A recent aggregate study on the effectiveness of ketamine treatments for depression conducted by Ezio Carboni, Anna Carta, Elena Carboni, and Antonello Novelli, and published by Frontiers in Neuroscience, shows ketamine has significant promise as a treatment option for chronic and treatment-resistant depression.

Ketamine, an anesthetic and analgesic drug first developed in the 1970s, has long been used in hospitals, clinics, and battlefields as a safe alternative to other anesthetics. Unlike other medications, ketamine does not depress the respiratory or circulatory systems of patients it is administered to; this factor has made it a go-to compound for surgical proceedings in hospitals worldwide.

Despite ketamine’s long and successful use as an anesthetic, it has only recently, within the last decade, started to gain notoriety as a breakthrough treatment for depression and substance abuse disorders. This recognition of ketamine’s potential for treating depression comes from its rapid onset and relatively low risk of severe side effects. Unlike traditional SSRIs that take several weeks or longer to begin working, ketamine has been shown to have a near-immediate impact on patients who receive the drug.

As reported by Carboni, ketamine and its derivative drug esketamine affect brain NMDA (glutamate) transmission. This impact on the available levels of glutamate is believed to be responsible for ketamine rapid antidepressant effects. However, research into this and other areas of depression treatment is hampered by a lack of available animal studies.

Carboni proposes that ketamine also significantly impacts other neural transmitters, such AMPA, BDNF, eEF2, and glycogen synthase kinase 3. All of which are thought to be partially responsible for depressive symptoms in patients. Furthermore, Carboni Et. Al. postulates that ketamine stimulating qualities also positively affect patients with depressive symptoms, particularly those with treatment-resistant depression.

This may be due to ketamine’s ability to alter background synaptic activity, changing how some synaptic pathways in the mind that have become locked into depression-related states transmit information. This rewiring of neural activity is thought to allow data to be processed in new ways, potentially relieving depressive symptoms.

Carboni shows that ketamine’s ability to break free locked in synapses was first noted in research conducted by Berman et al. in the early 2000s. Berman’s research showed that patients with depressive symptoms given ketamine showed significant improvement in as little as 72 hours. Notably, this rapid relief from depressive symptoms was not experienced by the control group who received a placebo only.

Furthermore, trials conducted by Yang et al., 2019a and Canuso et al., 2018 showed both esketamine (Spravato) and R-ketamine provide rapid relief to patients with treatment-resistant depression. Interestingly R-ketamine, while being less potent than esketamine, showed longer-lasting anti-depressive benefits and required less follow-up course of the drug to maintain its anti-depressive effects.

While research into ketamine and its derivatives is still relatively new, research and trials like those mentioned above show that the drug has strong therapeutic potential. Particularly for those with major mood disorders or treatment-resistant depression. One of the most critical aspects of research like that detailed in this article is its ability to inform the general public about these new tools in the fight against mental illness.

Unfortunately, the public has long viewed ketamine as a party drug, leading to widespread misinformation and stigma around its use. As knowledge about the benefits of drugs like ketamine and even other psychedelics grows, it will be critical that the people stay engaged and become part of the greater conversation around not just ketamine but mental health as a whole.

David Connell is a U.S. Air Force Veteran writer and author of Cooking with Magic: The Psilocybin Cookbook. David holds a B.A. in Communications and Creative Writing from the University of Tennessee, Knoxville. Connect with him about drug policy reform, his thoughts on research in novel psychedelic therapies, creative writing, and his unabashed love for Science Fiction on Twitter, LinkedIn, and Instagram.


Canuso, C. M., Singh, J. B., Fedgchin, M., Alphs, L., Lane, R., Lim, P., et al. (2018). Efficacy and safety of intranasal esketamine for the rapid reduction of symptoms of depression and suicidality in patients at imminent risk for suicide: results of a double-blind, randomized, placebo-controlled study. Am. J. Psychiatry 175, 620–630. doi: 10.1176/appi.ajp.2018.17060720

Carboni, E., Carta, A. R., Carboni, E., & Novelli, A. (1AD, January 1). Repurposing ketamine in depression and related disorders: Can this enigmatic drug achieve success? Frontiers. Retrieved December 16, 2021, from https://www.frontiersin.org/articles/10.3389/fnins.2021.657714/full

Yang, C., Wardenaar, K. J., Bosker, F. J., Li, J., and Schoevers, R. A. (2019a). Inflammatory markers and treatment outcome in treatment-resistant depression: a systematic review. J. Affect. Disord. 257, 640–649. doi: 10.1016/j.jad.2019.07.045

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