The anaesthetic ketamine — a hallucinogenic club drug also known as Special K — has tantalized researchers who are seeking new ways to treat depression. The drug can lift a person’s mood in hours, even when depression is severe. But several ‘ketamine-like’ medications have failed to alleviate depression in clinical trials over the past decade.

Now, some researchers think they know why. Emerging evidence suggests that scientists have misunderstood how ketamine fights depression. So they might have attempted to mimic the wrong biological mechanism when designing drugs to improve mood while avoiding the disorienting ketamine high.

On 20 May, researchers at a meeting of the Society of Biological Psychiatry in San Diego, California, will present results suggesting that some of ketamine’s power comes from its ability to affect brain cells called glia, which support neurons. Their finding adds to recent studies contradicting a long-held idea that the drug works mainly by blocking proteins called NMDA receptors, on the surface of brain cells, which transmit signals between those cells.

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