Types of Ketamine Therapy: How Dosages Are Determined

What Is Ketamine Therapy?

Ketamine therapy uses sub-anesthetic doses of ketamine to treat mental health conditions including depression, anxiety, and PTSD. Originally developed as an anesthetic, it was FDA-approved for that purpose in 1970 and has been on the WHO List of Essential Medicines since 1985.¹

Therapeutic ketamine differs significantly from anesthetic use. Sub-anesthetic dosing targets neuroplasticity and changes in neural signaling rather than sedation. Ketamine modulates glutamate signaling and NMDA receptor activity. Modulating these pathways can create conditions for new neural connections and shifts in entrenched thought patterns.² Ketamine therapy encompasses multiple administration routes, dosing protocols, and treatment settings.

Three variables define the type of ketamine therapy a person receives: the route of administration, the dosing protocol, and the care framework surrounding it.

What Are the Different Types of Ketamine Therapy?

Ketamine therapy is categorized primarily by how the medication is administered. Each route has distinct bioavailability, onset time, duration, setting requirements, and cost implications. Below is a breakdown of the six most common administration routes used in clinical practice.

Intravenous Ketamine Therapy

IV ketamine delivers the medication directly into the bloodstream through a vein. You typically receive IV infusions in a dedicated facility such as a ketamine clinic or hospital.

Intravenous delivery offers the highest bioavailability of any method, reaching close to 100%. Effects begin quickly, typically within minutes of starting the infusion. Sessions typically last 40 to 60 minutes of infusion time. The process requires in-facility administration with clinical staff present and vital-sign monitoring. Dosing is weight-based and titrated by the administering provider in real time. IV is often considered the most-studied route for depression.

IV ketamine requires dedicated facility visits and is typically the most expensive option per session. It is offered exclusively in supervised settings. IV suits individuals who prioritize the most precise dose control and real-time clinical monitoring.

Intramuscular Ketamine Therapy

IM ketamine is injected into a large muscle, typically the deltoid or gluteal muscle. The medication is then absorbed into the bloodstream from the tissue.

Approximately 93% of the administered dose reaches systemic circulation. Onset is slightly slower than IV, taking 5 to 15 minutes to begin. Intramuscular delivery does not require IV access or infusion equipment, which simplifies administration. A healthcare provider typically administers the injection in a supervised setting. Dosing is weight-based, and the session duration is comparable to IV.

IM ketamine offers a simpler setup than IV while maintaining high bioavailability. Some facilities use it as an alternative to IV infusion for clients who want a simpler delivery method. You still receive the in-person monitoring environment.

Intranasal Ketamine Therapy

Intranasal ketamine is sprayed into the nasal passages. The most well-known form is Spravato (esketamine), the only FDA-approved ketamine-derived medication, indicated with an oral antidepressant for adults with treatment-resistant depression and, separately, for depressive symptoms in adults with major depressive disorder with acute suicidal ideation or behavior. Generic racemic ketamine can also be compounded as a nasal spray for off-label use.

Spravato uses esketamine, the S-enantiomer of ketamine, rather than racemic ketamine. You must receive it in a certified healthcare setting under the Spravato REMS program. The program requires a mandatory two-hour observation period after each dose. Between 25 and 50% of the intranasal dose reaches systemic circulation. Compounded nasal sprays follow a different regulatory pathway than Spravato and are dispensed under standard prescribing rules rather than REMS oversight.³

Spravato's FDA approval reflects its specific regulatory pathway for treatment-resistant depression and major depressive disorder with suicidal ideation. FDA approval does not by itself indicate superiority over other ketamine routes. The choice of route depends on individual clinical factors and goals. Its delivery model requires in-office visits and post-dose monitoring, which shapes cost and accessibility. Compounded nasal sprays are an off-label intranasal ketamine option with a different regulatory pathway than Spravato, and they do not use Spravato's standardized dosing or REMS oversight.

Therapeutic-Dose Sublingual Ketamine Therapy

Therapeutic-dose sublingual ketamine involves placing a tablet, troche, or rapid-dissolve formulation between the cheeks and gums. You hold the medication for a specified period, typically 7 to 15 minutes, to allow absorption through the oral mucosa. Some protocols direct that the remaining medication is then spit out to avoid gastrointestinal upset, while others do not.

Sublingual bioavailability is reported in a range of approximately 25 to 35%, varying with the protocol used. Posted milligram amounts are higher than IV or IM doses for equivalent therapeutic effect because of this lower absorption rate. The prescribing specialist titrates the dose across sessions based on individual response. Sublingual administration produces a transient dissociative experience at therapeutic doses. Most people find the dissociative state therapeutically meaningful within a supervised setting.

