Ketamine and its analogs are known to have a rapidly developing and profoundly durable (some even say permanent) tolerance, and I find this is often glossed over, especially when studies don't evaluate it over a long enough time period
I think Ketamine itself isn't a real solution but hopefully some of the isolated metabolites will be
> tolerance. I find this is often glossed over
This was specifically and prominently addressed by the article:
>> However, at 25 days the effects had levelled out.
>> The study's authors suggest it could offer an effective rapid treatment for people severely depressed and at imminent risk of suicide and could help in the initial stages of treatment, as most anti-depressants take four to six weeks to become fully effective.
They see it as a bridge treatment which is temporarily useful until anti-depressants kick in. Because, as it said, after 25 days the benefits begin diminishing... which sounds perfectly reasonable and has the added benefit of reducing the risks of addiction.
I think the durability of that tolerance was what the parent was pointing out.
As in, it's potentially only useful as a bridge treatment once. If you decide to lapse your long term anti-depressant after several months and suddenly need another bridge treatment as you ramp back up again, the durability of the tolerance from your initial ketamine treatment would prevent it from being useful the second time.
Yeah, I would hope that we find more durable solutions.
I know some people have been on it for an extended interval without any sort of tolerance problem, which is how I initially heard about it firsthand, so it's one more of those strange biochemistry things that's inconsistent, because of course it is.
The interesting thing, to me, would be figuring out what the method of action is for the effect, in order to replicate it in other drugs, but we'll see.
(I'm also curious whether repeating the dense dosages would be effective again for me now, over a year later, or whether the tolerance would be, indeed, permanent.)
I'm curious about whether you've tried to push the dosages into more psychedelic ranges and whether that had an effect? Many researchers seem to think that at sub-dissociative levels the effectiveness is less, as the _experience_ of that state is what alleviates the depression, not the chemical (so to speak).
Most sub-dissociative levels were probably with nasal sprays; I can assure you, this was definitely dissociative levels every time, via IV.
We tried increasing the dosage, which made the dissociation more potent, but had no improved psychiatric benefits for me.
The supplement and drug industries are constantly finding ways to provide chemistry that will be most specific and bio-available. While this certainly has benefits, I worry that by bypassing precursors, we also often bypass important regulatory steps the body uses to avoid damage.
The idea that taking something that fixes a symptom, but then creates a permanent tolerance, makes me think that getting that chemical too directly in the past may have caused the tolerance that caused the initial symptom.
Your story reminds me of "Flowers for Algernon" (https://www.amazon.com/dp/B003WJQ74E). If you haven't read it, you might enjoy it for the parallels.
I've considered picking that up a couple of times from very positive reviews, but I'm rather concerned from having heard what the overall mood is at the end of the novel.
Ironically, perhaps when I find a sufficiently effective combination again, I'll give it a look. Thanks!
This easily explained:
Ketamine seems to repair some kind of cell damage, thereby increasing neural plasticity.
That is a huge asset, but long endured depressions leave many unhealthy neural circuits over the years. These have be unlearned one by one, which takes time.
Ketamine increases freedom of thought and emotion, but you still need a goal and long-term plan to precisely target and unwork all the patterns that circle back to depression.
Luckily the entrypoint away from happiness is discernable and it is bittersweet: giving up, thereby reducing stress. Which is sweet at first, but turns into hell fast.
Neuroprotective behavior is one of the theories I've heard about ketamine's efficacy, as well as lithium's, but that doesn't explain the immediate gross improvement, just the eventual semi-permanent tolerance in some cases.
In my case, while it was effective, I was a much more productive and healthy person than I'd ever been, cleaning up lots of mess and accumulated dross I'd never been able to convince myself to go through, more physical activity, more consistent eating...but then it all abruptly came crashing down, eventually, so either the learned behaviors have quite a thresholding behavior, or it's a more complex mechanism.
Humans feature meta-cognition. I suspect you felt better and more relaxed due to the mechanism, and that in turn gave you another big boost by showing you that you are still capable to feel and act different.
That reminds me of the short story "Beginner's Luck" By Poi Lass.
It is part of a series examining what happens to people that discover they have a minor super-power.
It was...possibly the single worst experience of my life,
feeling that slip away, and now having recent
crystal-clear memories of how much that fog had been
complicating my life.
Imho, dissos are for short term depression fixing, you need them psychedelics to open your mind for long term.
Just for a little anecdotal evidence: I ate some psychedelic mushrooms multiple times about 8 years and and haven't been depressed since. I was previously diagnosed with clinical depression and took a moderate amount of Seroquel for it. I haven't taken anything since and I've been great.
counter anecdote i know massive amounts of people who have taken psychedelics that are depressed.
similarly for ketamine.
Without specifying the relative proportion of those who went up, in your experience, along with the massive amount of people who went down, your counter anecdote is weakly armed.
I think either case is weak. Parroting Leary here seems appropriate - set and setting are just as important as dosage when it comes to these substances.
I think this is really what I'm trying to say - that these anecdotes about psychedelics curing / not curing depression to be profoundly useless.
Seroquel for clinical depression, really? I thought it only was used to treat psychotic episodes (I’ve taken it for that specifically).
Oh well, you learn something new every day.
I've heard it being used as an augment for people who have trouble with other treatments, or if they're also looking for synergies with the other effects of it.
A couple of antipsychotics or even more esoteric drug types are used (off-label and otherwise) for antidepressant effects, often at dosages lower than they'd usually be thought to be effective for whatever the primary usage would be. Why does it work? Ask again in 50 years, maybe.
