Ketamine: Benefits and Risks for Depression, PTSD & Neuroplasticity

The combined S/R- form of ketamine seems to be the most potent for relieving depressive symptoms. The S- form of ketamine is second best in terms of providing relief from depressive symptoms and is the one that's most commonly prescribed ... It appears that the R- form of ketamine is the least potent and effective in treating depression.

A k-hole is what's used to describe the subjective experience of when somebody takes ketamine, typically recreationally, and they end up in basically a pseudo-anesthetize state. What that means is that they took a dosage that, for them, put them beyond the boundary of the sub-anesthetic dose and has them transitioning into the anesthesia level dose of ketamine.

Going into anesthesia-like planes of consciousness, while not always deadly, can be deadly—and it certainly can be and has been deadly when people start to combine it with other drugs, in particular drugs like barbiturates or alcohol.

It appears based on the clinical data in humans... that the S- form of ketamine is more potent—that is, it can more robustly bind to the NMDA receptor. And in addition to that, the S- form of ketamine tends to produce less dissociation at a given dosage than does the combined S/R- form of ketamine or pure R- ketamine.

I know many of you are probably wondering, can you get addicted to ketamine? Indeed, people can get addicted to ketamine.

What we've learned over the last 30 or 40 years is that drugs that are designed to increase certain monoamines in order to treat depression only work in about 40% of depressed people that take them, and they have a lot of side effects.

What was really interesting about this study and others like it is that the patients experienced relief their depression almost immediately after taking the drug—so, within minutes to hours—and that it persisted for several days after taking the ketamine.

This is one of the things that makes ketamine an incredibly attractive drug for the treatment of depression, especially depression that hasn't responded to other forms of treatment, which is that people get relief very, very quickly—indeed the same day that they initiate the treatment.

If people do this twice a week dosing regimen—so, ketamine twice a week for three weeks total—they find that when they end that three weeks, they get some ongoing relief from their depressive symptoms, which can extend months or more before they have to repeat the twice a week for three weeks regimen.

There are several lines of evidence that suggest that ketamine-induced release of BDNF is one of the core mechanisms by which ketamine can relieve depression.

Ketamine can bind to various opioid receptors; and when opioid receptors are bound, we know that creates certain effects—things like pain relief, things like changes in psychic states, dissociation, for example. If enough of them are bound, you can get euphoric states...

What they observed is that when people were given ketamine, they got relief from depression ... If, however, individuals were given Naltrexone to block the opioid receptor pathway and they were given ketamine, well, then the antidepressant effects of ketamine were no longer observed.

It's now established that ketamine can improve connectivity... between areas of the brain that are associated with context-dependent strategy building and these reward pathways. In other words, it makes people more sensitive to whether or not they are getting the results they want from their efforts and to how to adjust their efforts so that they do get the results they want from those efforts.

The dissociative effects of ketamine are so profound for people that take them ... It has to do with an uncoupling of certain brain circuits, in particular neocortical brain circuits ... And it seems that when people take ketamine or phencyclidine (PCP), there's an uncoupling of those networks, a quieting of those networks, that starts to create a different dominant rhythm in the brain.

Most people don't realize that ketamine is very similar to another drug called PCP, or phencyclidine, which goes by the street names angel dust or sherm. It has some other street names as well.

Ketamine binds to the NMDA receptor present on inhibitory neurons, and in doing so, dramatically reduces the amount of inhibition coming from those inhibitory neurons on to excitatory neurons. When that happens, the excitatory neurons in specific circuits of the brain are allowed to increase their activity.