Breaking News! Ketamine’s Rapid Relief Depression

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In the last 15 years or so, breakthroughs led to experimental trials, then grew into more widespread use that seemed to be turning a corner on this long, arduous, uphill climb.

Barbaric treatments that all but put a depressed person out of commission gave way to less overwhelming medications and therapies that only helped some depressed patients. Suicides continued or increased.

Ketamine's rapid relief of depression represents a groundbreaking advancement in mental health treatment, offering hope to individuals who have struggled with treatment-resistant depression. Unlike traditional antidepressants, which may take weeks or even months to produce noticeable effects, ketamine has been shown to alleviate symptoms of depression within hours or days for many patients.

The rapid onset of action of ketamine is particularly significant for individuals experiencing severe depressive symptoms or those at risk of self-harm or suicide. By providing almost immediate relief, ketamine infusion therapy can offer a lifeline to individuals in acute distress, potentially saving lives in the process.

Moreover, ketamine's mechanism of action differs from that of traditional antidepressants, targeting the brain's glutamate system rather than the more commonly targeted serotonin or norepinephrine systems. This novel approach makes ketamine a promising option for individuals who have not responded to other treatment modalities, offering new hope where traditional treatments have fallen short.

Additionally, ketamine infusion therapy is generally well-tolerated, with few significant side effects reported. This makes it a viable option for individuals who may have experienced intolerable side effects from other antidepressant medications or who have medical conditions that contraindicate the use of certain drugs.

Overall, ketamine's rapid relief of depression represents a transformative breakthrough in mental health care, providing a new avenue of treatment for individuals who have not found relief from conventional therapies. As ongoing research continues to elucidate ketamine's mechanisms of action and refine treatment protocols, its potential to revolutionize the treatment of depression and other mood disorders becomes increasingly apparent.

But research pushed forward. Then, a small group tried an anesthesia medication on depressed patients and… Eureka! They felt better. And a new era began. More about that in a moment… but first, let’s take a look back…

Over 5000 Years to Crack the Depression Code Since the beginning of civilization, people have sought a solution to depression.

As far back as 2000 BC, in the ancient civilization of Mesopotamia, where psychiatric disorders were believed to be caused by demonic possession and were treated by priests rather than physicians.

Then, around 400 BC, Hippocrates, known as the father of medicine, called it melancholia and theorized its cause was an excess of black bile in the spleen. He gets credit for being the first physician to declare that illness was caused by physical problems in the body rather than gods or spirits.

Hippocrates offered treatments like blood-letting, among other things. But … he was trying to find help for his patients.

These meandering beliefs and others have accompanied the quest to understand the cause of depression and to find remedies that actually work.

IV Ketamine is Depression’s BREAKTHROUGH It’s only now, in the 21st century, that breakthroughs, knowledge, and effective treatment are emerging and gaining momentum.

We’ve learned a ton about ketamine in the past few years, and it’s important to keep it straight. Really understand it.

For instance, we’ve learned that it turns on mRNA which switches on DNA to infuse dynamic growth into the brain-derived-neurotrophic-factors (BDNF).

And that the BDNF is like a compost of sorts, that richly empowers the neurons (brain cells) to proliferate densely with branches and connections that double, triple, quadruple and turbo-charge the development of more synapse connections and branches.

We’ve learned that IV ketamine slides G proteins off the lipid rafts they’re piled upon in the cell membrane…and that gives the Gs the freedom to enhance the transmission of signals throughout the brain, which reverses depression. And we’ve learned that ketamine causes these things to take place fast. Within hours. We’ve learned it does all this in minuscule doses, much smaller than the doses used in anesthesia.

IV ketamine infusions have brought a dawn of new hope for patients with psychiatric mood disorders, and there’s more.

In addition to all this, ketamine also stops – erases – suicidal thoughts in 4 hours or less. We’ve never had any treatment that could do that. IV ketamine treatment is saving lives. Every single day.

And now, the hardworking and dedicated neuroscientists who’ve been studying, testing, and researching ketamine around the globe have made a breathtaking discovery.

Ketamine’s Rapid Relief of Depression: It BLOCKS Neuronal Bursts in the Lateral Habenula (LHb) We now know that IV ketamine blocks the bursts of brain cells in the lateral habenula that drive depression. This area is often called the “anti-reward” area of the brain because it prevents the reward area of the brain from functioning properly.

Ok, yes, I get that it sounds like Greek. Lateral habenula…who ever heard of it?? It’s not Greek, it’s Latin. Stay with me.