- Seroquel (off-label)
- Adderall/Ritalin for people with drive problems
- Wellbutrin is a smoking addiction aid, antidepressant, and SAD-specific antidepressant (because why not, biochemistry)
- Strattera is nominally an ADHD med but has been using it as an antidepressant off-label for at least 15y (source: I was given it for that, then)
- Abilify is on-label used as an anti-psychotic, anti-depressant augment, and Tourette's med, because again, why not
- Also, one thing a lot of people don't realize is that you don't want to mix a unipolar antidepressant with untreated bipolar, because surprise, side effects may include P(manic episodes) approaching 1, so the options for each of those can sometimes overlap and sometimes not
Biochemistry is really weird, and neurochemistry is one of the densest places for it in the body.
Where I live (Sweden), there are rigid restrictions on what a psychiatrist can prescribe, in the sense that off-label prescriptions aren’t a thing what so ever.
What you said makes perfect sense to me. My reply was just me being surprised by someone who apparently got an antipsychotic for clinical depression alone (... which turned out to not be the case, but yeah...)
The doctor thought I might also be bipolar or something but wasn't sure which is why it was chosen.
Seconded. Try mushrooms, acid, or DMT. Maybe mushrooms if it’s your first time. Watch some trip report videos on YouTube to get an idea of what you’re in for.
It doesn’t “cure” depression... it’s more like it gives you an audience with... something... that then tells you exactly what you need to know about life, the universe, and everything. It’s up to you to then make sense of it, integrate, and execute, which can in itself be difficult for people.
It’s not a cure, it’s a debugger for your brain.
Ketamine is itself a psychedelic.
With all psychedelics, it's very important to integrate the insights you gain during the experience back in to your ordinary life, or they are likely to fade.
It's also important to use psychedelics constructively: with a constructive intention, with an experienced sitter that you trust, in a safe setting. There are lots of other things one can do to prepare. I'd recommend reading "The Secret Chief Revealed" and "The Psychedelic Explorer's Guide".
 - https://www.amazon.com/Secret-Chief-Revealed-Myron-Stolaroff...
 - https://www.amazon.com/Psychedelic-Explorers-Guide-Therapeut...
I've posted this in other ketamine news stories before, but I'm offering it as a firsthand testimonial here.
Ketamine was both the best and most depressing depression treatment option I've ever tried.
Within a couple of weeks after having had the initial round of six treatments in two weeks, I was the most functional and productive human being I've _ever_ been - things that used to be impossible or utterly agonizing to complete were as trivial as they "should" be, I was enjoying life, it was great.
After a couple of months of periodic booster treatments, over the course of a week, I felt it completely drain out of me, and no variance or repetition of ketamine treatments has been able to reproduce it since. (We spent months varying dosage levels, frequency, and trying a few OTC things that the doctor had seen synergize ketamine response in people before, to no avail.)
It was...possibly the single worst experience of my life, feeling that slip away, and now having recent crystal-clear memories of how much that fog had been complicating my life.
Can confirm. I’m in a similar boat.
Some other tidbits of information:
- only thing that seemed to work even after TMS and other treatments.
- New pathways (SF and San Mateo locations) is really good.
- more and more treatment places opening up in different cities etc.
- uber assist or drive the patient home (full lucidity afterwards but you don’t want to drive).
- long-term benefits aren’t apparent after the first two treatments. After the third it seemed to last for 2-3 days. After the fourth longer.
- it really seems like a ‘break out of depression’ breakthrough treatment. Though no cure all (talk therapy or a good support system is important too).
- ketamine is used for many purposes (anesthesia, etc.). When given for depression it’s given in much low dosages (presumably without harmful liver or kidney side effects).
- usually the patient listens to music with headphones while the infusion is in progress.
- a nurse monitors BP and heart rate etc., but so far there have been no compications other than a nurse who was bad at putting in an IV (once).
- feel very thankful for it.
- I could see it going mainstream in the near future.
Do you have any idea what the dosage is? Is it an immersive 'K-hole' dose where you go deep and become unresponsive for a bit? Or are the infusions smaller doses just meant to build up the anti depressive afterglow effects in the body?
How easy would it be to do this at home by snorting half a gram but over the course of an hour?
half a gram seems pretty excessive to me. if you snorted that over the course of an hour, with zero tolerance, you'd very likely knock yourself out.
Half gram would knock you out cold.
A better "close to k-hole" dose would be 100mg. At least based on our experiences 100mg would get some people in the hole, while it took some others 50mg - 100mg more.
Where are you getting this treatment from? Did you directly ask for it?
New pathways ketamine treatment center. There’s a handful of other providers in the Bay Area too. Referred by psychiatrist (and internally recommended after TMS didn’t have beneficial effects - works for some though).
And yeah I’m not sure about the dosage. I know it’s much less than ketamine for pain management or for anesthesia. I’ll try to ask next time.
Thanks for the info, do you know if they allow people to come in on their own? I don't really want to try to get my doctor to refer me.
> We pay $375 for a 40-minute infusion
Having no knowledge on the matter, what's the price comparison to just buying ketamine illegally and taking it without a doctor's help?
Depression is like (or possibly is) a form of chronic pain. People suffering from it severely might be willing to do anything for relief. Here's good information that a currently-illegal drug can help but if you want to do it legally you might need to take on a third job just to pay the costs.
It reminds me a bit of the South Park episode where 'concentrated dose of about $180,000 shot directly into the bloodstream' is discovered as the cure to AIDS. Volunteers inform poverty-stricken Africa that all those suffering from AIDS have to do is inject themselves with piles of cash.
Ket will set you back anywhere from $50-$150 per gram, depending on where in the world you are, and is of varying quality. It looks like they're using up to 1/2 a gram for treatment.
I think the most of that $375 goes towards staffing costs, rather than the drug itself. Ketamine though legitimate channels costs about $5-$10 per gram from what I've heard.
> It looks like they're using up to 1/2 a gram for treatment.
Typically they use 0.5mg/kg. I think you may be confusing milligrams (mg) with grams (g).
