If you are like me, you get migraines often. You have seen doctors, and been prescribed a triptan, then another triptan that worked better for a while. You even tried preventative medications like CGRP inhibitors or Topamax. But nothing gave you relief. Your boss tells you to drink more water as if that would help, and life goes on. The days of sleeping with a warm compress may be coming to an end. All you needed were illicit drugs in your life.

Three takeaways to tell your friends:

• There was a study conducted on subjects reporting about 30 headaches per month who had tried four types of preventative medications.¹
• The 169 subjects received ketamine nasal spray to use for their headaches.¹
• 88% of the participants reported the spray was effective at relieving headaches, while 78% claimed it improved their quality of life.¹

I am not going to talk about a treatment for every person with headaches. This is for people diagnosed with refractory migraines. “Refractory migraine is defined by having failed all of the available preventatives [medications] and suffer from at least eight debilitating headache days per month for at least six consecutive months.”^{2 (p. 2)} Refractory migraine is no joke. These participants have tried at least three preventative medications before seeking relief through ketamine. The researchers made a point to highlight their ketamine research experience and were aware of its risks; with such a concerning new method, the researchers kept the participants educated and safe from addiction in many different ways:

• Participants received a treatment agreement point by point, detailing risks.¹
• All participants were required to detail long and short-term side effects.¹
• They advised the participants to start with 1-2 sprays and never exceed 20 per day.¹
• Participants only received 1-2 refills before a doctor’s visit was required to assess progress, side effects, and potential misuse.¹
• Prolonged and frequent use of the ketamine spray was discouraged to avoid other disorders.¹

What is ketamine, and why am I afraid of it? Well, it took our dear Matthew Perry, RIP. Ketamine is a highly addictive anesthetic. It inhibits several main excitatory neuronal pathways, including the most common excitatory receptor and the receptor responsible for firing neurons, all while activating the most common inhibitory receptor. Therefore, ketamine has an overall relaxing effect on the body and mind, like anesthesia. Ketamine’s overwhelmingly versatile functions in the brain make it a dangerously effective therapeutic. Ketamine is a pain reliever, anti-depressant, and anesthetic.³ Recently, ketamine administered intravenously improved headache symptoms.^4,5 However, intravenous administration is not plausible for frequent headaches. Additionally, ketamine administered through nasal spray showed equal pain relief to opioid treatment at 15 and 60 minutes following spray.⁶ So, the researchers in this study co-opted the headache-soothing power of ketamine along with its pain-relieving success as a nasal spray.

As reported by the participants, ketamine nasal spray effectively reduced headache symptoms. Regarding the overall effectiveness of the ketamine nasal spray, 49% of the participants said the spray was “very effective” while 88% deemed it generally effective.¹ Simultaneously, in reference to quality of life, 43% of participants said it was “much better” while 78% indicated an improvement in their quality of life.¹

In summary, ketamine nasal spray is effective at relieving pain from seemingly untreatable migraines. However, there are dangers of continued ketamine use. As repeatedly mentioned, this is for severe migraine cases only. Also, there were side effects from ketamine use observed in this study. Most commonly, fatigue and blurred vision.¹ Importantly, this entire study is under the spotlight of self-report bias. 242 people were screened, yet only 169 were in the experiment. What happened to the rest? Did they not report their results because it did not work? All I am saying is take this with a grain of salt. If you have severe migraines, please continue to get treatment and multiple opinions from different neurologists if you are not satisfied. Good luck.

REFERENCES

1.         Yuan H, Natekar A, Park J, Lauritsen CG, Viscusi ER, Marmura MJ. Real-world study of intranasal ketamine for use in patients with refractory chronic migraine: a retrospective analysis. Reg Anesth Pain Med. 2023;48(12):581-7.

2.         Sacco S, Braschinsky M, Ducros A, Lampl C, Little P, van den Brink AM, et al. European headache federation consensus on the definition of resistant and refractory migraine : Developed with the endorsement of the European Migraine & Headache Alliance (EMHA). J Headache Pain. 2020;21(1):76.

3.         Zanos P, Moaddel R, Morris PJ, Riggs LM, Highland JN, Georgiou P, et al. Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms. Pharmacol Rev. 2018;70(3):621-60.

4.         Pomeroy JL, Marmura MJ, Nahas SJ, Viscusi ER. Ketamine Infusions for Treatment Refractory Headache. Headache. 2017;57(2):276-82.

5.         Schwenk ES, Dayan AC, Rangavajjula A, Torjman MC, Hernandez MG, Lauritsen CG, et al. Ketamine for Refractory Headache: A Retrospective Analysis. Reg Anesth Pain Med. 2018;43(8):875-9.

6.         Li X, Hua GC, Peng F. Efficacy of intranasal ketamine for acute pain management in adults: a systematic review and meta-analysis. Eur Rev Med Pharmacol Sci. 2021;25(8):3286-95.