The lateral habenula is located deep in the center of the brain. And there are actually two. A right lateral and a left lateral habenula…connected to the hindbrain by nerve pathways. When viewed from above, this system looks something like a horse bridle, if the hindbrain is the horse’s nose, and the pathways are reins.

For this reason, the structure the nerve pathways connect to is named after the Latin root word for “rein.”

But that’s where the reference to equestrian activities ends. The habenulae, as in both of them, are part of the limbic system, which regulates emotion, motivation, learning, and memory.

Now, if you do something hoping for and expecting a reward — and the reward doesn’t happen — neurons in the LHb burst in rhythmic patterns to dampen the sense of reward. The idea is to help the brain understand to let go of the hope of reward and move on to something else.

The Problem with Bursting Cells But here’s the problem. When you’re depressed, those bursting cells go overboard, bursting far too much and too fast. And rather than just dampen expectation of reward, their bursting dampens everything. It renders you hopeless. Until you’re in despair.

A team of neuroscientists led by Hailin Hu, did a series of very elegant studies to see the effect of ketamine on the lateral habenula.

And it was pretty spectacular.

Working with laboratory animals, the team induced a depression-like condition on some of them. The depressed ones moved into despair so severe that they didn’t even try to survive in a severely stressful situation — they just gave up.

In this condition, researchers observed that a small portion of the neurons in their LHb fired in repetitive bursts in far greater numbers and speed than the LHb of normal, non-depressed mice. This overly excessive bursting of anti-reward rapid fire worsened their depressive condition.

Researchers also found that when the mice had gone through severely stressful experiences, they also had these quick rapid-fire bursts in far greater numbers than mice who were comfortable.

So severe depression and severe stress both resulted in an overabundance of rapid-fire anti-reward signals that drowned out any benefit from the reward center in their brains.

But look what happened: After researchers dosed the stressed, depressed, despairing mice with ketamine, the rhythmic bursting slowed way down… to almost normal. Which allowed the reward center to shower the mice with serotonin and dopamine and they quickly felt better.

Then, to test that response, the researchers forced those bursting cells to fire, and even when they did, the mice who had ketamine still showed no signs of depression.

Exciting, isn’t it??

Ketamine’s Rapid and Robust Antidepressant Effect So we’re beginning to understand how ketamine can act so fast. It releases the reward areas from those strong anti-reward signals. And the reward signals of dopamine and serotonin are able to find their mark and make you start feeling better very quickly.

All this suggests that as more medications for mood disorders are developed, medications that block the LHb anti-reward bursts could also effectively relieve depression. That opens all kinds of new ideas for researchers to pursue for depression relief.

We’re finally getting down to what really works. It’s about time. We’re finding new solutions for mood and anxiety disorders.

We’re learning more all the time. This new study has opened more doors and windows about another extraordinary benefit of IV ketamine treatment. The power to block the bursting, to stop the work of the anti-reward bursts, means that it can lift the brakes that have prevented you from feeling showered with relief, joy, and gratitude. When burst firing stops, you begin to flourish.

It’s just one more way ketamine works to smash depression.

If you suffer from depression, anxiety, panic disorder, social anxiety, bipolar disorder, PTSD, OCD, or suicidal thinking, IV ketamine treatment can relieve you so you can live a fulfilling and productive life again. You can enjoy initiative, creativity, motivation, joy, resilience… and you can function.

Tired of the sadness, numbness, anxiety, fear, emotional pain, mood swings, or thoughts of death? Call us. We can help you feel better, live better…and have hope for the future.

References https://www.loricalabresemd.com/blog/ketamines-rapid-relief-of-depression/

DEPRESSION IS A SERIOUS MOOD DISORDER

Depression is a serious mood disorder with symptoms that include prolonged periods of sadness, hopelessness, and irritability. The symptoms can affect how you feel, think, and handle daily activities. Depression is usually treated with medications, psychotherapy, or a combination.

Chronic stress can lead to symptoms of depression. Studies in animals have shown that chronic stress also leads to the loss of communication between brain cells (neurons) in the prefrontal cortex area of the brain. The neurons lose dendritic spines, the small outgrowths on brain cells that receive signals from neighboring neurons. This leads to altered communication between brain cells.

Earlier this year, the FDA approved a form of the drug ketamine to treat depression. Ketamine is a fast-acting antidepressant that relieves depressive symptoms in hours instead of the weeks or longer that previous drugs required. In addition to being a major advance in treatment, ketamine provides an opportunity for researchers to investigate the short- and long-term biological changes underlying its effects on depression.