I was told when I had it done that almost all of the cost was the paid time for a trained professional to do the IV, since ketamine for medical purposes costs on the order of cents per gram or less.
Do you have a source on that 1/2 gram number? My reading has lead me to believe that a typical therapeutic dose for these treatments is between 60-75mg. I could be way off, though.
It's .5mg/kg, so even 50 mg is enough for a pretty big guy. 500mg would knock you out for awhile. He might be misplacing a decimal there.
I was looking at studies earlier today, and the upper limit (assuming a 100 kg person) was 0.5 g from one of the studies.
That can't be right, 0.5g will knock out a horse for many hours
I think that the new part of this publication that they now have an easy to administer nose spray.
My doctor uses a sedative also to make sure you don't freak out during the treatment. I think most doctors do this. You need to factor that into the cost too.
Sedatives (probably benzodiazepines) are also very inexpensive (on the order of less than a dollar) compared to the $375 figure.
> Having no knowledge on the matter, what's the price comparison to just buying ketamine illegally and taking it without a doctor's help?
It's way cheaper on the black market. The actual cost of manufacture isn't very high, and I don't think it falls under any patents needing licensing. Probably you're mostly paying for the labor.
Doesn't ketamine stimulate growth in the same areas of the brain that exercise does, and does therapy prescribe routine daily exercise?
I can imagine there being a great short term benefit to ketamine, as people who are severely depressed can't exercise due to the depression. Has there been any mention switching from ketamine to daily exercise, or doing both?
Anecdote alert, but I get about 10 hours of exercise a week and at best it's stopping things getting worse.
I know exercise is good for depression, but this is an extremely patronising response to someone else's description of their medical treatment.
How is it patronising? GP is asking two questions. Maybe there's some subtle subtext that I'm missing, but even then it seems better to assume the more favorable interpretation that he's just asking questions.
Well that'll teach that poor bastard to ask a question here, good job!
Is it possible to ask a question in a patronising way?
I don't know, is it?
I would say yes.
Sorry. That wasn't the intent. I could have been clearer.
More, I don't know what ketamine does in the long term to the brain beyond stimulating the parts of the brain that get strengthened during exercise. Maybe it's doing something else and that was the motive for the curiosity. What exactly is ketamine doing in the long run to the brain?
The difference is that ketamine shows positive results in clinical trials (even for severe depression) while exercise doesn't, unless you include poor quality trials and you limit results to mild depression.
Whoa. Do you have a link to a meta-study or something like that?
I've posted this before. There's a newer study that has better results.
Exercise is moderately more effective than no therapy for reducing symptoms of depression.
Exercise is no more effective than antidepressants for reducing symptoms of depression, although this conclusion is based on a small number of studies.
Exercise is no more effective than psychological therapies for reducing symptoms of depression, although this conclusion is based on small number of studies.
The reviewers also note that when only high-quality studies were included, the difference between exercise and no therapy is less conclusive.
Attendance rates for exercise treatments ranged from 50% to 100%.
The evidence about whether exercise for depression improves quality of life is inconclusive.
The results are limited for Ketamine too.
How often did you have depression? Especially major depressive episodes where you have trouble to even motivate yourself to move out of the bed or do ANYTHING but just "exist" and even that seems hard?
If the answer is zero (which I think it is) do those who have it a favor and shut up. Depression is hard enough without "you just have to exercise, huahua" comments.
I over came decades of suicidal depression (as well as schizophrenia and bipolar) with a self concocted protocol which included psychedelics and now don't take traditional meds.
I read the OPs intention as "use K to get the person back from the bottom of depression and then leverage that boost in mood to start a habit of excersize"
That seems reasonable and a good approach. You want to reinvest the motivation and better mood into relationships and behaviors that will continue to compound feeling good.
I'd also recommend Gratitude as a practice and ultimately some sort of somatic work where you are encouraged to go deeply into any uncomfortable feelings with your full body.
Can you explain your protocol? That's pretty promising. I've had some good results to date but not sure how to use them in a more disciplined way to create permanent results
I'd be happy to Skype with you for 20 minutes sometime. You can email me firstname.lastname@example.org
While you are totally right, you could have phrased that a lot better, and don't tell people to shut up.
> If the answer is zero (which I think it is) do those who have it a favor and shut up
I get where you're coming from with this response - if you haven't been there, there is just no way you can understand how desperately bleak things can become.
But if someone is ignorant about mental health, why not try to educate that tell them to "shut up"?
We need to talk about these things, not humiliate and shut down anyone who doesn't understand.
>do those who have it a favor and shut up
Nothing is more irksome than the trend in public discussions to tell others to "shut up" if they haven't specifically experienced something.
This is a public forum. We're discussing a publicly posted article. The OP brought to the table a valid point. Let them talk.
I'll always remember a quote from a cancer researcher/professor on tv: "You don't have to be an elephant to talk about elephants." Sadly I don't have an elephant's brain so I don't remember the professor's name.
A lot of depressed people who have been able to pull themselves out of the hole can be pretty touchy about stuff like being told to exercise. OP was maybe a bit more aggressive than he needed to be, but it can be a pretty raw feeling, and mental illness has such a stigma.
When studies seem to suggest exercise helps, its pretty dangerous to shout down comments like this. Especially when you're completely misrepresenting the question.
The effects are so significant that I have gifted small amounts of ketamine to close friends who suffer from depression, so that they may store it long term as an emergency last resort to try in the event of irresistible suicidal ideation. It really is a lifesaver.
> and the potential that there are long term side effects that have yet to be discovered.
Not for medical which is maybe what you are referring to. But long term (recreational) ketamine use (abuse) is well known. Perhaps down to the method of injection (nasal) or the impurities in illicit ketamine, but there is a lot of information on bladder problems, stomach cramps along with heavy addiction
it seems likely to be the ketamine - http://ajp.amjpathol.org/article/S0002-9440(16)00073-0/fullt...
