8 ms·

> They gave volunteers ketamine while they were under general anesthesia, theoretically preventing the participants from going on a trip. Maybe it's the trip t

> They gave volunteers ketamine while they were under general anesthesia, theoretically preventing the participants from going on a trip. Maybe it's the trip that helps.

coldtea 3y ago
Not to mention other possible effects of being in general anesthesia (aside from the lack of consciousness) that prevent the effectiveness.
- cpncrunch 3y ago
  But you're neglecting the fact that this study found the same or higher effectiveness than non-blinded trials. In this trial, there was a 50% response rate and 40% remission [1], whereas in a meta-analysis of previous unblinded trials there was 40% response and 30% remission [2]. [1] https://www.medrxiv.org/content/10.1101/2023.04.28.23289210v1.full-text https://www.medrxiv.org/content/10.1101/2023.04.28.23289210v... [2] https://pubmed.ncbi.nlm.nih.gov/35688035/ https://pubmed.ncbi.nlm.nih.gov/35688035/ So it's not that this trial wasn't effective, just that the placebo effect is very effective, and it likely resulted in the improvements seen.
reubenmorais 3y ago
I see so many studies trying to somehow distill trippy drugs into an isolated, side-effect free, take a pill and get back to work treatment. Maybe there's something to be found there, would be huge, but my hope is that we don't waste all the will and funding down this path without more fully exploring the path where we admit that yes, the trip helps, and we'll just need to deal with the lack of blinding.
- tokai 3y ago
  Literally the last line of the article: "Future studies of novel antidepressants with acute psychoactive effects should make stronger efforts to mask treatment assignment to minimize the effects of subject-expectancy bias." Instead of pondering if their method is at fault for their negative result, the conclusion is to double down and working even harder at masking the effects.
  - mtlmtlmtlmtl 3y ago
    Well, what they're trying to do is provide better blinding. Doing proper blind studies of ketamine is quite hard because its subjective effects are far too noticable. That line just says people should do better at this in future to get more accurate results. It's not a statement about the ultimate form the treatment should take.
    - tokai 3y ago
      yes ofc, but if the treatment is the trip it will never work blinding it like this. If anything they should be looking for drugs that give comparable trips, with no potential for depression treatment.
      - mtlmtlmtlmtl 3y ago
        I agree in principle, though having tried most of the various types of trippy substances, I've yet to encounter one that hasn't showed potential for a short term antidepressant effect. I guess I haven't tried those weird delta opioid ligands(salvia divonorum). I guess deliriants(like diphenhydramine) would have about zero antidepressant effect too, but that would have possible negative effects, even being liable to cause trauma. I believe benzodiazepines have also been tried as an active placebo but I don't remember what the results were.
        oaktrout 3y ago
        Small correction, the active ingredient in Salvia is a kappa opioid agonist.
        mtlmtlmtlmtl 3y ago
        You're right, thanks for the correction! Really should check more of these things and not just do it from memory.
        tpm 3y ago
        Diphenhydramine as a first generation antihistamine acts on a large number of receptors and can even be used as a mild anxiolytic, so I'd guess it could very well have antidepressant effect. No idea about deliriants like atropine/scopolamine, but in low doses, they were traditionally used to spice up beer (hence Pilsen named for Bilsenkraut, black henbane), so I could imagine short antidepressant effect there too.
- SiempreViernes 3y ago
  One of the objections against the improvement observed that is mentioned in tfa is precisely that you can get "trips" from general anaesthesia: 'Schenberg points out that people often report dreamlike and visual, auditory, and affective experiences under anesthesia. “Maybe people who had dreamlike experiences during the anesthesia had more improvement than the people who didn’t,” he says.' So maybe the trip does indeed help, but evidently it is not necessary to be able to remember if you had one to get the reported benefits.
- PragmaticPulp 3y ago
  The problem is real, though. Drugs with overt recreational effects very frequently distract the patient from the therapeutic effect in unproductive ways. The recreational effects generally disappear quickly as tolerance develops, which can give patients the false impression that the medication “stopped working”. A common example would be ADHD stimulants, where the early stimulating and mood-boosting effects disappear over time while the concentration-enhancing effects mostly remain. This leads a lot of patients to assume the medication isn’t working because it doesn’t feel like those first few doses, which can lead to discontinuation or abuse. Ketamine has a similar story arc. The antidepressant effect doesn’t require full blown dissociation, but so many headlines and fame-seeking authors have hyped it as “psychedelic medicine” that some patients assume it isn’t working until they disassociate/hallucinate. This can create a sort of nocebo effect where patients may actually be improving but they think they’re not because they didn’t have the wild hallucinations they read about in some exaggerated internet article.
