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What is Ketamine?
Ketamine is an FDA-approved anesthesia medication that is used daily in hospitals across the country. The drug, which was first developed in the early 1960s has a number of remarkable properties. During early trials, volunteers described experiences like “a feeling of floating in outer space and having no feeling in their arms or legs.” This sensation of being “disconnected” from one’s environment resulted in ketamine being referred to as a dissociative anesthetic.
In addition to its dissociative properties, early research demonstrated that ketamine could provide rapid and profound pain reduction in the setting of surgery or trauma. During the Vietnam War, ketamine anesthesia was widely used for American soldiers because of its large margin of safety. Since the 1990s, clinical research has demonstrated that ketamine is also effective in the treatment of certain chronic pain syndromes, such as fibromyalgia, neuropathy and complex regional pain syndrome (CRPS).
Perhaps the most unique aspect of ketamine is its effect on mood disorders. In the late 1990s, ketamine was being used in a series of studies investigating its interaction with psychiatric medications used to treat schizophrenia. Unexpectedly, researchers observed that ketamine appeared to have anti-depressant effects in study subjects with depression. In 2000, the first placebo-controlled, double blinded, randomized controlled trial was published to assess the effects of a single dose of ketamine in subjects with major depression. Compared to placebo infusion (no ketamine), subjects with depression displayed statistically significant improvement in depressive symptoms 72 hours after the ketamine infusion.
Over the past twenty years, research has shown that ketamine may also be effective in treating anxiety, bipolar disorder, post-traumatic stress disorder (PTSD) and obsessive-compulsive disorder (OCD). If you are suffering from any of these conditions, ketamine may be able to provide relief.
How Does Ketamine Improve Mental Health and Chronic Pain Symptoms?
Ketamine appears to exert its pain-reducing and antidepressant effects through numerous pathways. The earliest studied and most well-known cellular target that ketamine acts upon is the NMDA receptor. The NMDA receptor is a glutamate receptor located on the surface of neurons (brain cells). Activation of the NMDA receptor by the neurotransmitter glutamate plays a major role in chronic pain and mood regulation. Ketamine is a NMDA receptor antagonist, meaning that it blocks the receptor from activating. This is thought to be the primary mechanism by which ketamine improves chronic pain syndromes, especially neuropathic pain. Ketamine, however, acts on numerous other cell receptors, including opioids receptors, GABAA receptors, sodium, potassium and calcium channels. Research has more recently focused on AMPA receptors, in which activation by a metabolite of ketamine has been implicated in ketamine’s rapid antidepressant properties.
On a system level, ketamine appears to alter connection patterns between different parts of the brain. One study, in which patients were administered a ketamine infusion dose in the range used to treat depression, demonstrated sustained functional disruption of frontoparietal networks with an increase in blissful feelings.
Want to learn more about ketamine? Check out Dr. Bradley Silva on a recent podcast discussing all aspects of ketamine therapy.
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Domino EF. Taming the Ketamine Tiger. Anesthesiology 2010; 113:678.
Li L, Vlisides PE. Ketamine: 50 Years of Modulating the Mind. Front. Hum. Neurosci. 2016; 10:612.
Cohen SP, Bhatia A, Buvanendran A, et al. Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Chronic Pain from the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Reg. Anesth. Pain Med. 2018; 43:521.
Krystal JH, D’Souza DC, Karper LP, et al. Interactive Effects of Subanesthetic Ketamine and Haloperidol in Healthy Humans. Psychopharmacology 1999; 145:193.
Berman RM, Cappiello A, Anand A, et al. Antidepressant Effects of Ketamine in Depressed Patients. Biol. Psychiat. 2000; 47:351.
Glue P, Neehoff S, Sabadel A, et al. Effects of Ketamine in Patients with Treatment-Refractory Generalized Anxiety and Social Anxiety Disorders: Exploratory Double-Blind Psychoactive-Controlled Replication Study. J. Psychopharmacol. 2020; 34:267.
Feder A, Parides MK, Murrough JW, et al. Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder. JAMA Psychiatry 2014; 71:681.
Rodriguez CI, Kegeles JS, Levinson A, et al. Randomized Controlled Crossover Trial of Ketamine in Obsessive-Compulsive Disorder: Proof-of-Concept. Neuropsychopharmacology 2013; 38:2475.
Zanos P, Moaddel, R, Morris PJ, et al. NMDAR Inhibition-Independent Antidepressant Actions of Ketamine Metabolites. Nature 2016; 533:481.
Muthukumaraswamy SD, Shaw AD, Jackson LE, et al. Evidence that Subanesthetic Doses of Ketamine Cause Sustained Disruptions of NMDA and AMPA-Mediated Frontoparietal Connectivity in Humans. J. Neurosci. 2015; 35:11694.