Ketamine for Migraines: What You Need to Know About Safety, Efficacy, and Emerging Treatment Options
Migraines are complex neurological events that affect millions of people worldwide. For many, traditional treatments like NSAIDs, triptans, and lifestyle changes provide relief. However, some patients continue to struggle despite conventional therapies. In recent years, ketamine has emerged as a potential option for treatment-resistant migraines. While often associated with anesthesia or recreational use, experts emphasize that ketamine can be safe and effective when administered properly.
In this article, we explore insights from Dr. Jordanna Quinn, DO and Dr. Amelia Scott Barrett, MD who discuss ketamine’s potential, its safety profile, genetic considerations, and practical ways it can be used to help migraine sufferers.
Understanding Ketamine and Its Role in Migraine Treatment
Ketamine is a medication used legally by physicians across the world. It is not a new drug—it has been used for decades in pediatric and adult anesthesia. Dr. Quinn explains:
“Ketamine is legal. So ketamine is a medication. It’s just as legal as amoxicillin. Any physician who graduates medical school or residency, when you have a license to prescribe, it is a legal medication.”
While ketamine is sometimes associated with recreational misuse, its clinical applications are distinct and safe when administered under supervision.
“I want to say that we would not use it in pediatric anesthesia, obviously, if it wasn’t very safe because we want to keep our children the most safe of all. So it is a very safe medicine and it is more new that it is used in the psychedelic realm.”
Ketamine’s use in migraine treatment is different from high-dose anesthesia—it relies on sub-anesthetic doses that can stimulate neuroplasticity rather than simply putting the patient to sleep.
How Ketamine Works for Migraines
One of the key benefits of ketamine for migraines comes from its effect on neuroplasticity—the growth of new neurons and synaptic connections. Dr. Barrett highlights:
“The benefit comes at those sub-anesthetic doses. It’s the lower doses that actually give people benefits… It stimulates neuroplasticity, growth of new neurons, new synaptic connections between existing neurons, and that’s where the magic is for ketamine.”
Unlike traditional migraine medications that act on blood vessels or serotonin receptors, ketamine modifies neural circuits, offering the potential for long-term changes in how the brain processes pain.
Different Methods of Administering Ketamine
Ketamine can be delivered in several forms for migraine management:
Intranasal spray – Patients may self-administer small doses multiple times a day.
IV infusion – Typically conducted in a hospital setting for several days. This method can induce temporary relief lasting weeks but is costly and not practical for most patients.
Intramuscular injection – A single injection that provides short-term dosing to stimulate neuroplasticity, offering a balance between effectiveness and practicality.
Dr. Barrett notes:
“The most promising way to use this drug is as an intramuscular injection because you can have a dose… enough to induce neuroplasticity and not so much that it’s like an anesthetic dose.”
Dr. Quinn also emphasizes that ketamine has shown high efficacy in pain patients, even if administered differently depending on the clinic:
“I dealt with a lot of pain patients. I didn’t personally do ketamine, but we would refer out for ketamine as a kind of end treatment. Some results were, I mean, I want to say a hundred percent of the people got benefit. The length of the benefit depended on just the patient.”
Safety Considerations and Media Misconceptions
While ketamine is safe under clinical supervision, media coverage can sometimes create misconceptions. Dr. Quinn clarifies:
“There’s been a lot of media, poor media press, think even in the past year, with like Matthew Perry dying of ketamine. I don’t think personally he died of ketamine. He was on 10 other different medications that can cause a lot of problems.”
It is important to distinguish between clinical use of ketamine at controlled doses and recreational misuse.
Dr. Barrett adds:
“The benefit comes at lower doses. You go in for a surgery and you get a huge dose of ketamine for that, that actually might not help you at all. It’s the lower doses that stimulate neuroplasticity… and that’s where the magic is.”
Who is Most Likely to Benefit from Ketamine?
