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Why the Government Legalized Esketamine and Not Ketamine

government legalized ketamine
Written by Sarah Friedman

The psychedelics boom is underway, and the first federal government legalized psychedelic (other than DXM) is esketamine, a half-brother to the well-known drug ketamine. So why this drug in particular, and why so quietly, when every other drug legalization is debated in the press? Perhaps the answer has to do with ketamine itself. Here’s a little bit to answer the question of why the federal government legalized esketamine for depression, and not ketamine.

Esketamine was legalized a few years ago, but why would the US government do that instead of legalized ketamine, the already popular half-brother? Good question, unfortunately we can only speculate for now why one was chosen over the other. Regardless of why, it makes clear that the psychedelics boom is clearly underway! We’re dedicated to covering this new industry, so for more articles like this one, remember to subscribe to the Psychedelics Weekly Newsletteryour #1 internet source for everything related to this new and growing market.

First off, what are ketamine and esketamine?

While the population at large might think of ketamine as a party drug originating in 1980’s dance clubs, the reality is that the drug has been around longer than that. Ketamine was discovered in 1962 at the pharmaceutical company Parke-Davis. The idea was to find a strong anesthetic, and ketamine fit the bill with its “cataleptic, analgesic and anesthetic action but without hypnotic properties.” The government legalized ketamine in 1970 for medical use, but only as an anesthesia, even as it had been found to work well to calm negative behaviors in prisoners in the 60’s.

Ketamine, with the chemical formula C13H16ClNO, has been described as a ‘dissociative anesthetic’, as users will describe the experience as feeling like different parts of their brain are being disconnected from each other. Though it has been found useful for dealing with psychological issues like depression, as well as pain issues, it has only been officially cleared as an anesthetic in people and animals.

Half-brother esketamine shares the same formula, but is much newer to the world, having been discovered in 1997. This happened in Germany, where it first came out as an anesthetic as well. It was discovered while being used in this way, that it can also provide anti-depressant effects.

esketamine therapy

This, of course, was already realized with ketamine, so the discovery isn’t shocking, and might have even been looked for. In the US, trials for treatment-resistant depression were finished in 2017, and Johnson & Johnson filed for a new drug application, which was subsequently approved. The first esketamine drug to hit the market for this purpose was Spravato, which came out on March 5th, 2019.

A thing to understand about this approval, is that it doesn’t allow the direct prescription of only esketamine, but actually continues to promote the standard monoamine antidepressant industry (think Prozac and Zoloft) by requiring use of one of these in conjunction with the esketamine. Meaning you can’t actually get esketamine treatment without use of another pharma antidepressant. Kind of odd since the whole idea of psychedelics for this purpose is to get away from the standard anti-depressant field, with a better working product.

As a testament to how well esketamine works, it was also cleared for use with suicidal thoughts in 2020, a designation that requires a very fast-acting medication, as suicidal thoughts often lead to suicide. While ketamine is administered via IV generally, esketamine was approved as a nasal spray.

How can ketamine be prescribed legally?

Now we know that esketamine and ketamine are closely related, and do the same general things. And this brings up the question of why the government legalized esketamine, but not ketamine, even though it was already known that ketamine worked for the same things, while also having name recognition value. My guess? It was probably as a way of trying to combat the ketamine gray market that had already sprouted up (and continues to grow), in the form of treatment clinics offering ketamine for off-label uses like help with depression and chronic pain.

How does this work? Remember, ketamine is a legal drug, and can be used legally as an anesthetic, as it’s a Schedule III compound. Of course, this is wildly different from being used as an anti-depressant, which it is not approved for. So how are clinics using it in this way not being shut down? By prescribing it for ‘off-label’ use. Off label use is defined as:

“The use of pharmaceutical drugs for an unapproved indication or in an unapproved age group, dosage, or route of administration. Both prescription drugs and over-the-counter drugs (OTCs) can be used in off-label ways, although most studies of off-label use focus on prescription drugs.” And it’s perfectly legal, even if it means entering the gray market.

legalized ketamine

How so? Well, as the FDA states: “Once the FDA approves a drug, healthcare providers generally may prescribe the drug for an unapproved use when they judge that it is medically appropriate for their patient.” So if a doctor with prescribing ability sees fit, they can prescribe ketamine for other uses like for pain management and depression control.

