Ketamine was developed in 1962 by chemist Calvin Stevens for Parke-Davis Company (today, a subsidiary of Pfizer). It was developed as a less hallucinogenic and shorter-acting anesthetic agent than phencyclidine1 , or PCP, which was also created as a pharmaceutical anesthetic. Phencyclidine caused prolonged hallucinations and took people longer to recover from the effects, however, and was discontinued.
Developed a decade after phencyclidine, ketamine’s duration and effects were much more palatable for use in medicine. Ketamine was given to humans for the first time in 1964. By 1970, ketamine became an FDA-approved anesthetic after clinical trials consistently showed its efficacy. Ketamine was used in the Vietnam War as a battlefield anesthetic to treat wounded soldiers.
While not considered a classic psychedelic, ketamine was the first “psychedelic” drug to receive2 breakthrough therapy status from the U.S. Food and Drug Administration (FDA) in 2013. Its off label use for mental health treatments helped generate greater support in the medical community and in popular culture for the use of psychedelic drugs to to treat mental health conditions. Now more generally accepted as medicines, ketamine and psychedelic-assisted therapies may play a critical role in addressing the present post-pandemic mental health crisis.
Ketamine is included in the World Health Organization List of Essential Medicines, and is now being used off-label3 to treat depression, among other conditions. Its derivative, esketamine4 , has been packaged as a pharmaceutical nasal spray called Spravato used to treat depression. Spravato is the first ketamine intervention to receive FDA approval (in 2019) specifically for a psychiatric disorder.
Things to Know
- Ketamine was developed as an anesthetic agent in 1962
- Ketamine has been FDA approved since 1970
- Ketamine potential to treat mental health conditions was first identified in the 1970s
- Ketamine received breakthrough therapy status as a mental health treatment in 2013
Ketamine’s therapeutic potential in the treatment of mental health was first identified in the 1970s. In Mexico, pioneering psychedelic therapist and researcher Salvador Roquet conducted some of the first research5 on ketamine’s positive impact on mental health6 .
At roughly the same time, physicians in Southern Iran were exploring7 similar qualities of ketamine as a way to treat hospitalized psychiatric patients.
Though the federal Controlled Substances Act does not classify ketamine as an illegal drug, as it does most other psychedelic compounds, research on ketamine as a treatment for mental health was limited until more recently.
Ketamine As a Club Drug
Ketamine usage increased by people using it for personal and recreational purposes throughout the 1970s, 80s, and 90s. It first entered the party scene in the 1970s, which led to it being labeled a “party drug.” It became particularly popular within rave and club cultures. Due to its proliferation as a party drug, it acquired a stigma by some researchers and members of the medical community.
In 1999, ketamine became a Schedule III federally controlled substance in the U.S. due to concerns around its growing recreational use.
Ketamine for Mental Health in the U.S.
In the 1990s and early 2000s, ketamine therapy showed promising results8 as a treatment for depression and addiction using intravenous infusions. Other early therapeutic applications include relieving chronic pain and alleviating anxiety in terminal patients. . Since then, a significant body of research has pointed to the effectiveness of ketamine therapy as a rapid-acting therapy for hard-to-treat conditions such as Major Depression and Treatment-Resistant Depression, including both unipolar and bipolar, as well as PTSD, OCD, and anxiety. It’s also being investigated as an intervention to address substance use disorder.
By 2012, there were dozens of clinical trials and studies that showed the efficacy of ketamine as a treatment for mental health. In 2013, Esketamine, a derivative of ketamine, received “Break-through therapy” status9 by the FDA as a treatment for depression. It received this designation again in 2016.
An Esketamine nasal spray, called Spravato, was approved by the FDA10 in 2019 as a treatment for people with depression.
Starting in 2021, ketamine therapy11 centers proliferated12 around North America13 and Canada with numerous in-person clinics providing these services. Due to the Covid-19 pandemic, telemedicine options also became more prominent around this time allowing people to get prescriptions for ketamine lozenges that could be consumed at home. Ketamine therapy, while expensive, remains the most widely accessible psychedelic therapy due to its Schedule III status.