That's still cheaper than a private psychologist or psychiatrist (after the initial course).
The cheapest per infusion cost is around $350 and the most expensive is around $1000. It's not actually cheaper.
And public / insurance covered ones are overworked as it is.
Infusion? Goodness grace, I got belonephobia and got scared shitless there. It doesn't have to be administered intravenous. The article is mainly referring to a nasal spray.
Typical infusion time is 40 minutes. How would one accomplish the same release with a nasal spray?
Yes, but is just the latest study.
My girlfriend receives ketamine treatment for her depression, so I’ve the results first hand. It’s truly astounding. She’s seen more improvement from the ketamine than from a decade of psychotherapy and traditional psychopharmacology.
The only downside is the cost (it’s not covered by insurance) and the potential that there are long term side effects that have yet to be discovered. We pay $375 for a 40-minute infusion. The recommended initial course is six infusions over two weeks. After that a booster or two is usually needed very two to six weeks. (It’s been about every three weeks for my girlfriend.)
It's expensive because doctors are using it to make a lot of money. The drug is cheap.
That and I bet the malpractice insurance for this kind of off-label use is going to be pretty high.
> - Ketamine seems to have a much larger effect size (-~0.99  vs -~0.35 for typical antidepressants ) [If anyone spots an error, please let me know]
I've heard that 35% figure bandied about for awhile now. Does this take into account multiple SSRI's? If one took Welbutrin and it didn't work, for example, and then one decides to try Paxil, is there still a 35% chance that Paxil will work? (both Paxil and Welbutrin are SSRI's)
Or is the 35% figure meaning that if one tried all the SSRI's out there, there is only a 35% chance that any of them at all will help you?
I tried reading your reference, but it doesn't seem to mention this.
Not sure about your questions, sorry. Perhaps try asking on reddit.com/r/askdrugnerds. And a minor correction to your comment: The ~0.35 is showing standardized mean difference which is more a measure of how much it reduces someone's depression by, as opposed to what you're asking about which is about what % of people respond to a given treatment.
Anyone know why it always seems to be given as an infusion, and not any other route?
If it was just about bioavailability, I guess they'd just give large oral doses.
I recall reading of people self treating with ketamine off the darknet, and I imagine they are not giving themselves an infusion?
Oral ingestion is unpopular due to inefficiency and the likelihood of stomach upset. People who are self-administering ketamine are most likely insufflating. I have friends who have reported very positive results with intramuscular injection, but most people don't have access to hygienic injection apparatus, nor any experience using it safely, so insufflation is most common.
Main upsides of Ketamine for depression vs typical antidepressants (SSRIs, etc)
- Ketamine seems to have a much larger effect size (-~0.99  vs -~0.35 for typical antidepressants ) [If anyone spots an error, please let me know]
For context, an SMD of 0.2 is small, >0.5 is medium, and >0.8 is large.
To me this seems to be by far the most important/interesting thing: Ketamine seems to have a much stronger antidepressant effect than our current antidepressants.
- Benefits occur within hours rather than weeks
- Doesn't seem to interfere with sexual function, unlike many antidepressants
Main downsides of Ketamine for depression
- Much more expensive and normally not covered by insurance
- It's less well studied
- You have to go in for additional ketamine infusions to maintain the effects, it seems roughly ~1x a month long term
(The SMD for typical antidepressants seems to range from ~-0.13 to ~-0.35, with Tricyclic antidepressants slightly higher at around -~0.42.)
I'm not a chemist either but as someone who as partaken and knows other people who have also partaken, the dosages you have to take in order for this to become an issue are way beyond what would seem reasonable for someone who's not heavily dependent and tolerant.
You would have to be taking grams and grams of the stuff on the regular; infrequent or one-off dosages won't cause bladder damage.
Edit: even in the article you can see that the guy developed "K bladder" after taking 15g per day. 15g is a truly scary amount of powder to be ingesting.
15g a day is a truly insane amount, i'm shocked the person mentioned didn't die... I've known 1/2 a gram leave people catatonic for hours.
Insufflating 15G of anything is physical a feat in and of itself
If you use Ketamine regularly you build up a long lasting resistance pretty fast. I've met someone who was doing 5-10 grams a day and it barley had any noticeable effect on him
My guess is that 0.5-1g/day, if ingested every day, is sufficient to cause bladder damage.
However, for use as an antidepressant, 100-200mg (0.1-0.2g) twice a month is sufficient, so it shouldn’t be an issue.
"However, for use as an antidepressant, 100-200mg (0.1-0.2g) twice a month is sufficient, so it shouldn’t be an issue. "
I will second that. A friend would use around that much and it would last almost 2 full weeks without feeling the need to take another 100mg. Once the 2 weeks hit though, he could feel his depression / anxiety coming back slowly.
From my research on the subject, ketamine bladder only happens if to chronic, long term users using several grams a week.
Most of the studies of using ketamine to treat depression are using under 1 gram per month.
Infrequent use of ketamine (less than once a week, less than 1 g), whether medical or recreational has no negative side effects.
It's also unknown whether it's actually caused by ketamine, or by whatever is being used to cut street ket.
Ketamine can do that under the extreme dosages used by recreational users. It's also important to remember that a lot of the bad long term effects of drugs can be attributed to impurities, which there should be next to nothing off when you get it from a doctor.
In this specific case the bladder damage is from the ketamine (metabolites) itself, not impurities.
> the bad long term effects of drugs can be attributed to impurities, which there should be next to nothing off when you get it from a doctor.
Ketamine is sourced pretty much exclusively from pharmaceutical manufacturers and is medical grade.
It is normally cut with other shit though to bulk it out and get more profit.
Ketamine has such a distinctive appearance in solid form that cutting it with anything else is quite difficult. Ketamine is relatively clean in the United Kingdom compared with other illicit chemicals.