  - vasco 3y ago
    I took LSD twice in my life only and it changed my outlook ever since. It's been almost 10 years. I wasn't depressed and had other benefits from it, but I can see how that experience could've fixed depression, and know of people who say it did for them even though I'm not in any hippy-like community or whatever. I think a possible reason why medical research prefers a pill that works forever for continued use is that if you buy something cheap twice in your life and it fixes whatever needs fixing the pharma industry can't make money off of you the same way they can put you on antidepressants for life. I'm not in the medical field so I'm just speaking out of my ass based on personal anecdotes though.
    - ativzzz 3y ago
      Or because it's not really medicine and person specific? I've taken LSD several times in varying doses and it's never been anything more than "a really really fun time". Nothing profound, but damn fun times, the same effect as any fun memorable party Perhaps if you are looking for something profound or want a change of mindset, psychedelics might be able to help you reach it - similar to how shamans used psychedelics to talk to their gods or whatever - but if you're just looking to have fun that's what you'll get
- deleted 3y ago
  [deleted]
causi 3y ago
Exactly. This is like testing to see whether scaring someone with a spider cures hiccups but in order to keep it blind only showing them the spider when their back is turned.
- webnrrd2k 3y ago
  It reminds me of an old Onion article, "Study: Dolphins Not So Intelligent On Land”[1]. [1] https://www.theonion.com/study-dolphins-not-so-intelligent-on-land-1819568299 https://www.theonion.com/study-dolphins-not-so-intelligent-o...
aftoprokrustes 3y ago
As a relatively seasoned meditator, I am absolutely sure that this is the trip that helps, not the chemistry. One way to look at meditation (and, I hear, psychedelics) that fits my experience is that it has the potential effect of opening the range of "ways of looking", to change the way one builds the perceived world. What propulsed my meditation to a totally different level was to see it as a practice of actively engaging with other ways to perceive the world, and let those act on the psyche, rather than as some form of "mental gym". As I understand, what makes a psychedelic a psychedelic is that it propulses the user into a state where the workings of the mind is apparent (Psyche-delic, this which reveals (delic) the mind (psyche)), and new ways of perceiving are opened. If one considers depression as primarily a form of "negative filter" that turns all external objects as dull and uninteresting, it makes sense that psychedelics can help get out of it, and that a necessary condition for that is to actually consciously experience those transformations of perception. Unfortunately, this means that the standard way of doing medicine research, with control group and placebo, is unlikely to ever be applicable to this area of research, and that a new epistemiology of medical research has to be developped for it. I find it super interesting. (side note: if the idea of meditation as active engagement with "ways of looking" is intriguing you, I highly recommend looking up the teachings of Rob Burbea)
- ModernMech 3y ago
  Indeed, I remember a while back there was a TikTok filter going around where it made old people look younger. One of the people using it said it basically had cured her self-perception issues; she had been bullied for her looks as a child and internalized that she was ugly. But as an adult when she saw her younger face in the app, she realized immediately how the characterization of that face as ugly was just the perception of child bullies. And it wasn't something that photographs could do for her -- it was the fact that it was her younger face superimposed on her current body, and that it was moving as she moved which gave her a new "way of looking" as you put it. In a sense, AI gave her a chemical-free trip.
  - GreenWatermelon 3y ago
    Depending on how I interpret what you wrote, I reach either a negative or positive conclusion. To start with the negative: She's basically fooling herself. She's avoiding the real problem of "not accepting herself for who she is, abd changing what can be changed" IMO, The filtr only shows her a big lie, merely suppressing the pain, and not helping solve the real psychological problem. On the positive hand, the filter allowed her to break a deeply-ingrained false belief about he past, which helps with one's healing journey. The question is: does she believe her current looks are pretty?
SiempreViernes 3y ago
And you object to them trying to find out if it does?
- api 3y ago
  The problem is that their conclusion is not going to be read as “wow, it’s the trip that helps more than just the chemical.” Instead it’ll be read as “well I guess this chemical doesn’t work at all.” The notion that the trip is the therapeutic element seems oddly frightening or threatening to a lot of people. … Or at least it’s not what they’re looking for. The quest is for a pill that works deterministically without any need to involve consciousness.
