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Treating Depression With Ketamine

Ketamine, supplemented with therapy, may help "reset" folks with depression.

Key points

  • Ketamine is a popular anesthetic now being used at lower doses to treat mental illnesses.
  • Ketamine may help people dissociate and reset from the way they tend to think about themselves and the world.
  • Depression is characterized by a loop of low motivation and negative thoughts about the self and the world.

More and more people are using ketamine to treat mental illnesses.1 I recently interviewed Steven Mandel, who is a pioneer in this field.2 He is an anesthesiologist who also has significant graduate training in clinical psychology. In the podcast, we recount his life and how he became interested in ketamine and why and how he came to see it as a powerful tool in our arsenal to treat depression and related conditions.

We were able to have a synergistic meeting of the minds, both in how to frame ketamine and on why it can be a useful medication for depression and related conditions. First, it is important to be aware that ketamine is a popular anesthetic that has long been used in both human and veterinary medicine. (It is sometimes called the “horse tranquilizer.”) At lower doses, it provides a shift in one’s sense of being in the world. Specifically, it tends to create a bit of a dissociative state, such that the normal felt sense of being a subject in the world shifts, and one has more of a third-person, or distant sense of one’s self and the world.

Why might such an experience help folks with depression? Well, one way to frame depression is as a “neurotic loop” that forms between the individual and the environment. First, there is usually a problem with loss or defeat or frustration, such that an individual is not on a path to fulfillment or has lost a cherished relationship. This sets the stage for a shift in depressed mood. A depressed mood shift can be thought of as the part of you that energizes you toward activities and goals going into a state of behavioral shutdown. A state of behavioral shutdown is when the behavioral activation portion of your being gets pulled down so that you lose energy, pleasure, and initiation. In addition, the behavioral avoidance domain gets jacked up, so that you are more sensitive to pain, disappointment, loss, and frustration.

This mindset then grabs the self-conscious portion of a person’s mind and orients it to start narrating things in ways that are aligned with the depressive shutdown. As Mandel notes, depressed people often start thinking that they are helpless, that their situation is hopeless, and that they are worthless. Once this narrative gets going, it feeds back on the body, creating a painful, dark loop from which it is difficult to escape.

This brings us to what might be a key mechanism of ketamine. It seems to shift the strong “grip” the normal self-system has on the self–world relationship. More specifically, people on ketamine seem to report a significant shift in the way they identify with their thoughts. And they seem to be able to distance (dissociate) themselves from their thoughts, which would lessen the power of the neurotic loop.

This is the way Mandel characterized what he was seeing in ketamine, and it is consistent with the way I have characterized depression. (For a guided self-help blog tour on how to deal with depression, see here.) In our video, we talk about how ketamine can be framed as giving folks a kind of “reset” on the painful self-world grip, and then how that sets the stage for psychotherapy and other shifts that might build from that freedom to create a path toward a more constructive and fulfilling way of being in the world.

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1. Sharon Kwon. I Went To A Ketamine Therapy Training. What Happened There Changed My Life. HuffPost. September 5, 2023.

2. Podcast: UTOKing with Gregg, Episode 71 with Dr. Steven Mandel, founder of the Ketamine Clinics of Los Angeles.

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