Not a chemist but according to the providers I’ve talked to the recreational dose is an order of magnitude larger than that given for depression. My understanding is the dose for depression is relatively small (even compared to what’s used during, say, anaesthesia).
Not an order of magnitude. Maybe 1.5-2x. Antidepressant doses are not far off of recreational for most recreational users.
The recreational doses are also relatively small (10-50%) compared to anesthetic doses, too. Being unconscious isn’t the recreational user’s aim.
I've had K for anesthesia at the oral surgeon's, and it did not make me unconscious. It put me in a K hole. I was conscious the way you're conscious in a narrative dream. I have pretty clear memories of the experience (trip) - just no memory of my teeth being extracted.
Daily, high doses can cause recrystallization in the bladder.
It's a problem, but seems to be limited to those exhibiting problem usage (even within the context of recreational use)
it's not prescribed long term
@HN's chemists - I was under the impression regular ketamine use caused irreversible bladder damage - Is that due to much higher recreational dosage vs medical, or would this be something that couldn't be prescribed long-term?
I recognize this kind of story. I also suffered pretty horrendous abuse from both parents growing up. I partly credit weed for self-treatment of extreme social anxiety, and being able to get out into the world and function, if only poorly. I also took LSD and MDMA, but not nearly as much. I'll certainly credit LSD with ... other things, but that's another story.
And also the power of music, dance, community. The archaic revival.
In the late 90s/early 2000s, I went to a lot of raves and everyone who partied and took club drugs used ecstasy and ketamine regularly, often in combination.
A lot of people that I used to hang out with back then are on a private email list now, where we talk about more boring stuff like our families and jobs and so on, since everyone basically aged out of the scene in our early 30s.
I recently made a post about how my mom had been abusive towards me as a kid.
Almost every single person on the email list responded with a similar story of abuse, sometimes of a horrific nature. And almost everyone talked about dealing with trauma and depression their whole lives — and how the rave scene and the drugs they took probably saved them. Several talked about suicide attempts before getting into raves.
I had known these people for almost 15 years and I had never really talked about this except for the random conversation on ecstasy with one or two of them where they or I as sort of worked out our issues with them at an after party or whatever.
I was pretty surprised at how consistent the story was. I know that’s how I felt about the drugs— that the combination of those two (and lsd to a lesser extent) and the community around the music probably saved my life — even though I took a lot of dumb chances and went well beyond the therapeutic info the hedonistic from time to time.
I went from being a lonely, closed up victim of abuse at home and a decade of bullying at school to being outgoing and popular in that scene - even to the point where I learned to DJ and played gigs in front of crowds of 1000+ people.
It helped me not just in the scene but in my personal life and my career. I learned to recognize some of my learned toxic behaviors that pushed people away from me and how to recognize them in other people. I distanced myself from my family and home town friends who had been treating me terribly, and my career took off — even with no degree — and largely because of connections I made in the scene.
I don’t know where I’m going with this, but it seemed transparently obvious at the time that MDMA, LSD and ketamine were near-miraculous substances and deserving of serious scientific study, and it always seemed perverse that the government was doing everything in its power to prevent people from taking them, while at the same time pushing people to take anti depressants and stimulants that were so much less helpful and enlightening.
I haven’t used drugs in nearly a decade and don’t intend to, but I’m glad that researchers are starting to take them seriously.
The very article you're commenting on directly contradicts what you're saying. Big pharma is actively running studies and trying to get this fast tracked for treatment in the US and Europe.
Granted the article is somewhat poor reporting because the title should read "esketamine" not ketamine.
Esketamine is the patentable isomer they're trying to use to enable this process of patenting + FDA so the drug companies can make a return. So the end result is a very expensive drug that insurance would pay for vs a cheap drug with 90% of the benefits that insurance won't pay for.
esketamine is simply the S-ketamine stereoisomer. TFA calls it part of the ketamine molecule but it is the ketamine molecule.
Yeah, this is basically a variation of the POTAXOR strategy . Well, whatever it takes to get it into the hands of sick people! But I think it is a commentary on the system that it will take decades after we had good evidence for ketamine's effectiveness.
> Pharma companies don't benefit from getting Ketamine approved (since it's no longer patent protected), so no one is putting it through FDA for depression.
This is incorrect.
There are ongoing phase 3 clinical trials for nasally applied esketamine that will lead to FDA approval if succesfully reviewed. These trials are conducted worldwide and are very encouraging. The specific application seems to be patentable. First results should be available around 2019ish or 2020.
You can find the trials here:
And one of the patent applications here:
> This is incorrect. There are ongoing phase 3 clinical trials for nasally applied esketamine that will lead to FDA approval if succesfully reviewed.
Specifically esketamine, not ketamine, because focusing on this specific isomer was the only way to get a new patent.
What if racemic ketamine performs better than esketamine? We'll never know because they won't test that.
> What if racemic ketamine performs better than esketamine? We'll never know because they won't test that.
It's quite likely some public institutions (e.g., universities, public research labs, etc.) or other countries (e.g., in India, China) will test exactly that. It's also in their interest to pubblish the results. So we'll get to know the differences between racemic ketamine, esketamine and arketamine.
The question is if different variants will also be approved, which is much more expensive.
Racemic ketamine is also dirt cheap, while esketamine might be absurdly expensive after being patented.
Do you have a source for that? You can get a patent on a new use for something that already exists if the new use is a non-obvious advance over the prior art.
Maybe Pineapple Fund can come to the rescue, they (he?) chipped in 4M to get MDMA through a clinical trial.
I get the feeling this is not a Gates kind of philanthropist, lol.
Do you think something like "FDA-approval of Ketamine" could be successfully crowdfunded?
