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.
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.
"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.
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.
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)
On one side it showed me (after a long time) how you can be very empathic for all people around you and also reminded me or showed me how really good happiness feels.
And while the effects lasted a little bit for 1-2 weeks, it also is something I know I could do again if I like to.
This definitely gave me an additional/new viewpoint.
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.
Yes, I've recently come to realise that ketamine allows me to slip into a meditative state as a result of its consciousness-suppressing anaesthesia. For someone such as myself with ADHD and aphantasia this is a revelation as normally I find myself unable to quiet my restless mind enough to get there. And explains why both my most profound epiphanies and my greatest changes of mindset have all involved ketamine in one way or another.
I look at it as shutting your computer off and plugging in a USB drive with repair software and wondering why nothing got fixed after you turned it back on. Aren't we just meat computers?
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].
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.
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.
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.
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.
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)
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.
This is rubbish. Ketamine is a life-saver and has been proven to relieve depression, regardless of the administration setting. It is not magic and does not work in every case, but the effects are proven across countless studies. S-ketamine has even gone fully through FDA approval.
Personally I have used it at home, and at a treatment center. There is no difference in the antidepressant properties, whether someone was helping me administer it in a medical setting, or not. The antidepressant properties do not relate to the effects of simply being in a clinical trial.
I strongly believe the antidepressant properties arise from the psychedelic/dissociative experience, and not directly from the physical effects. I'm not terribly surprised that ketamine may not produce strong antidepressant effects if the patient is not conscious.
Anyone looking to read more about ketamine antidepressant properties should read "The Ketamine Papers: Science, Therapy, and Transformation" by Phil Wolfson, M.D., and Glenn Hartelius, Ph.D.
> Ketamine is a life-saver and has been proven to relieve depression, regardless of the administration setting.
It’s really not uncommon for some trials to fail to differentiate from placebo when it comes to depression studies. That doesn’t make this study “rubbish”, it just shows that you need to examine the body of evidence rather than cherry-picking studies that appear to match the outcome you want while dismissing those that say the opposite.
Ketamine is a temporary boost for some people, but it has also been overhyped in recent years. The single biggest downside is that it’s not a long-term solution. The duration of the antidepressant effect is relatively short (days to weeks) and the antidepressant effect appears to diminish with repeated dosing.
It can be a great help for suicidal patients or for getting traditional treatment started, but it’s not a singular solution to depression for most people.
Ketamine prescribing also got out of control fast. I traveled to a city where Ketamine clinics were advertising on the radio and billboards and competing with coupons and discounts and exaggerated promises of efficacy. Reddit and other forums are also filling up with stories of people who think their ketamine “stopped working” because they weren’t properly informed that it was a temporary effect for most people that needed to be combined with traditional therapy. Way too many clinics and influencers looking to ride the hype train without honestly assessing the situation.
> It’s really not uncommon for some trials to fail to differentiate from placebo when it comes to depression studies. That doesn’t make this study “rubbish”, it just shows that you need to examine the body of evidence rather than cherry-picking studies that appear to match the outcome you want while dismissing those that say the opposite.
But this study doesn't say the opposite. It fails to show an effect. That's different from proving the absence of an effect. Every Ph.D. student in an empirical field learns this in their first year. I'm surprised this study gets so much attention.
You can make a study verifying that a pound gold and a pound feathers accelerate downwards at the same speed in a vacuum, and perhaps you messed up the vacuum, so they actually fall with different speeds in your study. Doesn't prove gravity is messed up. You just failed to prove that it's not. Can have many reasons. Same with this study.
I couldnt disagree more with your second paragraph.
I have a partner who has been prescribed Ketamine for the last 3 years. I firmly believe that the drugs ability to rebuild neural pathways and thus work around / resolve damage to be the only reason why partner is still alive today, and is now ready to return to work after so many years and such a brutal road.
In Australia, being prescribed Ketamine is very difficult, and thus very uncommon. While I do not believe it should be opened up to everyone, my experience over the last few years makes me a massive fan of the drug for specific situations.
Doing studies isn't bad in itself, of course they will produce conflicting outcomes and need to be studied as a large body of evidence.
