Low-cost ketamine could help people with severe depression, study finds
July 26, 2023 9:57 PM Subscribe
Low-cost ketamine could help people with severe, hard-to-treat depression, study finds. A cheap version of ketamine commonly used as a sedative might help some people with hard-to-treat depression, research finds, raising hopes that the off-label treatment could become less expensive.
To keep this thread on track, Just Say Neigh to lazy ketamine jokes.
posted by kaibutsu at 12:37 AM on July 27, 2023 [18 favorites]
posted by kaibutsu at 12:37 AM on July 27, 2023 [18 favorites]
Genuinely curious how you do a double-blind trial with a drug whose effects are as profoundly mind-altering as ketamine? Like, do they find another drug that induces dissociation and ego-death and use that as the "placebo"?
posted by parm at 3:41 AM on July 27, 2023 [5 favorites]
posted by parm at 3:41 AM on July 27, 2023 [5 favorites]
I see on closer inspection that yes, they say they use a "valium-like" drug as placebo, but I'd have thought the effects were still noticeably different enough to be able to tell?
posted by parm at 3:48 AM on July 27, 2023 [1 favorite]
posted by parm at 3:48 AM on July 27, 2023 [1 favorite]
presumably if research subjects hadn't had ketamine before, they'd have no basis for comparison
posted by Jon_Evil at 4:11 AM on July 27, 2023 [10 favorites]
posted by Jon_Evil at 4:11 AM on July 27, 2023 [10 favorites]
The financial incentives on stuff like this are so fucked up. It's not a new drug, there's no patents, it's a short dosage schedule and you're done. So, there's no money for this research, no drug companies hoping to rake in billions of dollars to fund the tests and the FDA filings to get it on label, because pharmabros vastly prefer to make an expensive drug you have to take every day for the rest of your life.
posted by seanmpuckett at 5:02 AM on July 27, 2023 [24 favorites]
posted by seanmpuckett at 5:02 AM on July 27, 2023 [24 favorites]
Yeah, they kind of bury the lede right at the bottom:
"The drug costs themselves are very low, but the service costs to administer it are not cheap."
After administering ketamine, the patient needs to be monitored by medical professionals for hours afterwards to watch out for any negative side effects. It's this labour that means ketamine treatments can cost hundreds of dollars.
Doesn't matter how cheap the drugs are if costs of administration and supervision remain high. And since the degree of dissociation and the therapeutic effect seem to be linked (IIRC), it seems unlikely that this will ever be approved for at home use without a medical professional present.
posted by Jobst at 5:38 AM on July 27, 2023 [5 favorites]
"The drug costs themselves are very low, but the service costs to administer it are not cheap."
After administering ketamine, the patient needs to be monitored by medical professionals for hours afterwards to watch out for any negative side effects. It's this labour that means ketamine treatments can cost hundreds of dollars.
Doesn't matter how cheap the drugs are if costs of administration and supervision remain high. And since the degree of dissociation and the therapeutic effect seem to be linked (IIRC), it seems unlikely that this will ever be approved for at home use without a medical professional present.
posted by Jobst at 5:38 AM on July 27, 2023 [5 favorites]
there are a load of slightly sketchy outfits already selling ketamine off-label so that might not be that much of a barrier in practice
as for home use, that's happening too, even if maybe it shouldn't
posted by BungaDunga at 5:39 AM on July 27, 2023 [3 favorites]
as for home use, that's happening too, even if maybe it shouldn't
posted by BungaDunga at 5:39 AM on July 27, 2023 [3 favorites]
It doesn’t have to be costly to administer. That’s nonsense. There are people right now who do off-label intranasal or suppository ketamine for depression at home without supervision. I’m one of them. You do it when a family member’s home, don’t get out of bed except very carefully and with assistance to pee for 2 hours (which is as long as they keep you in the office with the expensive on-label equivalent), and then go about your day. I mean, don’t drive for a few hours after that. I’ve been doing it for 2 years without incident. In combination with other meds, ketamine saved my life.
And to the person above who discussed other drugs and ego death, when I found out my previous doctor was stealing my meds by watering them down, there was a period where I had no ketamine and was in danger of death. Did some mushrooms in that period and they were helpful for a bit, but ketamine is a different kind of drug and operates on a completely different level. Hallucinogens are not interchangeable for this stuff. Ketamine is in its own category.
posted by vim876 at 6:10 AM on July 27, 2023 [21 favorites]
And to the person above who discussed other drugs and ego death, when I found out my previous doctor was stealing my meds by watering them down, there was a period where I had no ketamine and was in danger of death. Did some mushrooms in that period and they were helpful for a bit, but ketamine is a different kind of drug and operates on a completely different level. Hallucinogens are not interchangeable for this stuff. Ketamine is in its own category.
posted by vim876 at 6:10 AM on July 27, 2023 [21 favorites]
Also, if they require “medical supervision,” not only is it more expensive, but you can’t hold down a normal job and get treatments, which seems unfair, given the already serious unemployment rate of people with severe mental illness.
posted by vim876 at 6:12 AM on July 27, 2023 [5 favorites]
posted by vim876 at 6:12 AM on July 27, 2023 [5 favorites]
> The financial incentives on stuff like this are so fucked up. It's not a new drug, there's no patents, it's a short dosage schedule and you're done. So, there's no money for this research, no drug companies hoping to rake in billions of dollars to fund the tests and the FDA filings to get it on label, because pharmabros vastly prefer to make an expensive drug you have to take every day for the rest of your life
oh so there's a neat extra twist involved here that's worth talking about. as we know, ketamine's an old established drug, no patents, etc. etc. but ketamine is made of two components, called s-ketamine and r-ketamine. the molecules are identical except they're mirror images of each other. they have precisely the same effect when taken; there is no medical reason to separate s-ketamine from r-ketamine.
however!
the folks at johnson and johnson realized a little while back that if you isolate s-ketamine from r-ketamine, it's technically a different drug and therefore it can be patented. so they isolated s-ketamine from r-ketamine, paid for the tests to get this "new" drug approved, and then in 2019 released spravato, which consists of just s-ketamine and no r-ketamine, that works exactly like regular ketamine, but that has the advantage of costing about 30,000 dollars a year rather than costing pennies.
