Ketamine, an FDA-approved anesthetic drug, has recently become the star of the psychedelic medicine movement.
As psychedelics like psilocybin and MDMA draw closer to FDA approval for the treatment of a variety of mental health indications, ketamine is paving the way for the development of a country-wide industry around psychedelics-assisted psychotherapy.
Ketamine and its dissociative, psychedelic-like effects have been welcomed by the burgeoning psychedelics industry as a “gateway drug” into a new business ecosystem composed of specialized clinics, trained therapists and unique medical protocols.
Although, while clinics offering ketamine treatment are eager to present it as the “only legal psychedelic,” voices within academia are raising doubts about the compound’s touted psychedelic effects.
Does ketamine’s therapeutic action depend on its mind-altering effects? Should it be called a psychedelic at all? What are the consequences of this labeling for uninformed patients?
Why Defining Ketamine Is Important
Originally synthesized in the 1950s and approved in the U.S. as an anesthetic drug, Ketamine has recently gained attention in biomedical spheres for its fast-acting antidepressant effects.
Its legal status has allowed medical providers to offer it as an available means to supply the
growing demand for psychedelic medicine.
Today, most “classic psychedelics” (including psilocybin —or “magic mushrooms” -, LSD, mescaline or DMT) remain scheduled substances and will likely continue to be so until they can receive FDA approval for use in mental health and other indications.
In the meantime, as companies struggle to find early sources of revenue to finance the psychedelics boom, ketamine has been launched into the forefront of the psychedelics movement as a mind-altering drug with effects that could be in line with the goals of psychedelics treatment.
“People interested in establishing psychedelic clinics right now are promoting ketamine as a psychedelic, but mostly because it is accessible to physicians,” said Dr. Rachel Yehuda, director of the Center for Psychedelic Psychotherapy and Trauma Research at Mount Sinai Hospital in New York.
The Ketamine Clinics Directory shows dozens of clinics offering legal treatment with ketamine in the U.S., with locations in every major city. The directory only features clinics that “meet a standard of safe practices, have a history of ketamine service, and do not engage in questionable patient care,” meaning the number of ketamine clinics in the country is far larger than those featured on the site.
Ketamine Wellness Centers Arizona LLC, a chain of ketamine clinics with locations across eight U.S. states, recently reported having offered more than 60,000 ketamine treatments with revenues of $3.5 million in 2020 alone.
While ketamine’s efficacy in the treatment of symptoms of depression and other mental health disorders is no longer under doubt, the scientific establishment has not yet agreed on whether these effects come from the drug’s pure biological function (as most psychiatric drugs work), or from its ability to induce altered states of consciousness that can facilitate psychological growth (as psychedelics like LSD or psilocybin work in therapeutic contexts).
“It's a semantic argument,” said Hamilton Morris, an academic researcher and director of Hamilton's Pharmacopeia, in a documentary series on psychoactive drugs distributed by Hulu and Discovery.
“People talk about classical psychedelics with a somewhat precise definition. So if that's what you're talking about, classical or serotonergic psychedelics, then clearly ketamine is not an example, but the umbrella term psychedelic does encompass a number of pharmacologically and chemically unrelated substances,” said Morris, who has recently been hired as a scientific advisor by MindCure (CSE: MCUR) (OTCQB: MCURF) and Compass Pathways (NASDAQ: CMPS), two companies in the psychedelics space.
Is Ketamine Really A Psychedelic?
As psychedelic substances make their way back into the mainstream conversation, billions of dollars are being poured into an industry that aims to exploit their therapeutic potential to its maximum.
Being able to label a treatment under the “psychedelic” tag can be very beneficial when trying to attract clients who have heard about psychedelics and their therapeutic potential.
But if ketamine cannot be defined as a psychedelic, the issue of its definition ceases to be a problem of academic taxonomy, to become an issue of bioethics and commercial transparency.
Dr. Yehuda thinks that ketamine “is a dissociative anesthetic that has therapeutic properties that are absolutely not dependent on its psychedelic properties.”
“Ketamine may indeed influence peoples’ perception of passing of time, disconnection from or change in their bodily sensations, or other sensory experiences or thoughts, but the phenomenology and pharmacology of ketamine is different from classic psychedelics,” Yehuda said.
