Swedish scientists have scanned the brains of depressed people to understand why ketamine – abused by ravers for its hallucinogenic properties – can treat depression.
Researchers used positron emission tomography (PET) cameras to scan the brains of 30 people suffering from difficult-to-treat depression. Some were given the drug.
The researchers found that it acts on the brain’s serotonin receptors – a discovery which could lead to new drugs to treat depression.
The researchers found that 70% of those treated with ketamine responded to the drug.
Serotonin plays a key role in depression and low levels are thought to be linked to more serious disease.
Researchers at the Karolinska Institutet found that in low doses the anaesthetic drug has a rapid effect in treating those with depression.
Dr Mikael Tiger, researcher at the Department of Clinical Neuroscience, said: "In this, the largest PET study of its kind in the world, we wanted to look at not only the magnitude of the effect but also if ketamine acts via serotonin 1B receptors.
"We and another research team were previously able to show a low density of serotonin 1B receptors in the brains of people with depression."
Studies have shown that low doses of the anaesthetic drug ketamine are rapid acting on certain sufferers, but exactly how it works is unknown.
A nasal spray containing ketamine has recently been approved in the USA and EU for patients with treatment-resistant depression.
For their PET imaging, the researchers used a radioactive marker that binds specifically to serotonin 1B receptors.
They found that the ketamine operated via these receptors in a formerly unknown mechanism of action.
Binding to this receptor reduces the release of serotonin but increases that of another neurotransmitter called dopamine – this is part of the brain's reward system and helps people to experience positive feelings about life, something that is often lacking in depression.
Dr Johan Lundberg, also of Karolinska Institutet, said: "We show for the first time that ketamine treatment increases the number of serotonin 1B receptors.
"Ketamine has the advantage of being very rapid-acting, but at the same time it is a narcotic-classed drug that can lead to addiction.
"So it'll be interesting to examine in future studies if this receptor can be a target for new, effective drugs that don't have the adverse effects of ketamine."
The findings were published in Translational Psychiatry.