pretty cool, right? markets are so efficient.
posted by bombastic lowercase pronouncements at 6:16 AM on July 27, 2023 [43 favorites]
oh so there's a neat extra twist involved here that's worth talking about. as we know, ketamine's an old established drug, no patents, etc. etc. but ketamine is made of two components, called s-ketamine and r-ketamine. the molecules are identical except they're mirror images of each other. they have precisely the same effect when taken; there is no medical reason to separate s-ketamine from r-ketamine.
however!
the folks at johnson and johnson realized a little while back that if you isolate s-ketamine from r-ketamine, it's technically a different drug and therefore it can be patented. so they isolated s-ketamine from r-ketamine, paid for the tests to get this "new" drug approved, and then in 2019 released spravato, which consists of just s-ketamine and no r-ketamine, that works exactly like regular ketamine, but that has the advantage of costing about 30,000 dollars a year rather than costing pennies.
pretty cool, right? markets are so efficient.
posted by bombastic lowercase pronouncements at 6:16 AM on July 27, 2023 [43 favorites]
Re: blinding. My partner was involved with a trial where patients with depression were injected with ketamine while under general anesthesia, so they wouldn’t remember the psychedelic effects. They found it wasn’t any better than a placebo in that case. https://www.medrxiv.org/content/10.1101/2023.04.28.23289210v1
posted by getao at 6:27 AM on July 27, 2023 [14 favorites]
posted by getao at 6:27 AM on July 27, 2023 [14 favorites]
Yes. The intensity of the dissociative experience does have some correlation with effectiveness, ime. All that tells me is if Nixon hadn’t gotten a hard-on for using drug policy to imprison the left, I might have been adequately treated sooner.
posted by vim876 at 6:32 AM on July 27, 2023 [10 favorites]
posted by vim876 at 6:32 AM on July 27, 2023 [10 favorites]
which consists of just s-ketamine and no r-ketamine, that works exactly like regular ketamine
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704936/
"Racemic ketamine appears to be more efficacious than esketamine for the treatment of depression. Head to head comparisons are needed to confirm the present findings."
Recent studies seem to indicate that the dissociative effects are important for ketamine to be an effective antidepressant (see getao's comment above). Part of the reason why esketamine was chosen by J&J was that isomer had fewer dissociative effects, which would make it more attractive to docs. The problem is that those effects seem to be important for the drug to work as expected.
Also it seems as though J&J's marketing machine is hard at work distorting the truth as usual. I see multiple quotes online about how esketamine is stronger and more effective and therefore you don't have to take as much. Groovy. I don't really care if I get 90mg of esketamine or 200mg of ketamine as long as it makes me less depressed. And it looks like esketamine is hands down a worse drug than arketamine or ketamine. For depression anyway.
posted by ensign_ricky at 6:41 AM on July 27, 2023 [11 favorites]
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7704936/
"Racemic ketamine appears to be more efficacious than esketamine for the treatment of depression. Head to head comparisons are needed to confirm the present findings."
Recent studies seem to indicate that the dissociative effects are important for ketamine to be an effective antidepressant (see getao's comment above). Part of the reason why esketamine was chosen by J&J was that isomer had fewer dissociative effects, which would make it more attractive to docs. The problem is that those effects seem to be important for the drug to work as expected.
Also it seems as though J&J's marketing machine is hard at work distorting the truth as usual. I see multiple quotes online about how esketamine is stronger and more effective and therefore you don't have to take as much. Groovy. I don't really care if I get 90mg of esketamine or 200mg of ketamine as long as it makes me less depressed. And it looks like esketamine is hands down a worse drug than arketamine or ketamine. For depression anyway.
posted by ensign_ricky at 6:41 AM on July 27, 2023 [11 favorites]
This is very exciting. The only thing that's prevented me from being able to try ketamine for my treatment-resistant MDD is the cost (insurance basically laughs in my face).
posted by The Underpants Monster at 6:59 AM on July 27, 2023 [2 favorites]
posted by The Underpants Monster at 6:59 AM on July 27, 2023 [2 favorites]
@bombastic lowercase pronouncements:
You have touched on one of the main reasons that, if I were dictator for a day, one of my low-numbered orders would be to invalidate all US patents and fire everybody at the patent office.
posted by Aardvark Cheeselog at 7:05 AM on July 27, 2023 [2 favorites]
You have touched on one of the main reasons that, if I were dictator for a day, one of my low-numbered orders would be to invalidate all US patents and fire everybody at the patent office.
posted by Aardvark Cheeselog at 7:05 AM on July 27, 2023 [2 favorites]
I was lucky enough for Esketamine treatment to be very covered under my insurance; and unlucky enough for the maximum dose to do almost nothing at all (the dizzies, feeling slightly tipsy for about 10minutes, then fine).
I've also gone the route of non-insurnace covered injected ketamine treatments, which were far more intense, and seemed to help a little bit, but not enough compared to just how goddamn expensive it was.
Granted, it's an anecdotal point (from a human with lots of weird drug interactions no less), but the delivery methods even at the same dose really do seem to have a difference.
This is fantastic news for a lot of people, but YMMV, and it is not a panacea.
posted by furnace.heart at 7:08 AM on July 27, 2023 [6 favorites]
I've also gone the route of non-insurnace covered injected ketamine treatments, which were far more intense, and seemed to help a little bit, but not enough compared to just how goddamn expensive it was.
Granted, it's an anecdotal point (from a human with lots of weird drug interactions no less), but the delivery methods even at the same dose really do seem to have a difference.
