21 ms·

Ketamine's effect on depression may hinge on hope

183 points by cpncrunch 3y ago

xchip 3y ago
This should be off topic because it is not tech related. That is what mods say with Palestine related posts. Those rules should also apply here, shouldn't they?
Forgotthepass8 3y ago
If that House MD arc ends up being ahead of its time...
- JohnMakin 3y ago
  Which one?
  - sli 3y ago
    I didn't watch a lot of House MD but I believe I know what's being referred to. There was an arc where House was administered ketamine as part of a treatment for his leg and he started walking without his cane, suggesting that his condition was being caused by psychological trauma long after his leg had physically recovered.
    - JohnMakin 3y ago
      I vaguely remember this. thanks.
    - Forgotthepass8 3y ago
      That's a bingo
ClassyJacket 3y ago
This isn't specific to ketamine tho is it? The placebo effect is well studied.
- greenpresident 3y ago
  Notably, the placebo effect usually only effects suffer reported symptoms as in this case. It’s a folk wisdom that it has physiological effects, which is often not true.
  - quickthrower2 3y ago
    So placebo effects accuracy of self reporting? Making perhaps less or perhaps more accurate than without? I get this. Especially rating emotions 1 to 10 etc.
- standardly 3y ago
  Correct. It's important to remember the existence of a placebo effect isn't correlated with the efficacy of the drug being tested. I suppose that is obvious, but placebo studies tend to have a negative connotation.
scythe 3y ago
This is not the first trial of ketamine used under clinical anaesthesia to disguise its effects. A previous study using similar methods in 2018 found the usual effects of surgery: a transient increase in depressive symptoms. I'm no expert but my inclination is to blame this on postoperative pain. https://www.sciencedirect.com/science/article/pii/S0007091218303143 https://www.sciencedirect.com/science/article/pii/S000709121... The confidence interval in the new study includes zero, although the average beneficial effect is still surprising when considering the usual expected negative effects. I suspect that the real effect may simply be that general anaesthesia causes a susceptibility to suggestion. It's not clear if ketamine — or anything else — should be expected to work normally when it is administered to patients under general anesthesia. General anesthesia has profound effects on the functioning of the nervous system.
- kallistisoft 3y ago
  > It's not clear if ketamine — or anything else — should be expected to work normally when it is administered to patients under general anesthesia. General anesthesia has profound effects on the functioning of the nervous system. Very much this! Additionally when discussing ketmaine it's method of action (NMDA receptor antagonist) specifically could be disrupted by the effects of another anesthetic compound.
- nullindividual 3y ago
  Ketamine IV or compound medication without any other drugs is so profoundly different from Ketamine as part of a procedure where you’re otherwise unconscious. Just no comparison.
  - p1esk 3y ago
    Could you explain? What is the difference? I only had Ketamine once during surgery and I vividly remember the few hours after.
    - nullindividual 3y ago
      It of course depends on your IV dosage. You can see and hear things that aren't there. Even have a conversation with mythical, religious, or spiritual entities. You can experience 'past lives' (whether factual or not, which I don't believe so, experiencing something you THINK is a past life is interesting). And it can go south with disturbing or dark imagery.
deleted 3y ago
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omginternets 3y ago
Beyond the importance of controlling the placebo effect, I am worried that a lot of the drug-depression research is overlooking an important possibility: that the thing about ketamine/psilocybin/etc that is helping with depression is not some latent property of the molecule, but rather the actual transcendent experience of the trip. In other words, the trip is the point, not the mechanistic neuro-tinkering [0]. Importantly, this tracks with what we know about the protective effects of things like religiosity against depression. As such, the qualitative experience of the drug might not be something we can (or should) do away with. I would even go as far as suggesting that an absence of transcendence in one's life is precisely what causes a large segment of people to become depressed in the first place, and that perhaps drugs are helpful only insofar as they produce a transcendent experience. This isn't to say we can't take a scientific approach to treating depression, but that has to be balanced with something profoundly metaphysical: the actual qualia of life experience. Wellness isn't the absence of disease; it's the presence of thriving, and that includes within it a component of things like hope, inspiration, and elevation above the ordinary. We used to have various ceremonies designed to turn us towards the numinous, but we've pretty systematically dismantled those in favor of a grounded hyper-rationality [1]. As a scientist, I can't really object to rationality on its own, but it may be worth considering non-rational, transcendent experience as a fundamental psychological need. [0] If you're a materialist, you might object that neurological machinery is not differentiable from qualia. Fair enough! I even agree! My point is simply that medicine needs to consider qualia as a major parameter in the treatment of depression. Fixing depression is not like fixing a car. [1] I suspect most people here are familiar with Nietzsche's "God is dead quote". Many people in my entourage are floored to discover that he correctly predicted the dramatic increase in anxiety, depression, neuroticism and nihilism that is present in modern life.
- photonerd 3y ago
  If qualia are not different that our “neurological machinery” (and all available evidence shows this so far, not least the incoherence of definitions of qualia that try to exclude such) then medicine is already considering such as a major parameter. If they are different (and exist at all) then such needs to be demonstrated before they can be reliably considered. Given even proponents of qualia can’t reliably agree with each on what they even are defined as (other than using vague circular reasoning)… frankly, I’m not holding my breath.
jjgreen 3y ago
Good news for the leader of His Majesty's opposition https://www.independent.co.uk/business/sir-keir-starmer-reveals-special-k-nickname-on-visit-to-kellogg-s-factory-b1934831.html https://www.independent.co.uk/business/sir-keir-starmer-reve...
PlunderBunny 3y ago
I don't want to downplay depression (which I have no experience of), or come across as being flippant, but could the placebo effect in many of these kinds of trials be as simple as "a caring person (professional and/or stranger) interacting with the depressed subject improves their condition?"
- teaearlgraycold 3y ago
  That seems really easy to control for
  - pygy_ 3y ago