Key attributes of therapeutic-dose sublingual ketamine include:

• Onset: Effects typically begin within 10 to 15 minutes.
• Session duration: Most sessions last 45 to 60 minutes.
• Protocol: Hold-and-spit, or hold-and-swallow depending on the provider.
• Setting: Conducted at home with a required peer treatment monitor present.
• Oversight: Supervised by a licensed provider via telehealth protocols.

Sublingual delivery is the most common route for at-home ketamine therapy. It has the largest body of published real-world outcomes data in the at-home context. Mindbloom's peer-reviewed research studied this specific format.^4,9

Low-Dose, Daily Sublingual Ketamine Therapy

Some telehealth providers prescribe sublingual ketamine at sub-perceptual doses taken daily or near-daily. These protocols use significantly lower milligram amounts than therapeutic-dose sessions. They are not designed to produce a dissociative experience.

Daily low-dose administration is distinct from the therapeutic-dose sublingual model described above. The dosing is lower, the frequency is higher, and the intended mechanism differs. Daily low-dose protocols aim for a pharmacological antidepressant-like effect rather than a session-based neuroplastic experience. To date, there is not peer-reviewed efficacy evidence supporting low-dose daily sublingual ketamine for depression at the level that exists for therapeutic-dose protocols studied in controlled or real-world outcomes research.

Not all sublingual ketamine is the same, and this distinction has practical consequences for outcomes. Readers evaluating at-home options should understand the difference in evidence base, protocol design, and intended therapeutic mechanism between these two approaches.

Subcutaneous Ketamine Therapy

Subcutaneous ketamine is injected just beneath the skin, typically into the abdomen. You use a small insulin-type needle for the injection. It can be self-administered at home as part of a supervised care program.

The subcutaneous route delivers approximately 66% of the dose to systemic circulation, exceeding sublingual absorption. You can expect to feel initial effects within about 5 minutes. Subcutaneous delivery provides more consistent absorption and session intensity compared to sublingual. Bypassing oral mucosa variability and first-pass metabolism creates this consistency.

Key differentiators versus sublingual ketamine include:

• Faster onset: Effects begin in about 5 minutes.
• Higher bioavailability: More medication reaches systemic circulation.
• Consistent intensity: Bypasses absorption variables in the mouth.
• Administration: Uses a small insulin needle rather than a tablet.

Mindbloom is the only at-home ketamine provider currently offering subcutaneous administration in addition to sublingual tablets. Offering both options gives clients and providers an additional way to personalize the care experience based on medical needs and preferences.

Ketamine Pharmacokinetics and How Long It Stays in Your System

Pharmacokinetics describes how the body absorbs, distributes, metabolizes, and eliminates a drug. For ketamine therapy, pharmacokinetics vary meaningfully by route.

The following variables highlight how quickly effects begin, the duration of acute effects, and how long ketamine is detectable in the body:

• IV: Onset in minutes, acute effects last 45 to 90 minutes, cleared within hours.
• IM: Onset in 5 to 15 minutes, similar duration and clearance to IV.
• Sublingual: Onset in 10 to 15 minutes, effects last 45 to 90 minutes, clearance similar.
• Subcutaneous: Onset in about 5 minutes, duration and clearance similar to IM.
• Intranasal: Onset in 5 to 10 minutes, effects may be shorter depending on dose.
• Detection window: Ketamine has a plasma half-life of approximately 2 to 3 hours. Standard urine drug screens do not test for ketamine; specialized assays must be specifically ordered to detect ketamine or its metabolites.

The post-session period is a natural transition back to baseline, not a sign that something went wrong. Most people prefer to rest afterward, though experiences vary. Avoid driving until after a full night of sleep.

How Do Providers Determine a Ketamine Therapy Dose?

Providers determine and adjust your ketamine dose based on several interacting variables: your medical history, the administration route, how you respond session to session, and the specific protocol being used.

Medical History and Current Health Status

Your provider evaluates your full medical and psychiatric history, current medications, body weight, and cardiovascular health during the initial evaluation. These factors influence the starting dose and whether dose adjustments are needed.

Certain conditions, such as uncontrolled hypertension or active psychosis, may affect eligibility entirely. Your provider will evaluate these contraindications during screening.

Route of Administration and Bioavailability

The chosen route directly affects how much of the administered dose reaches systemic circulation. A given milligram amount delivered sublingually and the same milligram amount delivered intravenously are not equivalent in effect.