  - SiempreViernes 3y ago
    How is people misinterpreting the result that way a fair criticism of their work?
    - tonyarkles 3y ago
      > How is people misinterpreting the result that way a fair criticism of their work? Part of it comes down to overall scientific responsibility and being careful about defining the scope of the claims and conclusions. I haven't seen the final paper here, but if the Conclusions section says "This research indicates that ketamine given while patients are already sedated with general anesthesia doesn't not appear to provide a benefit for patients suffering from depression." then that's great. If their Conclusions section says "By isolating ketamine-the-substance from the ketamine trip by administering the substance while the patient is under general anesthesia, this work demonstrates that there is nothing inherently anti-depressant about ketamine and that ketamine treatment for anti-depression is no better than placebo.", that's going to potentially have a huge ripple effect. Throughout this thread there's a fair bit of discussion about "the trip is the treatment". The first conclusion leaves a number of other lines of inquiry open for exploration. The second conclusion opens the door for funding agencies and physicians to put an end to additional research and terminating treatments that are potentially effective. Scientific communication absolutely must be very careful with the breadth of the claims and state them loudly and explicitly. While journal and conference proceedings have historically been generally only consumed by other practitioners of a field, now that everything is online and accessible to the general public there is definitely an increased burden for clear communication with explicit, conservative, narrow unless otherwise warranted conclusions.
PragmaticPulp 3y ago
Ketamine depression treatment doesn’t have to induce a “trip” to elicit the effect, according to studies and the protocol. It can produce some sensory distortions, but anyone who is going into a full “k hole” is almost certainly taking too much. It’s not a case of more is better.
- pas 3y ago
  yes, but the phase 3 (efficacy) trial just barely crossed the threshold (if I remember correctly), mostly because the company wanted to use one stereoisomer because the other was not patentable (and this is the one that is less trippy) https://slatestarcodex.com/2019/03/11/ketamine-now-by-prescription/ https://slatestarcodex.com/2019/03/11/ketamine-now-by-prescr...
- palmer_fox 3y ago
  Is there a clear definition of a trip that these studies subscribe to? I would guess they attribute any change in perception to "tripping". K-hole is not the expected experience in most Ketamine-based treatments afaik.
kibwen 3y ago
In which case, the headline would be correct. If ketamine can only treat depression by inducing a trip, then it's the trip that treats the depression, not the ketamine, which suggests future avenues of research into trips themselves, possibly excluding ketamine altogether.
- aYsY4dDQ2NrcNzA 3y ago
  The trip could be necessary but not sufficient.
- alex_lav 3y ago
  Isn't this true of most drugs? It's not the NSAID that treated the pain, it's the reduction in inflammation...
  - aftoprokrustes 3y ago
    Not really. If it is the _experience_ that is the main cause for reduction of depressive symptoms, it means that other ways to generate similar experiences (such as meditation, talk therapy, prayer, sensory deprivation...) could have a similar effect. If it is the physical effect of the medicine on the brain which is responsible for the effect, it would mean that it might be possible to design drugs that have the same effectiveness without being psychoactive.
    - alex_lav 3y ago
      Ah, I understand the nuance you’re trying to capture now.
  - kibwen 3y ago
    The point being that if you identify the root cause, you can find different avenues to the same ends.
pcthrowaway 3y ago
Or general anesthesia prevents ketamine from having it's usual effect on the brain. This is such a stupid study, I hope they didn't anesthetize people just to study this
- belltaco 3y ago
  > I hope they didn't anesthetize people just to study this Why not? Apart from potential side effects of anesthesia, this sounds like a great study to find the mechanism of ketamine helping depression.
  - palmer_fox 3y ago
    Is it still a widespread theory that depression is a purely physical condition that can be treated with just a chemical intervention? I thought the medical community moved past this notion.
  - pcthrowaway 3y ago
    > Apart from potential side effects of anesthesia, Bingo. If they were going to study the effects of some drug on amputees, it would be better if they didn't amputate limbs to test it. People don't have a good understanding of the damage from general anesthesia, so it's probably easier to get them to agree to do this study (and therefore perhaps easier/cheaper than selecting people already undergoing general anesthesia, and coordinating with the anesthesiologist and controlling for confounding factors like why they're being anesthetised in the first place) But ethically, it would be much better if they didn't put people under to perform a stupid study on them, since it is damaging to the people getting anesthetized.

