Scientists have finally figured out how ketamine works as an antidepressant when other drugs don't.
Ketamine first attracted fans as a party drug, but it's quickly gaining clout as an ideal treatment for depression.
A new study, published in the journal Science Signaling, reveals the much discussed key to ketamine's antidepressant powers. Researchers from Southern Illinois University School of Medicine, Guangzhou Medical University in China, Howard Hughes Medical Institute in Baltimore, and Johns Hopkins School of Medicine found that ketamine alters the presynaptic side of neurons or nerve cells, where the neurotransmitters are, in order to receive messages from another neuron.
This mechanism alters the messages from one neuron to another, explained researcher Ke Zhang. "In our case, ketamine improved this 'message communication' between neurons," he told Motherboard. "The enhancement of neural activity benefits altering the depressing status of the patients."
Clinical trials have shown that a single dose of ketamine (.5 to 10 milligrams/kilogram) significantly curbed depressive symptoms within 72 hours, corresponding author Xiang Cai told Motherboard. The results were measured by the Hamilton Depression Rating Scales, a standard evaluation for depression.
"Compared with traditional antidepressants, the antidepressive-like actions of ketamine are persistent and fast," Cai said.
In the study, the researchers combined electrophysiological recording, which measures the flow of ions in biological tissues, with analysis of rodent behavioral responses. They also looked for molecular changes, and tested the ketamine's effect in vivo. They tested ketamine on mice genetically adjusted to have certain genes, or to not have the genes out, to investigate the role of specific molecules in ketamine-induced fast antidepressant effects.
Ketamine has been an FDA-approved anesthetic for half a century, Cai noted. It is already commonly used in clinics as a an antidepressant when other treatments have failed, as well as a "dissociative analgesic" for pain management, which means it induces a feeling of detachment and functions as a painkiller. But high amounts of ketamine have been associated with neurotoxicity and damage to other body systems.
"Ketamine as a 'club drug' may also raise serious addictive problems," Cai said.
Ketamine's antidepressant actions are also the subject of great controversy, but not because it's a recreational drug. "Before our study, there are different opinions about the molecular mechanism of how the antidepressant actions of ketamine," he said.
One group holds that ketamine reduces the power of inhibition system in the brain and results in enhanced excitatory system, while another group thinks ketamine directly enhances excitatory system. Cai said his group's study shows that ketamine indeed enhances "excitatory synaptic transmission," in the hippocampus, which helps the brain with antidepressant actions and consolidating memories.
Ketamine is gaining momentum and recognition has an effective antidepressant in cases where other treatments have failed. But, like marijuana or MDMT, it may take a while to be integrated into the larger health system.
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