Written by Dr. Ladan Eshkevari, PhD, CRNA, LAc, FAAN.
In This Post:
- What is Ketamine? An Overview
- The Ketamine Therapy Experience
- Ketamine Types (IV, SC, IM, Oral, Nasal)
- Another Type of Ketamine, Spravato
- Treating Pain with Ketamine
- IV Ketamine Sessions for Depression & Chronic Pain
- How Ketamine Works in the Brain
- Is Ketamine Safe?
Ketamine is a fascinating medicine known for its anesthetic, dissociative, pain-relieving, and mood-elevating properties. Doctors have harnessed the compound in surgery and pain management since the 1960s. Yet, ketamine is far from a mere numbing agent. It is an effective therapy for treatment-resistant depression, PTSD, anxiety, and suicidality. It is one of modern psychiatry’s greatest tools.
This article answers the question, “What is ketamine,” including how it works in the brain, evidence-based IV protocols, and critical safety considerations.
What is Ketamine? An Overview
Ketamine is a dissociative anesthetic medicine that provides diverse mental and physical health benefits. The FDA approved it for anesthesia, surgery sedation, and acute pain management in 1970. In 1985, The World Health Organization (WHO) recognized ketamine as an essential medication due to its efficacy and high safety profile.
In the last 25 years, clinicians have expanded ketamine administration to people with mental health conditions thanks to a proof-of-concept study showing its rapid antidepressant effects. Clinicians are also administering ketamine for chronic pain relief.
Mental Health Applications
Mounting clinical evidence indicates ketamine therapy can treat mental health conditions like:
- Treatment-resistant depression (TRD)
- Post-traumatic stress disorder (PTSD)
- Suicidality
- Anxiety disorders
- Substance use disorder (SUD)
- Bipolar Disorder
- Obsessive Compulsive Disorder (OCD)
Pain Relief
Additionally, ketamine infusions can offer lasting relief for chronic pain conditions, such as:
- Complex Regional Pain Syndrome (CRPS)
- Chronic migraines
- Fibromyalgia
- Persistent cancer pain
Recreational Use
Beyond clinical contexts, some people use ketamine (“Special K”) recreationally for its dissociative psychedelic effects. A ketamine-induced trance, known as a “K-hole,” disconnects people from reality, distorts perception, and often leaves them unable to move. High doses can cause dangerous side effects, including deadly overdoses. Repeated misuse also increases the risk of memory issues, bladder damage, and addiction.
The Ketamine Therapy Experience
Ketamine delivers distinct effects depending on the dosage. However, IV ketamine patients often describe the ketamine experience as a floating sensation with occasional psychedelic effects. Time can feel stretched, sped up, or completely irrelevant. Colors may seem brighter, sounds more immersive, and thoughts more fluid.
Common descriptions
- Light, floating sensation – A feeling of weightlessness or detachment from the body.
- Deep relaxation – A sense of calm, peace, or emotional release.
- Dissociation – Feeling disconnected from thoughts, emotions, or surroundings.
- Time distortion – Time may feel slower, faster, or completely unrecognizable.
- Dreamlike states – Vivid imagery, abstract thoughts, or an altered sense of reality.
- Euphoria or mood elevation – A sudden uplift in mood or a break from negative thought patterns.
Ketamine Types (IV, SC, IM, Oral, Nasal)
The main ketamine types fall into five categories: intravenous (IV), subcutaneous (SC), intramuscular (IM), oral, and intranasal (IN).
IV Ketamine
IV ketamine refers to the intravenous form of the anesthetic drug administered directly into the bloodIV (intravenous) ketamine refers to the intravenous form of the compound administered directly into the bloodstream for rapid effects with a nearly 100% absorption rate. Clinicians utilize this gold-standard method for anesthesia, acute pain relief, depression, and chronic pain at different dosages and frequencies.
Dosage protocols and duration
Clinicians recommend different IV ketamine dosage protocols depending on the condition and purpose.
