New Study on Ketamine Nasal Spray for Depression Raises Serious Concerns

The new drug has serious potential for abuse.

The notorious party drug ketamine has enjoyed a revival in the past few years as a legitimate treatment for major depressive disorder and potentially for migraines, too. While doctors usually administer the drug as an intravenous infusion in clinical settings, psychiatrists are now testing a ketamine nasal spray. And it’s just in time for music festival season!

In a paper published Monday in the American Journal of Psychiatry, researchers outline their findings from a small, double-blind, randomized, placebo-controlled study — the gold standard for testing medical interventions — of intranasal esketamine, a drug whose molecular structure and function mirror that of ketamine. The esketamine nasal spray was more effective than a placebo at treating major depression and some measures of suicidal ideation in the short term but not over the course of four weeks. This study tested the efficacy of esketamine against a placebo but not against intravenous ketamine, the more typical treatment.

Ketamine used illicitly is usually dried on glass and scraped up, but in a clinical setting it's administered by an intravenous infusion. Soon it could be given in a nasal spray, too

Wikimedia/ Coaster420

The study involved 68 patients diagnosed with major depressive disorder who had experienced severe suicidal ideations within 24 hours of arriving at an emergency room for treatment. All of the patients were put on antidepressants and divided into two groups, one that received nasal esketamine spray and one that received a placebo spray. Receiving these treatments twice a week for four weeks, the participants answered questions about their mental and emotional states, revealing the spray’s short-term efficacy. Out of all 68 patients, 49 completed treatment, and the researchers assert that the data from this small group provide a proof-of-concept for this treatment. Since it’s such a small group, however, the findings should be considered preliminary and certainly not definitive.

The study was a phase 2 clinical trial for the drug, the second-to-last phase before FDA approval. The drug, if it makes it through all rounds of testing, would be sold by pharmaceutical giant and baby powder manufacturer Johnson & Johnson. In an invited editorial published alongside the new study, a group of 21 doctors questions the moderate effects seen in this trial and raise serious concerns about a new ketamine product on the market mirroring the beginnings of the opioid epidemic, especially since ketamine has a long history of abuse and addiction. “The failure to demonstrate longer-term benefits [in this study] raises questions about the risk versus the benefit of long-term use,” they write.

This study is just one of many steps in the process for Johnson & Johnson to get an esketamine nasal spray approved for sale, so you won’t be seeing it in drug stores anytime soon. According to, the NIH’s registry of clinical trials, Janssen Research and Development, LLC, the lab conducting the trials, is recruiting for another clinical trial whose results are scheduled to be published in September 2021.

In addition to the ethical concerns about pushing forward the development of a drug with potential for abuse and addiction, almost all of the doctors involved in the study disclose that they have stocks, stock options, or both from Johnson & Johnson. While this doesn’t mean their research is unreliable, it does mean they stand to personally benefit from the development of this drug. So maybe a new ketamine formula that patients are meant to snort — the way it’s most often abused — isn’t something that should be taken lightly.

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