This is fantastic news for a lot of people, but YMMV, and it is not a panacea.
posted by furnace.heart at 7:08 AM on July 27, 2023 [6 favorites]
(insurance basically laughs in my face)
Insurance is the big issue that needs to be fixed with ketamine. At this point, if you want insurance to cover treatment, you have to go with Spravado, and some insurance doesn't cover even that. Since Ketamine isn't scheduled for use with depression / TRS, most health insurance doesn't cover it. Mindbloom costs me about $500/mo out of pocket which is a good chunk of change, but I'd pay just about anything for ketamine at this point because it literally changed my life. And tbh, it probably has saved my life a couple of times too.
posted by ensign_ricky at 7:09 AM on July 27, 2023 [2 favorites]
Insurance is the big issue that needs to be fixed with ketamine. At this point, if you want insurance to cover treatment, you have to go with Spravado, and some insurance doesn't cover even that. Since Ketamine isn't scheduled for use with depression / TRS, most health insurance doesn't cover it. Mindbloom costs me about $500/mo out of pocket which is a good chunk of change, but I'd pay just about anything for ketamine at this point because it literally changed my life. And tbh, it probably has saved my life a couple of times too.
posted by ensign_ricky at 7:09 AM on July 27, 2023 [2 favorites]
I wonder what dose they are using? Having to watch them for 2 hours afterwards seems excessive, although they should have a responsible adult with them for the rest of the day. I sometimes use ketamine as a component of a general anesthetic and generally patients are ready to leave the recovery room in 30 minutes to an hour.
As for the discussion about enantiomers (mirror-image molecules) of ketamine, it is pretty well documented that there can be significant differences in pharmacologic activity of drugs based on their chirality. This makes sense, as the receptors for drugs can also be chiral.
posted by TedW at 7:44 AM on July 27, 2023 [10 favorites]
As for the discussion about enantiomers (mirror-image molecules) of ketamine, it is pretty well documented that there can be significant differences in pharmacologic activity of drugs based on their chirality. This makes sense, as the receptors for drugs can also be chiral.
posted by TedW at 7:44 AM on July 27, 2023 [10 favorites]
> it is pretty well documented that there can be significant differences in pharmacologic activity of drugs based on their chirality.
my favorite fun fact about chirality is that the molecules that make the flavours wintergreen and spearmint are mirrors of each other.
also i fuckin' love saying chirality, 1: because it's fun, just a whole lot of fun sounds put together 2: because if people say "wait, what was that word?" i can say "chirality. like, you know, handedness." why do i find this fun? your guess is as good as mine.
but anyway: yeah, totally, isolating mirror molecules from each other can result in drugs with different effects. however, this does not appear to be the case with ketamine unless there's more recent research that i don't know about. as others have mentioned above, if there's a difference it's that s-ketamine is somewhat less effective than the regular mix of s-ketamine and r-ketamine.
posted by bombastic lowercase pronouncements at 8:11 AM on July 27, 2023 [5 favorites]
my favorite fun fact about chirality is that the molecules that make the flavours wintergreen and spearmint are mirrors of each other.
also i fuckin' love saying chirality, 1: because it's fun, just a whole lot of fun sounds put together 2: because if people say "wait, what was that word?" i can say "chirality. like, you know, handedness." why do i find this fun? your guess is as good as mine.
but anyway: yeah, totally, isolating mirror molecules from each other can result in drugs with different effects. however, this does not appear to be the case with ketamine unless there's more recent research that i don't know about. as others have mentioned above, if there's a difference it's that s-ketamine is somewhat less effective than the regular mix of s-ketamine and r-ketamine.
posted by bombastic lowercase pronouncements at 8:11 AM on July 27, 2023 [5 favorites]
My only ketamine story is it was what was used at my zoo school to anesthetize a very fierce and strong baboon for her vet checkup, and she just sat there peacefully staring into space. It was our first chance to actually touch her, gently, to look at her marvelous little hands with fingerprints just like ours and be close enough to her huge fangs to see her little eyelashes.
posted by The otter lady at 8:26 AM on July 27, 2023 [42 favorites]
posted by The otter lady at 8:26 AM on July 27, 2023 [42 favorites]
i can think of few things better than a drug that can help you treat your depression and also can help you meet an ape
posted by bombastic lowercase pronouncements at 8:28 AM on July 27, 2023 [58 favorites]
posted by bombastic lowercase pronouncements at 8:28 AM on July 27, 2023 [58 favorites]
Not to derail but polymorphs come to mind when discussing chirality. Drugs that stop working because a different polymorph seeded a different shape for the molecule?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479028/
If there's interest in this, I'll work on a fpp on polymorphs for more discussion?
Feel free to nuke this if it is a derail.
posted by ensign_ricky at 8:47 AM on July 27, 2023 [12 favorites]
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4479028/
If there's interest in this, I'll work on a fpp on polymorphs for more discussion?
Feel free to nuke this if it is a derail.
posted by ensign_ricky at 8:47 AM on July 27, 2023 [12 favorites]
> If there's interest in this, I'll work on a fpp on polymorphs for more discussion?
oh hell yes plz do that
posted by bombastic lowercase pronouncements at 8:50 AM on July 27, 2023 [10 favorites]
oh hell yes plz do that
posted by bombastic lowercase pronouncements at 8:50 AM on July 27, 2023 [10 favorites]
It should be a good FPP. Metafilter favorite Derek Lowe (Things I Won't Work With) has discussed polymorphs before, so it should have a few dashes of chemist humor too.
posted by ensign_ricky at 8:52 AM on July 27, 2023 [2 favorites]
posted by ensign_ricky at 8:52 AM on July 27, 2023 [2 favorites]
Ketamine always felt like the 'villain' drug to me, like a bit mean but still safe and fun, and that's my take on why it works for healing trauma.
To explain, ketamine helped me heal from lingering subcsoncious scars I'd had after a bad 'acid' trip. For years part of my subconscious still believed what it had experienced during that trip, that the world was made of teeth and eyes, that an alien being was taking over all of our brains, that those eyes would be back if I focused on certain shadows. Ket let me into those psychadelic spaces but without the hurt or the trauma, it let me feel those fears and visions while feeling separate, protected from them. And so move past them.
Another time at a festival, I saw myself from all of the bad angles, all of the photos of me I'd looked at and then had to immediately reject because I looked too ugly or weird or off or... Ket let me see those angles and think 'fine, yeah okay that's me, that's my body. I'm here.'
To me, Ket makes the world feel weird and off, but still fun and interesting and okay in its offness.
I don't know if the research supports this theory but it makes sense to me that ket helps so much with PTSD if it allows you to access the traumatised parts of yourself as dark and traumatised, and integrate them.
posted by litleozy at 8:54 AM on July 27, 2023 [14 favorites]
To explain, ketamine helped me heal from lingering subcsoncious scars I'd had after a bad 'acid' trip. For years part of my subconscious still believed what it had experienced during that trip, that the world was made of teeth and eyes, that an alien being was taking over all of our brains, that those eyes would be back if I focused on certain shadows. Ket let me into those psychadelic spaces but without the hurt or the trauma, it let me feel those fears and visions while feeling separate, protected from them. And so move past them.