    That's the reason why drugs are tested in double-blind, randomized controlled trials. The placebo effect is a major part of the effect of SSRI, which only improve 1 in 6-8 patients if you subtract the placebo effect [1]. The "number needed to treat" (NNT) mentioned below is the average number of patients that need to recieve the treatment for one of them to be in a better condition than if all of them had recieved a placebo. 1. https://www.cambridge.org/core/journals/psychological-medicine/article/antidepressant-standoff-why-it-continues-and-how-to-resolve-it/2EA210EEDC83005BC299AF3095941532 https://www.cambridge.org/core/journals/psychological-medici...
  - robocat 3y ago
    However giving randoms drug trials is rather evil.
- thom 3y ago
  This is neither downplaying depression nor flippant - the therapeutic relationship is clearly very important and I don't think anybody denies that. But I suspect a lot of this is about your inherent world-view. Some people do well after purely online CBT, some don't. Some do well in talking therapy, some don't. It seems likely that how your brain perceives the world (and itself) affects which interventions help.
calibas 3y ago
A big part of depression is negative thinking, so it's not too much of a stretch to believe that positive thoughts, like hope, would lessen depression.
- supportengineer 3y ago
  In a late-stage capitalism world, where the climate is collapsing, and homes are unaffordable, where does hope come from?
  - moshegramovsky 3y ago
    This doesn't get said nearly enough. Social media is also to blame. I know one person who got upset about his credit score (low 700s) from watching videos about it and then kept consuming information until he was seriously depressed about his (good) finances. When I was in my twenties and early thirties, I never worried about any of this at all.
    - doubled112 3y ago
      I couldn't imagine worrying about it, but maybe it's because I think I'm doing fine. Credit score is such a strange game to me. Closed a loan? That costs me points, somehow. Dad got a new cell phone and they ran the wrong person's credit? That cost me points too, because clearly their screw up was my fault. Hope he was still approved. I rent and the cars are old. Sometimes I feel like I play on hard mode by having a $3000 VISA as my only debt. If I make a $2000 purchase, they report it Tuesday, I pay that back to them Thursday, and I check my score? Woah, dropped 80 points! What a delinquent! That might have become more of a rant than I intended. I should probably just apply for more credit stop the large points changes like this.
  - NickM 3y ago
    Not to downplay the current world problems, but you could make similar arguments at any point in history about any number of big problems humanity has faced. Yet, people still find hope and keep solving problems.
3cats-in-a-coat 3y ago
It's shocking how much of medicine is just based on trust and word of mouth. Studies made decades ago that turn out completely wrong and not reproducible. We flatter ourselves that we're enlightened and based on science, but the more you dig the more you realize it's all a game of trial and error and fighting cultural wars to get your "remedy" out there and profit. It's rather shocking to someone who's not familiar with the inner workings of the pharma industry and medicine in general. In particular in psychiatry, we have working theories about how the various agents work to achieve anti-depressive or anti-psychotic effects, which are taken as the gospel or proven fact. And then those models turn out absolutely wrong. And we have to face the fact we're prescribing drugs to sick people we have no clue how and why they work. And whether they work at all, often. It's especially the case when a given drug must be taken for months before any effect is seen. It's essentially impossible to control for other variables over MONTHS of someone's life. You can easily convince them they feel slightly better now because they've been months on end taking Zoloft. They may've easily been better if they hadn't taken it.
- mirpa 3y ago
  It is kind of ironic that study hints about hope/placebo. What I experienced were always side effects, no relief and then different drug, rinse and repeat. Left with original problem, worried what the next drug gonna bring as side effect with more and more diminishing hope it will ever help - despair.
  - 3cats-in-a-coat 3y ago
    Some may criticize me for saying this, but I'll explain my observations. In general I've noticed when a drug works, it immediately gets restricted in use, because it has abuse potential, or a dangerous dose. There's no vast conspiracy here (well, sort of), but a simple principle: anything that is demonstrable to be USEful, is demonstrable to be abUSEable. No one is restricting homeopathic remedies, they don't have side-effects, or drug interactions, and that's because they don't do anything. Many antidepressants also don't require too strict of a regime, that's because they actually have very poor therapy effects overall, but even when they do, their effect and side-effects are so stretched out in time, it's very hard to show a hard cause-effect relationship. Despite reading the list you see all sorts of conditions on a drug that may occur as a side-effect, often many of those just occurred during a study, but had little relation to a drug, while other effects were underreported (say often around sexual function as people are embarrassed, or things people can't feel, and aren't tested about, things which doctors don't expect they need to check). So basically "long-running drugs" are a big question mark, and often turn out to be garbage. But stimulants like Ritalin, Adderall, Vivanse, Concerta and so on are known to instantly alleviate a number of symptoms of ADHD, depression and so on. Not in months. But within AN HOUR of taking a pill. You can immediately see how it works. But of course you can abuse them, and your body craves them over time, because the body and mind adapts to everything, that's the whole point of homeostasis. So they're restricted and you're told they're not good for you because they can be abused. But this cause-effect relationship is only visible because their effect is also apparent. Not just to medicine, but also to your own body. Your mind makes the cause-effect relationship "this makes dopamine good, circuits work better, take again". But the fact of the matter with drugs is they're all poison, and the therapeutic effect is in the right dose and application. There's no way around it. If it was nice and fun at any quantity, it's at best just sugar, or at worst some random chemical that few bad studies pushed through, which doesn't at all act like it's supposed to. This doesn't apply just to stimulants. I have issues with my circadian rhythm so I found a brand of melatonin of Jamieson that is 10mg, slow release. I notice on the first night it works. Other smaller doses from random supplement companies did nothing, heck who knows if they even had the active ingredient. So I'm in EU. And lo and behold, the EU notices melatonin is USEful at dose over 3mg. Therefore also abUSEable, and has side-effects in some. Very minor I might add. But it was immediately pulled from shelves, so a long and tedious registration can begin for it as a medication rather than a supplement, and until then, EU people who need it are screwed I guess. It's absurd, but it follows the principle that if it works, it becomes controlled. So the irony in all this is that we have easiest access to garbage that doesn't help, and the drugs that do help, have high prices and restricted access due to over-regulation. One of those things of the modern world.