Not all migraine patients will respond equally to ketamine. It is most effective for people with neurotransmitter imbalances or specific genetic predispositions. For instance:
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Serotonin pathway variations (e.g., 5-HTTLPR, TPH2)
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Dopamine pathway differences (e.g., DRD2)
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BDNF variations that affect neuroplasticity
Dr. Barrett explains:
“The same genes that cause migraine also cause anxiety and depression. So what’s the effect of ketamine on anxiety and depression? Now that’s where the interesting stuff is.”
Real-world studies support this, showing that patients with anxiety or depression may experience additional benefits:
“…even with just four injections on average, the improvement was thirty-eight percent for depression, fifty percent for anxiety with good p values for both of those.”
Ketamine vs. Other Psychedelics
Ketamine’s mechanism is distinct from classic psychedelics like psilocybin or LSD. While many psychedelics bind to serotonin receptors, ketamine inhibits an inhibitory receptor in the brain, creating a stimulatory effect:
“Ketamine does not bind to your serotonin receptors at all. It actually inhibits an inhibitory receptor in your brain and therefore it’s like a double negative. It has a positive response.”
Dr. Quinn uses a helpful analogy to explain why ketamine is different:
“Just because they fall all under the umbrella of psychedelics, they all have very different flavors essentially. And so one doesn’t equal all of them.”
This is especially important for patients who may have tried other psychedelics without benefit—ketamine could still work for them.
Limitations and Practical Considerations
Despite promising results, ketamine therapy has limitations:
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Small studies: Most research involves small sample sizes, making large-scale conclusions difficult.
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Cost: IV infusions, in particular, can cost tens of thousands of dollars.
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Hospital-based therapy: Long hospital stays for continuous infusion are often impractical.
Dr. Barrett emphasizes the need for practicality:
“Continuous ketamine infusion in the hospital for several days… does last a good four to six weeks, which is fair, but for spending three days in the hospital I don’t think that’s practical for most people.”
Intramuscular injections often provide a more accessible and feasible option.
Dr. Quinn notes:
“We looked at a lot of different factors with migraine patients, including diet, stress, and sleep… A comprehensive approach often yields the best results.”
Setting Realistic Expectations
Ketamine is not a cure-all, but it can be life-changing for some patients:
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Benefits are dose-dependent and occur mostly at sub-anesthetic levels.
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Response varies by individual genetics and comorbid conditions.
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Combining ketamine with lifestyle, diet, and stress management strategies enhances results.
Dr. Barrett summarizes:
“If you know your genetics or if you have a history of anxiety or depression, you may be one of the people who’s more likely to benefit.”
Future Directions in Migraine Treatment
The future of migraine therapy is moving toward personalized, integrative approaches. Research in genetics, neuroplasticity, and novel therapeutics promises treatments that target the root causes of migraines, rather than just masking symptoms.
Dr. Quinn expresses optimism:
“Some results were… I want to say a hundred percent of the people got benefit. The length of the benefit depended on just the patient.”
With advances in medicine and a deeper understanding of migraine biology, ketamine may play an increasingly important role in comprehensive migraine care.
Key Takeaways
*Ketamine is legal, safe, and clinically proven in controlled settings.
*Lower, sub-anesthetic doses—particularly intramuscular injections—stimulate neuroplasticity for migraine relief.
*Not all ketamine approaches are the same; the route, dose, and patient profile matter.
*Patients with neurotransmitter imbalances, anxiety, or depression may benefit most.
*Ketamine is part of a broader strategy, including diet, lifestyle, supplements, and holistic care.
Always work with a qualified medical professional to assess suitability, dosing, and safety.
Conclusion
Ketamine is an emerging option for patients with treatment-resistant migraines, offering benefits beyond traditional therapies. Its unique mechanism, safety profile, and ability to stimulate neuroplasticity make it a compelling alternative, especially for patients with specific genetic or neurotransmitter profiles.
“Ketamine is used every day, all day in anesthesia… It is very safe. And for migraine patients, the magic happens at lower doses, stimulating neuroplasticity and promoting real change in the brain,” says Dr. Quinn.
By combining ketamine therapy with lifestyle modifications, dietary adjustments, and holistic approaches, patients can take actionable steps toward better migraine management and improved quality of life.