In her view, drug classifications should not solely be made on the basis of a compound’s
subjective characteristics, like the fact that it can sometimes cause dissociation or psychoactive effects. “When we talk about chemistry and drug development, we should mostly be defining a psychedelic drug on the basis of the chemistry of the molecule, its pharmacokinetics and its mechanism of action.”
Does Ketamine’s Healing Potential Come From Its “Psychedelic” Properties?
Dr. Celia Morgan, professor of psychopharmacology at the University of Exeter in the U.K., agrees with Yehuda’s call for better classifications for psychedelic drugs. However, in her view, the subjective (or “felt”) effects should serve as the basis for these classifications.
“I guess that's my perspective as a psychologist. I see these agents (and I include ketamine in there) as catalysts for psychological therapy. They can be effective on their own because they enable you to take a different perspective on your life and you think about your problems in different ways,” Morgan said.
The researcher believes it’s “kind of reductive just to base that purely on pharmacology” because that “doesn't encapsulate the full potential of these substances.”
In 2019, Janssen Pharmaceuticals, a Johnson & Johnson (NYSE: JNJ) subsidiary, released Spravato, an FDA-approved nasal spray containing esketamine (a ketamine derivative) for the rapid treatment of depression symptoms.
While the drug produces a dissociative effect, this was not the reason it was approved.
“The versions of ketamine that have passed FDA approval for indications like depression were able to distill their therapeutic properties down to the pharmacology, the mechanism of action of ketamine and the biologic systems that were believed to be restored to alleviate depression and suicide and maybe even PTSD symptoms,” Yehuda explained.
In the case of Spravato, its action on NMDA receptors is believed to produce the antidepressant effect.
“The unanswered question in all of this is whether the transpersonal state is what heals you or whether it's something about the molecule. It’s also important to understand if ketamine’s effect on depression and suicide are based on its neurochemical effects at brain “targets” that are causing these symptoms,” Yehuda added.
This means that, while ketamine can induce altered states of consciousness and also treat depression, the two characteristics are not necessarily tied, as ketamine’s dissociative effects could be a by-product of its therapeutic action on a neurochemical level.
For Morgan, who also serves as head of ketamine-assisted psychotherapy at Awakn Life Sciences (NEO: AWKN) (OTCQB: AWKNF), emerging literature is showing that the dissociative effects of ketamine are actually very important in its therapeutic action.
“With [ketamine’s] unique subjective effects, where you have a kind of out-of-body experience, often people have a different perspective on their life. And that's when you give ketamine alongside psychological therapy. That's what enables it to work really well. And it kind of catalyzes these therapeutic processes because it gives you a completely different perspective,” Morgan told Benzinga.
In her extensive experience researching the therapeutic effects of ketamine, Morgan refers to patients who consistently report “becoming pure white light and being completely separate from their bodies,” or “looking back on their past lives and feeling profound forgiveness.”
“To me, that's not encapsulated properly in the word dissociative,” said Morgan, who believes
ketamine should be rightfully named a psychedelic for its therapeutic potential.
Set, Setting And Ketamine
In the clinical trials using psychedelics like psilocybin and LSD for depression, PTSD and other psychiatric indications, the molecules are as important as the context in which they’re used when looking to produce a therapeutic impact.
Psychedelics-assisted psychotherapy works by providing patients with a context in which to work with the insights gathered from their experiences with these drugs.
In Yehuda’s view, “classic psychedelics” are tryptamines like LSD, psilocybin and phenethylamines like MDMA, wherein the chemical properties are not necessarily doing all the healing but facilitating or occasioning a psychological insight.
The researcher noted that, while ketamine could offer improved benefits when accompanied by psychotherapy, this has not yet been clinically proven.
“It's an empirical question. It has to be asked and answered through the appropriate clinical trial. The dissociation or psychoactive effects of ketamine might be incidental. They occur. But that's not necessarily why the healing is happening,” Yehuda explained.
Morgan added that in ketamine’s long history of use, psychiatrists that led research failed to ask questions around the compound’s subjective effects.
“We've looked to see if any of ketamine's effects are related to its dissociative symptoms. In our review, about thirty percent of studies found a link between these dissociative effects and the antidepressant effect of ketamine,” Morgan said.
In her own research, Morgan intends to answer these questions with clinical accuracy, though conclusive results have not been published yet.
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