram of body weight delivered slowly over 40 minutes through an infusion pump. Some providers use doses up to 1 mg/kg depending on the patient’s response.
Because the dose can be adjusted in real time, IV infusion gives clinicians the most control over the experience. It’s administered in clinical settings where vital signs are monitored throughout. The rapid onset also means effects wear off relatively quickly once the infusion stops.
Intramuscular Injection
An intramuscular (IM) injection delivers ketamine into a large muscle, typically the thigh or upper arm. Bioavailability is 93%, nearly as high as IV, with peak effects arriving in about five minutes. This route is simpler to administer than an IV since it doesn’t require placing a line, making it a practical option in certain clinical and emergency settings.
Nasal Spray
Nasal administration comes in two forms. The FDA-approved version, sold as Spravato, uses esketamine, a more potent mirror-image molecule of standard ketamine. Each nasal spray device delivers 28 mg, and a typical session uses two or three devices for a total dose of 56 or 84 mg. Compounding pharmacies also prepare racemic ketamine (the standard form) as a nasal spray.
Both versions have a bioavailability of roughly 40 to 50%, with peak effects at about 15 minutes. The drug absorbs through the thin tissue lining the nasal passages, bypassing the digestive system.
Spravato carries strict supervision requirements. It can only be dispensed and used in certified healthcare settings. Patients self-administer the spray under direct observation of a provider, then stay for at least two hours of monitoring, including pulse oximetry to track breathing. For treatment-resistant depression, sessions start at twice weekly for four weeks, then taper to once weekly or every two weeks during maintenance.
Sublingual Lozenges and Tablets
Sublingual (under the tongue) formulations are among the most commonly prescribed forms for at-home use. These include troches (medicated lozenges) and rapid-dissolve tablets. You hold the lozenge in your mouth, letting it dissolve slowly so the ketamine absorbs through the mucous membranes under and around the tongue.
Bioavailability ranges from 25 to 40%, with peak effects typically arriving in 15 to 30 minutes. There’s a meaningful difference between letting the medication absorb in your mouth versus simply swallowing it. When you swallow ketamine, it passes through the liver before reaching the rest of your body. The liver breaks down a significant portion of the drug on this first pass, which is why oral bioavailability is so much lower. Sublingual absorption partially skips this process, allowing more of the drug to reach the brain.
A study comparing 50 mg sublingual ketamine to 50 mg swallowed ketamine found that the oral version had a slower onset, though both ultimately provided similar pain relief. In practice, some of the lozenge inevitably gets swallowed with saliva, so absorption is a mix of both pathways. This contributes to the considerable variability patients experience from session to session.
Oral Liquid
Ketamine can also be compounded as a flavored liquid that you swallow. This is the least efficient route, with only 15 to 25% of the dose reaching the bloodstream. Peak effects take one to two hours to develop, the slowest onset of any common method. The liver metabolizes most of the drug before it circulates, which is why such a large portion is lost.
Despite the lower bioavailability, oral liquid is still used clinically, particularly for pain management. Providers simply adjust the dose upward to compensate for the losses.
Rectal Suppository
Less commonly, ketamine is compounded as a rectal suppository. Bioavailability falls in the 25 to 40% range, similar to sublingual forms, with peak effects at 20 to 45 minutes. This route is occasionally used when patients cannot take medication by mouth.
How the Route Affects Your Experience
The practical differences between these routes go beyond simple absorption numbers. Faster-acting methods like IV and IM produce more intense but shorter experiences. You feel the effects almost immediately, and they resolve relatively quickly after the session ends. Slower routes like oral liquid produce a more gradual onset and a longer, sometimes less predictable experience.
Variability is another key factor. The American Society of Ketamine Physicians notes that bioavailability for non-IV routes can fluctuate significantly even across sessions in the same person. Factors like nasal congestion (for sprays), how long you hold a lozenge in your mouth, and whether you’ve recently eaten all influence how much drug gets absorbed. IV infusion avoids this problem entirely since 100% of the dose enters the bloodstream by definition.
Clinical Supervision Requirements
The level of medical oversight depends heavily on the route. IV infusions are always performed in a clinical setting with continuous monitoring. Spravato nasal spray requires a certified facility, direct observation during dosing, and at least two hours of post-dose monitoring. These restrictions exist because ketamine can cause sedation, dissociation, drops in awareness, and changes in blood pressure and breathing.
Sublingual lozenges and oral formulations are the routes most often prescribed for at-home use, though this practice remains controversial. The American Society of Anesthesiologists has raised concerns that patients using ketamine at home may not have routine access to vital sign monitoring, rescue personnel, or emergency equipment. Their position is that ketamine should be held to the same safety standards as other anesthetic medications regardless of setting. At minimum, at-home protocols typically involve periodic in-person visits with the prescribing provider and a comprehensive treatment plan that extends beyond the medication itself.