Brief: The Promises & (Mostly) Perils of Ketamine Therapy
Though not specifically a psychedelic — ketamine is a dissociative anesthetic — ketamine therapy is being touted as a depression treatment and, for some, a new form of spiritual healing. And indeed, some of the results are promising. But with Ketamine Wellness Centers and Field Trip Health both shutting down ketamine clinics across the country, leaving clients scrambling to find relief. Are these psychedelic entrepreneurs placing too much emphasis on scaling and shareholders and not enough on healing, even though their marketing efforts claim the opposite?
Derek looks into the sordid developments of ketamine therapy, including the botched trials that ultimately received FDA approval.
Show Notes
Ketamine infusion: The new therapy for depression, explained
New analysis claims the FDA rushed ketamine’s approval for depression treatment
Excessive drinking costs $249 billion. Can one dose of ketamine curb alcoholism?
‘I’m terrified’: Patients scramble for treatment after 13 ketamine clinics shut down
How ketamine-fueled dreams can promote a spiritual approach to mental health and therapy
Learn more about your ad choices. Visit megaphone.fm/adchoices
This happened often in New Brunswick and Jersey City and New York City, trying to smoke a joint while walking on the street.
Or just being out in public, high, worried someone would be able to tell.
Back then, New York was especially anxiety-inducing, given the police jump-out vans.
Giuliani had created a task force to round up the dangerous reefer smokers on a nightly basis.
If you were the first person they picked up, you might have to drive around for hours until they filled the van with other scum.
It was more a lesson in humiliation.
Thankfully, I never got caught in all those years, but horror stories abound.
But there were other layers to my paranoia, and those involved psychedelics.
I won't indulge on my experiences in the many stress-producing nights given their prior illegality, but nothing can ruin a transformative experience like the threat of the police showing up.
Once, during an ayahuasca ceremony in Topanga, that did happen, though again thankfully nothing came of it.
Out of all of my experiments, though, there were two substances that left a bad taste in my mouth.
Angel dust, and a peculiar substance that was synthesized from angel dust.
Ketamine.
The K-hole is like nothing I've ever experienced or would want to experience again.
One evening, after a bag of ketamine, I laid down on my friend's bed.
Then I sat up.
Then I stood up.
As someone who prides himself on solid proprioception, for the life of me I couldn't distinguish between those three positions.
And while I was in a relatively safe space that evening as I slid deeper into that hole, it's not an enjoyable place.
You spend most of your available consciousness trying to crawl your way back out of that hole.
So when a few years ago the notion that ketamine could treat addiction and depression started surfacing, I was surprised.
But perhaps I shouldn't have been.
I know that dose matters.
And even in my own experience, the difference between a bump and a line and a bag is everything.
Oh, and if it's not clear by now, nothing I say today or ever on this podcast constitutes medical advice.
I realize that my anecdotes are not indicative of anyone else's health.
But I also know that psychedelics were extremely important in my life, for both my craft of writing and for my life itself, and I believe for my mental health.
While I let off with a problem of doing a bag of ketamine, I had a few uplifting experiences thanks to a bump.
So ketamine being explored as an intervention wasn't that surprising, even if my attention at the time had been on substances I had a bit more faith in, like psilocybin and MDMA.
Yet I was also worried, in the same way I was worried about the legalization of marijuana.
Namely, the rush of money that I knew would pour into the burgeoning psychedelics industry, and the results of potential therapeutic substances being beholden to shareholder returns.
Cannabis is a bit different given its widespread adoption, even before it became legal.
And yes, I know it's still not federally legal, which is just plain stupid, and I know state laws can still make it anxiety-producing.
And I'm sorry if you live in one of those states or countries.
But the mainstreaming of psychedelics is just different.
And in the last few weeks, we're starting to witness the damaging effects of speculators being a little too ambitious.
Because of their frantic rush to this new gold mine, we're also now seeing collateral damage.
On March 10th, Kevin Nicholson, the CEO of Ketamine Wellness Centers, sent out an email stating that all 13 of their ketamine clinics were shutting down, in a half an hour from when the email was sent.
Patients at these centers were left out in the cold.
Because ketamine therapy depends on a continued regimen, they had to find other clinics before they relapsed.
And this is no small number of clients.
According to documents, these centers had performed 12,000 infusions at 13 clinics in 2022 alone.
12 of these clinics were in the VA's network, as veterans have found success with substances like MDMA and Ketamine for the treatment of depression and PTSD.
And so veterans were forced to scramble, which really sucks if they were actually finding relief.