temptemptemp111 3y ago
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progmetaldev 3y ago
I'm more interested in the effects of Ketamine on anxiety. I know that it's not as effective, but haven't seen any statistics specifically related to anxiety. I have gotten my Ketamine through Mindbloom, and just need to schedule my treatment and follow up dates. My depression effects are due to my suffering through anxiety for over 20 years (started in 1999). My anxiety also seemed to correlate with 2 bad trips from LSD in the late 90s, that resulted in my being hospitalized and injected with Thorazine to abort the trip. While I have had some depression from divorce and breakups, those bouts aren't lasting the way my anxiety is, and persists in day to day life. I imagine it is related to my being hospitalized at night for LSD, but I do not suffer anxiety unless I drive at night. I have seen various psychiatrists, psychologists, therapists, and have undergone biofeedback and cognitive behavioral therapy with limited success. I find that when my life as a whole is less stressful, my anxiety at night is less pronounced and sometimes non-existent.
- nullindividual 3y ago
  They will give Ketamine and benzos together as K can cause anxiety symptoms (or terror with a K-hole).
  - progmetaldev 3y ago
    I actually take a benzo only as needed, and try not to take it if I can absolutely help it. I was told that taking a benzo(diazepine) the day of a Ketamine treatment actually cancels out the positive effect of the Ketamine. I believe it as well. Benzodiazepines definitely have a beneficial effect, but if you are trying to get through a psychedelic crisis, or even a horrible panic attack, taking it will 100% negate any kind of benefit you would get by pushing through the uncomfortable negativity. I'm speaking from personal experience, but I feel Benzos cancel out anything positive from learning in regards to a psychically negative experience. Sometimes your anxiety is so bad you need them, I know I have been in that place where I'm responsible for another person, and can't deal with the anxiety and still help this other person. I'm also terrified as I've heard Benzos increase the odds of getting Alzheimer's by something like >80%. I have Alzheimer's on my dad's grandmother's side, and my mom's father's side. Unless it skips a generation, and favors mother's or father's side, and the side it skips works out, I'm screwed!
insickness 3y ago
>The take-away should not be that ketamine “is just a placebo,” Heifets emphasized. This is the very definition of placebo and why double blind studies are done. The control group and the actual group both improved thinking they got the drug. > In fact, there may be physiological resonance between the placebo effect — in other words, hope — and how ketamine works. This is just mumbo jumbo. There's no 'resonance effect' if it works the same in the control group.
- hcks 3y ago
  This is insane, people are really unwilling to let go the idea that illegal psychoactive drugs may have any beneficial effects for depression.
  - dannyw 3y ago
    Illegality is a societal construct, not a medicinal one.
  - bowsamic 3y ago
    I don't understand why they are so desperate for it. I suppose it's because they have a purely mechanistic view of the brain, and that if there isn't some chemical you can change to help, you're fucked
tstrimple 3y ago
Ketamine treatment is something I've seriously considered for my depression. It's hard not to be lured in by all the miraculous claims by folks who have been down the same path and found relief. I've been through the rounds with traditional ADHD and depression treatment with side effects that rival the underlying symptoms and have tried a few different prescriptions. I'm just so tired. Doing simple things like paying your electric bill or getting out of bed when you don't have external demands shouldn't be so damn hard.
andrewedstrom 3y ago
Alternative explanation: ketamine isn’t better than placebo for treating depression when given to someone who’s under anesthesia. You have to be awake. Similarly, I bet that if you gave psilocybin to someone under anesthesia, they wouldn’t get the same benefits as someone who took it while awake.
- kromem 3y ago
  Another alternative explanation: general anesthesia's disassociation alone combined with an expectation of transformative psychological change results in transformative psychological change similar to ketamine's disassociation combined with such an expectation. Ruling out the general anesthesia as having an effect because general anesthesia without expectation of depression improvement doesn't improve depression seems like it toys with a false negative in ignoring the possibility of combined factors (specifically psychological disassociation plus expectations of change).
quickthrower2 3y ago
Relevant comic: https://xkcd.com/1526/ https://xkcd.com/1526/
suzzer99 3y ago
Related to the psychological vs. physiological discussion: I can say with confidence that the first time I did ecstasy changed how I look at the world. We went for a walk barefoot on warm pavement and it was the most wonderful thing I ever felt. I realized on a visceral level that so much of our personal happiness is based on how we look at things, not what happens to us. I don't know if I got any chemical benefit from subsequent use, other than fun (with the consistently worsening serotonin crash afterwards). But just being able to step outside my usual angsty 19-year-old brain for a few hours had a profound effect.
- crtified 3y ago
  Fun is arguably the best (some might say the only authentic) way to cure depression.
  - suzzer99 3y ago
    Yeah but that serotonin crash afterwards was bleak. At this point in my life I can do E about once a year. Any more than that and I get really depressed afterwards. Although I do know people who are clinically depressed, and the hangover/crash doesn't bother them as much, because it's their normal state anyway.
  - amp108 3y ago
    Dancing is arguably the best (some might say the only authentic) way to cure quadriplegia.
    - crtified 3y ago
      I take your point. I meant it in the context of an earlier poster - if not the title topic, itself - who drew a line between ketamine_as_medication and ketamine_for_fun, and implied that that recreational drugs as a form of depression therapy were merely a way to have 'a fun trip', and not of any real benefit. However, insofar as fun is synonymous with happiness, which is antonymous with depression, every cure for depression involves the end goal of fun - one way or another. Pharmaceutically / chemically, emotionally, socially, intellectually, spiritually, you-name-it. Therefore, regarding this topic, I was positing that, where usage of recreational drugs as a novel cure for depression is concerned, the fun is the curative. But I can see how my generalisation could be interpreted as minimalising, if viewed as a pithy solution precluding all nuance - which it was not intended as!