What I do not understand from a market perspective is why insurers don't cooperate more to fund such research. If a treatment goes from 20k to 1k p.a. the benefits for insurers are clear. They could even fund such research in an equity-fashion, that way steering clear of anti-competition law and free-rider problems (just sell it to the non-cooperators for 20k).
That is an incentive to insurers only if they are paying the price or if the lower costs to a specific group of consumers increases their market share. Since most costs are passed on to the consumers and most consumers don't get to pick their insurance (in the U.S.) , the incentives aren't there.
Employers do pick insurance companies, and cost is a big factor.
But if the cost is passed on to employees, that cost does not impact the employers.
If said cost applies to only some of the employees, the employer won't have much in the way of even indirect incentives.
It's happened with MDMA via maps.org
Why not? Probably need about $25M - $50M
Also Ketamine seems to be pallative vs. a cure, if I'm not mistaken.
I'd probably run a "crowdfunding" round involving people at the level of billionaire - Bill Gates, Peter Thiel, Bezos, etc.
Get 50 of those to each chip in $1 mill - it's pocket-change to them.
Clinical trials a pretty damned expensive.
Yes, healthcare sounds pretty screwed up. But even though ketamine for depression might never get FDA approved, I think it's still good that these positive effects are still being reported on. The fact that there are new articles on ketamine shows that there is still some interest.
And this interest isn't completely fruitless just because the pharma industry will never support it. Individuals (admittedly, only those who can afford it) can still try to benefit from e.g. off-license prescriptions.
If that is the case then why is this not widely available in the UK?
Healthcare in the UK moves at a snail's pace. NICE requires a lot of evidence before they will permit new treatments. The bigger issue though are the "Daily Mail politics" of using drugs that can be abused - it's seen as politically toxic with a particular segment of voters. Take cannabis as an example - it was moved back to class B years ago, purely for political reasons. And as other nations are starting to use it therapeutically, we still seem light years away.
Generic pharma is still big business. And there's patents for novel ways to deliver the medication (e.g., Vyvanse and Concerta in the ADD stimulants space)
Is ketamine approved/endorsed for treating depression in some other countries?
I would think given compelling enough research that there would be plenty of private foundation dollars to complete trials.
A pair of researchers told me the same about cannabidiol.
Getting a drug approved by the FDA is pretty expensive. Abolishing the FDA, thereby reducing the cost of introducing the drug, might be the real solution here.
I find public health inspectors also make it more expensive to run a restaurant. Perhaps the solution to their tight margins would be to abolish health inspections.
>abolish health inspections.
Well, it would be interesting to look at impartial cost/efficiency research regarding "health inspections". I routinely travel to countries where those inspections are just a pure formality, or completely non-existent - and, I must say, in most cases there's no trouble finding a good, safe place to eat.
While you're at it, tax makes it more difficult to run a business and making a living. Let us abolish tax as well.
Just because a thing exists (the FDA or taxes for instance), doesn't make it a good thing.
Although I don't disagree with your point, that wasn't my point. My point is that these things have different aspects (some of which are arguably useful, some perhaps in your eyes less so or not) but removing them has serious consequences. It is easy to be against something (for example, paying taxes) but removing taxation has serious consequences which have to be accounted for.
Keeping them as they are also has serious consequences that are rarely examined, or even raised for consideration.
The public interest is for medical treatments to have the following qualities: safe, effective, affordable. The business interest for healthcare providers is for medical treatments to have the following property: profitable. Those interests only partially overlap.
It is possible to imagine many different institutional architectures that cater to the public's interests, and a large number of them are theoretically better than the actual results yielded from the FDA and the rest of the modern American health care system.
Thus, one of the consequences of maintaining the status quo is the foregone advantage of moving to a different and wholly incompatible system. That's the kind of argument only an economist could love, because it ties your brain up in knots trying to figure it out, and you can plausibly justify any prejudicial opinion you might care to support.
> Keeping them as they are also has serious consequences that are rarely examined, or even raised for consideration.
Yes, but the burden of proof lies with those who prefer an alternative. If you want to demonstrate an alternative is better, you need an honest and in depth comparison with the current. Just saying "the current sucks" isn't an argument.
I do agree it is difficult for drugs like ketamine, psilocybin, and MDMA(/MDA/MDE/etc) to get research funding, but that doesn't mean the current options are useless; we know they are useful, just not in every case. Nor does it mean that those mentioned drugs are better; we do not know.
> Yes, but the burden of proof lies with those who prefer an alternative. If you want to demonstrate an alternative is better, you need an honest and in depth comparison with the current. Just saying "the current sucks" isn't an argument.
That burden of proof lay originally with those that introduced, e.g., the FDA. We could go back to investigate whether we find that proof sufficient, if any was even provided, but your interpretation of the proof would perhaps be different than mine.
But decisions like creating an FDA are not based on proof, I would argue. It is based on other factors, especially on what can give government more power and what people will vote for. The average voter does not investigate any proof on the matter, but instead rely solely on gut feeling, for instance the feeling that drug companies are greedy enough to deliberately release drugs they know will harm people.
US government is not set up to A/B test the efficacy of its own agencies.
You can't set up an alternative to the FDA in order to test it, because the FDA is the supreme dictator over the regulatory domain, and you can't get around Mom saying "no" by asking Dad behind her back.
You can, however, look at the European pharmaceuticals regime, and note that an identical drug costs three times in the US the amount it costs in France.
Clearly, the FDA is not optimal. Equally clearly, we do not demand meta-studies proving that the FDA itself is safe and effective for its stated purpose.
Wow look, an ancap in 2018!
Yeah. I feel pretty lonely here... :'(
Anarcho-capitalism largely depends on a belief that human nature is essentially good, and prone to spontaneous cooperation. It is also heavily dependent on reputation, which scales poorly, or on trustless technologies, which aren't yet mature.
I'm still anarchist in 2018, but I haven't been anywhere near the an-cap territory of it since around 2006. Sticking to a political dogma out in the libertarian hinterlands is really only good for pointlessly arguing with other libertarians on the Internet.
