top of page
Search
Writer's pictureJohn F. Calabrese

Ketamine, Synaptic Plasticity, and Cognitive Therapy:

Updated: May 6, 2022


Inducing Synaptic Plasticity in the Treatment of Cognitive Dysfunction


Ketamine was originally introduced into clinical medicine as an anesthetic. It had significant benefits. Namely, it produced a profound analgesia without the respiratory depression associated with other anesthetic medications. Ketamine, however, does cause other effects through its action on a wide array of brain receptor sites. Some of these receptor variants cause cognitive, psychotropic, and emotional side effects that have limited its clinical use. Interestingly, its action at some NMDA-type glutamate receptors has shown a previously unappreciated effect: synaptic nerve growth. The Long Term Potentiation (LTP) of these NMDA-type receptors is thought to be the basis for the maintenance and enhancement of brain nerve circuitry. Moreover, persistent LTP specifically at amino-hydroxy-methyl-isoxasole (AMPA) receptors enhances post-symaptic action potentials and normalizes connectivity between multiple brain areas. Ketamine also increases the effects of brain-derived neurotrophic factor (BDNF). BDNF stimulates gamma-wave brain oscillations associated with higher cognitive functions, and reduces the symptoms of clinical depression.


These findings have important implications for us as we try to understand brain function and recovery from injury. You see, historically the brain was thought to undergo minimal changes after late childhood. Now the continuous changeability of brain neural networks is accepted as a defining feature of the brain function. We refer to this changeability of neural networks as “neural plasticity”. It is a natural part of brain activity where neural connections are being altered by perceptual experience, memory consolidation, and in recovery from brain injury and diseases. The brain is pruning old and sprouting new synaptic connections. It is essentially rewiring itself, and Ketamine enhances that process by stimulating synaptic growth. Another benefit of Ketamine is its anti-inflammatory effects. Those effects may be useful in the treatment of brain degenerative diseases such as Alzheimer’s and Parkinson’s, where immune-inflammatory cell activity at the synaptic cleft contributes to disease progression. The goal in treating with Ketamine is to stimulate synaptic growth at high density NMDA receptor areas, and reduce the accumulation of immune-inflammatory cell waste material at the synapse. Potentially, Ketamine can contribute to those treatment goals.


Recently a novel Ketamine therapy for cognitive dysfunction has been introduced. It is designed as a combination therapy to enhance synaptic plasticity and long-term Cognitive Therapy outcomes. In this model, an extended series of IV Ketamine infusions are followed in 24-48 hours (the peak post-infusion synaptic growth period) with Cognitive-Behavioral Therapy and Cognitive Performance Deficit Training. The goal is to stimulate the synaptic growth with IV Ketamine and increase the persistence of neural circuitry created during post-infusion Cognitive Therapy. This model may be beneficial in the treatment of traumatic brain injury (TBI), post-traumatic stress (PTS), brain disease dementias, mild cognitive impairments (MCI), and major depression.


Assessing the benefits of this these treatments will require outcome research. A good starting place may be research that examines IV infusion and therapy protocols for specific types of cognitive dysfunction. We will discuss this research here as it emerges. Any comments on this discussion or contributions on new outcome research findings will be appreciated by all. Please contribute.



19 views0 comments

Recent Posts

See All

Why Ketamine by IV Infusion?

Ketamine is a very unique medication. It has multiple effects and uses. This characteristic makes the effects of Ketamine very patient...

Ketamine Infusion for You?

1. When choosing a provider, always start by confirming that a physician with advanced medical residency training in the use of IV...

Comments


bottom of page