Ketamine: Anesthetic, rave drug, and now a potential antidepressant

By Olivia Parlow

“Steve, what’s your favorite drug you’ve ever done?” “Probably ketamine.” My eyes widened as I heard that. My first day as a waitress and that’s the conversation I walk into? A group of waitresses were standing at the hostess stand surrounding the head waiter, Steve. They too were wide eyed, but not in the same way as I was. I was horrified. I couldn’t believe what I had just heard, and they were gawking at Steve as if he was a celebrity. 


I didn’t know much about ketamine at the time, but the opinions I did have on it were negative. I was in high school. I was a straight A student. I was a rule follower. My fifth grade dare poster stated, “Take the lead, don’t do weed.”  I had never dreamt of doing drugs or even knowing someone that did ketamine. So obviously after hearing that, I was perplexed, confused, interested, and a little scared. Steve didn’t look like someone that did ketamine. He was fit, healthy looking, kind, and spoke intelligently. I couldn’t imagine someone like him doing a drug like ketamine. I had to learn more. I spent a summer working alongside Steve, and I got to know him. I learned that he didn’t use ketamine in the way I had initially imagined. He didn’t use ketamine in a dusty, dirty basement. He used ketamine in a doctor’s office. He didn’t use ketamine recreationally to get high with his friends. He used it to cope with childhood trauma because he suffered from abuse when he was younger.  


Ketamine is a highly effective anesthetic and analgesic that has been used since the 1970s. Ketamine also produces hallucinogenic effects, which led the drug to be used recreationally, especially in the rave, party scene. In 1999, the United States labeled ketamine as a Schedule III drug, meaning it has moderate to low potential for psychological and physical dependence. In the 2000s, research began to investigate the use of ketamine to treat depression and studies have shown promising results of treating patients that have exhausted other treatment options, such as serotonin reuptake inhibitors (SSRIs), and have what is known as treatment resistant depression. 


SSRIs were introduced in the 1980s due to a popular theory known as the serotonin hypothesis, which asserted that people with depression had low levels of a neurotransmitter called serotonin. SSRIs are still a very popular treatment option for depression, however, the serotonin hypothesis does not totally explain depression. Further research showed that the neurotransmitters SSRIs drugs target account for less than 20 percent of the neurotransmitters in a person’s brain. The other 80 percent are neurotransmitters called GABA and glutamate.  That’s where ketamine comes in. Ketamine triggers glutamate production, which prompts the brain to form new neural connections. This makes the brain more adaptable and able to create new pathways, and gives patients the opportunity to develop more positive thoughts and behaviors. Researchers at Yale have led much of the investigation of ketamine as a treatment option for depression and in several of their studies, more than half of participants show a significant decrease in depression symptoms after just 24 hours. These are patients who felt no meaningful improvement on other antidepressant medications.  


The traditional way of administering ketamine is via an IV in a clinic. However, in 2019, the FDA approved Spravato, a nasal spray that administers esketamine, which is one version of the ketamine molecule. This obviously makes ketamine more accessible than its IV counterpart, which causes concern for increased abuse and misuse due to it being more readily available. 


For many ketamine researchers and supporters, the talk of ketamine is very positive and it does seem promising when you read about the drug on various ketamine clinic websites, as I did. However, it is important to note that ketamine is not the new savior for the field of mental health. Firstly, ketamine is not meant to be the first treatment pursued by a patient. It is primarily aimed to treat those with treatment resistant depression. Secondly, many clinicians recommend that ketamine be a part of a comprehensive treatment plan, not just used on its own in a single dose. Dr. Sanacora from Yale believes that ketamine may be most effective when combined with cognitive behavioral therapy (CBT). Lastly, I and other researchers believe that more research needs to be done on the long term effects of ketamine use, as well as the likelihood of depressive symptom relapse in the long term. A narrative review of 14 meta-analyses and 15 trials showed that ketamine may provide a rapid and robust antidepressant effect on Major Depressive Disorder and Bipolar Depression, but the benefits are short lasting, according to the research. More research is needed on repeated administration at higher doses due to the risk of serious liver damage, uro-nephrogenic damage or dependence as observed in recreational users (Corriger & Pickering). 


Nonetheless, ketamine research is one step in the right direction of new treatment options for depression, a disorder that affects roughly 17.3 million American adults. Patient testimonies, like my coworker Steve’s, are very encouraging and optimistic, especially for those who have suffered from depression for a very long time and have never experienced relief or improvement from any other treatments.




Sources:
Chen, Jennifer. “How Ketamine Drug Helps with Depression.” Yale Medicine, Yale Medicine, 9 Mar.         2022, www.yalemedicine.org/news/ketamine-depression.

Corriger, Alexandrine, and Gisèle Pickering. “Ketamine and Depression: A Narrative Review: DDDT.” Drug Design, Development and Therapy, Dove Press, 27 Aug. 2019, doi.org/10.2147/DDDT.S221437.

“Depression Statistics.” Depression and Bipolar Support Alliance, 12 July 2019, www.dbsalliance.org/education/depression/statistics/.

Li, Jih-Heng, et al. “To Use or Not to Use: An Update on Licit and Illicit Ketamine Use.” Substance Abuse and Rehabilitation, U.S. National Library of Medicine, 16 Mar. 2011, www.ncbi.nlm.nih.gov/pmc/articles/PMC3846302/.

“Understanding Ketamine Treatment for Depression.” Columbia University Irving Medical Center, 14 July 2023, www.cuimc.columbia.edu/news/ketamine-treatment-depression-what-you-need-know. 

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