Ketamine and depression
According to Dr. John Krystal, ‘ Ketamine is thought to exert antidepressant effects by disinhibiting the release of glutamate by the presynaptic neuron .’ 1 This antagonism triggers a cascade of events; brain cells initiate the release of an additional neurotransmitter called glutamate, which then interacts with AMPA receptors. This engagement sets forth a sequence that ultimately culminates in the growth of new synapses – the connection between brain cells. In the words of Dr. Lisa Monteggia, an American neuroscientist, ‘ One way of thinking about it is that the ketamine has reset the normal activity that was disturbed .’ 2 Predominantly, ketamine’s ability to restore NMDA receptor functioning and augment synaptic plasticity presents the potential for the rewiring of neural circuits compromised by depression. As the brain’s communication pathways regain their balance, it is possible that individuals may experience a notable alleviation of depressive symptoms.
Glutamate pathways and neurotransmitter balance
Glutamate is an excitatory neurotransmitter that plays a significant role in upholding balanced levels within the extracellular region. ‘ Just about every circuit in the central nervous system uses glutamate, so, in theory, drugs that target glutamate signalling have the potential to treat almost any brain disorder .’ 3 This statement by Emily Singer suggests a well-balanced glutamate level is essential for optimal brain function and mood management. Even so, the brain can sometimes produce too much or too little glutamate, which can contribute to mood imbalances and the onset of depressive symptoms. Thus, ketamine interferes to restore the balance by obstructing NMDA receptors and modulating glutamate’s impact ; depressive feelings can be potentially alleviated when the glutamate level is adjusted. Through its role in fine-tuning glutamate levels in synapses, ketamine possesses the capacity to recalibrate the br ain’s mechanisms of mood modulation. As Sam Wong states : ‘D epression affects the structure of neurons, and glutamate helps to repair the damage. ’ 4
Synaptic connections and the BDNF pathway
The human brain is a vast communication network where neural connections act as channels, enabling the transfer of information among brain cells. Their importance spans across memory generation and emotional stability. Regarding depression, disruption can take place along these neural routes, and they will be blocked, impeding smooth information transmission, and profoundly affecting mood. This is the point at which ketamine comes into play with its distinctive attributes. Brain-Derived Neurotrophic Factor (BDNF) is a protein that fosters and reinforces neural connections. Picture it as a proficient maintenance team with the responsibility of preserving these vital pathways in an optimal condition. BDNF levels might decrease when faced with depression, affecting the 1 Krystal, J. Rapid-acting glutamatergic antidepressants: the path to ketamine and beyond. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3671489/. Consulted: 15/8/23. 2 Szalavitz, M. Tackling Depression with Ketamine . https://www.newscientist.com/article/mg19325876-600- tackling-depression-with-ketamine/. Consulted: 15/8/23. 3 Singer, E. The Master Switch . https://www.newscientist.com/article/mg18124375-400-the-master-switch/. Consulted: 16/8/23. 4 Wong, S. Ketamine . https://www.newscientist.com/definition/ketamine/ Consulted: 16/8/23.
141
Made with FlippingBook - PDF hosting