How Does Ketamine Work?
This drawing illustrates how ketamine works on some brain cells. On the far left, ketamine turns off the cell that acts like a brake (brown cell) for the other 2 cells (green and blue cells). When this brake is turned off, the other brain cells are free to release chemical signals that promote brain cell growth and connection, known as neuroplasticity.
Signals between brain cells are transmitted by chemicals and electrical currents that cause many complicated negative and positive feedback loops. The human brain is very complicated, our knowledge of what goes on is somewhat superficial and just beginning to become sophisticated. At this point, we can only scratch the surface of the complexities of the effects of any particular substance on the brain’s activity, much less begin to formulate theories on the interactions between brain and consciousness.
However, it appears that ketamine affects communication and signaling between brain cells. Ketamine acts upon many different receptors in the brain, but its main effect is as an NMDA-receptor antagonist. This means that it blocks a particular type of receptor, the N-methyl-D-aspartate (NMDA) receptor, on certain brain cells. One way ketamine seems to work is that it stops a type of brain cell whose job is to stop the activity of a different type of brain cell. Basically it takes the foot off the brakes, and allows some specific brain cells to be more active.
On the left is an example of the dendrites from a normal brain cell. The dendrites are like roots that connect the brain cell to other brain cells. The middle illustration shows how the dendrites become “pruned” in a cell from a brain that has been exposed to chronic stress. The illustration on the right shows how those dendrites regrow just 1 day after ketamine treatment.
This increased activity can bring about new connections and interactions between different areas of the brain. For example, it seems that ketamine turns down activity in what has been called the default mode network while at the same time promoting new connections in other regions of the brain. These effects likely explain some of the changes in consciousness in the minutes, hours, and days after administration of ketamine. There is evidence that ketamine actually stimulates the growth of brain cells and strengthens and creates new connections between brain cells. In this way, it seems that ketamine can enhance neuroplasticity, or the ability for the brain to change its connections and even structure.
This is an illustration of how ketamine actually changes the network connections in the brain. The illustration compares the brains of people suffering from depression who received ketamine with those who received a placebo. The blue dots are areas of the brain that are less active in those receiving the ketamine than those receiving the placebo. Interestingly, many of these areas are part of the default mode network.