0xDEAFBEAD 3y ago
>Even in blinded trials in which participants are not told which they received, ketamine’s oftentimes trippy effects are a dead giveaway. How about randomizing between ketamine and some other drug that makes people trip? At a certain point you have to wonder if any sufficiently trippy experience helps with depression, anesthesia included.
topherPedersen 3y ago
I broke my leg skydiving a few months ago. The EMTs gave me ketamine and fentanyl before they loaded me up in the ambulance. That stuff sent me to another dimension! I never want to go back there. Was pretty terrifying to be honest. Maybe a low dose could help with depression? I think a high dose would probably scare people and they wouldn't want to do it again.
- astrange 3y ago
  That's a pretty traumatic situation, so it suggests you shouldn't try to be cured of depression right after breaking your leg.
  - saiya-jin 3y ago
    Yeah that's one of the worst possible combinations (maybe apart from tripping sky high in actual war zone) - drugs and bad traumatic experience, while being loudly transported by strangers to hospital. You can't make up much worse set for trip. No wonder you had a bad trip, although I have absolutely 0 idea about those drugs or their combined effect on one's mind.
- apatheticonion 3y ago
  A friend of mine needed a bunch of morphine before a major surgery. Right before the doctor administered it he said "don't worry, people pay a lot of money for this" Always thought that was a pretty funny line
- brap 3y ago
  Former EMT here. The paramedics/doctors I used to work with would administer ketamine from time to time, but they would always pair it with this other drug (maybe midazolam? I don’t quite remember), for the sole purpose of preventing hallucinations. They made it very clear that the only reason for this mix was that ketamine hallucinations of that dose are often violent or sexual or both, and you don’t want to deal with those kind of allegations. I personally tried low dose pure ketamine (intramuscular) and it was quite pleasant.
hopefully60 3y ago
[dead]
yosito 3y ago
From what I understand about Ketamine, a large portion of the benefits hinge on being conscious.
- raverbashing 3y ago
  Yeah the experiment might be confounding the effect of the anesthesia itself and/or playing this down
thejazzman 3y ago
After reading research about this a few months ago, I made https://ketamine.games https://ketamine.games It's totally free, private, with no tracking analytics, and many Reddit users have reported increased success using.
- hyperdimension 3y ago
  Not to take away from your neat-looking site (I'm still looking through it) but in case you see this comment, under the 'install' link in the footer, you repeat yourself redundantly again, twice: > On your Android device, open Chrome Chrome
deleted 3y ago
[deleted]
Xenoamorphous 3y ago
Possibly offtopic: whenever I hear about drugs for mental issues it seems to be always depression or anxiety. But is there anything out there for things like, say, addiction?
- sph 3y ago
  Iboga is very interesting against opiate addiction: https://en.wikipedia.org/wiki/Tabernanthe_iboga https://en.wikipedia.org/wiki/Tabernanthe_iboga
pbj1968 3y ago
If any of this stuff actually worked we’d already be using it. Similarly how every medical problem hadn’t gone away in states that legalized marijuana.
- digbybk 3y ago
  This reminds me or the joke where an economist refuses to look down when told that there’s a $20 bill on the ground: “if there was really $20 on the ground, someone would have picked it up already”. Seriously though, we’re just getting started studying it, how can we know whether or not this stuff works? There’s a lot of positive anecdotal evidence. We’re not talking about marijuana, and no one ever expected it to solve every medical problem. That particular substance has done a lot of good with people experiencing discomfort, like cancer patients and the elderly, including members of my family.
- mrkeen 3y ago
  > how every medical problem hadn’t gone away in states that legalized marijuana. The problem was that people were being locked up.
- dragonwriter 3y ago
  Medical marijuana isn’t a cure, its a treatment. The point isn’t to make medical problems go away, it is reduce the adverse impact (more effectively and/or with less of its own adverse side effects than other alternatives.) We do use it, and it does work, and “we” were using it for those problems even when it was illegal, a condition that didn't not occur as the outcome of a rational evaluation of scientific evidence of utility vs. harm on either recreational or medical use, but based on vibes (and, in no small part, racism.)
user3939382 3y ago
I knew someone who used the "it cures depression!" line as an excuse to be addicted to it and go into K-holes 3x a day while it ruined their life.
EL_Loco 3y ago
From a pretty good essay written by someone who lived through the original "psychedelics will expand your mind" era of the 60s and 70s: "“Enlightenment in a pill,” many have pointed out, is a quintessentially American concept. Who’s got time for all that prayer and study and meditation and practice when there’s an easier, faster way? But there isn’t. Therein lies the great danger of LSD and its dopey cousin, marijuana. By offering a simulacrum of spiritual and intellectual growth – a very convincing simulacrum at times – it takes you everywhere except where you need to be, which is doing the long, hard work of learning to live." I resonate with what he says because, like the author mentions later on, I also have many friends who went deep into the psychedelics journey while claiming it was 'freeing their minds', 'enlightening' them, or whatever other concept they liked to use, only to end up, a decade or two later, in either a regular struggling life like so many others, or a downright bad place. I'm probably wrong to generalize, as I'm sure it can help many, but the drugs still can't substitute the individual's effort and struggle to grow, and overcome, and the learning of how to live a meaningful life.
- omscs99 3y ago
  > only to end up, a decade or two later, in either a regular struggling life like so many others, or a downright bad place It isn’t like they transform into the ubermensch and transcend the bodily functions of eating and shitting. At the end of the day we all have insecurities You can be struggling, you can be in a bad place, but that’s orthogonal to feeling connected and spiritually awake And I’m not saying drugs are how you can (or should) get there, just that the material conditions that someone is living in have nothing to do with being “there” And by “there”, I mean a sense of abandonment of self to the fabric that you arose out of. Which is not the same thing as conformity, more like a sense of understanding and acceptance of where you belong in the grand scheme of things

