IV vs. Sublingual Ketamine: Understanding the Differences

Choosing the Right Route

When it comes to ketamine therapy for depression, anxiety, or PTSD, one of the first decisions is how the medication is delivered. Intravenous (IV) and sublingual ketamine are two of the most effective and widely used routes, each with distinct advantages.

This guide breaks down the pharmacology, benefits, and trade-offs so you can make an informed choice with your provider.

How Each Route Works

Both IV and sublingual ketamine work through the same mechanism — blocking NMDA receptors and activating AMPA receptors to stimulate neuroplasticity and synaptic repair. The difference lies in how the medication enters your bloodstream.

IV Ketamine

IV ketamine delivers full bioavailability and precise dosing, making it the most controlled and rapid-acting option — particularly valuable for severe or acute depressive episodes.

Sublingual Ketamine

Sublingual ketamine offers a slower, gentler rise in blood levels and a longer-lasting effect, making it well-suited for at-home or maintenance therapy under medical guidance.

Can Sublingual Achieve the Same Depth?

Yes. While sublingual bioavailability is lower, patients can still experience meaningful dissociation and therapeutic depth when properly dosed. Achieving similar intensity typically requires approximately 2–3 times the IV-equivalent dose.

In structured programs, dosing is carefully titrated to each patient's tolerance and therapeutic goals — ensuring safety while maximizing antidepressant benefit.

Comparing Benefits

IV Ketamine

• Rapid relief — reduces depressive symptoms within hours; especially useful in crisis situations
• Clinical oversight — continuous monitoring of vitals
• Adjustable dosing — real-time titration during the session
• Same-day availability — no wait for compounding pharmacy

Sublingual Ketamine

• Convenience — taken at home, reducing clinic visits
• Sustained benefit — effects can last longer than IV sessions
• Comfort — non-invasive and needle-free
• Affordability — typically more cost-effective than in-clinic infusions
• Autonomy — self-administered under structured medical oversight

Side Effects

Because both routes share the same mechanism of action, their side effects overlap — though intensity and timing differ.

Common to both:

• Mild dissociation or dreamlike sensation
• Nausea or dizziness
• Short-term elevation in blood pressure or heart rate
• Fatigue or sedation after the session

IV-specific: Dissociation and perceptual changes can be stronger and appear quickly. Requires in-clinic monitoring.

Sublingual-specific: Dissociation is typically more gradual. Some patients experience mild oral numbness or bitter taste. Can be managed at home.

How to Choose

The best route depends on several factors:

• Urgency — Crisis situations may favor IV for speed
• Setting preference — In-clinic vs. at-home treatment
• Cost — Sublingual is generally more affordable
• Previous response — Some patients respond better to one route
• Lifestyle — At-home treatment offers more flexibility

At Discreet Ketamine, we specialize in sublingual ketamine delivered through telemedicine, with treatment plans personalized to your medical profile, comfort level, and long-term goals. For a full overview of every delivery method, see our guide to all the ways ketamine can be given.