Until now, the link between club drug ketamine and the alleviation of depression has been unknown. But a new study claims that the antidepressant effect is caused by the metabolic breakdown of the drug, rather than the drug itself.
The study, published in Nature, found that a compound called (2R,6R)-hydroxynorketamine was responsible for a lift in mood in mice given ketamine. The metabolite is a product of the molecular breakdown of ketamine in the body – and when given this metabolite, mice did not experience any of the side effects commonly associated with ketamine – for examine disassociation and an alteration in spatial perception – even when they were given doses 40 times higher than the average antidepressant dose.
The mice were also not dependent on the metabolite – instead of pressing a level to self-administer the drug, as they previously had when given pure ketamine, they "did not tend to press the lever when given the option".
The metabolite also worked through a different set of receptors to traditional ketamine – AMPA receptors rather than NMDA receptors – which the team says may explain why full antidepressant effects had not worked when targetting these receptors.
The discovery could now be used to treat depression in human subjects, though the team warn that it could take many years. If successful, however, it could provide a way to administer the drug without the side effects that many people find distressing or unappealing.
"The whole field has become interested in ketamine," Todd Gould, who led the study, told Nature. "It does something different in patients than any other drug we have available."
Recent studies have found other benefits of drugs - one recent study found that LSD can 'unify' the brain's processes, and an Israeli company have developed a strain of marijuana that gives medicinal benefits without the 'high' normally associated with the drug.