Another time at a festival, I saw myself from all of the bad angles, all of the photos of me I'd looked at and then had to immediately reject because I looked too ugly or weird or off or... Ket let me see those angles and think 'fine, yeah okay that's me, that's my body. I'm here.'
To me, Ket makes the world feel weird and off, but still fun and interesting and okay in its offness.
I don't know if the research supports this theory but it makes sense to me that ket helps so much with PTSD if it allows you to access the traumatised parts of yourself as dark and traumatised, and integrate them.
posted by litleozy at 8:54 AM on July 27, 2023 [14 favorites]
For those of us now interested in trying ketamine, what would those of us who use it recommend?
posted by The otter lady at 9:06 AM on July 27, 2023 [4 favorites]
posted by The otter lady at 9:06 AM on July 27, 2023 [4 favorites]
Is anybody like, holding any right now?
posted by DirtyOldTown at 9:07 AM on July 27, 2023 [12 favorites]
posted by DirtyOldTown at 9:07 AM on July 27, 2023 [12 favorites]
The otter lady: if you'd like to try at home ketamine, Mindbloom has done well by me. Their theory seems to be that a high dose every few days is the right way to go. I really like their philosophy of letting you determine how often you take the med. For me, I found that every 6 days or so was perfect, so their 6 treatment package lasts for 5-6 weeks. You'll meet a psych doc for an evaluation so have info about docs, previous treatment and so on handy. Then you'll get a guide who will be available for questions, motivation, etc. Mindbloom's protocol has you hold the troches in your mouth for 8 minutes, then spit everything out. I believe this is so that the dissociation lasts a short period of time. If you swallow the spit, you'll get a stronger, much longer dissociation and that's not a great thing for most people.
litleozy: I've had experiences similar to yours I think. When I'm under the influence of the med, it's like all of my filters disappear. My Judeo-Christian filter falls and I start to think about poly married couples and other ideas that seem "wrong" when I'm not under the influence. The guilt and shame that pokes into my consciousness is all gone too. My thinking becomes very Spock-like without any filters, which is very refreshing. In addition, it does take my depression away within minutes, most notably the constant rumination that is at the core of my depression. My mind is calm, and I can actually process things. Ketamine seems to move depression out of the way so I can feel sad and happy and all kinds of emotions I haven't felt for a lot of years. After my first couple of treatments, I felt seriously sad for a few days processing the loss of my mother. I hadn't dealt with it at all, preferring to hide all of those emotions behind a wall of depression.
posted by ensign_ricky at 9:22 AM on July 27, 2023 [7 favorites]
litleozy: I've had experiences similar to yours I think. When I'm under the influence of the med, it's like all of my filters disappear. My Judeo-Christian filter falls and I start to think about poly married couples and other ideas that seem "wrong" when I'm not under the influence. The guilt and shame that pokes into my consciousness is all gone too. My thinking becomes very Spock-like without any filters, which is very refreshing. In addition, it does take my depression away within minutes, most notably the constant rumination that is at the core of my depression. My mind is calm, and I can actually process things. Ketamine seems to move depression out of the way so I can feel sad and happy and all kinds of emotions I haven't felt for a lot of years. After my first couple of treatments, I felt seriously sad for a few days processing the loss of my mother. I hadn't dealt with it at all, preferring to hide all of those emotions behind a wall of depression.
posted by ensign_ricky at 9:22 AM on July 27, 2023 [7 favorites]
Mushrooms have fixed me, it seems. I followed the Johns Hopkins and Huberman Lab recommendations. 2g to 3g each time as a tea. Laid down, dark + cool room, wore a sleep mask (blocking all visuals is important), listened to the Johns Hopkins playlist.
Weirdly, I would get sleepy and very relaxed for 40-60 minutes and then wake up (even if not asleep) and feel great. It only improved as days went on. My wife is amazed that after 3g of mushrooms made into a tea, I'd just pop back up without any real effects during or after. We split a tea once and she tripped so they're good mushrooms. ADHD brain strikes again.
I did have to stop taking my SSRI, but that wasn't helping and completely blunted all my emotions. I'm much better feeling now. Had a few great cathartic cries yesterday listening to music to do just that. I'd go try ketamine if I felt like I needed to, but it seems like this has done the trick for now in a way that no drug or mindfulness or therapy ever has.
posted by OnTheLastCastle at 9:32 AM on July 27, 2023 [10 favorites]
Weirdly, I would get sleepy and very relaxed for 40-60 minutes and then wake up (even if not asleep) and feel great. It only improved as days went on. My wife is amazed that after 3g of mushrooms made into a tea, I'd just pop back up without any real effects during or after. We split a tea once and she tripped so they're good mushrooms. ADHD brain strikes again.
I did have to stop taking my SSRI, but that wasn't helping and completely blunted all my emotions. I'm much better feeling now. Had a few great cathartic cries yesterday listening to music to do just that. I'd go try ketamine if I felt like I needed to, but it seems like this has done the trick for now in a way that no drug or mindfulness or therapy ever has.
posted by OnTheLastCastle at 9:32 AM on July 27, 2023 [10 favorites]
Let it be known you can achieve similar if lesser effects with dextromethorphan, aka DXM, which is available over the counter as - yep - cough syrup, but you want to find the stuff with just DXM in it and no guaifenesin or other OTC meds, especially acetaminophen or pseudoephedrine or whatever it is they're using now to replace ephedrine.
It was recently approved to treat depression but only as a bupropion cocktail, which is kind of dumb and see also dumb patents.
I accidentally discovered this about DXM in high school when my friends and I got in to messing around with recreational/breakthrough doses of DXM syrup and suddenly I was A) no longer depressed from then ongoing childhood abuse and PTSD and B) suddenly getting straight As in all of my classes and able to pay attention in class.
And, later, a friend of mine made up a fake company with fake letterhead and managed to write to a chemical supply company and procure something like a 12 oz bottle of lab grade DXM salts for very little money that was equivalent of something like hundreds/thousands of bottles of OTC cough syrup and we never finished it.
