Ketamine: From party drug to breakthrough depression treatment

Ketamine was first synthesized by American chemist Calvin Stevens in 1962 at the University of Michigan. Initially, it was used as a new anesthetic agent. It is an organic chemical compound with the molecular formula C₁₃H₁₆ClNO and a 237.73 g/mol molar mass. The pharmacological action of ketamine mainly involves NMDA receptor antagonism and is similar to chemical compounds such as dextromethorphan and phencyclidine. However, it stands out due to its significantly shorter duration and fewer side effects, which is why it has been popular in medicine for many years.

Ketamine induces a specific type of anesthesia known in medicine as "dissociative anesthesia." It selectively inhibits certain central nervous system structures, leading to a loss of consciousness while simultaneously stimulating others. It causes symptoms such as catalepsy (specific muscle rigidity), eye movements, and hallucinations. The dose of ketamine that induces anesthesia is typically 0.45–0.91 mg per pound of body weight.

On both global and national drug markets, new synthetic drugs, called modified or designer drugs, continue to appear. They are usually derivatives of "classic" psychoactive substances, including medications. An example of such a substance is methoxetamine, a structural analog of ketamine. Ketamine itself is also sometimes used as a recreational drug because, when used improperly and uncontrollably, it induces a sensation of detachment from one's body, which may be accompanied by euphoria and hallucinations.

Unfortunately, these symptoms are only temporary. The subsequent effects of recreational ketamine use include abdominal pain, nausea and vomiting, seizures, memory and concentration disorders, vision problems, and paranoia. These negatively affect health, well-being, daily life, and interpersonal relationships. Ultimately, it leads to deterioration and can pose a direct threat to life, similar to many other drugs.

Interestingly, the illegal use and abuse of ketamine began shortly after its introduction to the market, more precisely in 1970. Returning soldiers from Vietnam, who had ketamine used on them as an anesthetic, reported vivid hallucinations. There were also initial reports of healthcare workers abusing this medication. In recent years, ketamine has been termed a club drug because it is usually used during various types of parties. Repeated administration of ketamine leads to the development of behavioral tolerance, meaning increasingly larger doses are necessary to achieve the desired narcotic effect.

Numerous scientific studies have confirmed that ketamine when used in moderate, controlled amounts, can have antidepressant effects. This is especially true for patients with severe forms of depression that do not respond to classic pharmacotherapy methods. One study found that depression symptoms in patients taking specific doses of ketamine significantly improved within a few hours after administering a single dose. Meanwhile, a single infusion of ketamine usually exerts a rapid antidepressant effect, which can last for several days. During this time, psychotherapy, essential for achieving long-term remission of the disorder, can be undertaken.

Previously, antidepressant pills were the first-line treatment for patients diagnosed with depression. Often, they prove effective; however, for 40% of patients, the effects are insufficient, and the longer wait time for complete efficacy is a drawback. Therefore, ketamine seems to be a medication of the future in the treatment of depression and certainly requires further careful scientific studies.

References

1. Messer M., Irina H., Ketamine maintenance therapy allows for long-term remission in depression, Psychiatry after Graduation, 3/2010.

2. Pochwat B., Ketamine – a long journey from anesthetic to prototype antidepressant medication. Review of potential mechanisms of action, Psychiatry Poland 2022; 56(5): 1017–1032.

3. Ross S., Ketamine and Addiction, Psychiatry after Graduation, 2/2009.