On top of all this, most Ketamine Wellness Center employees only learned that day that they were now unemployed.
Perhaps this too shouldn't have been surprising though.
There was a red flag in 2021 when Delic Corp, the self-proclaimed leading psychedelic wellness platform, bought Ketamine Wellness Centers.
I worked for another Delic property, the website Reality Sandwich, for three weeks in an editorial position.
And without getting into specifics, let's just say I'm not really surprised to hear that there was mismanagement.
In my entire career, there's only one company I ever worked for for three weeks.
I was also an original Reality Sandwich writer back in 2008 when Daniel Pinchbeck launched the site, so I have a bit of history with both the psychedelic space and that property in particular.
But the email that Nicholson sent out confirms my suspicion.
So he writes about the acquisition of Ketamine Wellness Centers by Delicorp.
The purpose of the acquisition was to expand quickly with the promised funding, yet stay on as operators and employees.
We opened three new clinics and had two immature clinics at the time.
In one year's time, ketamine wellness centers became the funding arm of Dellek instead of the recipient.
Nice.
That's some good business there.
And it's exactly the problem.
Then again, anyone slapping corp behind a psychedelics company should raise suspicion.
Now sadly, the growth issue in ketamine isn't only affecting this chain of centers.
Fieldtrip Health lost $6.9 million in one quarter last year, resulting in the shuttering of clinics in five locations just this month.
But at least they gave their patients a month's lead time.
And at least from what I can tell, their closure is the result of overambition and not anything nefarious, though I can't claim that for certain.
I talked to Fieldtrip CEO Ronan Levy when he opened the world's first psilocybin research center in Jamaica in 2019, and there honestly seemed to be positive momentum with the company.
Of course, there's always going to be the question of monetizing hallucinogens and psychedelics, which is another story that needs to be addressed.
Regardless of these poor business decisions, what really sucks are people finding relief from ketamine being abandoned because these clinics are more concerned with scaling than helping.
So before we talk about a potential future for things like ketamine, let's look a little more
in depth at what it is and some of the problems with its rush to clinical use.
In March 2019, the FDA approved the usage of ketamine under the trade name Spravato,
which is known as S-ketamine, for clinical use in treatment-resistant depression therapy.
Peace.
Treatment-resistant means you've tried two other interventions, like antidepressants, and they didn't work.
And so alongside racemic ketamine, which is commonly used in ketamine infusion therapy, ketamine became the first hallucinogen approved for therapeutic usage in the United States.
Now technically, ketamine is not a psychedelic, but rather a hallucinogen and a disassociative.
While ketamine does have psychedelic effects, traditional psychedelics bind to the 5-HT2B receptor.
Still, psychedelic therapy advocates recognize ketamine as a gateway for traditional psychedelics, such as psilocybin and LSD.
And so, it has been considered for therapeutic use to treat mental health issues and lumped together with the other psychedelics that are being studied to do so.
But it's been used clinically for generations.
In 1962, chemistry professor Calvin Stevens synthesized ketamine while researching alpha-hydroxyamine rearrangements.
The first human tests were conducted on prisoners in 1964.
Ketamine soon replaced fensiculidine, or PCP, as the go-to anesthetic in hospitals, and PCP, of course, is angel dust.
Ketamine was initially used on soldiers during the Vietnam War following FDA approval in 1970.
Thanks to its success on the battlefield, ketamine was placed on the World Health Organization's list of essential medicines.
Ketamine has been used broadly as a sedative and anesthetic, to aid in emergency surgeries in war zones, as a bronchodilator for severe asthmatics, to treat certain types of seizures, and in post-operative pain management.
Besides use in depression treatment, ketamine is showing potential efficacy in treating chronic pain and suicidal ideation, though more research needs to be done on all of these fields.
Of all those uses, ketamine has predominantly been used as an anesthetic in humans and animals.
While it restricts breathing less than other similar medications, ketamine also produces hallucinations, thus it's labeled as a disassociative anesthetic.
The list of potential side effects from ketamine is long and it does warrant caution.
They include nausea, double vision, breathing problems, impaired memory, liver enzyme abnormalities, urinary tract problems, and even increased depression, which is an alarming possibility given its growing use as an antidepressant replacement.
But again, dose matters.
Small-scale studies on ketamine to treat depression were conducted as far back as 2000 and 2006.
Further research confirmed its role in alleviating depressive symptoms, including the possibility that the antidepressant effects of a single dose can persist for weeks.
