Sunday, March 13, 2022

Is Ketamine a Psychedelic?

Patients often ask “Is Ketamine a Psychedelic?”

There is no consensus as to whether the effects that Ketamine produces can be defined as “psychedelic” and this is partly because the word psychedelic can mean different things to different people.

There is probably nothing wrong with using this term to describe the effects that Ketamine produces if one is comfortable with that term but for some this term has a lot of baggage associated with it.

Given that people generally experience the effects of Ketamine differently, one person might describe the effects as psychedelic and another could adamantly disagree.

The term psychedelic is not a well defined term and people use the term to describe aspects of things that are not even psychoactive compounds. The term is even used to describe genres of music and styles of art.

The term psychedelic was coined by psychiatrist Humphrey Osmond and is a mix of the Greek words psyche, meaning “soul” or “mind”, and delein, meaning “to manifest.” So the term psychedelic sort of means “mind manifesting” or “soul manifesting”. What does it even really mean to have something be mind manifesting or soul manifesting?

Some argue that the term psychedelic should only be used to describe compounds that interact with the serotonin 2A receptor. The term “classical psychedelics” is sometimes used for 5-HT2A receptor agonists (agents that bind to and activate that receptor). When people refer to classical psychedelics they generally are referring to lysergic acid diethylamide (LSD), mescaline, and psilocybin. These substances are in a class of compounds referred to as tryptamines. Using the receptor that a substance binds with or acts on to define if it is psychedelic or not is problematic in that there are compounds that bind to this receptor that are not psychoactive and psychoactive compounds that mimic the effects of tryptamines that do so without binding to this receptor. Examples of non-psychedelic 5HT2A receptor agonists are lisuride and ergotamine.

Ketamine does have actions on the 5HT2A receptor but more weakly than tryptamine compounds. Ketamine is known to be more active at the 5HT1B receptor. Most of Ketamines actions are on the NMDA receptor and on the neurotransmitter glutamate but ketamine acts on many receptors and modulates many systems throughout the brain and body.

By class ketamine is a arylcyclohexylamine and many use the term “dissociative anesthetic” or just a “dissociative” to describe it. For most, Ketamine has effects other than just producing dissociation but this depends on the dose received, how it’s given and the person that is receiving it.

So why do some people say Ketamine is a Psychedelic?

Many people report the effects of Ketamine to share similarities to the effects that other classical psychedelics cause. Effects such as visual and auditory effects, closed eye visuals including geometric patterns, colors and shapes, and synesthesia. There is a study that was done exploring the effects of ketamine at different plasma concentrations. The study determined that “Subanesthetic doses of ketamine produce psychedelic effects in healthy volunteers. The relation between steady-state venous plasma ketamine concentrations and effects is highly linear between 50 and 200 ng/ml.” and that the “Hallucinogen rating scale scores were similar to those found in a previous study with psychedelic doses of N,N-dimethyltryptamine, an illicit LSD-25-like drug.”

So the research points to Ketamine having effects similar to other compounds that are generally regarded as classic psychedelics but these effects are more apparent at different doses. It is the case that there are doses of Ketamine that are not as psychedelic, other doses that are more psychedelic, and dose ranges that the dissociative effects tend to override the psychedelic effects. Meaning a dose too low or too high may not produce effects that mimic classic psychedelics but a dose in the middle probably would for most people.

So why might one person experience psychedelic effects and another person not?

The main reason for this would be the dose that was supplied and how that dose was given but there are other factors. Genetically, everyone metabolizes Ketamine differently, it is possible that due to individual genetic variations in how one metabolizes Ketamine such as specific genetic polymorphisms, this might influence how psychedelic Ketamine is for them. There has not been research done on how individual differences in metabolism influence the subjective effects of Ketamine.
Another factor may be interfering medications. Medications like lamotrigine (Lamictal) and benzodiazepines may decrease the effects of Ketamine that people often describe as psychedelic. It is well known that lamotrigine will generally interfere with the dissociative effects of Ketamine.

Ketamine is an odd psychoactive compound in that it has more variability in its subjective effects session to session than many other studied psychedelic compounds. Compounds like LSD, MDMA, and psilocybin can have more predictable effects across different people than Ketamine does.

Patients often report throughout the Ketamine treatment series that one session felt “completely different” than all the other sessions. Patients that do maintenance treatments over a course of time still sometimes report that each session is different and that the types of experiences they have under the effects of Ketamine continue to evolve and change over time.

Although, it might be nice if Ketamine was more consistent in its effects person to person and session to session, it is also its variability that is one of the wonderful aspects of Ketamine. The fact that Ketamine experiences can be different each time might be part of how it can be useful therapeutically in treatment resistant individuals. If one experience did not yield much therapeutically then maybe the next one will yield something entirely different.

At Transcend, we do not view the psychoactive, psychedelic, psycholytic, psychotomimetic (or whatever term you want to use to describe the effects) of Ketamine as a side effect. Many people have experiences that they would rate as one of the most meaningful experiences of their lives during Ketamine Assisted Psychotherapy sessions. Some clinics do not see it this way. There are even Ketamine clinics that administer powerful benzodiazepine medications (such as midazolam brand name Versed) alongside Ketamine infusions to reduce the experiential aspects of Ketamine. Transcend sees doing this as a potential missed opportunity. There is also evidence that administering benzodiazepines with Ketamine can dampen its antidepressant benefits.

It is the case that people can experience reductions in symptoms of depression when measures have been taken to minimize the psychoactive effects of Ketamine. An example of this would be when Ketamine is given to patients in surgery. There are reports of people receiving Ketamine while under surgical anesthesia from other agents experiencing less depression symptoms after the surgery.

Over the thousands of sessions we have done at Transcend it is hard to ignore how the experiential aspects of Ketamine tend to be the driver of therapeutic content. We believe Ketamine treatment should be an active process for patients to experience benefits that are not transient. Some people do have reductions in symptoms when Ketamine is administered in a way that minimizes the psychedelic effects, but it is unlikely that those benefits will stand the test of time.

However you define the effects Ketamine produces, they are not anything to be afraid of as long as someone is well prepared and supported throughout the experience.

So is Ketamine a psychedelic? It depends on who you ask, who received it, how it was given, what it is given with, and how you define the term psychedelic in the first place.

Is Ketamine a Psychedelic?
March 13, 2022
Will Ratliff
Director of Operations