Sublingual bioavailability is a fraction of IV bioavailability. Your care team sets the milligram amount with the route's bioavailability in mind so that the effective dose lands in the therapeutic window.

Session Response and Side Effect Profile

Your prescriber adjusts dosing based on your therapeutic response (symptom changes and depth of experience) and tolerability after each session.

Tolerability includes side effects like nausea, elevated blood pressure, or intensity of dissociation. Your dose may be increased if the therapeutic window has not been reached or decreased if side effects are disproportionate. Adjusting the dose is an iterative, session-by-session process.

Session Duration and Personalized Treatment Frequency

How often sessions occur and how many sessions are in a treatment program also factor into dosing strategy. Session frequency is personalized based on individual needs and clinical guidance.

Sessions may be more frequent at the outset to establish therapeutic momentum. Frequency is adjusted over time based on progress and goals. Mindbloom offers programs of 6, 12, or 18 sessions. After you select a program, a licensed provider conducts a comprehensive clinical evaluation to confirm your eligibility and personalize your care plan.

The Specific Protocol Being Used

Protocol design is itself a dosing variable. The same milligram amount under different protocols can produce different treatment experiences and different systemic exposures.

Sublingual bioavailability is reported in the literature at approximately 25 to 35%, with the specific figure depending on the protocol used. Hold-and-spit and hold-and-swallow methods rely on different absorption pathways and produce meaningfully different absorption profiles from the same posted milligram amount.

Hold-and-spit protocols rely on absorption through the oral mucosa during the hold period. The remaining medication is then discarded, which limits the amount of ketamine reaching the gastrointestinal tract. Hold-and-swallow protocols add gastrointestinal absorption to the mucosal portion, but swallowed ketamine undergoes extensive first-pass hepatic metabolism that converts a substantial proportion of the drug to norketamine before it reaches systemic circulation. Increased GI exposure is also associated with greater nausea and prolonged sedation.

Mindbloom uses a 7-minute sublingual hold followed by spitting out the remaining saliva, which is deliberately shorter than the 10- to 15-minute hold-and-swallow protocols used by some other providers. The 7-minute spit method is designed to maximize sublingual absorption while minimizing GI exposure, norketamine conversion, and the side effects that come with them.

When comparing dosing across providers or routes, the protocol matters as much as the milligram number. A 900 mg dose under a 7-minute hold-and-spit protocol delivers a different effective treatment than 900 mg under a hold-and-swallow protocol or 900 mg of any other formulation.

Why Set, Setting, and Intention Often Matter More Than Dose Alone

"Set" refers to a person's psychological state going into a session, including mindset, expectations, and emotional readiness. "Setting" refers to the physical and social environment. "Intention" refers to the goals or focus a person brings to the experience.

Together, these non-pharmacological factors shape the quality and therapeutic value of a ketamine session. A 2018 study published in Frontiers in Pharmacology found that pre-session psychological state was a stronger predictor of avoiding a challenging in-session experience than drug dose itself.⁵

The same study found that having clear intentions independently predicted a mystical-type experience. That experience in turn predicted well-being increases at two and four weeks post-session. Dose is one input among several. A well-prepared client in a safe, familiar environment with clear therapeutic intentions may have a more productive session than someone receiving a higher dose without preparation or support.

Mindbloom's care model is built around this evidence, with protocol-driven session preparation, integration, and curated session environments alongside individualized dosing.

Conclusion

Route of administration determines bioavailability, setting, and cost. Dosing is individualized by your prescriber based on medical history, route, session response, and protocol design.

Non-pharmacological factors like set, setting, and intention are evidence-backed predictors of session quality and outcomes. The most important variable is the care framework surrounding the medication, not any single number on a prescription. If you're considering ketamine therapy, discuss your options with a licensed clinician to determine which route and protocol fit your needs.

Important Safety Information

Ketamine is not FDA-approved for PTSD, depression, or anxiety. Common side effects include dissociation, increased blood pressure, nausea, dizziness, and cognitive impairment. Ketamine has abuse potential and is not appropriate for patients with uncontrolled hypertension, psychotic disorders, or substance use disorders. Do not drive or operate machinery until the day after treatment. Individual results may vary. Full safety information: www.mindbloom.com/safety-information

Off-Label Use Disclosure

Ketamine is FDA-approved only as an anesthetic. Use for mental health conditions represents off-label prescribing by licensed clinicians based on clinical judgment. Schedule III Controlled Substance - DEA regulations apply.