Ketamine is currently the only fully FDA-approved psychoactive compound for clinical treatment of depression and for good cause.
Within hours of an initial dose, ketamine has been shown to reduce suicidal thoughts on as many as two-thirds of patients with results lasting for several weeks.
While these results are truly impressive and replicable, the exact mechanism of ketamine's anti-depressant effects is not yet fill known. A recent article by Science Alert explores the new research findings that might explain the inner workings of this treatment.
"Some scientists think ketamine's therapeutic power relies on its influence over glutamate, a neurotransmitter that is secreted by the ends of certain neurons in the brain. But while ketamine appears to increase glutamate release in some parts of the brain in both mice and humans, in other parts of the mammalian brain, the drug seems to decrease this release.
"Elevated glutamate release has been linked to stress, depression and other mood disorders, so lowered glutamate levels may explain some of the effects of ketamine," explains neuroscientist Per Svenningsson from the Karolinska Institutet in Sweden.
Now, new results from experiments on mice and their neurons further support that hypothesis - at least for the prefrontal cortex, which is connected to complex cognitive behavior and the modulation of emotion." reports Science Alert.
Researchers have discovered that ketamine seems to reduce the glutamate levels in laboratory mice almost immediately
Measuring glutamate levels among free-moving and anesthetized mice, Svenningsson and colleagues have found ketamine reduces the persistent release of this neurotransmitter almost immediately.
"These effects could contribute to the efficacy of ketamine to instantly alleviate depressive symptoms and suicidal ideation, taking into account that excessive glutamate levels have been linked to MDD and other mood disorders," the authors write.
Further analysis under the microscope suggests ketamine acts on the neurons that usually receive glutamate, causing these cells to release more of a neurotransmitter called adenosine.
Adenosine then enters the space between neurons, known as the synapse, to tell the presynaptic neurons to stop producing so much glutamate.
When researchers blocked ketamine receptors on the postsynaptic neuron to test its role, they were able to completely prevent the decrease in glutamate from the presynaptic neuron."
Researchers are currently attempting to see if they can isolate the effects of ketamine on glutamate and adenosine as a potential pathway to offer the treatment without the psychoactive effects of ketamine which are a barrier for some patients with low tolerance to altered states.