183 points by cpncrunch 3y ago

This should be off topic because it is not tech related. That is what mods say with Palestine related posts. Those rules should also apply here, shouldn't they?

Forgotthepass8 3y ago

If that House MD arc ends up being ahead of its time...

JohnMakin 3y ago
Which one?
- sli 3y ago
  I didn't watch a lot of House MD but I believe I know what's being referred to. There was an arc where House was administered ketamine as part of a treatment for his leg and he started walking without his cane, suggesting that his condition was being caused by psychological trauma long after his leg had physically recovered.
  - JohnMakin 3y ago
    I vaguely remember this. thanks.
  - Forgotthepass8 3y ago
    That's a bingo

ClassyJacket 3y ago

This isn't specific to ketamine tho is it? The placebo effect is well studied.

greenpresident 3y ago
Notably, the placebo effect usually only effects suffer reported symptoms as in this case. It’s a folk wisdom that it has physiological effects, which is often not true.
- quickthrower2 3y ago
  So placebo effects accuracy of self reporting? Making perhaps less or perhaps more accurate than without? I get this. Especially rating emotions 1 to 10 etc.
standardly 3y ago
Correct. It's important to remember the existence of a placebo effect isn't correlated with the efficacy of the drug being tested. I suppose that is obvious, but placebo studies tend to have a negative connotation.

scythe 3y ago

This is not the first trial of ketamine used under clinical anaesthesia to disguise its effects. A previous study using similar methods in 2018 found the usual effects of surgery: a transient increase in depressive symptoms. I'm no expert but my inclination is to blame this on postoperative pain. https://www.sciencedirect.com/science/article/pii/S0007091218303143 https://www.sciencedirect.com/science/article/pii/S000709121... The confidence interval in the new study includes zero, although the average beneficial effect is still surprising when considering the usual expected negative effects. I suspect that the real effect may simply be that general anaesthesia causes a susceptibility to suggestion. It's not clear if ketamine — or anything else — should be expected to work normally when it is administered to patients under general anesthesia. General anesthesia has profound effects on the functioning of the nervous system.

kallistisoft 3y ago
> It's not clear if ketamine — or anything else — should be expected to work normally when it is administered to patients under general anesthesia. General anesthesia has profound effects on the functioning of the nervous system. Very much this! Additionally when discussing ketmaine it's method of action (NMDA receptor antagonist) specifically could be disrupted by the effects of another anesthetic compound.
nullindividual 3y ago
Ketamine IV or compound medication without any other drugs is so profoundly different from Ketamine as part of a procedure where you’re otherwise unconscious. Just no comparison.
- p1esk 3y ago
  Could you explain? What is the difference? I only had Ketamine once during surgery and I vividly remember the few hours after.
  - nullindividual 3y ago
    It of course depends on your IV dosage. You can see and hear things that aren't there. Even have a conversation with mythical, religious, or spiritual entities. You can experience 'past lives' (whether factual or not, which I don't believe so, experiencing something you THINK is a past life is interesting). And it can go south with disturbing or dark imagery.

deleted 3y ago

[deleted]

omginternets 3y ago

Beyond the importance of controlling the placebo effect, I am worried that a lot of the drug-depression research is overlooking an important possibility: that the thing about ketamine/psilocybin/etc that is helping with depression is not some latent property of the molecule, but rather the actual transcendent experience of the trip. In other words, the trip is the point, not the mechanistic neuro-tinkering [0]. Importantly, this tracks with what we know about the protective effects of things like religiosity against depression. As such, the qualitative experience of the drug might not be something we can (or should) do away with. I would even go as far as suggesting that an absence of transcendence in one's life is precisely what causes a large segment of people to become depressed in the first place, and that perhaps drugs are helpful only insofar as they produce a transcendent experience. This isn't to say we can't take a scientific approach to treating depression, but that has to be balanced with something profoundly metaphysical: the actual qualia of life experience. Wellness isn't the absence of disease; it's the presence of thriving, and that includes within it a component of things like hope, inspiration, and elevation above the ordinary. We used to have various ceremonies designed to turn us towards the numinous, but we've pretty systematically dismantled those in favor of a grounded hyper-rationality [1]. As a scientist, I can't really object to rationality on its own, but it may be worth considering non-rational, transcendent experience as a fundamental psychological need. [0] If you're a materialist, you might object that neurological machinery is not differentiable from qualia. Fair enough! I even agree! My point is simply that medicine needs to consider qualia as a major parameter in the treatment of depression. Fixing depression is not like fixing a car. [1] I suspect most people here are familiar with Nietzsche's "God is dead quote". Many people in my entourage are floored to discover that he correctly predicted the dramatic increase in anxiety, depression, neuroticism and nihilism that is present in modern life.

photonerd 3y ago
If qualia are not different that our “neurological machinery” (and all available evidence shows this so far, not least the incoherence of definitions of qualia that try to exclude such) then medicine is already considering such as a major parameter. If they are different (and exist at all) then such needs to be demonstrated before they can be reliably considered. Given even proponents of qualia can’t reliably agree with each on what they even are defined as (other than using vague circular reasoning)… frankly, I’m not holding my breath.

jjgreen 3y ago

Good news for the leader of His Majesty's opposition https://www.independent.co.uk/business/sir-keir-starmer-reveals-special-k-nickname-on-visit-to-kellogg-s-factory-b1934831.html https://www.independent.co.uk/business/sir-keir-starmer-reve...

