Is Ketamine Psychedelic?

Ketamine is undeniably trippy — but what does it take for something to be considered "psychedelic?"

Ketamine has been considered a dissociative anesthetic for most of its 60-year existence. No more than a decade ago, very few people would have considered it "psychedelic." The latest psychedelic "renaissance" has other plans. 

The issue here is language more than it is the substances themselves.

Drugs like magic mushrooms, LSD, mescaline, and DMT are typically referred to as "classical psychedelics." Nobody is arguing whether or not these substances are psychedelic, as they all target the same serotonergic receptors to produce trippy visuals and deep introspective thought patterns.

Many exclude compounds like MDMA or ketamine from the "psychedelic" umbrella, while others fight to include things like cannabis.

Now, ketamine clinics around the country are marketing ketamine as an important part of "psychedelic therapy." 

A lot of new research on ketamine also involves psychedelic language — like this paper from 2019, which clarifies that "Although ketamine does not appear to primarily target the serotonergic system, it is nonetheless capable of inducing psychedelic states."  

So what, exactly, makes something psychedelic? And where does ketamine fit?

Psyche + Delic: "Mind Revealing"

Psychiatrist Humphry Osmund first coined the term in a letter to author Aldous Huxley in the 1950s. Psychedelic combines two Greek words — "psyche," which means mind, and "delos," meaning reveal.

Other terms for psychedelics have been used over the years. Early attempts to define the experience of the drugs compared the effects with psychosis, calling the drugs psychotomimetic, meaning "psychosis mimicking."

In 1979, a group of researchers, including Carl Ruck, Jeremy Bigwood, Danny Staples, Jonathan Ott, and Gordon Wasson, coined the term "entheogen." This term is also a combination of two Greek words — "entheos," meaning "full of god," and "genésthai," meaning "to come into being."

However, neither term became as widely accepted as psychedelics. "Hallucinogen" is popular but has negative associations and is avoided by modern enthusiasts.

Even with so much language to choose from, it's notoriously tricky to stuff the psychedelic experience into a neat little box.

As ethnobotanist and psychedelic philosopher Terence McKenna put it, "You can't english it." Nonetheless, we keep trying.

Defining Psychedelics

There isn't a consensus on what psychedelics are in academic circles. 

The topic of whether or not ketamine is psychedelic has been a spicey debate on psychedelic Twitter (X, whatever). Many hold that ketamine's impact on the NMDA receptors and lack of serotonergic action limit the drug to the category of dissociative anesthetic — while others consider the deep introspective and trippy states it produces qualify the drug as a full-blown psychedelic.

This is an argument over chemistry/pharmacology versus subjective experience as the defining factor for the classification of a drug as psychedelic.

In an interview with Benzinga, Dr. Racehl Yehda, a Professor of Psychiatry and Neuroscience of Trauma at Mt. Sinua University in New York, spoke in favor of using neurochemistry to define psychedelics.

A boilerplate explanation of "classical psychedelics" are compounds eliciting effects through activation of the 5-HT2A serotonin receptors in the body. Research conducted by Franz Vollenweider has shown that by blocking this receptor, psychedelic drugs no longer work. Drugs such as DMT, LSD, psilocybin, mescaline, and even MDMA all work this way.

A recent paper by prominent pharmacologist and medical chemist David Nichols in Psychedelic Medicine also supports this view. Nichols has also previously suggested distinctions within psychedelics by defining two structural types — indoleamines and phenylalkylamines, which we won't get into here.

However, computational neurobiologist, pharmacologist, and chemist Andrew Gallimore points out in his newsletter Alien Insect On Drugs that the definition excludes drugs like Salvia divinorum, a wildly potent plant with effects few would debate are psychedelic. Salvia is unique in that it works almost exclusively through the kappa-opioid receptors.

There are also drugs like diphenhydramine (DPH) and other antihistamines, datura, brugmansia, and mandrake, that produce powerful hallucinations. None of these drugs have any particular affinity for the 5HT2A receptors.

How Does Ketamine Work?

Ketamine primarily works by binding to the NMDA receptors. These receptors are involved in a wide range of neurological functions, including consciousness, memory, and imagination. 

Blocking these receptors slows down brain activity and puts users in a state of dissociation and anesthesia. Here, the user remains conscious but completely detached from their body. On the outside, it looks like the user is asleep, but inside, they continue to exist in a different space, often far outside the norms of what we consider waking consciousness.

While in this dissociated state, users experience profound and ineffable visuals and experiences — such as being "outside of time itself." Some users experience a strange sensation of watching themselves from somewhere else in the room or teleporting to new dimensions.

Newer research has discovered a powerful antidepressant after taking ketamine. This effect lasts anywhere from a few days to two weeks. 

Some attribute this effect to ketamine's ability to induce a state of dissociated "euphoric nothingness." Within this state, the user is able to take a glimpse at their psyche and its unconscious toxic or self-deprecating patterns. The lack of emotion during this experience helps users confront uncomfortable parts of themselves that can then be integrated later for more long-lasting change.

If this isn't considered "mind-revealing," I'm not sure what it is.

As weird and trippy as the ketamine experience is, it has little to no direct impact on the 5HT2A receptors and, therefore, doesn't make it into the exclusive "classical psychedelic" group based on neurochemical definitions.

Salvia: Another Psychedelic Outlier

The discussion of Salvia divinorum (diviner's sage) is relevant for the discussion of what makes something psychedelic or not as well. 

Many consider salvia one of the most powerful psychedelics in existence. It's known for creating extremely potent and immersive experiences comparable to DMT. 

However, like ketamine, salvia has almost no direct impact on the 5HT2A receptors. Instead, its psychoactive effects rely on the kappa-opioid receptors.