- Anesthesia: Anesthetic ketamine usually uses higher doses based on weight (calculated as mg/kg). Such high amounts induce rapid unconsciousness.
- Mood disorder: Treatment-resistant depression and other mood disorders begin at much lower ketamine doses than anesthesia. Clinicians often titrate up based on weight and response to the treatment over a 40 to 60-minute session.
- Pain: The IV ketamine dosage for acute pain usually falls between the mood disorder and anesthesia levels. Chronic pain infusions run for about 4 hours, with adjustments to optimize benefits.
Efficacy
A significant advantage of IV ketamine is its potency and real-time dose adjustability. The clinician can promptly increase the dose if a patient wishes to deepen their experience. Conversely, if the patient desires to exit the experience or feels discomfort, the provider can instantly reduce the amount or discontinue the infusion. This level of control offers a tailored treatment approach, enhancing safety and efficacy for depressive symptoms.
Ketamine troches (oral ketamine)
Ketamine troches are dissolvable tablets made to be taken under the tongue. These lozenges release ketamine gradually as they melt, providing a slow and steady effect. Liquid ketamine is another option for oral use.
Clinics, like Avesta Ketamine and Wellness (Avesta), sometimes prescribe troches in between IV sessions as a booster to improve outcomes from chronic pain, depression, PTSD, and other conditions. Many patients like these tablets because they’re easier to take at home.
Oral ketamine dosage and duration
Ketamine troche dosages vary from 25 to 600 mg, depending on the treatment goal. Effects typically last longer than IV because the medication is released more slowly. The downside is that the body absorbs less of it—only about 24–32.2%.
Efficacy
Scientists are still studying how well oral ketamine works for depression. A recent meta-analysis found it offered only slight benefits for major depressive disorders. Researchers must conduct more studies to understand its full potential.
Intramuscular (IM) Ketamine
IM ketamine is an injection delivered directly into the muscle for relatively fast absorption. Most people feel it within 5 to 15 minutes, and the body absorbs about 90% of the dose. Psychiatrists and pain specialists are the ones who typically administer IM.
Dosage and duration
Clinicians base IM ketamine doses on weight (mg/kg) and adjust them to fit each patient’s needs. Effects can last several hours.
Efficacy
Early research suggests IM ketamine may help with severe depression, bipolar disorder, and pain. However, scientists need more studies to confirm its long-term benefits and the best treatment protocols.
Subcutaneous (SC) Ketamine
SC ketamine is an infusion injected into the fatty layer beneath the skin. First effects appear within 10 to 20 minutes; complete absorption can take up to an hour. Like IM ketamine, SC injections have about 66% bioavailability.
Dosage and duration
Doctors adjust SC ketamine doses based on weight (mg/kg) and tailor them to the patient. Effects can last several hours.
Efficacy
SC ketamine shows promise for treating severe depression, bipolar disorder, and pain, but researchers are still studying its full potential. More clinical trials will help determine how effective it really is.
Intranasal Ketamine (nasal ketamine spray)
Intranasal ketamine comes in a spray that absorbs through the nasal lining and enters the bloodstream within 15 minutes. This method offers a less invasive alternative to IV or IM ketamine. Clinicians usually supervise its use, but some prescribe it for at-home treatment.
Dosage and duration
Nasal ketamine doses vary, but research on depression suggests 25 to 50 mg per application. The effects typically last about two hours, and bioavailability is around 45%.
Efficacy
Studies show nasal ketamine can help with depression and chronic pain, but researchers are still figuring out the best doses and protocols. More long-term studies and clinical trials are needed to confirm its full potential.
Another Type of Ketamine, Spravato
Spravato is a nasal spray containing esketamine, a slightly modified version of ketamine approved by the FDA in 2019 for treatment-resistant depression. Unlike standard nasal ketamine sprays, patients must take Spravato at a clinic under medical supervision while also using an oral antidepressant.
