How Does Ketamine Work Differently from Other Psychedelics?

May 26, 2021

Drugs like LSD, psilocybin and DMT are known as ‘psychedelics’ due to the quality of experience they invoke. They are grouped by their similar actions on the body’s serotonin receptors. Ketamine, although considered a psychedelic by some, is profoundly different. And its differences may make it preferable as a treatment for various mental health disorders.

Psychedelics are known to conjure powerful and sometimes challenging experiences. Depending on the person’s pre-existing mental state, intention and the environment in which they take the drugs—together known as set and setting—they can evoke deeply moving encounters that can be both challenging and illuminating.

This is one of the reasons why treatment protocols call for at least one therapist to be present at all times during treatment, so they may ensure these powerful experiences are more constructive than destructive.

Subjective experiences of ketamine, however, are often quite different. While treatment protocols also involve at least one therapist to be present throughout, people using ketamine for therapeutic purposes report it to be substantially gentler than psychedelics.

Whereas psychedelics can evoke challenging states of mind and thoughts early on, ketamine more consistently evokes a gentle ‘lifting’ of existential burden. This is often referred to as a ‘dissociative’ effect and seems to somewhat free people from their anchors to physical reality.

While the space they enter is often said to be strange, they often report a sense of dream-like familiarity, something that is less common with psychedelics.

What causes the differences between ketamine and psychedelics?

Ketamine and psychedelics work in profoundly different ways. Ketamine primarily works by relaxing chandelier cells in the brain, which have powerful control over when pyramidal cells (neurons that do the lion’s share of ‘thinking’) fire and pass their messages on to other neurons. They do this by literally wrapping around pyramidal cells’ axons (tail-like structures that send information from one neuron to another) with a ‘stranglehold’ grip.

In relaxing this grip, ketamine allows the brain’s pyramidal cells to become more active and more interactive. This then produces an expanded state of awareness of a more whole self.

Psychedelics, on the other hand, work differently. They directly stimulate pyramidal cells in a way that overrides the grip of the chandelier cells. Rather than relaxing them, psychedelics work by overwhelming them.

In addition, as psychedelics work on the body’s serotonergic system, they can affect the gut, increasingly known as the ‘body’s second brain.’

Humans have a high density of serotonin receptors in the gastrointestinal tract, and activating these can cause both nausea and vomiting. While there may be therapeutic value in purging during psychedelic sessions, it can be unpleasant.

The jury is out though on whether ‘purging’ helps or not. Many subjects report feeling that it can be beneficial as it helps unite the body, mind and spirit to clear outdated programming and offload maladaptive beliefs.

Given the fundamental differences between how ketamine and psychedelics work, it is easy to see how psychedelic experiences can be more turbulent than those with ketamine.

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