> They gave volunteers ketamine while they were under general anesthesia, theoretically preventing the participants from going on a trip. Maybe it's the trip that helps.

coldtea 3y ago

Not to mention other possible effects of being in general anesthesia (aside from the lack of consciousness) that prevent the effectiveness.

cpncrunch 3y ago
But you're neglecting the fact that this study found the same or higher effectiveness than non-blinded trials. In this trial, there was a 50% response rate and 40% remission [1], whereas in a meta-analysis of previous unblinded trials there was 40% response and 30% remission [2]. [1] https://www.medrxiv.org/content/10.1101/2023.04.28.23289210v1.full-text https://www.medrxiv.org/content/10.1101/2023.04.28.23289210v... [2] https://pubmed.ncbi.nlm.nih.gov/35688035/ https://pubmed.ncbi.nlm.nih.gov/35688035/ So it's not that this trial wasn't effective, just that the placebo effect is very effective, and it likely resulted in the improvements seen.

reubenmorais 3y ago

I see so many studies trying to somehow distill trippy drugs into an isolated, side-effect free, take a pill and get back to work treatment. Maybe there's something to be found there, would be huge, but my hope is that we don't waste all the will and funding down this path without more fully exploring the path where we admit that yes, the trip helps, and we'll just need to deal with the lack of blinding.

tokai 3y ago
Literally the last line of the article: "Future studies of novel antidepressants with acute psychoactive effects should make stronger efforts to mask treatment assignment to minimize the effects of subject-expectancy bias." Instead of pondering if their method is at fault for their negative result, the conclusion is to double down and working even harder at masking the effects.
- mtlmtlmtlmtl 3y ago
  Well, what they're trying to do is provide better blinding. Doing proper blind studies of ketamine is quite hard because its subjective effects are far too noticable. That line just says people should do better at this in future to get more accurate results. It's not a statement about the ultimate form the treatment should take.
  - tokai 3y ago
    yes ofc, but if the treatment is the trip it will never work blinding it like this. If anything they should be looking for drugs that give comparable trips, with no potential for depression treatment.
    - mtlmtlmtlmtl 3y ago
      I agree in principle, though having tried most of the various types of trippy substances, I've yet to encounter one that hasn't showed potential for a short term antidepressant effect. I guess I haven't tried those weird delta opioid ligands(salvia divonorum). I guess deliriants(like diphenhydramine) would have about zero antidepressant effect too, but that would have possible negative effects, even being liable to cause trauma. I believe benzodiazepines have also been tried as an active placebo but I don't remember what the results were.
      - oaktrout 3y ago
        Small correction, the active ingredient in Salvia is a kappa opioid agonist.
        mtlmtlmtlmtl 3y ago
        You're right, thanks for the correction! Really should check more of these things and not just do it from memory.
      - tpm 3y ago
        Diphenhydramine as a first generation antihistamine acts on a large number of receptors and can even be used as a mild anxiolytic, so I'd guess it could very well have antidepressant effect. No idea about deliriants like atropine/scopolamine, but in low doses, they were traditionally used to spice up beer (hence Pilsen named for Bilsenkraut, black henbane), so I could imagine short antidepressant effect there too.
SiempreViernes 3y ago
One of the objections against the improvement observed that is mentioned in tfa is precisely that you can get "trips" from general anaesthesia: 'Schenberg points out that people often report dreamlike and visual, auditory, and affective experiences under anesthesia. “Maybe people who had dreamlike experiences during the anesthesia had more improvement than the people who didn’t,” he says.' So maybe the trip does indeed help, but evidently it is not necessary to be able to remember if you had one to get the reported benefits.
PragmaticPulp 3y ago
The problem is real, though. Drugs with overt recreational effects very frequently distract the patient from the therapeutic effect in unproductive ways. The recreational effects generally disappear quickly as tolerance develops, which can give patients the false impression that the medication “stopped working”. A common example would be ADHD stimulants, where the early stimulating and mood-boosting effects disappear over time while the concentration-enhancing effects mostly remain. This leads a lot of patients to assume the medication isn’t working because it doesn’t feel like those first few doses, which can lead to discontinuation or abuse. Ketamine has a similar story arc. The antidepressant effect doesn’t require full blown dissociation, but so many headlines and fame-seeking authors have hyped it as “psychedelic medicine” that some patients assume it isn’t working until they disassociate/hallucinate. This can create a sort of nocebo effect where patients may actually be improving but they think they’re not because they didn’t have the wild hallucinations they read about in some exaggerated internet article.
- vasco 3y ago
  I took LSD twice in my life only and it changed my outlook ever since. It's been almost 10 years. I wasn't depressed and had other benefits from it, but I can see how that experience could've fixed depression, and know of people who say it did for them even though I'm not in any hippy-like community or whatever. I think a possible reason why medical research prefers a pill that works forever for continued use is that if you buy something cheap twice in your life and it fixes whatever needs fixing the pharma industry can't make money off of you the same way they can put you on antidepressants for life. I'm not in the medical field so I'm just speaking out of my ass based on personal anecdotes though.
  - ativzzz 3y ago
    Or because it's not really medicine and person specific? I've taken LSD several times in varying doses and it's never been anything more than "a really really fun time". Nothing profound, but damn fun times, the same effect as any fun memorable party Perhaps if you are looking for something profound or want a change of mindset, psychedelics might be able to help you reach it - similar to how shamans used psychedelics to talk to their gods or whatever - but if you're just looking to have fun that's what you'll get
deleted 3y ago
[deleted]

