ABSTRACT
Ketamine has a unique ability to quickly reverse severe depression in individuals who have failed standard treatments. One of the drawbacks in using ketamine for anesthesia has been the frequent reports of adverse psychiatric side effects. Descriptions of the ketamine experience gleaned from online conversations among recreational users include: “It’s the one of most insanely bizarre and alien experiences.” Ketamine activates the mammalian target of rapamycin (mTOR), inhibits glycogen synthase kinase 3beta (GSK-3ß), and disinhibits eukaryotic elongation factor 2 (eEF2) which is essential for the synthesis of proteins by cells. The intracellular mediators of ketamine, mTOR, GSK-3ß, and eEF2, are evolutionarily ancient and deeply embedded in cell biology. Kinases, such as GSK-3ß, are a class of enzymes that act by donating a phosphate group to other enzymes and proteins inside the cell and thereby activating or inactivating them. The active form of the thyroid hormone, triiodothyronine, is often successful as an augmentation when antidepressants are ineffective.