PlunderBunny 3y ago

I don't want to downplay depression (which I have no experience of), or come across as being flippant, but could the placebo effect in many of these kinds of trials be as simple as "a caring person (professional and/or stranger) interacting with the depressed subject improves their condition?"

teaearlgraycold 3y ago
That seems really easy to control for
- pygy_ 3y ago
  That's the reason why drugs are tested in double-blind, randomized controlled trials. The placebo effect is a major part of the effect of SSRI, which only improve 1 in 6-8 patients if you subtract the placebo effect [1]. The "number needed to treat" (NNT) mentioned below is the average number of patients that need to recieve the treatment for one of them to be in a better condition than if all of them had recieved a placebo. 1. https://www.cambridge.org/core/journals/psychological-medicine/article/antidepressant-standoff-why-it-continues-and-how-to-resolve-it/2EA210EEDC83005BC299AF3095941532 https://www.cambridge.org/core/journals/psychological-medici...
- robocat 3y ago
  However giving randoms drug trials is rather evil.
thom 3y ago
This is neither downplaying depression nor flippant - the therapeutic relationship is clearly very important and I don't think anybody denies that. But I suspect a lot of this is about your inherent world-view. Some people do well after purely online CBT, some don't. Some do well in talking therapy, some don't. It seems likely that how your brain perceives the world (and itself) affects which interventions help.

calibas 3y ago

A big part of depression is negative thinking, so it's not too much of a stretch to believe that positive thoughts, like hope, would lessen depression.

supportengineer 3y ago
In a late-stage capitalism world, where the climate is collapsing, and homes are unaffordable, where does hope come from?
- moshegramovsky 3y ago
  This doesn't get said nearly enough. Social media is also to blame. I know one person who got upset about his credit score (low 700s) from watching videos about it and then kept consuming information until he was seriously depressed about his (good) finances. When I was in my twenties and early thirties, I never worried about any of this at all.
  - doubled112 3y ago
    I couldn't imagine worrying about it, but maybe it's because I think I'm doing fine. Credit score is such a strange game to me. Closed a loan? That costs me points, somehow. Dad got a new cell phone and they ran the wrong person's credit? That cost me points too, because clearly their screw up was my fault. Hope he was still approved. I rent and the cars are old. Sometimes I feel like I play on hard mode by having a $3000 VISA as my only debt. If I make a $2000 purchase, they report it Tuesday, I pay that back to them Thursday, and I check my score? Woah, dropped 80 points! What a delinquent! That might have become more of a rant than I intended. I should probably just apply for more credit stop the large points changes like this.
- NickM 3y ago
  Not to downplay the current world problems, but you could make similar arguments at any point in history about any number of big problems humanity has faced. Yet, people still find hope and keep solving problems.

3cats-in-a-coat 3y ago

It's shocking how much of medicine is just based on trust and word of mouth. Studies made decades ago that turn out completely wrong and not reproducible. We flatter ourselves that we're enlightened and based on science, but the more you dig the more you realize it's all a game of trial and error and fighting cultural wars to get your "remedy" out there and profit. It's rather shocking to someone who's not familiar with the inner workings of the pharma industry and medicine in general. In particular in psychiatry, we have working theories about how the various agents work to achieve anti-depressive or anti-psychotic effects, which are taken as the gospel or proven fact. And then those models turn out absolutely wrong. And we have to face the fact we're prescribing drugs to sick people we have no clue how and why they work. And whether they work at all, often. It's especially the case when a given drug must be taken for months before any effect is seen. It's essentially impossible to control for other variables over MONTHS of someone's life. You can easily convince them they feel slightly better now because they've been months on end taking Zoloft. They may've easily been better if they hadn't taken it.

mirpa 3y ago
It is kind of ironic that study hints about hope/placebo. What I experienced were always side effects, no relief and then different drug, rinse and repeat. Left with original problem, worried what the next drug gonna bring as side effect with more and more diminishing hope it will ever help - despair.
- 3cats-in-a-coat 3y ago
  Some may criticize me for saying this, but I'll explain my observations. In general I've noticed when a drug works, it immediately gets restricted in use, because it has abuse potential, or a dangerous dose. There's no vast conspiracy here (well, sort of), but a simple principle: anything that is demonstrable to be USEful, is demonstrable to be abUSEable. No one is restricting homeopathic remedies, they don't have side-effects, or drug interactions, and that's because they don't do anything. Many antidepressants also don't require too strict of a regime, that's because they actually have very poor therapy effects overall, but even when they do, their effect and side-effects are so stretched out in time, it's very hard to show a hard cause-effect relationship. Despite reading the list you see all sorts of conditions on a drug that may occur as a side-effect, often many of those just occurred during a study, but had little relation to a drug, while other effects were underreported (say often around sexual function as people are embarrassed, or things people can't feel, and aren't tested about, things which doctors don't expect they need to check). So basically "long-running drugs" are a big question mark, and often turn out to be garbage. But stimulants like Ritalin, Adderall, Vivanse, Concerta and so on are known to instantly alleviate a number of symptoms of ADHD, depression and so on. Not in months. But within AN HOUR of taking a pill. You can immediately see how it works. But of course you can abuse them, and your body craves them over time, because the body and mind adapts to everything, that's the whole point of homeostasis. So they're restricted and you're told they're not good for you because they can be abused. But this cause-effect relationship is only visible because their effect is also apparent. Not just to medicine, but also to your own body. Your mind makes the cause-effect relationship "this makes dopamine good, circuits work better, take again". But the fact of the matter with drugs is they're all poison, and the therapeutic effect is in the right dose and application. There's no way around it. If it was nice and fun at any quantity, it's at best just sugar, or at worst some random chemical that few bad studies pushed through, which doesn't at all act like it's supposed to. This doesn't apply just to stimulants. I have issues with my circadian rhythm so I found a brand of melatonin of Jamieson that is 10mg, slow release. I notice on the first night it works. Other smaller doses from random supplement companies did nothing, heck who knows if they even had the active ingredient. So I'm in EU. And lo and behold, the EU notices melatonin is USEful at dose over 3mg. Therefore also abUSEable, and has side-effects in some. Very minor I might add. But it was immediately pulled from shelves, so a long and tedious registration can begin for it as a medication rather than a supplement, and until then, EU people who need it are screwed I guess. It's absurd, but it follows the principle that if it works, it becomes controlled. So the irony in all this is that we have easiest access to garbage that doesn't help, and the drugs that do help, have high prices and restricted access due to over-regulation. One of those things of the modern world.

