How Ketamine Works
Since Ketamine Clinics Los Angeles opened in early 2014, our knowledge and understanding of ketamine infusion treatment for mood disorders has expanded significantly, much in thanks to the scientific and medical community’s developments. Additionally, we have exclusively focused on providing IV Infusions of ketamine for depression and other mood disorders full time since we opened, enabling us to gather significant data and real world experience during the administration of 14,000 infusions. Researchers continue to explore all of the ways in which ketamine infusions impact the mind and brain while doctors and therapists are exploring how the actual infusion experience changes people’s perceptions of themselves and the world around them in such a rapid, profound way.
Before we explain the science, it’s important to understand that this information is exclusive to intravenous ketamine infusions in which the medication is given gradually, via IV, at a sub-anesthetic dose. This route of administration (ROA) is crucial for achieving the maximum therapeutic effect and safety of ketamine for depression, PTSD and other mood disorders. IV infusions of ketamine comprise approximately 90% of all available research on ketamine to date.
Ketamine IV Infusion for Depression and Other Mood Disorders
Ketamine is a decades-old medicine long esteemed for its use as an anesthetic and analgesic, and is now breaking barriers as an effective treatment for depression, suicidal thinking, anxiety, PTSD, OCD, and other mood disorders. Since ketamine’s antidepressant effects were first documented at Yale University in 1999, more than 140 clinical ketamine trials have been conducted proving the efficacy of ketamine IV therapy for depression, with 65 of them sharing published results, as of 2022. The real question is no longer “does it work” but “how does it work?”
Ketamine IV Infusion Therapy works by enhancing the functionality of certain receptors in the brain that regulate how the brain processes thoughts and emotions. On a cellular level, ketamine works to restore and repair synaptic connections in the prefrontal cortex that have been found to be depleted in patients with depression and other mood disorders. By generating synaptic connectivity in the prefrontal cortex and normalizing the abundance of neuronal connections, ketamine repairs atrophied neurons, forms new neural pathways, and enhances neuroplasticity.
Is Ketamine Right For Me?
Ketamine and Neuroplasticity
While scientists continue to research and theorize why ketamine is so effective at easing depression symptoms, there is much that remains a mystery. Much of ketamine’s antidepressant mechanics are thought to lie in its ability to enhance neuroplasticity, the body’s ability to reorganize and adapt itself by creating new circuitry and neural connections. Furthermore is ketamine’s unique ability to initiate synaptogenesis, or repair and create new synaptic connections within the parts of the brain responsible for regulating mood and emotions.
The Pharmacokinetics of Ketamine
Each and every action, thought, and emotion you experience are the result of billions of neurons firing in your brain every moment of every day. The space between these connecting neurons, the synaptic cleft, is where neurotransmitters like serotonin, dopamine, and glutamate move from one neuron to the next. It’s within this small gap between the two neurons that the antidepressant effects of ketamine are catalyzed. It’s also causal, on a grander scale, to your thoughts, emotions, what you perceive as your reality, and how you engage with the world around you.
Neurotransmitters come in two forms: excitatory and inhibitory. Excitatory transmitters increase the likelihood that a neuron will fire an action potential, or, in layman’s terms, begin transmission into the next neuron. Inhibitory transmitters slow a neuron and make it less likely to fire an action potential, or slow the transmission into the next neuron. Glutamate is one of the most abundant excitatory neurotransmitters in the brain and plays an important role in cognition, learning, and forming memories. Early studies of ketamine neurotransmitters showcase the transmission of glutamate is much less apparent in the brains of depressed patients when compared to nondepressed controls.
Each neuron has a number of different binding sites for glutamate, but the two most significant in regards to ketamine are the NMDA receptor (N-methyl-D-aspartate) and the AMPA receptor (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid). These receptors are two of the many channels through which a signal can be transmitted. Ketamine acts as an NMDA receptor antagonist and binds to NMDA receptors, inhibiting the action of glutamate, while simultaneously increasing its quantity. Meanwhile, glutamate instead binds to the adjacent AMPA receptors while ketamine induces the neuron to produce additional AMPA receptors. The result is an abundance of glutamate, activated alternatively by AMPA receptors rather than NMDA receptors.
Increasing glutamate levels while also shifting the activation from NMDA to AMPA receptors initiates a unique cascade of events that help to explain ketamine’s efficacy in treating mood disorders. Through this, ketamine increases the release of BDNF (brain-derived neurotrophic-factor), a protein necessary for the health of neurons and important in learning and memory. Ketamine IV infusions also stimulate the mTOR (mammalian target of rapamycin) signaling pathway, a structure important in regulating the cell cycle and physiology, and necessary for cell growth and long-term memory. The increase in ketamine BDNF paired with the stimulation of mTOR caused by the infusion process improves synaptic connectivity in parts of the brain associated with emotional regulation.
Ketamine’s activity within the brain extends further than its inhibition of glutamate neuroreceptors. Studies suggest that ketamine also activates eEF2 (eukaryotic elongation factor 2) and GSK-3 (glycogen synthase kinase 3), two very important messenger systems involved in the production of both BDNF and mTOR in their own unique ways. Through a series of protein synthesis these systems trigger reversal of depression symptoms and help stabilize mood to give ketamine its unique antidepressant properties.
