The findings of a small study examining the antidepressant effect of intravenous ketamine in 18 subjects with treatment-resistant depression surprised the mental health treatment community in early August 2006. The significance of the study, published in the Archives of General Psychiatry, centers on evidence of the unprecedented speed of symptom relief. Alleviation of major depression is typically measured in terms of weeks. In this study, relief of symptoms was experienced within hours.

Subjects were given one injection of ketamine HCl at 0.5 mg per kg of body weight (e.g. 35 mg for a 70 kg/154 lb person) and one injection of inactive placebo on two test days, one week apart. In the ketamine group, symptoms were significantly improved in half the subjects within two hours. By the next day, antidepressant effects were noted by 71 percent of subjects. Nearly one third of the subjects were still experiencing a significant reduction of symptoms seven days later.

Compared to either anesthetic or recreational use of ketamine, the doses used in this study were quite modest. At these low doses, researchers reported that some subjects experienced short-lived "adverse effects" including "perceptual disturbances, confusion, elevation in blood pressure, euphoria, dizziness, and increased libido". These effects are categorized among the "emergent phenomena" that make ketamine problematic as an anesthetic.

It is amusing to note that "euphoria" (a state of happiness or well-being) is considered an "adverse effect" in the treatment of depression. Euphoria is basically the antithesis of the depression being treated. Many Schedule I substances can be considered acute antidepressants in that they cause a mood lift, exactly the effect that is being sought by those who seek them out. Adverse effects that were more common after the inactive placebo than after ketamine included "gastrointestinal distress, increased thirst, headache, metallic taste, and constipation".

The goal of the research was "to determine whether a rapid antidepressant effect" could be achieved with ketamine. Common antidepressants such as bupropion, SSRIs, and venlafaxine may take up to eight weeks to manifest such effects. The director of the National Institute of Mental Health remarked that it would be "terrific" if the quick antidepressant effect of ketamine were borne out in future studies.

The results of the study were covered in articles by major media outlets such as The Washington Post and The Boston Globe. They were also published, along with a cited excerpt from a ketamine report from the Erowid Experience Vaults, in an article titled "Comfortably Numb" in the October 2006 issue of the scientific journal Nature.