temptemptemp111 3y ago

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progmetaldev 3y ago

I'm more interested in the effects of Ketamine on anxiety. I know that it's not as effective, but haven't seen any statistics specifically related to anxiety. I have gotten my Ketamine through Mindbloom, and just need to schedule my treatment and follow up dates. My depression effects are due to my suffering through anxiety for over 20 years (started in 1999). My anxiety also seemed to correlate with 2 bad trips from LSD in the late 90s, that resulted in my being hospitalized and injected with Thorazine to abort the trip. While I have had some depression from divorce and breakups, those bouts aren't lasting the way my anxiety is, and persists in day to day life. I imagine it is related to my being hospitalized at night for LSD, but I do not suffer anxiety unless I drive at night. I have seen various psychiatrists, psychologists, therapists, and have undergone biofeedback and cognitive behavioral therapy with limited success. I find that when my life as a whole is less stressful, my anxiety at night is less pronounced and sometimes non-existent.

nullindividual 3y ago
They will give Ketamine and benzos together as K can cause anxiety symptoms (or terror with a K-hole).
- progmetaldev 3y ago
  I actually take a benzo only as needed, and try not to take it if I can absolutely help it. I was told that taking a benzo(diazepine) the day of a Ketamine treatment actually cancels out the positive effect of the Ketamine. I believe it as well. Benzodiazepines definitely have a beneficial effect, but if you are trying to get through a psychedelic crisis, or even a horrible panic attack, taking it will 100% negate any kind of benefit you would get by pushing through the uncomfortable negativity. I'm speaking from personal experience, but I feel Benzos cancel out anything positive from learning in regards to a psychically negative experience. Sometimes your anxiety is so bad you need them, I know I have been in that place where I'm responsible for another person, and can't deal with the anxiety and still help this other person. I'm also terrified as I've heard Benzos increase the odds of getting Alzheimer's by something like >80%. I have Alzheimer's on my dad's grandmother's side, and my mom's father's side. Unless it skips a generation, and favors mother's or father's side, and the side it skips works out, I'm screwed!

insickness 3y ago

>The take-away should not be that ketamine “is just a placebo,” Heifets emphasized. This is the very definition of placebo and why double blind studies are done. The control group and the actual group both improved thinking they got the drug. > In fact, there may be physiological resonance between the placebo effect — in other words, hope — and how ketamine works. This is just mumbo jumbo. There's no 'resonance effect' if it works the same in the control group.

hcks 3y ago
This is insane, people are really unwilling to let go the idea that illegal psychoactive drugs may have any beneficial effects for depression.
- dannyw 3y ago
  Illegality is a societal construct, not a medicinal one.
- bowsamic 3y ago
  I don't understand why they are so desperate for it. I suppose it's because they have a purely mechanistic view of the brain, and that if there isn't some chemical you can change to help, you're fucked

tstrimple 3y ago

Ketamine treatment is something I've seriously considered for my depression. It's hard not to be lured in by all the miraculous claims by folks who have been down the same path and found relief. I've been through the rounds with traditional ADHD and depression treatment with side effects that rival the underlying symptoms and have tried a few different prescriptions. I'm just so tired. Doing simple things like paying your electric bill or getting out of bed when you don't have external demands shouldn't be so damn hard.

andrewedstrom 3y ago

Alternative explanation: ketamine isn’t better than placebo for treating depression when given to someone who’s under anesthesia. You have to be awake. Similarly, I bet that if you gave psilocybin to someone under anesthesia, they wouldn’t get the same benefits as someone who took it while awake.

kromem 3y ago
Another alternative explanation: general anesthesia's disassociation alone combined with an expectation of transformative psychological change results in transformative psychological change similar to ketamine's disassociation combined with such an expectation. Ruling out the general anesthesia as having an effect because general anesthesia without expectation of depression improvement doesn't improve depression seems like it toys with a false negative in ignoring the possibility of combined factors (specifically psychological disassociation plus expectations of change).

quickthrower2 3y ago

Relevant comic: https://xkcd.com/1526/ https://xkcd.com/1526/

suzzer99 3y ago

Related to the psychological vs. physiological discussion: I can say with confidence that the first time I did ecstasy changed how I look at the world. We went for a walk barefoot on warm pavement and it was the most wonderful thing I ever felt. I realized on a visceral level that so much of our personal happiness is based on how we look at things, not what happens to us. I don't know if I got any chemical benefit from subsequent use, other than fun (with the consistently worsening serotonin crash afterwards). But just being able to step outside my usual angsty 19-year-old brain for a few hours had a profound effect.

crtified 3y ago
Fun is arguably the best (some might say the only authentic) way to cure depression.
- suzzer99 3y ago
  Yeah but that serotonin crash afterwards was bleak. At this point in my life I can do E about once a year. Any more than that and I get really depressed afterwards. Although I do know people who are clinically depressed, and the hangover/crash doesn't bother them as much, because it's their normal state anyway.
- amp108 3y ago
  Dancing is arguably the best (some might say the only authentic) way to cure quadriplegia.
  - crtified 3y ago
    I take your point. I meant it in the context of an earlier poster - if not the title topic, itself - who drew a line between ketamine_as_medication and ketamine_for_fun, and implied that that recreational drugs as a form of depression therapy were merely a way to have 'a fun trip', and not of any real benefit. However, insofar as fun is synonymous with happiness, which is antonymous with depression, every cure for depression involves the end goal of fun - one way or another. Pharmaceutically / chemically, emotionally, socially, intellectually, spiritually, you-name-it. Therefore, regarding this topic, I was positing that, where usage of recreational drugs as a novel cure for depression is concerned, the fun is the curative. But I can see how my generalisation could be interpreted as minimalising, if viewed as a pithy solution precluding all nuance - which it was not intended as!

