Ketamine has been on a long journey of its own for the past 60+ years.
1956: PCP or phencyclidine was the predecessor to ketamine. It had too many adverse side effects for humans and was taken off market.
1962: Calvin Stevens, a chemist and consultant for Parke-Davis synthesized this next-generational structural analog to PCP. Since the compound was a ketone and an amine, it was named ketamine.
1964: The first human trial of ketamine was administered. Researchers noticed that as they experimented with sub-anesthetic doses, subjects would report feeling spaced out or be in what we might call today a psychedelic state with therapeutic potential. The researchers wanted to call this effect ‘dreaming’, but Parke-Davis didn’t approve the term. One of the researcher’s wives coined the term ‘dissociative anesthetic’ instead to describe these unique properties of ketamine.
1966: Ketamine was used as a battlefield anesthetic in the Vietnam war. It could be administered quickly and safely in situations where there wasn’t a high need for monitoring.
1970: FDA approval as an anesthetic.
Late 1960’s and 1970s: Ketamine was adopted by early researchers in psychedelics for psychiatric symptoms such as Salvador Roquet, John C Lilly, Khorramzede & Lofty, and Fontana. Early circles in America began to understand the power of ketamine for psychotherapy and mystical experiences. However, ketamine’s potential went mostly unnoticed.
Early to mid-1980’s: Ketamine hit the dance club and rave scenes. It became known as a horse tranquilizer because it was easier to divert it from veterinarians and sell on the illegal market.
1985: World Health Organization placed ketamine on list of essential medicines as safe to use in unmonitored settings because it doesn’t lower respiration or blood pressure.
Mid-1980’s: Krupitsky, a Russian psychiatrist, began combining behavioral psychotherapy with ketamine. Eventually he pivoted to more humanistic types of therapy with existential and transpersonal models. His research on addiction work and ketamine used a ketamine-assisted psychotherapy model for psychedelic research. He treated heroin and stimulant addictions, OCD, PTSD and even some personality disorders.
1994: Psychiatrist, Eli Kolp, began using ketamine with therapy. He treated addiction, end-of-life anxiety, depression and anxiety. He moved to the US from Russia where he was mentored by Krupitsky.
1999: Ketamine was made a federally controlled substance, Schedule III by the DEA, in an attempt to stop it’s recreational use.
Late 1990s: The National Institute of Mental Health (NIMH) began to look at the antidepressant effects of ketamine while searching for treatments that were more effective than SSRIs.
2000: Berman & Krystal out of Yale published the first landmark study on ketamine as an antidepressant. Carlos Zarte with NIMH replicated their research in 2006 with his paper on IV ketamine for treatment-resistant depression
2015: Stephen Hyde, psychiatrist, published ‘Ketamine for Depression’. This author demonstrated that clients didn’t need to go to an IV clinic at considerable expense, but could be successfully treated with low-dose sublingual ketamine and take it safely at home.
2016 Formation of American Society of Ketamine Physicians who are working to establish a standard of care for off-label use of ketamine
2019: ‘Science’ published an NIMH study finding that ketamine repairs neural activity that was damaged from depression and stress. It also pointed to dendritic spine regrowth that could be a consequence of ketamine-induced rescue of prefrontal cortex circuit activity.
2019: Janssen, a subsidiary of Johnson & Johnson, successfully patented and received FDA approval for esketamine (Spravato) for treatment-resistant depression to be administered intranasally and in conjunction with a SSRI/SNRI. It was possible for them to get a patent because by removing the arketamine (generic) compound from the ketamine formula, they were able to say it was a new drug which resulted in FDA approval and financial gain. Nevertheless, the benefit of Spravato and its FDA approval is that it lays the foundation in terms of racemic (generic) ketamine’s clinical use for off-label indications like depression, anxiety, trauma, and other issues.
2020: The UK’s National Health Service (NHS) issued a statement of not recommending Spravato for treatment resistant depression due to a lack of clinical and cost effectiveness.
2024: There have been thousands of research papers on the use of ketamine as an antidepressant and other psychiatric symptoms for the last 15 years.
New research is coming out all the time on the benefits of ketamine and ketamine-assisted therapies. This research is mostly from a medical or mental health perspective.