Outside of the Brain and into the Mind
In addition to the chemical processes that demonstrate ketamine’s effectiveness, the dissociative state induced by the medicine often leads patients to profound positive shifts in psyche and consciousness; this is the infusion experience. The experiences people have during their infusions can be invaluable and instrumental in their healing and much less easily explained by science. Each individual has a unique journey and even among individuals, each infusion is different from the one prior. So many variables outside of the clinical protocol come together (mindset, setting, mood, your schedule, life circumstances, etc.) to produce the infusion experience. Many patients report feeling part of something greater than themselves, a sense of closure and compassion towards trauma and other life experiences, feelings of compassion towards self, out-of-body experiences, etc. While harder to measure than neurotransmitters, there is a correlation between the experience one has during an infusion and the benefit they receive after.
At Ketamine Clinics LA, we strive to find the sweet spot in the rate of infusion between “not altered at all” and “completely sedated.” Therewithin lies an opportunity for a quieting of the mind, specifically a part called the default mode network (DMN) which is the endless internal chatter we all endure, and unobscured thoughts and feelings to arise. The experience can be beautiful, spiritual, relaxing, reflective, peaceful, and it can also be difficult, sad, or even troubling at times. But when enabling a ketamine DMN, the great thing is that even a difficult infusion is not a “bad” infusion, as most of the time what comes up during that one hour of time and space away from everything else in a patient’s life, is exactly what that person needed. Perhaps these realizations come as a direct result of a ketamine default mode network.
How Long Does Ketamine Take To Work For Depression?
Many patients who undergo Ketamine IV Infusion Therapy begin to find relief from their symptoms in as few as 1-3 infusions, however it is most common to start feeling the beneficial effects after 3-4 infusions. As depression is a heterogeneous condition that is experienced differently among individuals, relief can also look different for each person. Many report a general feeling of returning to wellness, and an increase in function and productivity. Cognition may feel sharpened, and a lift of “mental fog” is often reported early on in the initial series. These feelings influence an elevation in mood, increased motivation, energy, and a more positive outlook on life. The dread and sorrow that once clouded patients’ days may be replaced with feelings of joy, contentment, acceptance and optimism. People start seeing what was once a dark and gray world as a bright spectrum of colors.
Ketamine’s antidepressant effects last long after the infusion is turned off and the medicine is cleared from the body. The benefits are often felt for many weeks, if not months beyond the final infusion date. At KCLA, patients average 2-3 months of relief, with some going much longer. It is common for patients who implement positive lifestyle changes to achieve 6 months of relief. A small handful of patients have gone more than 2 years before requiring any follow-up care. Some of the lifestyle optimizations we recommend are engaging in talk therapy, establishing a regular exercise routine, eating a healthy diet, practicing good sleep hygiene, and fostering positive interpersonal relationships. Ketamine often serves as the catalyst to a life free of depression, and long-term remission is possible for many people.
Ready to begin your Ketamine IV Therapy experience? Contact KCLA today for any questions regarding our treatment process to become a patient. All inquiries are confidential and all consultations are free.
Lauren – Mother of PTSD and depression patient
I saw my son once again.
Although all the medical treatment Matt has received was valuable in some way, the only time in 16 years I saw the person who is my son once again quietly emerge, was after the ketamine infusions.
Allen – Engineer
My successes have been phenomenal.
I have cut down on my Effexor to 75 Mg per day. I have eliminated lithium from my regiment and haven’t needed ambien for about month now to sleep. My klonopin I’ve reduced to once every other day. The infusions really helped my depression and chronic pain in my neck. My depression has never been better and I am cutting down on my other medications with great success. Thank you, thank you Dr. Mandel!
Katharine – Registered Nurse
When I found Ketamine Clinics of Los Angeles,
When I found Ketamine Clinics of Los Angeles and began to research the treatment, I felt my spirits lift. I felt hope. From the moment I called their office, I knew I was in good hands. As someone who works in healthcare, I couldn’t believe how kind and attentive Dr. Mandel and his entire staff were. I know they really care about me. The treatment is the only thing in more than 30 years that has produced such rapid and dramatic improvement in my mood.
Keith – Lawyer
My doctor recommended that I try ketamine
My doctor recommended that I try ketamine at this time because he considers that there is now enough clinical information to make an informed decision about its effectiveness and side effects, and specifically recommended Dr. Mandel, who even with a glowing recommendation from someone for whom I have tremendous respect, vastly exceeded all of my expectations.
Alex – Teacher
Dr. Mandel has truly made my unlivable life, livable again.
Dr. Mandel has truly made my unlivable life, livable again. My ability to get out of bed early and or nearly right as I wake up has significantly improved. I’m able to keep up with my incredibly hectic schedule. My overall mood is high and lethargy is low. My social anxiety is at an all time low, and I haven’t had a panic attack since my first infusion.