0xDEAFBEAD 3y ago

>Even in blinded trials in which participants are not told which they received, ketamine’s oftentimes trippy effects are a dead giveaway. How about randomizing between ketamine and some other drug that makes people trip? At a certain point you have to wonder if any sufficiently trippy experience helps with depression, anesthesia included.

topherPedersen 3y ago

I broke my leg skydiving a few months ago. The EMTs gave me ketamine and fentanyl before they loaded me up in the ambulance. That stuff sent me to another dimension! I never want to go back there. Was pretty terrifying to be honest. Maybe a low dose could help with depression? I think a high dose would probably scare people and they wouldn't want to do it again.

astrange 3y ago
That's a pretty traumatic situation, so it suggests you shouldn't try to be cured of depression right after breaking your leg.
- saiya-jin 3y ago
  Yeah that's one of the worst possible combinations (maybe apart from tripping sky high in actual war zone) - drugs and bad traumatic experience, while being loudly transported by strangers to hospital. You can't make up much worse set for trip. No wonder you had a bad trip, although I have absolutely 0 idea about those drugs or their combined effect on one's mind.
apatheticonion 3y ago
A friend of mine needed a bunch of morphine before a major surgery. Right before the doctor administered it he said "don't worry, people pay a lot of money for this" Always thought that was a pretty funny line
brap 3y ago
Former EMT here. The paramedics/doctors I used to work with would administer ketamine from time to time, but they would always pair it with this other drug (maybe midazolam? I don’t quite remember), for the sole purpose of preventing hallucinations. They made it very clear that the only reason for this mix was that ketamine hallucinations of that dose are often violent or sexual or both, and you don’t want to deal with those kind of allegations. I personally tried low dose pure ketamine (intramuscular) and it was quite pleasant.

hopefully60 3y ago

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yosito 3y ago

From what I understand about Ketamine, a large portion of the benefits hinge on being conscious.

raverbashing 3y ago
Yeah the experiment might be confounding the effect of the anesthesia itself and/or playing this down

thejazzman 3y ago

After reading research about this a few months ago, I made https://ketamine.games https://ketamine.games It's totally free, private, with no tracking analytics, and many Reddit users have reported increased success using.

hyperdimension 3y ago
Not to take away from your neat-looking site (I'm still looking through it) but in case you see this comment, under the 'install' link in the footer, you repeat yourself redundantly again, twice: > On your Android device, open Chrome Chrome

deleted 3y ago

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Xenoamorphous 3y ago

Possibly offtopic: whenever I hear about drugs for mental issues it seems to be always depression or anxiety. But is there anything out there for things like, say, addiction?

sph 3y ago
Iboga is very interesting against opiate addiction: https://en.wikipedia.org/wiki/Tabernanthe_iboga https://en.wikipedia.org/wiki/Tabernanthe_iboga

pbj1968 3y ago

If any of this stuff actually worked we’d already be using it. Similarly how every medical problem hadn’t gone away in states that legalized marijuana.

digbybk 3y ago
This reminds me or the joke where an economist refuses to look down when told that there’s a $20 bill on the ground: “if there was really $20 on the ground, someone would have picked it up already”. Seriously though, we’re just getting started studying it, how can we know whether or not this stuff works? There’s a lot of positive anecdotal evidence. We’re not talking about marijuana, and no one ever expected it to solve every medical problem. That particular substance has done a lot of good with people experiencing discomfort, like cancer patients and the elderly, including members of my family.
mrkeen 3y ago
> how every medical problem hadn’t gone away in states that legalized marijuana. The problem was that people were being locked up.
dragonwriter 3y ago
Medical marijuana isn’t a cure, its a treatment. The point isn’t to make medical problems go away, it is reduce the adverse impact (more effectively and/or with less of its own adverse side effects than other alternatives.) We do use it, and it does work, and “we” were using it for those problems even when it was illegal, a condition that didn't not occur as the outcome of a rational evaluation of scientific evidence of utility vs. harm on either recreational or medical use, but based on vibes (and, in no small part, racism.)

user3939382 3y ago

I knew someone who used the "it cures depression!" line as an excuse to be addicted to it and go into K-holes 3x a day while it ruined their life.

EL_Loco 3y ago

From a pretty good essay written by someone who lived through the original "psychedelics will expand your mind" era of the 60s and 70s: "“Enlightenment in a pill,” many have pointed out, is a quintessentially American concept. Who’s got time for all that prayer and study and meditation and practice when there’s an easier, faster way? But there isn’t. Therein lies the great danger of LSD and its dopey cousin, marijuana. By offering a simulacrum of spiritual and intellectual growth – a very convincing simulacrum at times – it takes you everywhere except where you need to be, which is doing the long, hard work of learning to live." I resonate with what he says because, like the author mentions later on, I also have many friends who went deep into the psychedelics journey while claiming it was 'freeing their minds', 'enlightening' them, or whatever other concept they liked to use, only to end up, a decade or two later, in either a regular struggling life like so many others, or a downright bad place. I'm probably wrong to generalize, as I'm sure it can help many, but the drugs still can't substitute the individual's effort and struggle to grow, and overcome, and the learning of how to live a meaningful life.

omscs99 3y ago
> only to end up, a decade or two later, in either a regular struggling life like so many others, or a downright bad place It isn’t like they transform into the ubermensch and transcend the bodily functions of eating and shitting. At the end of the day we all have insecurities You can be struggling, you can be in a bad place, but that’s orthogonal to feeling connected and spiritually awake And I’m not saying drugs are how you can (or should) get there, just that the material conditions that someone is living in have nothing to do with being “there” And by “there”, I mean a sense of abandonment of self to the fabric that you arose out of. Which is not the same thing as conformity, more like a sense of understanding and acceptance of where you belong in the grand scheme of things