causi 3y ago

Exactly. This is like testing to see whether scaring someone with a spider cures hiccups but in order to keep it blind only showing them the spider when their back is turned.

webnrrd2k 3y ago
It reminds me of an old Onion article, "Study: Dolphins Not So Intelligent On Land”[1]. [1] https://www.theonion.com/study-dolphins-not-so-intelligent-on-land-1819568299 https://www.theonion.com/study-dolphins-not-so-intelligent-o...

aftoprokrustes 3y ago

As a relatively seasoned meditator, I am absolutely sure that this is the trip that helps, not the chemistry. One way to look at meditation (and, I hear, psychedelics) that fits my experience is that it has the potential effect of opening the range of "ways of looking", to change the way one builds the perceived world. What propulsed my meditation to a totally different level was to see it as a practice of actively engaging with other ways to perceive the world, and let those act on the psyche, rather than as some form of "mental gym". As I understand, what makes a psychedelic a psychedelic is that it propulses the user into a state where the workings of the mind is apparent (Psyche-delic, this which reveals (delic) the mind (psyche)), and new ways of perceiving are opened. If one considers depression as primarily a form of "negative filter" that turns all external objects as dull and uninteresting, it makes sense that psychedelics can help get out of it, and that a necessary condition for that is to actually consciously experience those transformations of perception. Unfortunately, this means that the standard way of doing medicine research, with control group and placebo, is unlikely to ever be applicable to this area of research, and that a new epistemiology of medical research has to be developped for it. I find it super interesting. (side note: if the idea of meditation as active engagement with "ways of looking" is intriguing you, I highly recommend looking up the teachings of Rob Burbea)

ModernMech 3y ago
Indeed, I remember a while back there was a TikTok filter going around where it made old people look younger. One of the people using it said it basically had cured her self-perception issues; she had been bullied for her looks as a child and internalized that she was ugly. But as an adult when she saw her younger face in the app, she realized immediately how the characterization of that face as ugly was just the perception of child bullies. And it wasn't something that photographs could do for her -- it was the fact that it was her younger face superimposed on her current body, and that it was moving as she moved which gave her a new "way of looking" as you put it. In a sense, AI gave her a chemical-free trip.
- GreenWatermelon 3y ago
  Depending on how I interpret what you wrote, I reach either a negative or positive conclusion. To start with the negative: She's basically fooling herself. She's avoiding the real problem of "not accepting herself for who she is, abd changing what can be changed" IMO, The filtr only shows her a big lie, merely suppressing the pain, and not helping solve the real psychological problem. On the positive hand, the filter allowed her to break a deeply-ingrained false belief about he past, which helps with one's healing journey. The question is: does she believe her current looks are pretty?