At some point in college undergrad years he flushed the rest down the toilet and I'm still kind of peeved about it.
And in hindsight I now realize I was microdosing (or minidosing) DXM because I was doing stuff like 1-2 ounce 10mg/5ml doses about every 2-4 days before school and going to school like that, and it seems to have anti-depression effects at doses even lower than that.
But with dissociative grade or breakthrough/threshold doses more in the 8 oz of syrup in the 10mg/5ml range there was definitely an "afterglow" effect that lasted days/weeks, but like ketamine this is a bit of a commitment lasting 4-8 hours and you should definitely be in a safe place and not operating any vehicles or machinery and might want a responsible adult around.
Also in hindsight I now recognize that that afterglow effect and sense of calm and contentment was really about the lack of depression and anxiety that I was experiencing after a dissociative level dose.
posted by loquacious at 9:58 AM on July 27, 2023 [11 favorites]
It was recently approved to treat depression but only as a bupropion cocktail, which is kind of dumb and see also dumb patents.
I accidentally discovered this about DXM in high school when my friends and I got in to messing around with recreational/breakthrough doses of DXM syrup and suddenly I was A) no longer depressed from then ongoing childhood abuse and PTSD and B) suddenly getting straight As in all of my classes and able to pay attention in class.
And, later, a friend of mine made up a fake company with fake letterhead and managed to write to a chemical supply company and procure something like a 12 oz bottle of lab grade DXM salts for very little money that was equivalent of something like hundreds/thousands of bottles of OTC cough syrup and we never finished it.
At some point in college undergrad years he flushed the rest down the toilet and I'm still kind of peeved about it.
And in hindsight I now realize I was microdosing (or minidosing) DXM because I was doing stuff like 1-2 ounce 10mg/5ml doses about every 2-4 days before school and going to school like that, and it seems to have anti-depression effects at doses even lower than that.
But with dissociative grade or breakthrough/threshold doses more in the 8 oz of syrup in the 10mg/5ml range there was definitely an "afterglow" effect that lasted days/weeks, but like ketamine this is a bit of a commitment lasting 4-8 hours and you should definitely be in a safe place and not operating any vehicles or machinery and might want a responsible adult around.
Also in hindsight I now recognize that that afterglow effect and sense of calm and contentment was really about the lack of depression and anxiety that I was experiencing after a dissociative level dose.
posted by loquacious at 9:58 AM on July 27, 2023 [11 favorites]
the folks at johnson and johnson realized a little while back that if you isolate s-ketamine from r-ketamine, it's technically a different drug and therefore it can be patented
Yeah I think this is what’s actually going on with the reference to “a cheap version of ketamine.” The research said regular racemic ketamine was as good if not better before Spravato was even approved. Also I don’t think S-ketamine itself could possibly be on-patent at this point because it’s been sold for anesthesia for a long time so there was just some specific formulation that was approved for depression? I forget.
In reality in the U.S. it seems a little under-regulated if anything and there’s been a boom in clinics and services that will just give you ketamine off-label (but as somebody else said you may have to pay out of pocket).
posted by atoxyl at 10:26 AM on July 27, 2023 [2 favorites]
Yeah I think this is what’s actually going on with the reference to “a cheap version of ketamine.” The research said regular racemic ketamine was as good if not better before Spravato was even approved. Also I don’t think S-ketamine itself could possibly be on-patent at this point because it’s been sold for anesthesia for a long time so there was just some specific formulation that was approved for depression? I forget.
In reality in the U.S. it seems a little under-regulated if anything and there’s been a boom in clinics and services that will just give you ketamine off-label (but as somebody else said you may have to pay out of pocket).
posted by atoxyl at 10:26 AM on July 27, 2023 [2 favorites]
https://patents.google.com/patent/US20130236573A1/en
I'm not a patent attorney and I'm struggling to figure out what novel compound or process was patented here. It looks like they're saying that esketamine + an optional med + the spray bottle = something unique to patent? Can anyone with some patent experience explain what they're claiming here?
posted by ensign_ricky at 10:41 AM on July 27, 2023
I'm not a patent attorney and I'm struggling to figure out what novel compound or process was patented here. It looks like they're saying that esketamine + an optional med + the spray bottle = something unique to patent? Can anyone with some patent experience explain what they're claiming here?
posted by ensign_ricky at 10:41 AM on July 27, 2023
Let it be known you can achieve similar if lesser effects with dextromethorphan, aka DXM, which is available over the counter as - yep - cough syrup, but you want to find the stuff with just DXM in it and no guaifenesin or other OTC meds, especially acetaminophen or pseudoephedrine or whatever it is they're using now to replace ephedrine.
I have heard - not a euphemism, I never fucked around with this particular substance, I just keep abreast of such things - that there’s a company that currently sells a line of unusually potent DXM-only products, advertised as cough suppressants, in significant quantity online. I mean in a way that suggests they know what they are doing.
posted by atoxyl at 10:48 AM on July 27, 2023 [4 favorites]
I have heard - not a euphemism, I never fucked around with this particular substance, I just keep abreast of such things - that there’s a company that currently sells a line of unusually potent DXM-only products, advertised as cough suppressants, in significant quantity online. I mean in a way that suggests they know what they are doing.
posted by atoxyl at 10:48 AM on July 27, 2023 [4 favorites]
Oops, maybe that was the initial patent (filed by a different pharma company), whereas this is the J&J one?
https://portal.unifiedpatents.com/patents/patent/US-11173134-B2
Again, it kind of looks like they're saying that esketamine in a spray bottle is something novel and unique. Sigh.
posted by ensign_ricky at 10:49 AM on July 27, 2023 [1 favorite]
https://portal.unifiedpatents.com/patents/patent/US-11173134-B2
Again, it kind of looks like they're saying that esketamine in a spray bottle is something novel and unique. Sigh.
posted by ensign_ricky at 10:49 AM on July 27, 2023 [1 favorite]
i have been chasing this for months. insurance won't cover it. legit providers are nowhere near me and even the ones 3 hours away (which really, is an excessive distance) won't return my calls. it could change my live after 35+ years with treatment resistant depression but as usual in the us i can't get the help i need.