A research team led by Dr. Conor Liston of Weill Cornell Medicine investigated how ketamine affects the brain after mice experience chronic stress. They used high-resolution imaging to focus on neurons in the prefrontal cortex. The study was funded in part by NIH’s National Institute of Mental Health (NIMH). Results were published in Science on April 12, 2019.

The researchers examined neurons in the prefrontal cortex of mice exposed to long-term stress. They found that mice showing behaviors related to depression had an increased loss of, and decreased formation of, dendritic spines in their prefrontal cortex compared with mice not exposed to stress.

Dendritic spine remodeling. Images taken at baseline, after chronic stress, and after a single dose of ketamine. Red arrows point to eliminated spines; blue arrows to new spines, Conor Liston, Science

Treatment with ketamine rapidly relieved the abnormal behaviors in the stressed mice. The drug also quickly restored the coordinated activity of prefrontal neural circuits that were disrupted by chronic stress. However, the researchers found that ketamine didn’t work by halting the stress-induced spine loss. Instead, the drug led to formation of new functional spines.

The initial effects of ketamine on mouse behavior occurred independenily of its effects on spine formation. While the drug affected behavior within three hours, formation of the new spines took 12 to 24 hours. Formation of spines in the mice correlated with their behavior two to seven days after treatment. Further experiments showed that the newly formed spines were crucial for sustained reversal of the negative effects from stress. When the ketamine-induced spines were eliminated, the mice again showed depression-like behaviors.

These insights into ketamine’s effects on brain circuits could guide future advances in managing mood disorders. “Our results suggest that interventions aimed at enhancing synapse formation and prolonging their survival could be useful for maintaining the antidepressant effects of ketamine in the days and weeks after treatment,” Liston says.

https://www.nih.gov/news-events/nih-research-matters/how-ketamine-relieves-symptoms-depression

Ketamine and Weaning of Psychiatric Medications Ketamine treatments can be useful in the process of tapering or discontinuing psychiatric medications. This is due to the phenomenological and neurobiological effects of ketamine and the durability of the experience even after the treatment session has passed. ** Neurobiological Effects**

There are many resources that explore the beneficial neurobiological (physical) effects of ketamine in more detail, but the primary area of focus is that ketamine can have positive effects on the brain itself by increasing the overall health, growth, and resiliency of the brain. This can help an individual regulate their emotions, create new behavioral patterns, and maintain this new baseline of health in the long term. Ketamine can facilitate this process through a few mechanisms:

Upregulating Neuronal Production - Ketamine increases the production of new neurons, supplying the brain with healthy and vital neurons. This is the basis for more effective and harmonious connections in the brain

Upregulating Release of BDNF (brain-derived neurotrophic factor) - BNDF, colloquially referred to as ‘fertilizer for the brain’, helps promote neuron growth, overall health, and ongoing maintenance.

Stimulating mTOR - mTOR regulates many processes involved in cell growth and healing worn out synaptic connections. It also stimulates activity/growth in the prefrontal cortex and hippocampus, areas essential for emotional regulation.

Phenomenological Effects

Alongside the neurobiological effects, ketamine also presents immediate and long term phenomenological (mental and emotional) effects. Some of the benefits include:

Novel Insights - With dissociation comes a sense of being separate from yourself. This perspective allows individuals to spot certain behavioral patterns, environmental triggers, or see how they act in a new way. These insights can catalyze a short-term respite or a long-term positive behavioral/mood change.

Embodied Feelings - The ketamine experience can induce a number of embodied emotions/feelings. For those with depression, having an embodied experience of joy, calm, contentment, or elation can be a powerful reminder or positive reinforcement that these states are available to them. This can affect long-term perspectives and actions.

Cognitive Distancing - Both during and after (for a brief window) a ketamine session, it’s possible that individuals may notice more ‘space’ between an external stimulus and their internal reaction to it. This space can provide the room to change behavior and remove automatic self-sabotaging habits.

The combination of neurobiological benefits and significant phenomenological experiences creates a favorable context for an individual to feel better and move closer towards healing and wholeness. This experience in patients often creates the circumstances that lead them to begin questioning whether or not its possible to wean off of or completely discontinue their psychiatric medications. This is paired with what is called the “durability” of the ketamine experience in which these benefits are not only experienced during the dosing session, but can last upwards of 7-10 days after the session. If a comprehensive tapering schedule is paired with the ketamine therapy protocol, the positive benefits of a ketamine treatment can help equip an individual to better handle the direct and side effects of weaning off of psychiatric medications.

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