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.
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.
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.
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.