Chemistry and Life

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Can an old hallucinogen be a new antidepressant?

Ketamine is an anesthetic and sedative drug developed in the 1960s. It’s not widely used anymore, primarily because there are better options. Among its side effects are dissociative and hallucinogenic effects. Because of these effects, ketamine has also been used as recreational drug with the street name “Special K”.

Ketamine exerts its effects by modulating the neurotransmitter glutamate. Specifically, it blocks the function of a type of glutamate receptor in the brain called NMDA receptors.

In addition to its approved uses, ketamine has also been used off-label as an antidepressant, but its usefulness for this purpose is not well established. The only way to know for certain is to conduct well controlled clinical trials. It appears that Johnson & Johnson is trying to do exactly this (through its subsidiary Janssen). Like many organic molecules, ketamine can exist in either of two mirror images. Ketamine as used in medicine is an equal mixture of the two. J&J is investigating just one of them, named esketamine.

For a pharmaceutical company it is a bit of risk to take a drug that is abused recreationally into clinical trials. The path to regulatory approval won’t be easy. Although ketamine already has established medical uses and one might think that the existing approval for current uses would make approval for a new use simpler, but I’m not sure that’s going to be the case. Ketamine, when used as an anesthetic is given intravenously, but J&J is looking at nasal delivery. This could make a big difference. Intravenous drugs are generally given in a doctor’s office or hospital, while a nasal drug for depression will almost certainly be intended to be taken home by the patient where the potential for abuse is higher.

It will be interesting to see how this plays out.

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