That can be fun sometimes, but it's not as entertaining as it used to be, what with everyone pointing at Twitler and saying "You see? This is exactly as (insert libertarian variant) predicted!"
Anarcho-capitalism largely depends on a belief that human nature is essentially bad, and that magically, goodness manifests itself from the concentration of badness.
Honest question: consumers are notoriously ill-informed, companies are good at propaganda and fake "clinical" evidence, and finding out if medicines ate effective AND safe is really complex.
How do you imagine abolishing the FDA would improve outcomes instead of increasing supplies (and marketing) of snake oil?
You know who is also good at propaganda? Government and state.
Can you prove that FDA improves the outcome? Is FDA somehow free from lobbying, or are the people working there consistently uninfluenced by certain counterproductive incentives? How could we go about ever proving that the absence or existence of a government agency has improved conditions overall? Sorry if this comes off as lecturing, but these are questions that I think should be asked and is not intended for you specifically.
In any case, you cannot take away that FDA approval likely costs millions of dollars and makes it more costly to introduce a drug. It is self-evident that making something more expensive to do reduces the incentive to do it (weighed against the potential profit).
> It is self-evident that making something more expensive to do reduces the incentive to do it (weighed against the potential profit).
No argument - but you didn't answer my questions at all other than to say "FDA is fallible!"
I can't prove the FDA is non-evil/non-fallible. I don't have numbers to share, so I'm going off of very fallible impressions. However, those impressions are that the FDA has done a better job of keeping crappy products off the market than a free-market world.
You complain about the opposite - good products being prevented because of lack of incentives. It's impossible to measure what hasn't happened, but do we have evidence that lack of incentive cause more harm than preventing crap/toxic/poisonous products that we have a recorded history of?
We have a solution today, a solution with problems, but a solution that I'm confident is better than the original problem. What is your basis to claim that removing the solution will in fact be better than the problem?
Same with Vitamin D, almost. If it were patent-protected, you'd probably get a big list of features promoted for an almost "miracle pill" that would probably cost a few dollars per pill.
But Vitamin D is not patent protected and it's dirt cheap, so not only does Big Pharma have no interest in promoting it, but it would rather you take much more dangerous drugs and much more expensive drugs to cure the same things Vitamin D does.
This is what a private healthcare system gets you, where profit is always a bigger priority than the well-being of the patient.
VitD became a fad topic over a decade ago and has been studied endlessly since then.
This is a very odd comment thread. Lots of people criticizing our health system for not studying things it actually does study a lot.
If you're an American, every time you read a new article on Ketamine for depression your thought should be "Jeese, healthcare is screwed up". Pharma companies don't benefit from getting Ketamine approved (since it's no longer patent protected), so no one is putting it through FDA for depression. As a result insurance will never cover it (under the current model).
The reason this treatment isn't mainstream isn't because "the research is still out" (though that may still be). It's because there are no financial interests to get it over the hoops into the highly convoluted state that enables affordable medical care.
Mowing up a gram of ket every weekend is going to kill any therapeutic benefits you get from it.
That's different to a small dose once a month in a medically supervised environment.
One big problem with recreational drugs (from personal experience) is that you get conditioned to them if you overuse them, then life seems sort of shit without them.
With MDMA, you can even permanently lose the magic if you take too much too often.
Pretty sure the permanent damage thing is mostly a myth except you talk about a Seratonin syndrome which however doesn't increase in probability with the frequency you take it (mdma)
I am not sure what the medical amount for ketamin would be, but i would think the average is more around 100mg a month (and using about every 3) within my circle. Which is not exactly that much.
As far as I know are long term studies still lacking of a proper sample size as well.
So the levels of neurotoxicity for MDMA are not known. It's almost certainly neurotoxic to some degree but not any where near the levels purported by that study that used massive amounts of meth on rats (remember alcohol is also neurotoxic).
However, over use can certainly habituate a user to it such that it "loses its magic" as in the psychoactive effect is far far far less than what it originally was.
I haven't kept up with the research since graduating, but there have been studies that showed damage to serotonin receptors from repeated mdma usage.
Just as a different perspective ketamine is (and was) pretty common in my circle and the idea that it works as anti depressant slowly faded.
It never really worked for me as that, at least not more than lsd or so would. And some friends claim that it has way less effect on them today even thought it seemed have to worked before.
It may is the abuse (probably higher amount on some occasions) it may are long term effects.
But it surely is not the magic cure some make it out to be.
It's not a breakthrough because it has been used in the clinic for patients with suicidal ideation for a long time. You are hearing about it now because a small group of doctors have found a new income stream.
Contrary to the posts in this thread there isn't a body of evidence that suggests Ketamine's anti-depressant effect lasts longer than a week.
I think the posts here are almost all about comparing repeated-dose regimens of Ketamine vs SSRIs; otherwise if we were comparing the effectiveness of single doses, we might as well claim there isn't a body of evidence that suggests SSRIs have an anti-depressant effect for much longer than just a single day, right? Or do you mean that the repeat dose just a week later (, and so on,) would have little anti-depressant effect?
Doctors and patients are claiming that the effects last much longer than a week between maintenance infusions. I'm not making any comparison with SSRI's. It's a costly treatment and the duration of effect as reported is probably bullshit. Buyer beware.
My psychiatrist was mentioning this to me a few months ago. The data he’s seen mirrors the study referenced here.
This could be a breakthrough for individuals in the midst of major depressions, which are often very hard to treat, considering how long it can take for other anti-depressants to start to work.