posted by misanthropicsarah at 11:19 AM on July 27, 2023 [2 favorites]
posted by misanthropicsarah at 11:19 AM on July 27, 2023 [2 favorites]
Ketamine Wellness Centers, Veterans Affairs Community Care Network Partner to Provide Free Treatments to Veterans With PTSD (Nov. 24, 2021, Pharmacy Times) "New partnerships will allow veterans with post-traumatic stress disorder (PTSD), major depression, and chronic pain to access ketamine treatments at no out-of-pocket cost when other treatments have been unsuccessful"
Abrupt closure of ketamine clinic chain blindsides veterans and others with severe depression and chronic pain (NBC, March 23, 2023) "Patients and employees of the Ketamine Wellness Centers, or KWC, said they were blindsided when the company, one of the nation’s largest operators of ketamine clinics, announced on its website on March 10 that it had shuttered all 13 of its locations in nine states. 'I cried for days,' said a U.S. Navy veteran, who relied on the free treatment he received at the Ketamine Wellness Centers."
"The high-profile stumbles at Field Trip Health & Wellness and Ketamine Wellness Center highlight the fraught environment the half-a-century-old drug faces in treating mental health at scale" (Behavioral Health Business May 17, 2023) is an interesting look clinic financials. Recently: FDA’s Draft Guidance for Psychedelic Research Could Pave Way for More Widespread Adoption (Behavioral Health Business, July 10, 2023).
Psychedelic Drugs: Considerations for Clinical Investigations / Guidance for Industry (FDA) This guidance document is being distributed for comment purposes only. Comments and suggestions regarding this draft document should be submitted within 60 days of publication in the Federal Register of the notice announcing the availability of the draft guidance. Submit electronic comments to https://www.regulations.gov.
posted by Iris Gambol at 11:20 AM on July 27, 2023
Abrupt closure of ketamine clinic chain blindsides veterans and others with severe depression and chronic pain (NBC, March 23, 2023) "Patients and employees of the Ketamine Wellness Centers, or KWC, said they were blindsided when the company, one of the nation’s largest operators of ketamine clinics, announced on its website on March 10 that it had shuttered all 13 of its locations in nine states. 'I cried for days,' said a U.S. Navy veteran, who relied on the free treatment he received at the Ketamine Wellness Centers."
"The high-profile stumbles at Field Trip Health & Wellness and Ketamine Wellness Center highlight the fraught environment the half-a-century-old drug faces in treating mental health at scale" (Behavioral Health Business May 17, 2023) is an interesting look clinic financials. Recently: FDA’s Draft Guidance for Psychedelic Research Could Pave Way for More Widespread Adoption (Behavioral Health Business, July 10, 2023).
Psychedelic Drugs: Considerations for Clinical Investigations / Guidance for Industry (FDA) This guidance document is being distributed for comment purposes only. Comments and suggestions regarding this draft document should be submitted within 60 days of publication in the Federal Register of the notice announcing the availability of the draft guidance. Submit electronic comments to https://www.regulations.gov.
posted by Iris Gambol at 11:20 AM on July 27, 2023
my favorite fun fact about chirality is that the molecules that make the flavours wintergreen and spearmint are mirrors of each other
I was pretty sure wintergreen was methyl salicylate so I had to look this up. Wiki says the non-spearmint carvone isomer is more of a caraway flavor.
posted by atoxyl at 11:59 AM on July 27, 2023 [4 favorites]
I was pretty sure wintergreen was methyl salicylate so I had to look this up. Wiki says the non-spearmint carvone isomer is more of a caraway flavor.
posted by atoxyl at 11:59 AM on July 27, 2023 [4 favorites]
Ah, DXM as "psychedelic."
It is not for everybody. It is profoundly disorienting, unfathomably strange. Afterwards, there can be a kind of amnesia about what it was like. There was a time in the '90s when it was talked about as harmless, but ISTRC some later results suggesting there could be excitotoxicity in the affected neurons, during acute intoxication.
Never have tried K, but have a notion that it's not so... Recondite? Refractory?
posted by Aardvark Cheeselog at 12:08 PM on July 27, 2023 [1 favorite]
It is not for everybody. It is profoundly disorienting, unfathomably strange. Afterwards, there can be a kind of amnesia about what it was like. There was a time in the '90s when it was talked about as harmless, but ISTRC some later results suggesting there could be excitotoxicity in the affected neurons, during acute intoxication.
Never have tried K, but have a notion that it's not so... Recondite? Refractory?
posted by Aardvark Cheeselog at 12:08 PM on July 27, 2023 [1 favorite]
It is not for everybody. It is profoundly disorienting, unfathomably strange. Afterwards, there can be a kind of amnesia about what it was like. There was a time in the '90s when it was talked about as harmless, but ISTRC some later results suggesting there could be excitotoxicity in the affected neurons, during acute intoxication.
Never have tried K, but have a notion that it's not so... Recondite? Refractory?
If you're talking about the Olney's lesions thing, AFAIK that study was discounted and it involved a study with rats being administered very large doses every day for a month.
Anyway, the prophylactic to that neurotoxicity apparently is as simple as antioxidants like vitamin C. Or, duh, not taking large doses every day for a month or more straight.
I will agree that breakthrough/dissociative doses are very disorienting but on par (or less than) breakthrough/dissociative doses of ketamine. Almost all dissociatives (including nitrous oxide) are profoundly weird and not for everyone.
Both DXM and ketamine have weird stimulant-like effects not unlike cocaine at higher doses, too, but with ketamine if you go too far you go into the proverbial K-hole and basically completely black out or go into a sedated state.
I should also note that - just like ketamine - you absolutely should not ever take DXM while taking an SSRI or MAOI due to the very large risk of serotonin syndrome. Or grapefruit juice. (This is all noted in the wikipedia article and any recreational drug guides worth their salts.)
In any case, therapeutic doses for DXM would and should be likely be much less than the equivalent of drinking a whole 8 oz bottle of syrup. I was seeing favorable results for depression and PTSD on 1-2 ounces or less with very little impairment or dissociation, and 1-2 ounces isn't really that much more than what someone would take as directed in a day for a cold or cough.
YMMV and I'm definitely not a doctor and this is not medical advice. But everything I've seen or experienced with DXM is that it has very similar effects (and risks) of ketamine except you can go get it without a prescription.
