The anesthetic ketamine, which first came into use for surgical procedures more than 40 years ago, may be successful at treating one of two \u201ccardinal symptoms\u201d of major depressive disorder and bipolar disorder. These two cardinal symptoms are depressed mood and loss of interest in normally pleasurable activities. Loss of interest and excitement is officially known as anhedonia, and it is a component of both unipolar depression and bipolar depression that is often resistant to treatment. Now, a trial conducted by the National Institutes of Health (NIH) suggests that ketamine may have untapped potential as a rapid and effective treatment for this component of depression. Ketamine has been the subject of several recent studies that suggest it may be an effective alternative to conventional antidepressants. In order to test ketamine\u2019s potential as treatment for anhedonia, the NIH researchers administered the drug or a placebo by infusion to 36 patients with bipolar disorder who were in a depressive phase of their illness. The study team then evaluated levels of anhedonia using brain scan technology as well as rating scales for anhedonia and depression. Brain scans of the patients who received the drug showed increased activity in the front and deep right areas of the brain that are associated with reward seeking. The rating scales also showed significant improvements in the depressive symptoms reported by the patients who received ketamine. Ketamine Quickly Targets Anhedonia Most antidepressants take two to four weeks to have an effect. However, the results of this study found that ketamine reduced symptoms of depression after only two hours. Furthermore, ketamine appeared to have an even more rapid effect on anhedonia. The researchers isolated the scores on the depression rating scale that were specific to anhedonia and found that these symptoms showed improvement after just 40 minutes. The NIH researchers believe that these results are important not just because they identify a potentially effective treatment for a serous illness, but because they add to the evidence that depression can be broken into component symptoms and that treatment can target these components individually. Ketamine as an Antidepressant As an antidepressant, ketamine works in a different way than the commonly prescribed antidepressants currently on the market. The drug binds to a protein in the brain that is known as the NMDA receptor, and by doing so it blocks a chemical messenger called glutamate. Exactly how this process influences depression symptoms is still a mystery. Researchers are not even sure whether blocking glutamate is the direct cause of depression-relieving effects, or whether this blockage results in a chain reaction in which the crucial depression-treating effect occurs later on. Ketamine Has Some History of Abuse Ketamine does have a history of being abused as a club drug and carries the potential for tolerance and dependence. The drug is known as a dissociative anesthetic, and abusing ketamine can result in feelings of detachment along with sight and sound distortions. High doses of ketamine can cause hallucinations, dreamlike states, delirium and amnesia. Abuse of ketamine is not particularly widespread and has decreased since its peak years between 2000 and 2002. However, its history as a recreational drug does set it apart from the current class of antidepressants, which have almost no potential for abuse or addiction. Partly because of these concerns and partly because the research on ketamine\u2019s antidepressant potential is still quite new, the Food and Drug Administration has not approved ketamine as a treatment for unipolar or bipolar depression.