Which means, even though ketamine has not been cleared officially for these purposes, the clinics that offer treatment are not technically operating outside the law, creating what is essentially a ketamine loophole. This is unlike other psychedelics like MDMA, LSD, or psilocybin which are Schedule I, and therefore not able to be utilized in this way.

What’s the difference in getting ketamine vs esketamine?

Interestingly, this makes ketamine the better choice for getting around regulation, as esketamine must be administered according to very strict guidelines. Ketamine, technically doesn’t, as its uses for these purposes are not regulated by the federal government. No states have regulation set up for ketamine clinics either, meaning it fully operates as only an off-label use item, and without government interference.

To be clear, these clinics are still legitimate medical clinics, and as such, must operate under general regulation for such operations. This can include standards of cleanliness, capacity requirements, or other such protocols. But it won’t include patient safety regulations specifically related to ketamine, as none exist.

Since a prescription must be obtained for esketamine by a specialist (and won’t likely be given by a primary care physician), this means the doctor does have to agree with use of the medicine. So if a doctor is anti-psychedelics, for whatever reason of old-school fear tactics winning out, it means a person might have to go to different doctors to find one on-board.

Conversely, as no guidelines exist for ketamine to be used in these ways, a patient can get a prescription from any doctor willing to give it, or simply go to a ketamine clinic where the doctors can do an evaluation and directly provide the prescription. It should be remembered that off-label or not, ketamine is still being used medically, and does require a doctor’s approval. This is not for recreational use.

ketamine therapy

Why the government legalized esketamine and not ketamine?

So why did the US government seemingly randomly legalize esketamine and not ketamine? Is it possible that it foresaw the inability to get the already existent ketamine market under control, and didn’t want to risk another fiasco like with cannabis, where legal markets can’t compete well with black markets (which has already led to the need for a bailout in California)?

It’s impossible for me to say, but it is an interesting question. And the US government legalization does come with one factor that could make it appealing for those who want therapy. Because it’s an approved medication, it can be covered by insurance. And this can drastically reduce the cost. Ketamine therapy might be gaining popularity of late, but it sure ain’t cheap. If you can shell out hundreds of dollars per treatment session, it could be a great answer, but how many people can do that?

Esketamine can be obtained for much more reasonable prices with medical coverage, making it a more financially viable option. Plus, it does come with the (possible) benefit of regulation for safety issues, though I stipulate ‘possible’ because the pharmaceutical industry really isn’t known for its overall caring about safety, and considering the opioid epidemic, neither is the government.

Apart from these benefits, it does come with the major detraction of requiring a doctor to be cool with prescribing it (which a lot won’t be due to decades of smear campaigns), and even worse, the need to be on an antidepressant to access it, even though the two are unrelated. Kind of seems like the government threw that one in to help out big pharma, probably with the understanding that it was up against a lot with the already-existing ketamine gray and black markets.


In the end, I expect the government legalized esketamine because it saw that it worked better than monoamine antidepressants and knew that’s where people would go. It probably didn’t want to compete directly with (and likely lose to) the market that already exists, and so released a tweaked version instead. Of course, the government is made up of people who care more about their own interests and those of large corporations, so rather than be smart about it to really compete, it made a lot of wonky rules that will probably do to a possible esketamine industry, what high taxes did to legal cannabis markets. Tank it out!

If you think ketamine might work for you, and don’t want the government telling you how to take it, get yourself to a clinic, and ask about dose sizes and frequency. Perhaps you can find a clinic that provides bigger doses and fewer of them, which might make it more cost effective. This directory should help you get started. On the other hand, if you think esketamine is the better way to go, you can find centers that administer it here.

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DisclaimerHi, I’m a researcher and writer. I’m not a doctor, lawyer, or businessperson. All information in my articles is sourced and referenced, and all opinions stated are mine. I am not giving anyone advice, and though I am more than happy to discuss topics, should someone have a further question or concern, they should seek guidance from a relevant professional.

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About the author

Sarah Friedman

I look stuff up and and write stuff down, in order to make sense of the world around. And I travel a lot too.