And so in 2016, the FDA fast-tracked ketamine trials for depression, given the continued problems a lot of people are having with SSRIs and other antidepressants.
And yet there's been no consensus on how ketamine actually addresses depression.
Antidepressants act on the body's serotonin and noradrenaline systems.
Ketamine is different.
As a 2017 study published in the journal Nature explains, ketamine is responsible for blocking the N-methyl-D-aspartate or NMDA receptor, which causes an immediate alleviation of depressive effects.
While another metabolite in the drug helps the effect last for hours.
This blockage is also what causes the hallucinogenic effects.
Small intravenous doses of esketamine seem to lift depressed patients out of their funk.
So does Spravato, which is the nasal spray that can only be administered under supervision in a doctor's office or clinic.
Since the therapy is generally not covered by insurance, treatments range from $300 to $2,000 per session.
The field trip treatment program, which I mentioned earlier and which includes psychotherapy and 6 infusions, runs $4,700.
So already you can see a lot of people are priced out of such treatments, which is a shame.
Unfortunately, therapeutic implementation has not always lived up to federal requirements, and this could be playing into the scaling problem that the aforementioned clinics face.
Reports of patients quitting antidepressants and psychotherapy to use esketamine as their primary source of treatment are more common than you might think.
Since medical professionals with no mental health training, such as nurse practitioners, anesthesiologists, and pain physicians can legally administer ketamine, patients are being left to process the drug's effects with little to no guidance.
So it's not really that surprising that efficacy has been mixed.
People with minor depressive issues are likely better candidates for ketamine therapy than those with treatment-resistant depression, which is the very cohort the drug is purported to target.
As stat news editor Megan Philking writes, studies vary but have found response rates to ketamine as high as 70% among people with major depression who have failed a few other antidepressants, but the rate is lower for patients with extremely treatment-resistant depression, and how long any improvement lasts varies from one patient to the next.
This all coincides with what I think is the biggest issue.
The rushed FDA approval trials.
A 2020 analysis published in the British Journal of Psychiatry concludes that we're just moving too fast with this intervention.
Here's what author Mark Horowitz writes.
Out of the three short-term trials conducted by Janssen, Janssen Pharmaceuticals is the company that brought it to market.
Only one showed a statistically significant difference between S-ketamine and placebo.
These were even shorter than the 6-8 week trials the FDA usually requires for drug licensing.
That requires a little background.
Clinical trials generally last 3 months.
The approved ketamine trials only lasted 4 weeks, and they barely showed efficacy above placebo.
Now more concerning, the FDA allowed Janssen to submit a discontinuation trial with a study design flaw as evidence of efficacy.
Okay, let's pull back because that's really important.
This means that side effects were treated as evidence of relapse and not withdrawal symptoms, which is crazy!
So even more alarmingly, six people in the Asketamine Group died during the trials, including three by suicide, two of which had previously shown no signs of suicidal ideation.
When Janssen stated that the problem wasn't esketamine but the underlying conditions, the FDA accepted the reasoning even though no conclusive evidence was provided.
So let me put it another way.
People who were depressed took ketamine, and then when they stopped taking it, they committed suicide, including two people who weren't suicidal before the trial began.
Janssen argued that it was their depression that caused them to take their own lives and not due to the sudden stopping of ketamine, which, to my knowledge, doesn't have a known tapering protocol.
And the FDA accepted it, so that's how it became legal.
All of this doesn't mean ketamine therapy isn't potentially therapeutic for some people, but it does suggest that its approval was rushed and we're seeing the downstream effects of these companies rushing in to try to monetize and capitalize on this.
Psychiatrist Lori Calabrese, who offers ketamine infusion for depression and anxiety in her clinic, puts it best when she says, The pace of ketamine treatment in real-world practices has outstripped what researchers are able to do and publish.
Time will tell if this treatment proves more beneficial than dangerous and mental health treatments, but unfortunately for all these people who are on it and were suddenly dropped, what are they going to do?
Now, I want to be clear here.
I'm all for interventions that work.
In fact, there's another possible therapeutic case for ketamine.
Alcoholism.
One study published in the journal Nature Communications found that heavy alcohol drinkers reduced their intake after a single ketamine injection.
The researchers speculate that in this regard, ketamine appears to rewire the process of memory consolidation after just one dose.
Specifically, it overwrites maladaptive reward memories, which they write are learned associations that encode the contingencies between drug-predictive environmental stimuli, such as the smell and taste of beer, and drug reward.
The study's lead author, Dr. Ravi Das, explains that drug and alcohol addiction are caused by this sort of association.