On balance I think that clinically administered ketamine is maybe slightly less weird or disorienting than DXM but I think that might mainly be a dosage and setting thing.
I should also note that abuse of DXM has the same kind of risks as abuse of ketamine and can be habit forming or even very negative psychological effects and issues. This was a known thing with recreational users and abusers of DXM that things could and would definitely get weird and not in good ways.
Like there are a ton of "trip reports" out there of long term or heavy users having disturbed behavioral issues and incidents like sleepwalking outside naked or in their underwear and missing time, but this seems to be true of most dissociatives when abused, especially chronically.
posted by loquacious at 2:00 PM on July 27, 2023 [3 favorites]
Never have tried K, but have a notion that it's not so... Recondite? Refractory?
If you're talking about the Olney's lesions thing, AFAIK that study was discounted and it involved a study with rats being administered very large doses every day for a month.
Anyway, the prophylactic to that neurotoxicity apparently is as simple as antioxidants like vitamin C. Or, duh, not taking large doses every day for a month or more straight.
I will agree that breakthrough/dissociative doses are very disorienting but on par (or less than) breakthrough/dissociative doses of ketamine. Almost all dissociatives (including nitrous oxide) are profoundly weird and not for everyone.
Both DXM and ketamine have weird stimulant-like effects not unlike cocaine at higher doses, too, but with ketamine if you go too far you go into the proverbial K-hole and basically completely black out or go into a sedated state.
I should also note that - just like ketamine - you absolutely should not ever take DXM while taking an SSRI or MAOI due to the very large risk of serotonin syndrome. Or grapefruit juice. (This is all noted in the wikipedia article and any recreational drug guides worth their salts.)
In any case, therapeutic doses for DXM would and should be likely be much less than the equivalent of drinking a whole 8 oz bottle of syrup. I was seeing favorable results for depression and PTSD on 1-2 ounces or less with very little impairment or dissociation, and 1-2 ounces isn't really that much more than what someone would take as directed in a day for a cold or cough.
YMMV and I'm definitely not a doctor and this is not medical advice. But everything I've seen or experienced with DXM is that it has very similar effects (and risks) of ketamine except you can go get it without a prescription.
On balance I think that clinically administered ketamine is maybe slightly less weird or disorienting than DXM but I think that might mainly be a dosage and setting thing.
I should also note that abuse of DXM has the same kind of risks as abuse of ketamine and can be habit forming or even very negative psychological effects and issues. This was a known thing with recreational users and abusers of DXM that things could and would definitely get weird and not in good ways.
Like there are a ton of "trip reports" out there of long term or heavy users having disturbed behavioral issues and incidents like sleepwalking outside naked or in their underwear and missing time, but this seems to be true of most dissociatives when abused, especially chronically.
posted by loquacious at 2:00 PM on July 27, 2023 [3 favorites]
Older (from 2016) but useful article from the Multidisciplinary Association for Psychedelic Studies: Review of The Ketamine Papers: Science, Therapy, and Transformation
posted by wicked_sassy at 2:19 PM on July 27, 2023
posted by wicked_sassy at 2:19 PM on July 27, 2023
i feel kinda square because this is legitimately the first time i’ve seen someone say that robodosing has therapeutic effects reminiscent of ketamine’s. well, and it’s also the first time that i’ve seen someone describe robodosing as being at all fun. i guess i’ve got it filed away in the “things kids do when they’re not cool enough to get real drugs” category alongside huffing and stuff like that, which is apparently a wrong impression?
posted by bombastic lowercase pronouncements at 2:26 PM on July 27, 2023
posted by bombastic lowercase pronouncements at 2:26 PM on July 27, 2023
I suspect the big medical issue with ketamine may be bladder damage with long term use. There are studies of ketamine addicts that consume up to a max of 4gm a day(!) with bladder lesions. otoh that's 30x more ketamine than a script for 400mg troches every 3 days, which seems to be kind of an average dose for the telemed ketamine.
For me, it's a reasonable risk to take. Maybe I'll feel differently if low dose long term use does do damage to my bladder. For now, being more happy than not on a regular basis for the first time in a bunch of years feels like it's worth the risk.
posted by ensign_ricky at 2:57 PM on July 27, 2023 [1 favorite]
For me, it's a reasonable risk to take. Maybe I'll feel differently if low dose long term use does do damage to my bladder. For now, being more happy than not on a regular basis for the first time in a bunch of years feels like it's worth the risk.
posted by ensign_ricky at 2:57 PM on July 27, 2023 [1 favorite]
If you're talking about the Olney's lesions thing, AFAIK that study was discounted and it involved a study with rats being administered very large doses every day for a month.
It’s a well-replicated finding in animals and don’t think the possibility of NMDA antagonist neurotoxicity in humans can really be discounted but we are probably less vulnerable than mice? And the effect was always seen to be stronger with more potent, longer-lasting antagonists, so less potent short acting ones like ketamine or N2O are probably safest. There are some studies on heavy recreational ketamine users showing abnormalities, but we’re talking daily use for a few years here.
I think there’s some suggestion (from rodent studies) that serotonin agonism could be protective (and DXM incidentally has some SSRI-like activity). We’re getting into speculative territory so I’ll link Serotonergic Agents That Activate 5HT2A Receptors Prevent NMDA
Antagonist Neurotoxicity without direct comment. This one is really for the people who know where it’s going when they see “5HT2A receptors” but it does go there explicitly.
posted by atoxyl at 3:30 PM on July 27, 2023 [2 favorites]
It’s a well-replicated finding in animals and don’t think the possibility of NMDA antagonist neurotoxicity in humans can really be discounted but we are probably less vulnerable than mice? And the effect was always seen to be stronger with more potent, longer-lasting antagonists, so less potent short acting ones like ketamine or N2O are probably safest. There are some studies on heavy recreational ketamine users showing abnormalities, but we’re talking daily use for a few years here.
I think there’s some suggestion (from rodent studies) that serotonin agonism could be protective (and DXM incidentally has some SSRI-like activity). We’re getting into speculative territory so I’ll link Serotonergic Agents That Activate 5HT2A Receptors Prevent NMDA
Antagonist Neurotoxicity without direct comment. This one is really for the people who know where it’s going when they see “5HT2A receptors” but it does go there explicitly.
posted by atoxyl at 3:30 PM on July 27, 2023 [2 favorites]
I should also note that - just like ketamine - you absolutely should not ever take DXM while taking an SSRI or MAOI due to the very large risk of serotonin syndrome.