SiempreViernes 3y ago

And you object to them trying to find out if it does?

api 3y ago
The problem is that their conclusion is not going to be read as “wow, it’s the trip that helps more than just the chemical.” Instead it’ll be read as “well I guess this chemical doesn’t work at all.” The notion that the trip is the therapeutic element seems oddly frightening or threatening to a lot of people. … Or at least it’s not what they’re looking for. The quest is for a pill that works deterministically without any need to involve consciousness.
- SiempreViernes 3y ago
  How is people misinterpreting the result that way a fair criticism of their work?
  - tonyarkles 3y ago
    > How is people misinterpreting the result that way a fair criticism of their work? Part of it comes down to overall scientific responsibility and being careful about defining the scope of the claims and conclusions. I haven't seen the final paper here, but if the Conclusions section says "This research indicates that ketamine given while patients are already sedated with general anesthesia doesn't not appear to provide a benefit for patients suffering from depression." then that's great. If their Conclusions section says "By isolating ketamine-the-substance from the ketamine trip by administering the substance while the patient is under general anesthesia, this work demonstrates that there is nothing inherently anti-depressant about ketamine and that ketamine treatment for anti-depression is no better than placebo.", that's going to potentially have a huge ripple effect. Throughout this thread there's a fair bit of discussion about "the trip is the treatment". The first conclusion leaves a number of other lines of inquiry open for exploration. The second conclusion opens the door for funding agencies and physicians to put an end to additional research and terminating treatments that are potentially effective. Scientific communication absolutely must be very careful with the breadth of the claims and state them loudly and explicitly. While journal and conference proceedings have historically been generally only consumed by other practitioners of a field, now that everything is online and accessible to the general public there is definitely an increased burden for clear communication with explicit, conservative, narrow unless otherwise warranted conclusions.

PragmaticPulp 3y ago

Ketamine depression treatment doesn’t have to induce a “trip” to elicit the effect, according to studies and the protocol. It can produce some sensory distortions, but anyone who is going into a full “k hole” is almost certainly taking too much. It’s not a case of more is better.

pas 3y ago
yes, but the phase 3 (efficacy) trial just barely crossed the threshold (if I remember correctly), mostly because the company wanted to use one stereoisomer because the other was not patentable (and this is the one that is less trippy) https://slatestarcodex.com/2019/03/11/ketamine-now-by-prescription/ https://slatestarcodex.com/2019/03/11/ketamine-now-by-prescr...
palmer_fox 3y ago
Is there a clear definition of a trip that these studies subscribe to? I would guess they attribute any change in perception to "tripping". K-hole is not the expected experience in most Ketamine-based treatments afaik.

kibwen 3y ago

In which case, the headline would be correct. If ketamine can only treat depression by inducing a trip, then it's the trip that treats the depression, not the ketamine, which suggests future avenues of research into trips themselves, possibly excluding ketamine altogether.

aYsY4dDQ2NrcNzA 3y ago
The trip could be necessary but not sufficient.
alex_lav 3y ago
Isn't this true of most drugs? It's not the NSAID that treated the pain, it's the reduction in inflammation...
- aftoprokrustes 3y ago
  Not really. If it is the _experience_ that is the main cause for reduction of depressive symptoms, it means that other ways to generate similar experiences (such as meditation, talk therapy, prayer, sensory deprivation...) could have a similar effect. If it is the physical effect of the medicine on the brain which is responsible for the effect, it would mean that it might be possible to design drugs that have the same effectiveness without being psychoactive.
  - alex_lav 3y ago
    Ah, I understand the nuance you’re trying to capture now.
- kibwen 3y ago
  The point being that if you identify the root cause, you can find different avenues to the same ends.

pcthrowaway 3y ago

Or general anesthesia prevents ketamine from having it's usual effect on the brain. This is such a stupid study, I hope they didn't anesthetize people just to study this

belltaco 3y ago
> I hope they didn't anesthetize people just to study this Why not? Apart from potential side effects of anesthesia, this sounds like a great study to find the mechanism of ketamine helping depression.
- palmer_fox 3y ago
  Is it still a widespread theory that depression is a purely physical condition that can be treated with just a chemical intervention? I thought the medical community moved past this notion.
- pcthrowaway 3y ago
  > Apart from potential side effects of anesthesia, Bingo. If they were going to study the effects of some drug on amputees, it would be better if they didn't amputate limbs to test it. People don't have a good understanding of the damage from general anesthesia, so it's probably easier to get them to agree to do this study (and therefore perhaps easier/cheaper than selecting people already undergoing general anesthesia, and coordinating with the anesthesiologist and controlling for confounding factors like why they're being anesthetised in the first place) But ethically, it would be much better if they didn't put people under to perform a stupid study on them, since it is damaging to the people getting anesthetized.