Essentially, the drug hijacks the brain's inbuilt reward learning system so that you end up associating environmental triggers with the drug.
These produce an exaggerated desire to take the drug.
Unfortunately, once these reward memories are established, it's very difficult to relearn more healthy associations, but it's vital in order to prevent relapse.
As any good researcher should say, Das calls the study experimental and not clinical.
Yet we've long known that addiction relies on psychological association and your environment plays a role.
So you either need to change your environment or change your relationship to your environment and it appears that ketamine might help with the latter.
Unlike the substances I mentioned earlier, like cannabis and psilocybin, ketamine has largely escaped both scrutiny and being labeled as a panacea.
But it has fallen into this general category of psychedelics, which represents a sizable contingent of the wellness space's back-to-nature ethos.
I can't tell you the number of yoga instructors I've seen over the last few years who start calling themselves shamans or psychedelic guides and work supposed therapy sessions into their offerings even though they have no clinical training whatsoever.
I mean, it's cool if you are a trained therapist, but I know that many of them are not, and that's dangerous territory they're treading.
If someone has a severe psychotic episode during a session, there's no way they're going to be able to deal with it.
So then what's that person going to do?
Now, what's more, psychedelics are being framed as antidotes to big pharma, but that doesn't make any sense.
There's no consistency being applied to the term psychedelic at this point.
Okay, so, like, consider all of these.
Psilocybin is a naturally occurring substance in over 200 forms of mushrooms.
And while companies are trying to synthesize and patent molecules from it, it truly does fit the bill as quote-unquote natural.
But the rest?
I mean, tick cannabis.
Which is certainly natural.
But we also know that quite a lot of science has gone into producing the extremely THC-heavy strains sold in dispensaries today.
I've been in some pretty large grow houses, and if you think there aren't fertilizers going into the strains you purchase, even the organic strains, you're kidding yourself.
And then you have LSD, which was synthesized in a lab in 1938 from an ergot alkaloid.
So yeah, it originally comes from fungi and plants, but it required laboratory processing to bring us what we know today.
And yes, I know, maybe some witches in Salem really were tripping out on old bread, but that's really not how we use it today.
Now as I mentioned, ketamine was derived in a laboratory from PCP, which was initially made in a laboratory 6 years prior, so that's pretty synthesized.
And then you have MDMA, one of the most promising therapeutics for mental health treatment, and that was first synthesized as a blood clotting agent in 1912 by Merck.
So look, Everything is chemistry.
We've talked about that on podcast for years, since inception.
Essential oils are chemistry.
The food you eat.
Everything is a chemical interaction in our body and dose always matters.
So assigning one substance is natural and therefore good and another is synthetic and therefore bad, it just doesn't match up when we're talking about the relatively small realm of hallucinogens and psychedelics.
I mean as I said, much can be said about medicine at large and the foods that we eat.
Of course there is a difference between foods we pull from the ground and highly processed foodstuffs.
So this is just to say that the natural argument is often fallacious and it's definitely not a binary.
And there's the natural argument, but then there's also this increasing spiritual argument, which in some way plays into the same conversation.
As I was working on this brief, I came across an excerpt from a forthcoming book called The Ketamine Breakthrough – How to Find Freedom from Depression, Lift Anxiety, and Open Up to a New World of Possibilities.
Now already you can tell from that subtitle there's issues because none of those things are really proven yet and there's a lot of in-between spaces for who it'll affect and who not.
So that general title is a red flag.
Now, the book was written by psychotherapist Mike Dow and Ronan Levy, who is the founder of Field Trip, I mentioned earlier.
And the book is being published by Hay House, which we've flagged at our podcast as a very problematic house for a number of reasons way back in episode 22.
We had our guest Rebecca Baruchi on that episode, so if you've never heard it, I highly suggest going back and listening to what Hay House puts forward and how they operate.
Now, not everything they publish is bad, so I want to be clear on that.
But let's just say in this instance, blurring the lines between spirituality and therapy isn't surprising, and even from the excerpt I read, we should take a little caution with this line of therapeutics.
Now one thing Matthew has pointed out before is relevant.
Therapists who position themselves as influencers are troublesome.
Now I don't mean therapists who become popular and have a social media following.
I mean specifically the ones who market themselves as influencers.
You would generally hope that your therapist is about healing you, not promoting themselves.
And I know some will argue, well, I can heal more people if I have a bigger following, whatever.
It's bullshit, right?
So when I hit Mike Dow's website, I read that he's a highly sought-after psychotherapist and, this one, America's go-to therapist.