I don’t think SSRIs are contraindicated with ketamine? SSRIs and MAOIs are contraindicated with DXM because, as I said above, DXM actually is an SRI (and looking it up right now suggests may also compete for metabolism).
posted by atoxyl at 3:36 PM on July 27, 2023
I don’t think SSRIs are contraindicated with ketamine? SSRIs and MAOIs are contraindicated with DXM because, as I said above, DXM actually is an SRI (and looking it up right now suggests may also compete for metabolism).
posted by atoxyl at 3:36 PM on July 27, 2023
Interesting about DXM, I do not recall reading much in the way of experiences I was eager to have; first time or otherwise. Too much vomiting.
Erowid - DXM Experiences
posted by snuffleupagus at 4:32 PM on July 27, 2023
Erowid - DXM Experiences
posted by snuffleupagus at 4:32 PM on July 27, 2023
Not listed on that particular erowid page is Jim Hogshire's write up Electric Cough-Syrup Acid Test from 1993. (erowid.com can be much of a rabbit hole and it's not always easy to find the most, cough, interesting stuff.)
posted by Insert Clever Name Here at 5:18 PM on July 27, 2023 [3 favorites]
posted by Insert Clever Name Here at 5:18 PM on July 27, 2023 [3 favorites]
loquacious, I am always surprised how similar experiences we had living in such different circumstances. More than once I have not written q comment because it felt like rephrasing yours. We only met once IRL, and we did not talk much.
I told the full story elsewhere, the shirt version is that illegal drugs saved my life more than once. DXM was the first thing I tried after alcohol and pot, and maybe large doses of Dramamine.
I did not know how to get access to the cool drugs, and had not learned to find mushrooms and peyote. DXM was easy, brand name syrups all had guaifenesin, but the cheap generic brand only had DXM. Being uncontrolled I also pretended to be a business and ordered a box of retail bottles.
I ended up doing high doses 5 or 6 times in one summer, and did not feel the need to do it again more than once every couple of years. Got rid of a lot of my anxiety and suicidal thoughts.
Now it is very hard to find here without other active ingredients that can do anything from make you puke to kill your liver if you take the syrup at the doses needed.
The one that works best for me is magic mushrooms. I would do heroic doses every couple years and small doses throughout the year.
Ketamine for me felt similar to DXM, but it leaves a real bad aftertaste in my brain.
Now I take other medications that mean that I have to carefully plan any recreational or off-label at least 8 weeks in advance to ramp down on my legal meds.
If anyone here is thinking of going DIY with ketamine, DXM, or similar stuff, please do your research on drug interactions! Even having taken some OTC cough medicine in the weeks prior can have very bad consequences..
posted by Dr. Curare at 6:31 PM on July 27, 2023 [6 favorites]
I told the full story elsewhere, the shirt version is that illegal drugs saved my life more than once. DXM was the first thing I tried after alcohol and pot, and maybe large doses of Dramamine.
I did not know how to get access to the cool drugs, and had not learned to find mushrooms and peyote. DXM was easy, brand name syrups all had guaifenesin, but the cheap generic brand only had DXM. Being uncontrolled I also pretended to be a business and ordered a box of retail bottles.
I ended up doing high doses 5 or 6 times in one summer, and did not feel the need to do it again more than once every couple of years. Got rid of a lot of my anxiety and suicidal thoughts.
Now it is very hard to find here without other active ingredients that can do anything from make you puke to kill your liver if you take the syrup at the doses needed.
The one that works best for me is magic mushrooms. I would do heroic doses every couple years and small doses throughout the year.
Ketamine for me felt similar to DXM, but it leaves a real bad aftertaste in my brain.
Now I take other medications that mean that I have to carefully plan any recreational or off-label at least 8 weeks in advance to ramp down on my legal meds.
If anyone here is thinking of going DIY with ketamine, DXM, or similar stuff, please do your research on drug interactions! Even having taken some OTC cough medicine in the weeks prior can have very bad consequences..
posted by Dr. Curare at 6:31 PM on July 27, 2023 [6 favorites]
It's so depressing that being sick makes you poor, which puts any hope of treatment for your illness out of reach.
posted by The Underpants Monster at 8:13 PM on July 27, 2023 [4 favorites]
posted by The Underpants Monster at 8:13 PM on July 27, 2023 [4 favorites]
it's not always easy to find the most, cough, interesting stuff
nasty cough you’ve got there - I know just the thing for that
posted by atoxyl at 8:34 PM on July 27, 2023 [1 favorite]
nasty cough you’ve got there - I know just the thing for that
posted by atoxyl at 8:34 PM on July 27, 2023 [1 favorite]
wait'll you guys hear about what you can do with 500 morning glory seeds and a gill of petroleum ether
posted by logicpunk at 6:55 AM on July 28, 2023 [3 favorites]
posted by logicpunk at 6:55 AM on July 28, 2023 [3 favorites]
Depends on where you live, but for me gathering and extracting a kilo of Ipomoea corymbosa seeds is too much work and an inferior product than waiting for August rains and picking some shrooms, they grow everywhere.
But I guess nutmeg and morning glory experiments are a decent rite of passage for teenage psychonauts.
posted by Dr. Curare at 2:32 PM on July 28, 2023 [1 favorite]
But I guess nutmeg and morning glory experiments are a decent rite of passage for teenage psychonauts.
posted by Dr. Curare at 2:32 PM on July 28, 2023 [1 favorite]
there’s a region-specific mushroom identification forum that i started following back when they took a very strong public stand for black lives and against police brutality, and then kicked out everyone who thought that a mushroom identification forum shouldn’t be “political.”
anyway, i mention this because most times of year the questions are either:
anyway, i mention this because most times of year the questions are either:
- what’s this cool weird thing in my backyard?
- can i eat this?
- are these the droids?
- these aren’t the droids you’re looking for
- these are the droids you’re looking for
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posted by grumblemf at 11:16 PM on July 26, 2023 [5 favorites]