Ketamine works great for depression and other conditions, and costs $10/dose; the new FDA-approved "ketamine" performs badly in trials and costs a fortune


Originally published at:


Where are the studies showing ketamine works great as an anti-depressant? Where are the replicated trials?


As a jogger and cyclist I am absolutely terrified of the idea of people driving around while on Special K, most people taking the street version know better but those with a prescription will definitely think it’s literally a license to drive on it

If you doubt that logic, I am constantly stunned by the number of people driving while stoned now and it’s not even fully legal in my state, only “medical” but that’s enough to make people think it’s a free pass and okay to use anywhere and DUIs somehow don’t count

The number of times people have rounded corners at full speed without even slowing down and almost hitting me in the crosswalk is now more than I could count on my fingers, though that may be from driving while texting, who knows (if self-driving cars will stop that, might be worth the other deaths it causes)


Ketamine is a mixture of two chemical isomers. R-ketamine and S-ketamine. Aka esketamine.

S-ketamine is considered the isomer responsible for ketamine being effective for depression. So in theory, it should work the same as ketamine, but with fewer side effects. So if S-ketamine is doing badly in trials, it implies regular ketamine would do worse (no better therapeutically, but worse side effects).

Isomers can have radically different effects on people. Thalidomide is made up of two isomers, only one of which appears to cause birth defects. The safe isomer is also thought to be the therapeutic one.


As someone with lifelong depression, I’ve been on many different antidepressant medications and found only a few to be slightly helpful, and never longterm.

If ketamine works better, and politics and/or bureaucracy restrict its use to a less-effective clone of some sort, that’s more than unfortunate and definitely infuriating. I’d go so far as to call it criminal.

For what it’s worth, I did find one therapy that has alleviated my depression more than any drug ever has. It’s been half a year since I underwent transcranial magnetic stimulation treatment — which is a medically approved therapy that my insurance covered almost fully — and I’m still good. If anyone reading this has depression, I’d urge you to talk to your doctor or psychiatrist (and your insurance). It’s noninvasive and the most common side effect is a slight headache after treatment. The worst side effect is a slight seizure, and is very rare.


When I read this, I kind of suspected what you’re saying. Seems like the odds are good that regular ketamine will perform the same or worse as nega-ketamine when subjected to actual clinical trials.


Don’t worry, ketamine is not in danger of being further restricted. It just isn’t an approved drug for depression, so it cannot be marketed for depression. i.e. ketamine makers and distributors can’t say “Hey Doc, did you know you can use ketamine for depression?” Doctors however are still permitted to prescribe it “off label.”


I have to say, giving an intensely depressed person a dissociatve hallucinogen, and requiring them stay in the clinic for two hours seems like a very reasonable protocol.


Methamphetamine is the same way. Levomethamphetamine is a mild stimulant, comparable to caffeine.

Dextromethamphetamine: where are my pants? fuck it, who cares?

Prescription meth is strictly L-mAmp.


Since it can’t be (re)patented, nobody is going to spend the money to do those studies or trials.


Never discount that there are simply a lot of terrible drivers out there.


Since this seems to be misunderstood, there are several things about a drug that can be pattented. The drug itself is one of them. The method of delivery is another. The form of the drug can be another.

But, my question stands, Cory asserts that there’s proof that Keatmine is an effective and safe anti-depressant. Where’s the data?


Big review artlice from last year, describing and citing all the research about the pharmacology, mechanism of action, and depression clinical trial results.

Molero P, Ramos-Quiroga JA, Martin-Santos R, Calvo-Sánchez E, Gutiérrez-Rojas L, Meana JJ (May 2018). “Antidepressant Efficacy and Tolerability of Ketamine and Esketamine: A Critical Review”. CNS Drugs . 32 (5): 411–420. doi:10.1007/s40263-018-0519-3

Try this share link if that’s behind a paywall for you.


Okay, so the data shows that it’s somewhat effective as a short term anti-depressant, but the long term utility is unknown. The safety isn’t touched on either. The administratment of the treatment requires the parient to be sedated as the medication has hallucinatory and (I love this word) psychotomimetic effects. That means that it can cause in the patient a heightened experience of whatever you’re trying to treat.

If this even pans out, it’s going to be a very specialized treatment, it’s not going to be something that your shrink is going to write you a script for and send you home. This is more equivalent to a major surgery where your health will need to be evaluated, you’ll need to be treated under supervision, and you’ll need to be monitored for some time after treatment. And it may only be effective for a few weeks. Side effects are possibly going crazy or destroying your kidneys.

Note also, that the data so far is what’s been used to get J&J into these trials with so little data. This treatment research is at very early days.

So, even if a doze of ketamine costs $10 on the street, that’s got nothing to do with what’s happening here. It’s not like some street lab is going to be able to produce a medical grade version of the enantiomer.


Review article with references.


The explanation why regular ketamine hasn’t been approved for depression is at once, less sinister and more sinister than the conspiracy theories.

Less sinister in that it’s a function of how the FDA approves drugs and devices. In order for the FDA to even review whether a drug or device should be approved, a party has to apply for approval. The application itself has to show evidence that the drug or device is safe and effective for the approved use. For something like this, where a known drug is being used for a new purpose, the normal pathway would be for a pharmaceutical company to apply to do a study on safety and effectiveness for the therapeutic purpose, then negotiate with FDA on a study design, perform the study, then apply for approval with the results of the study, the indications and labeling that they want to use, and any additional testing that supports the application. That process usually costs millions to tens of millions of dollars to complete.

If no drug company sees a pathway to recoup their money on going through the approval process, then it doesn’t get done and the drug doesn’t get approved.

And that’s the more sinister part. No one has to suppress inexpensive and effective treatments in order to keep them off the market, because the whole system is set up such that effective treatments that are so inexpensive that no one can make at least, say $10M off of them just will never even be tested.

There are a couple of mechanisms that can help (humanitarian use exemptions and orphan drug pathways) but for something like ketamine, that has no patent and is easy to manufacture, there isn’t even enough drive to go through those pathways.


To be clear: plain ol’ ketamine is racemic ketamine, i.e., it’s a 50/50 mixture of R-ketamine and S-ketamine. “Esketamine” is only S-ketamine. So it’s not “the mirror image of the ketamine molecule”, it’s one of the two mirror-image molecules that comes in “plain ol’ (racemic) ketamine”.

And the patent derives from the route of administration: Esketamine can be administered as a nasal spray, while racemic ketamine must be injected.

The approval of esketamine doesn’t alter the existing approvals for ketamine (which include low-dose use for chronic pain.) Ketamine is not yet approved for use as an antidepressant, but is used off-label for that purpose by many doctors and an increasing number of “ketamine clinics.”

Off-label use is perfectly legal, and a common practice with many applications of many drugs. It may affect insurance coverage, but doctors can prescribe an approved-for-sale drug for any purpose, including ones not mentioned in the FDA product insert,


Minor disagreement. Racemic ketamine can be dose intranasally or orally, but these are not “approved” routes. Back in my ICU days, I utilized this fact fairly often to sedate kids for painful procedures and it was quite effective. No personal experience using it for depression, but as far as route of administration, I do have knowledge of its usefulness.


Replication is an issue (but let’s be honest it is just an issue all around lately), but preliminary studies are out there. There are a bunch more, but that should get you started.


NOT true deedub. I was, and STILL AM, part of that Jannsen study. My highly qualified doctor told me that Jannsen spent $1 BILLION on this study, WORLDWIDE. Yeah, they want to make a large profit. But this psychedelic drug WORKS … and fast! After 3 years, I am still depression free.