Ketamine therapy is administered through several routes, with intravenous (IV) infusion and a nasal spray being the most common in clinical settings. The method your provider recommends depends on the condition being treated, whether you’re in an induction or maintenance phase, and what’s available at your clinic. Each route delivers ketamine differently, and the experience, timing, and setting vary accordingly.
IV Infusion: The Most Established Method
Intravenous ketamine is the route with the longest track record for treating depression. A standard dose falls in the range of 0.5 mg/kg of body weight, infused slowly over about 40 minutes. Some clinics use lower doses (under 0.2 mg/kg) or higher ones (above 0.5 mg/kg) depending on how you respond and what you can tolerate. For someone weighing around 155 pounds, a standard dose would be roughly 35 mg delivered directly into the bloodstream.
A typical initial course involves treatments twice per week for four to five weeks. Many clinics start with a “ketamine challenge,” a series of three to five infusions given every other day or twice weekly, to see whether you respond before committing to a full course. After the induction phase, sessions taper off in frequency.
During an IV session, you sit in a reclining chair while a nurse places a small catheter in your arm. Staff monitor your oxygen levels, blood pressure, heart rate, and sedation level throughout the infusion. The entire appointment, including setup and recovery time, typically runs longer than the 40-minute infusion itself. You won’t be allowed to drive afterward.
Nasal Spray: The FDA-Approved Option
Esketamine (brand name Spravato) is a nasal spray and the only form of ketamine with full FDA approval for depression. It uses a slightly different molecule than standard ketamine, but works through a similar mechanism. The spray comes in two doses: 56 mg and 84 mg.
The dosing schedule is more structured than IV protocols. For treatment-resistant depression, you spray twice per week during the first four weeks, then drop to once weekly for weeks five through eight, and eventually move to every one or two weeks after that. For people with major depression and active suicidal thoughts, the protocol is 84 mg twice weekly for four weeks.
You self-administer the spray under a clinician’s direct observation, not at home. After each dose, you’re required to stay at the clinic for at least two hours so staff can monitor you for sedation, dissociation, and any breathing changes. This two-hour observation period is mandated by the FDA through a special safety program called REMS. Only certified healthcare settings can dispense the spray, and you must be enrolled in the program to receive it. Pharmacies cannot send it to your home.
Intramuscular Injection
Some clinics administer ketamine as a shot into the muscle, typically the upper arm or thigh. Doses range from 1 to 3 mg/kg of body weight, which is higher than IV doses because less of the drug reaches the brain through this route. The tradeoff is simplicity: no IV line, no infusion pump, and a faster start to the appointment.
Effects kick in within about five minutes. The experience tends to come on more abruptly than an IV drip, where the dose ramps up gradually. You’re observed for at least 30 minutes afterward, though many clinics keep you longer depending on your response.
Oral and Sublingual Forms
Ketamine can also be taken as a lozenge (sometimes called a troche), a rapid-dissolve tablet placed under the tongue, or a liquid swallowed by mouth. These are the forms most commonly prescribed for at-home use between clinic visits. The purpose is generally to extend the benefit of in-clinic sessions or lengthen the gap between appointments.
The key difference with these routes is bioavailability, meaning how much of the drug actually reaches your system. A sublingual lozenge or tablet delivers roughly 25 to 40 percent of the ketamine into your bloodstream. Swallowed liquid is even less efficient, at about 15 to 25 percent. This variability matters: to match a standard IV dose of 0.5 mg/kg in a 155-pound person, you’d need around 100 mg in lozenge form or about 200 mg as a swallowed liquid. Bioavailability can also shift from session to session, so the intensity of the experience isn’t always predictable.
These forms are prescribed at a provider’s discretion and are not FDA-approved specifically for depression. They represent off-label use of ketamine, which is legal and common but means less standardized oversight compared to the nasal spray or in-clinic infusions.
What a Treatment Session Feels Like
Regardless of the route, ketamine produces a dissociative state. You may feel detached from your body, experience changes in how you perceive time and space, or have vivid visual or emotional experiences. This is expected, not a side effect. Many clinics design the treatment room to support this experience: dim or warm lighting, reclining chairs, noise-canceling headphones loaded with curated music playlists, and sometimes nature projections on the walls or ceiling. Some clinics use aromatherapy with essential oils to create a calming atmosphere.
The dissociative effects typically peak during the infusion or within 15 to 20 minutes of a spray or injection, then fade over the next hour or two. Blood pressure often rises temporarily during treatment, which is why it’s monitored throughout. Most people describe feeling groggy or “floaty” for a period afterward. You’ll need someone to drive you home, and most clinics advise against making important decisions or operating machinery for the rest of the day.
Who Can and Can’t Receive It
Ketamine therapy is primarily used for treatment-resistant depression, meaning you’ve tried at least two antidepressant medications without adequate relief. The nasal spray also has a specific approval for people with major depression and acute suicidal ideation.
Cardiovascular conditions are a major concern because ketamine raises blood pressure and heart rate. Uncontrolled hypertension, a history of aneurysm, or recent stroke can disqualify you. A history of psychosis or active psychotic symptoms is another common exclusion, since ketamine’s dissociative properties could worsen those conditions. Active substance use disorders, particularly involving ketamine or similar drugs, also factor into screening decisions.
Before starting treatment, expect a thorough medical and psychiatric evaluation. Providers will review your medication history, mental health diagnoses, cardiovascular health, and substance use history to determine whether ketamine is appropriate for you.
Safety Requirements Across All Routes
The American Society of Anesthesiologists recommends that any ketamine given by IV, injection, or nasal spray for mental health conditions be administered under the supervision of a physician who is immediately available and familiar with ketamine’s full range of effects. The treatment setting must have rescue equipment on hand in case of a rare serious reaction.
In practice, this means a registered nurse or other clinician stays with you or nearby during treatment, monitoring your oxygen saturation, vital signs, and level of sedation. The monitoring is less intensive than full anesthesia but more involved than a typical outpatient appointment. Clinics that cut corners on monitoring fall outside professional guidelines, so it’s reasonable to ask about staffing and safety protocols before your first session.