Scientists announced they have unravelled how the anaesthetic-turned-club drug known as 'Special K' can ease depression in humans.
Ketamine, which can also cause feelings of detachment, could pave the way for new treatments for people suffering from depression, the researchers added.
Their study, published in the Archives of General Psychiatry, found ketamine restores to normal the orbifrontal cortex, an area of the brain located above the eyes that is overactive in depressed people.
The area is believed to be responsible for feelings of guilt, dread, apprehension and physical reactions such as a racing heart, said Bill Deakin, who led the study.
'The study results have given us a completely novel way of treating depression and a new avenue of understanding depression,' said Deakin, a neuroscientist at the University of Manchester.
Depression is a leading cause of suicide and affects about 121 million people worldwide, according to the World Health Organisation.
In their study, Deakin and his team gave intravenous ketamine to 33 healthy male volunteers and took minute-by-minute brain scans to see what was happening as the drug took effect.
Images from the scans showed that the drug, which was originally developed as a battlefield anaesthetic during the Vietnam War, worked quickly, Deakin said.
The results were surprising because the researchers had expected that the ketamine would instead affect the part of the brain that controls psychosis, he added.
'There was some activity there but more striking was the switching off of the depression centre,' Deakin said.
Previous research had shown that ketamine improved symptoms in depressed people after just 24 hours, far faster than the month it can take for Prozac to kick in, but until now they did not know exactly how.
The latest findings give researchers a specific target to design new drugs and offer hope for the many people who do not respond to Prozac or other standard medicines, Deakin added.
Prozac was initially introduced by U.S. drugmaker Eli Lilly and Co in 1987 and belongs to a class of compounds called selective serotonin reuptake inhibitors (SSRIs). It is now off patent and widely available generically as fluoxetine.
'Many people don't respond to treatment,' he said in a telephone interview. 'This offers a potential way of treating them.'