Dosage and duration
Doctors prescribe Spravato in specific doses of 56 mg or 84 mg. Effects begin within 5 to 15 minutes and typically last about two hours. Since it’s a regulated prescription, only authorized providers can administer it.
Efficacy
Research on Spravato shows mixed but generally positive results for patients who haven’t responded to other antidepressants. However, many experts agree that IV ketamine works better due to its higher absorption rate. The main advantage of Spravato is its ease of use and the possibility of insurance coverage.
Dr. Ladan Ashkevari, co-CEO and founder of Avesta, has over 20 years of experience with ketamine in anesthesia, pain management, and alternative medicine. Her clinical work shows that IV infusions are more effective than nasal sprays.
“I believe patients experience better and more lasting results with ketamine IV infusions [compared to nasal sprays], mainly due to better absorption rates.”
How Ketamine Works in the Brain
Ketamine, in all forms, works by crossing the blood-brain barrier and disrupting communication between nerve cells.
- It blocks NMDA receptors, which interrupts usual neural activity and indirectly boosts glutamate levels—a key neurotransmitter for learning, memory, pain-signaling, and emotions.
- Higher glutamate levels activate AMPA receptors, helping brain cells communicate better and form stronger connections. This process is called synaptic plasticity.
- At the same time, ketamine boosts Brain-Derived Neurotrophic Factor (BDNF), a protein that helps neurons grow and connect.
As these changes unfold, ketamine elevates mood, relieves pain, and induces dissociation and altered perceptions.
Mental Health Research
Scientists have studied ketamine for mental health since the early 2000s, and the results have been promising. The first major study, published in Biological Psychiatry, found that IV infusions had immediate antidepressant effects. Since then, countless studies have confirmed that ketamine is highly effective, especially when traditional SSRIs, anti-anxiety medications, and anti-psychotics don’t work.
Treatment-Resistant Depression Research & Observation
- The largest comparative trial on ketamine and electroconvulsive therapy (ECT) found that ketamine helped more patients. In a study of 403 people, 55% saw their depression improve by at least 50% with ketamine, compared to 41% with ECT. The trial ran from March 2017 to September 2022.
- A 2022 retrospective chart review of patients with TRD found that repeated ketamine infusions produced a 47.2% reduction in depression symptoms. No evidence of cognitive impairment occurred.
- At Avesta, Dr. Eshkevari has observed and quantified patient experiences over eight years of administering IV ketamine infusions in Washington, D.C., Bethesda, Columbia, Maryland, and McLean, Virginia. She finds that around 80-85% of patients exhibit significant improvement in depressive symptoms following the clinic’s recommended infusion protocols.
Post Traumatic Stress Disorder (PTSD)
- A 2014 proof-of-concept study from the Icahn School of Medicine tested IV ketamine’s effect on 41 chronic PTSD patients. Ketamine significantly reduced symptoms of PTSD and depression 24 hours post-infusion. The findings suggested ketamine is a promising, tolerable treatment for chronic PTSD.
- A 2021 randomized controlled trial of 30 patients with chronic PTSD analyzed results after six infusions of ketamine or a placebo over two weeks. The results showed that ketamine significantly reduced PTSD and depression symptoms, with 67% of participants responding positively to the treatment compared to only 30% in the placebo group; it was also well-tolerated.
Treating Pain with Ketamine
Several studies and case reports find that ketamine can effectively treat chronic pain syndromes such as Complex Regional Pain Syndrome (CRPS), fibromyalgia, and migraines. Most research focuses on neuropathic pain. However, ketamine may have anti-inflammatory pain relief mechanisms as well.
Chronic neuropathic pain
- A 2021 systematic review of clinical studies for chronic neuropathic pain found that ketamine infusions reduced pain and improved function in patients with CRPS in 13 of 14 studies. The review concluded that ketamine infusion therapy is a promising option for patients with CRPS who have not responded to other treatments.
