Ketamine

DEFINITION: Ketamine hydrochloride is a short-acting anesthetic. It has pain-killing and hallucinogenic properties.

• CATEGORY: Substances
• ALSO KNOWN AS: K; special K; vitamin K
• STATUS: Legal in the United States for use as an anesthetic in medical settings; nonmedical use is illegal
• CLASSIFICATION: Schedule III controlled substance
• SOURCE: Synthetic drug with no natural sources; supplies are diverted from legal sources for illegal use
• TRANSMISSION ROUTES: Intravenous, intramuscular, ingestion, inhalation

History of Use

Ketamine was first synthesized in 1962 in the laboratories of the Parke-Davis pharmaceutical company. It was developed as an alternative to phencyclidine (PCP) for use as an anesthetic. Clinical use in short-term surgery in humans was initiated in 1975. Many patients began reporting hallucinations while under the drug’s influence. Its use became limited in humans, but it had more widespread applications in veterinary medicine. The drug was soon diverted from hospitals, medical offices, and medical supply houses.

By the 1990s, ketamine had become a popular drug for recreational use among teenagers and young adults in the club scene. The United States Drug Enforcement Administration (DEA) added ketamine to its list of emerging drugs of abuse in the mid-1990s. It was classified as a Schedule III controlled substance in 1999.

Meanwhile, as ketamine faced increasing scrutiny from the US government during the 1990s and early 2000s, various institutions began conducting studies to determine whether ketamine could safely be used as an antidepressant and mood stabilizer. With one of the first small studies conducted at the US National Institutes of Health (NIH), other larger studies began at Yale University and Mount Sinai Hospital. Based on the potential for ketamine to relieve depression within hours, researchers continued to test the drug's effect on depression in patients for whom other medications have not worked. Yale eventually emerged as a leading center for this type of study.

During the late 2010s and early 2020s, ketamine attracted increased attention from researchers, medical professionals, and individuals interested in alternative therapies for depression, post-traumatic stress disorder (PTSD), and other mental health conditions. In 2019, the US Food and Drug Administration (FDA) approved Spravato (esketamine), an esketamine nasal spray derived from ketamine, to be used along with an oral antidepressant. In 2025, the FDA extended approval for Spravato as a standalone medication to treat treatment-resistant depression. Throughout the early 2020s, ketamine clinics, where patients could receive doses of ketamine under medical supervision, saw a surge in popularity. However, medical professionals noted that despite the potential benefits of ketamine for some patients, they cautioned that the drug could still trigger adverse side effects, including psychosis, in others.

In late 2024, researchers with the Centers for Disease Control and Prevention (CDC) published a study of fatal overdoses in which ketamine was involved or detected between July 2019 and June 2023, as recorded in a national drug overdose database. According to their study, while ketamine was involved or detected in less than 1 percent of all fatal drug overdoses during that period, case numbers had increased. The authors of the study cautioned against applying their findings to the US as a whole because their analyses were limited to a subset of US jurisdictions, and toxicology testing varied across these jurisdictions.

In 2025, experiments conducted by Vanderbilt University found ketamine to have a positive impact on patients with treatment-resistant depression, and by using a drug called BCI, it may be possible to extend the benefits of one dose of ketamine to last for several weeks. This would limit the risk of ketamine use and extend the benefits. Also in 2025, the FDA approved KETARx (racemic ketamine) for pain relief management following surgery, and granted fast-track status to the ketamine-based NRX-100, intended to treat suicidal ideation.

Effects and Potential Risks

Primary side effects of ketamine observed in medical settings include increased heart rate and blood pressure, impaired motor function and memory, numbness, nausea, and vomiting. While sedated, patients are unable to move or feel pain. Once the drug wears off, patients have no memory of what occurred while they were sedated. Researchers studying the potential therapeutic effects of ketamine noted the drug's ability to trigger the production of glutamine, which encourages the brain to produce new neural pathways and can make it easier for people with depression and other mental health challenges to develop more positive thinking and other behaviors.

In unmonitored situations, ketamine produces a dose-related progression of serious adverse effects from a state of dreamy intoxication to hallucinations and delirium. A “trip” on ketamine has been described as being cut off from reality—“going down into a K hole”—and as an out-of-body or near-death experience. Some people may be unable to interact with others around them or even see or hear them. Ketamine has been used as a date rape agent because the survivor often has no memory of what occurred.

Because those who abuse ketamine feel no pain, they may injure themselves without realizing they are doing so. Chronic use can lead to panic attacks, rage, and paranoia. High doses or prolonged dosing can lead to respiratory depression or arrest and even death. Ketamine is often mixed with heroin, cocaine, or ecstasy. Any of these combinations can be lethal.

Bibliography

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Dillon, Paul, et al. “Patterns of Use and Harms Associated with Non-Medical Ketamine Use.” Alcohol and Drug Dependence, vol. 69, 2003, pp. 23–28.

“Ketamine.” United States Drug Enforcement Administration, April 2020, www.dea.gov/sites/default/files/2020-06/Ketamine-2020.pdf. Accessed 17 Oct. 2025.

McGovern, Gilligan. "FDA Approves Ketamine for Surgical Pain Management." Pharmacy Times, 11 Aug. 2025, www.pharmacytimes.com/view/fda-approves-ketamine-for-surgical-pain-management. Accessed 17 Oct. 2025.

"New Ketamine Study Promises Extended Relief for Depression." Science Daily, 22 May 2025, www.sciencedaily.com/releases/2025/05/250522183206.htm. Accessed 17 Oct. 2025.

Rogers, Lindsay Smith. "What to Know about Ketamine." Johns Hopkins Bloomberg School of Public Health , 26 Jan. 2024, publichealth.jhu.edu/2024/what-to-know-about-ketamine. Accessed 17 Oct. 2025.

Rosenbaum, Steven B., et al. "Ketamine." StatPearls, National Library of Medicine, 30 Jan. 2024, www.ncbi.nlm.nih.gov/books/NBK470357. Accessed 17 Oct. 2025.

Smith, Dana G. “Psychedelics Are a Promising Therapy, but They Can Be Dangerous for Some.” The New York Times, 20 Oct. 2023, www.nytimes.com/2023/02/10/well/mind/psychedelics-therapy-ketamine-mushrooms-risks.html. Accessed 17 Oct. 2025.

Vivolo-Kantor, Alana M., et al. "Ketamine Detection and Involvement in Drug Overdose Deaths—United States, July 2019–June 2023." Morbidity and Mortality Weekly Report, vol. 73, no. 44, 2024, pp. 1010–12, www.cdc.gov/mmwr/volumes/73/wr/pdfs/mm7344a4-H.pdf. Accessed 17 Oct. 2025.

Winter, Caroline. "Is Ketamine the Best Hope for Curing Major Depression?" Bloomberg Businessweek, 19 Aug. 2015, www.bloomberg.com/graphics/2015-ketamine-depression-treatment. Accessed 17 Oct. 2025.