Mechanistically, there is a large difference between ibuprofen and ketamine. Ibuprofen does not work on the NMDA receptor, as ketamine does. NMDA activity modulation is associated with psychological phenomena:
"""NMDA receptor antagonists can mimic these problems; they sometimes induce "psychotomimetic" side effects, symptoms resembling psychosis. Such side effects caused by NMDA receptor inhibitors include hallucinations, paranoid delusions, confusion, difficulty concentrating, agitation, alterations in mood, nightmares, catatonia,;ataxia, anesthesia, and learning and memory deficits.""" (From Wikipedia)
Ibuprofen hits the COX enzymes, for which no psychological effects are noted.
Edit: of course I'm not discounting your own observations, just regurgitating some textbook knowledge.
Pain killers can affect your emotional state indeed:
Thank you for the link, that's interesting. In my case any dulling of the emotional state when in a depressed situation is probably helpful. A return toward an emotionally-colder systematizer's state of mind seems, again in my case, to be associated with healthier outcomes.
Ketamine is a dissociative rather than your typical anaesthetic or pain killer. Id's mechanisms of action are not that well researched.
The real question is, how long do the effects last and what are the side effects.
Warning for long-term ibuprofen users:
Thank you. I'm not sure what to make of the study itself, but that is one of the most approachable write-ups I've ever read.
There could be some connection, since physical and mental pain activate similar brain regions. I can see how pain killers may help to some degree with emotional pain. (Not a doctor)
Ibuprofen actually does work, believe it or not.
I appreciate the link! I find this all very fascinating.
Your emotional body is your physical body, to a large degree. Emotional pain can be mitigated with ibuprofen just as easily as physical pain can.
Congrats on the self study and experimentation and on finding an over the counter solution.
Have you tried any non-ordinary states of concioisness work, like Holotropic Breathwork?
I haven't ever heard of holotropic breathwork, will give it a go, thanks. I have had really good results from meditation, especially when sleep is out of the question.
Paracetamol, metamizol, acetil acid, diclofenac and ibuprophen all fall into the same category (I have chronic headaches) but I really doubt any of them are good for depression. For stress I take small amount of frontin (xanaxish thing) and it acts all differently (for me at least) from the rest.
Ketamine isn't a pain reliever. It's a dissociative hallucinogen. It works by disconnecting you from sensory input and putting you in something like a lucid dream.
This isn't true. Ketamine infusions are also administered to patients with chronic pain.
That it’s given for pain does not make it anything like what people think of as a pain reliever. It’s nothing like Tylenol, ibuprofen, or opiates.
It makes it a pain reliever.
I've taken ibuprofen for sports injuries a fair amount. Some times a lot of it. I've never noticed any effects on my depression.
I never noticed a anti depressive use of ibuprofen. Ketamine however actively puts you into a 'better mind space'
Ketamine is an anesthetic. Has anyone compared it to e.g. ibuprofen for this use case? Ibuprofen works very well for me when experiencing depressive symptoms. I'm down to about 2h max per depressive episode (logged at 10-30 depressing thoughts per minute, compared to none after). Mechanism intuitively "feels" inflammatory and looking at my logs seems related to exhaustion due to over-productivity, lack of rest, etc.
Not at all. Not proud of it per se but... I've used them often to get high in random places.
Ketamine dissolves pretty well in water.
Not at all. I know people who have done this. They claim it works well.
You can also get these handy personal dispensers, have a look on eBay for "snuff bullet".
How hard would it be to create a ketamine nasal spray at home, if you possess some in powder form?
From what we know now, nearly every habitual behavior is likely to affect your biome. Excersize still has a larger effect than most drugs, but we can't seem to perscribe it.
I've heard that ketamine usage long term can affect your microbiome , which seems to play a much greater role in depression that previously thought . Has anyone had similar experiences?
I was wondering about this. A co-worker's daughter was given ketamine during a spinal tap. After the procedure, she said that she no longer felt real.
That sounds like a case of depersonalization/derealization which dissociatives are sometimes known to produce
Don’t get caught in a k-hole or it might have some fast acting disadvantages for depression.
It depends on the drug and it's usage, but "because of their size and comparatively long duration, Phase III trials are the most expensive, time-consuming and difficult trials to design and run" .
It's possible to get the nasal spray prescribed and filled by a compounding pharmacy. Those doctors will want you to spend $3,000 for the initial infusions. It won't matter to them that you had the initial infusions elsewhere. They want the full treatment experience as well.
It's possible that the J&J spray will be approved in 2018.
In some countries in Europe it's already possible for a psychiatrist to request (legally) such preparation from a pharmacy and they will prepare it.
Legend has it some first responders are carrying ketamine nasal sprays as a first help for depressed people wanting to commit suicide. I wonder if it's true.
> The nasal spray is now undergoing phase three trials before it can be licensed for treatment.
Can anyone comment on how long it might take for it to hit the market, from this stage?
I'm gonna stick with exercise.
One part of it, at least for me, is the psychadelic "converging on rebirth" feeling. It's a very geometric type of high, most likely due to the NMDA agonism, induced dissociation / depersonalization. Much shorter duration than LSD, and less chance of bad thoughts/actions since you are pretty much sedated and unable to panic. Ketamine is really therepeutic mentally.
The doses given therapeutically are lower than recreational ones.
That's not true. I've done ketamine recreationally and also through an MD via infusion. The infusion had me in a k-hole for an hour or two. Recreationally, I've been in a k-hole for maybe 15-30 minutes.
Others here in this thread agree that therapeutic doses are smaller, and after a brief search it seems papers do too.
Perhaps your effects were down to the ROA?
Not fully. One part is pretty persistent NMDA receptor blockade. How does that tie into depression if at all, we do not know.
"Ketamine lifts depression via a byproduct of its metabolism" <https://www.sciencedaily.com/releases/2016/05/160504141131.h...
highly debatable at the moment. Nothing is even sure on animal models
Is the mechanism of action known?
What stereoisomers are used?
Googles ketamine. It's guys snorting something with dollar bills. I think people figured this out already.