- A 2022 Journal of Pain Research study found that ketamine led to a statistically significant reduction (28% to 46%) in pain intensity one week and 30 days after treatment. This study called for future large-scale studies to confirm the results.
Fibromyalgia & migraines
- A 2023 Journal of Clinical and Diagnostic Research study evaluated the effectiveness of escalating ketamine intravenous infusions in reducing pain and disability for fibromyalgia syndrome. The study included 60 patients and showed that the infusions effectively reduced pain and disability in fibromyalgia syndrome.
An observational study in 2022 observed six hospital patients with treatment-resistant chronic migraines who received a five-day ketamine infusion. The treatment provided significant short-term pain relief, reducing patients’ average pain ratings from 7.4 to 3.7 when they left the hospital. However, pain levels returned to their original baseline by the six-week follow-up.
IV Ketamine Protocol at Avesta
IV ketamine clinics like Avesta craft personalized, evidence-based treatment plans for each individual that varies based on their background and goals.
For depression
IV ketamine therapy for depression at Avesta typically consists of the following:
- Six therapy sessions
- 40-60 minutes per appointment
- Over two to three weeks
For chronic pain
Ketamine infusion protocols for pain at Avesta typically consist of:
- Five therapy sessions
- 4 hours per appointment
- Over several days
For everyone
Avesta prioritizes safety, comfort, and personalized care for every patient. Each session follows a structured process to ensure the best possible experience.
Step 1: Check-In and Baseline Vitals
Before treatment begins, Avesta’s practitioner checks vital signs—blood pressure, heart rate, and oxygen levels. This step helps track each patient’s physiological state and ensures a safe, tailored experience.
Step 2: Infusion and Relaxation
Once the IV starts, patients relax in a private, calming space with an eye mask and music of their choice. The team ensures patients feel comfortable as they ease into a dissociative state. They also monitor vitals throughout the session.
Step 3: Results and Long-Term Support
Most patients feel antidepressant effects within the first four treatments. However, ketamine isn’t a cure-all. Long-term mental health requires ongoing support, and Avesta encourages patients to combine ketamine therapy with integration counseling or other treatments.
Step 4: Maintenance and Follow-Up
After completing the initial IV ketamine series, Avesta creates a plan based on each patient’s response. This plan may include oral ketamine booster doses and future IV maintenance sessions.
Every patient’s journey is different, and Avesta guides each one every step of the way.
Is Ketamine Safe?
Ketamine is highly safe when patients take it in a controlled clinical environment. However, the compound does carry risks, and the ketamine experience can be disorienting at first.
Addiction Risk: Ketamine is not physically addictive, unlike opioids. However, people can and do misuse ketamine, potentially causing addiction and overdose. This risk is nearly non-existent when used in moderation in structured settings.
Cardiovascular Effects: Elevated blood pressure and heart rate can occur during ketamine administration. Practitioners closely monitor patients’ vitals during infusion therapy to ensure they remain in a safe range.
Psychological Effects: Dissociation and psychedelic-like effects are a normal and temporary part of the ketamine experience. Many patients find these shifts in perception insightful and therapeutic, but some may feel unsettled by hallucinations or altered awareness. Compassionate clinics like Avesta provide support throughout the session and can adjust IV doses if needed to ensure a comfortable and controlled experience.
Temporary disorientation: Patients commonly feel groggy and unsteady, a sensation akin to feeling slightly drunk for a few hours post-infusion. These effects emphasize the need for a responsible adult to assist the patient post-treatment.
Most of the adverse effects are dose-dependent and subside shortly after infusions.
The Bottom Line
Ketamine is a multifaceted compound with a rich history and a critical role in modern medicine. Once viewed as a surgical anesthetic, it is now on the front lines of mental health and chronic pain treatment.
To find out if ketamine IV infusions are appropriate for your depression, PTSD, anxiety, or chronic pain, we invite you to schedule a free consultation with our Avesta team today.
