Ketamine may rapidly relieve depression by blocking overstimulation of the lateral habenula

 Ketamine and the Lateral Habenula, the Brain’s Reward Center

Ketamine may rapidly relieve depression | Los AngelesThe medical community is increasingly excited by the ever-growing body of scientific literature exploring the unique anti-depressive effects of the well-known anesthetic ketamine. Many of these studies have focused on the effectiveness of Ketamine Infusion Therapy—a type of treatment in which ketamine is slowly delivered directly into the blood stream in sub-anesthetic doses—and the results are promising: they demonstrate that most patients experience a very rapid decrease in depressive symptoms, while experiencing minimal negative side effects.

What seems to be less well understood is how ketamine interacts with the brain to relieve depression. Some studies have focused on ketamine’s role as an NMDA receptor antagonist and an AMPA receptor stimulator guiding levels of the neurotransmitter glutamate within the brain. Other studies seem to indicate that ketamine may activate the opioid system in addition to the glutamate system.

Most recently, an article published in Nature suggests that ketamine may have an entirely different mechanism of action. This study suggests that ketamine may work by blocking bursts of neuron activity in the lateral habenula; overstimulation of the lateral habenula seems to be linked to depression and depressive symptoms. This exciting study offers yet more evidence that Ketamine Infusion Therapy may indeed present one of the greatest breakthroughs in the treatment of depression in recent decades!


What is the lateral habenula and how is it linked to depression?

The lateral habenula is one of two small swellings found in the epithalamus area of the brain, near the pineal gland (the two swellings together are the habenulae, traditionally divided into the lateral and medial habenula.) The habenulae seem to be one of the areas of the brain responsible for reward processing because of its involvement in the release of dopamine and serotonin. Put simply, when our brain receives a “reward”, the brain increases dopamine activity, which helps the brain remember that reward as a positive stimulus. When a reward is smaller than expected, the habenula seems to become more excited, while when the reward is larger than expected, the habenula seems to become less excited. Moreover, the habenula seems to become more activated when we respond to a punishment or negative stimuli; therefore, scientists hypothesize that the lateral habenula in particular is responsible for helping us learn how to avoid negative or unpleasant experiences.

Although the exact mechanisms are not as yet fully understood, there seems to be a link between hyperactivity in the lateral habenula and the pathophysiology of depression. There is some evidence that neurons within the lateral habenula have excessive bursts of activity during episodes of depressive symptoms. In some cases, structural abnormalities of the lateral habenula have been identified in some individuals suffering from severe depressive disorders. In other words, evidence from both animal and human studies seems to indicate that overstimulation of the lateral habenula may be associated with depressive symptoms, including helplessness, lack of pleasure, pessimism, and general depression.


How Does Ketamine Impact the Lateral Habenula and Depression?

The recent study published in the journal Nature hypothesizes that ketamine may work by blocking the bursts of activity within the lateral habenula driving depressive symptoms and depression. The study theorizes that the increased burst-like firing of neurons in the lateral habenula are driven by NMDA receptor activity; therefore, as an NMDA receptor antagonist, ketamine helps to prevent these particular neurons from firing inappropriately. In other words, its ability to block the brain’s overactive response to negative stimuli may explain its rapid anti-depressive impact on the brain. This exciting avenue of research is likely to lead to a far greater understanding of the complex mechanisms of the brain, especially as related to depression, mental illness, and mood disorders, which in turn will offer us truly promising treatment options—like Ketamine Infusion Therapy—for individuals whose lives have been disrupted by depression and other mental illness.


Contact Ketamine Clinics of Los Angeles

If you or someone you love is struggling with depression and you believe IV Ketamine Infusion Therapy might offer a solution, we encourage you to contact Dr. Steven L. Mandel at Ketamine Clinics of Los Angeles immediately to find out if IV Ketamine Infusion Therapy may offer a solution.

Please visit our website at or contact us at 424-343-8889 to schedule an appointment.
For more information about Ketamine Infusion Therapy treatments for depression, bipolar, anxiety, post-traumatic stress disorder (PTSD), obsessive compulsive disorder (OCD), fibromyalgia, pain syndromes and other conditions contact us at Ketamine Clinics of Los Angeles in Southern California (Orange County) by clicking here or calling  310-270-0625.

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