And that's just a red flag.
And honestly, the excerpt that was published reads like marketing copy.
The extrapolations and suppositions are quite a stretch.
So even in this piece, after briefly introducing Freudian and then Jungian approaches to therapy, I mean briefly like a paragraph each, this graph really jumped out to me.
In many ways, Ketamine Assisted Psychotherapy's foundation is quite similar to Jungian-based psychotherapy.
Jung's humanistic, holistic, and positive view of emotional health is theoretically aligned with KAP.
Both are biopsychosocial-spiritual approaches to mental health.
That's a word.
KAP can be thought of as a type of Jungian dreamwork.
In a way, Ketamine helps the client dream, and the integration session provides the interpretation of symbols, images, sensory experiences, and archetypes that come up in the session.
While some scientists still scoff at the idea that these spiritual concepts We can tell you that we've seen many clients report and draw strikingly similar themes, symbols, and images after their exploration sessions.
And both of us in our personal journeys with ketamine have experienced the same.
Okay, flagging that's an anecdote.
Not surprising that people have symbolic sessions on psychedelics or hallucinogens, disassociatives.
All that makes sense.
The interpretation is another story, but let's move on.
Whether you believe these universal archetypes and symbols Universal architects are just projections of a mind under the influence of a medicine or are coming from an even deeper source is up to you.
But we find it helpful if people keep an open mind to these concepts.
Look, I like Jung.
He added a lot to our general understanding of psychology.
I personally think his concept of introversion and extroversion, even though some of it is debated, is a very helpful framework for understanding your inner life.
But one of his last books was about how UFOs are the collective unconscious's projection of a cosmic mandala in the sky, as well as symbols of technological and salvationist fantasies.
And never mind the fact that almost all UFO sightings happen in America, and I mean by a lot.
It seems a rather narrow sample if you're discussing the collective unconscious, though to be fair many Americans do believe that the way we see the world is the only way to see the world.
And I don't know, if I'm being sold a therapeutic protocol, telling people to keep an open mind to concepts of universal archetypes, it seems pretty ambiguous and not exactly helpful to someone grappling with real world problems.
So this all reads more like spiritual bypassing than psychotherapy.
And as I said, I can't account for the entire book, so I want to be fair.
But if you're leading with that as an excerpt, I have concerns.
Sadly, everything we hold dear has the potential to be distorted as it scales.
When I was in high school, bands would be considered sellouts if they got record deals.
But how else would they have survived if not for the label backing?
It's the conundrum of success.
And it shouldn't be applied to medicine and therapeutics.
But it is.
Because we live in a free market economy and a for-profit healthcare system.
I'm currently reading a book about the creation of the city I now live in, Portland, Oregon, and I've read a few other books about the creation of this state.
And there were two major reasons for Oregon's statehood and subsequent population explosion.
First, it was created as a white nationalist post-abolition haven as Southerners escaped their homeland to take advantage of Oregon's cheap land and black exclusionary laws.
and around the same time from the spillover effects of the California Gold Rush including a minor gold rush in Oregon's mountains as well.
In both cases something amazing, amazing to these particular people mind you, was promised and a rush ensued.
So in 1850, Oregon had 12,000 residents, and within 10 years it was 52,000.
And that's what humans do.
They sniff out opportunity, and they rush to be the first to capture its value.
And maybe I'm just being romantic by hoping that psychedelics wouldn't fall prey to that phenomenon, so that's on me.
I just hope that as more entrepreneurs enter this space, they proceed with caution, and not for their bottom line, but for the collateral damage that will follow their failed attempts while panning for gold.
That collateral is the mental health of other human beings.
People who deserve better than the false promises of someone else's unfettered and uncaring ambition.
So I will say this, with a company like Fieldtrip, I'm very happy that they included psychotherapy in the model to go along with the drug.
And I think that is the only model you can do if you're working with disassociatives, hallucinogens, and psychedelics.
You can't possibly give these substances to people and send them off on their own and expect them to find healing.
I mean, maybe for a minor group, sure, but in general, it's just not going to happen.
So I do appreciate that model, and I really do appreciate people doing good work and trying to help people.
But we have to think about what we're doing here.
These substances have been used for a very long time, usually in ritual settings and almost always in communal settings as modes of healing.
And it's fine that we're trying to fit them into a society we've constructed that's much different than what those other cultures look like.
There's no problem with that.
But we have to be able to disassociate capitalism from the healing potential of these substances.
Because if we don't, we're only going to hurt more people than we help.