Yes, it cannot be used as a long-term solution. It's more of a fast-acting effect and has been over-hyped beyond its capabilities.
My immediate reaction was just that their conclusion ("has no short-term effect on the severity of depression symptoms" and what the co-author said in the linked article) is not reasonable to draw based on the study they designed, because they failed to consider whether the therapy needed a conscious patient or not.
> It can be a great help for suicidal patients or for getting traditional treatment started, but it’s not a singular solution to depression for most people.
Is there any singular solution to depression for most people?
The study actually shows ketamine works as well with anesthetia (45%) as without (40%), if you read the non-anesthetia study linked in https://news.ycombinator.com/item?id=36030251.
(Of course you can argue they are not using enough K at the 0.5 mg/kg mark, because disccociation starts at 1 to 3 mg/kg per StatPearls.)
> Of course you can argue they are not using enough K at the 0.5 mg/kg mark, because disccociation starts at 1 to 3 mg/kg
Dissociation isn’t necessary for the antidepressant effect, according to studies. In fact, many of the more responsible clinics target longer duration, lower peak dose infusions for this reason.
>I'm not terribly surprised that ketamine may not produce strong antidepressant effects if the patient is not conscious.
That's incorrect, it actually produced larger antidepressant effects (50% response rate and 40% remission [1]) than when the patient is conscious (40% response rate and 30% remission according to a large meta-analysis [2]).
They only measured response for the next three days. Is it possible k has an effect for longer than three days while placebo only lasts three days or so?
> It is not magic and does not work in every case,
That is exactly what they are saying in the study. No better than placebo means Ketamine does not cure depression. If ketamine cured depression it would work in every case.
Increasing serotonin receptor density trough Ketamine use may relieve depression, but so can being cared for.
Your beliefs do not matter, biology matters. And it may in fact be that your "strong beliefs" in ketamine are why it helps you.
Something can be effective, especially more effective than a placebo, without being a cure. We have many "treatments" for all sorts of illnesses where the treatment isn't a cure. SSRIs for depression are a treatment, not a cure, just as one example. Hell, even Nyquil is a treatment for symptoms without being a cure.
When it comes to mental health we also have these big umbrella categories (depression, schizophrenia) that are made up of groups of illnesses. Schizophrenia has so many different causes, and thus different treatments, that viewing it as a single illness can actually be problematic.
Anyways, my point is that what you're saying makes no sense at all.
I don't have a position on the paper (I haven't even read it), but this statement you just made seems unjustified:
> If ketamine cured depression it would work in every case.
Depression can have many different causes, and people have many different biological variables, so it should not be surprising that a given treatment isn't 100% effective.
There are many example of this in the real world. With your logic, one might say: the sars covid-19 virus doesn't cause illness because some exposed people showed no symptoms. The families of the dead people would disagree.
The FDA does not approve medicine based on beliefs.
I am sharing my personal perspective, alongside the fact that controlled studies have proven it is one of the most effective treatments known to exist.
Nobody thinks ketamine cures depression, it is one treatment.
Anyone who talks in such terms shouldn't have their opinions on medicine listened to. There's a reason that medicine typically sticks to such terms as QALY (quality adjusted life year) and other such terms to produce the best outcomes in a resource constrained environment.
By your reasoning, many things are "life savers", but not every intervention is equal, is it?
Unusual is an understatement. This just seems ill-conceived to me. You can't eliminate one effect on the brain by introducing other effects on the brain that might have their own consequences for the results.
All this shows is that ketamine while under general anaesthesia is not more efficacious than placebo. Ok then. This just seems like a failed attempt to introduce better blinding to me. I'm not convinced it sheds any light on the mechanism by which ketamine is effective.
Actually, what it shows is both that getting ketamine while under general anaesthesia is roughly as effective as when taken without anaesthesia (40% here vs 45% in [1]), and as effective as just taking anaesthesia (their placebo treatment).
I see. But this seems to cast even more doubt onto the use of general anaesthesia as an active placebo. I mean, usually people waking from it don't feel great because they're very ill or had major surgery. Maybe in the abscence of things like that it could have some antidepressant effect.
Things similar to this have been used as treatment in the distant past of psychiatry as well, when ethics was nowhere to be found. Induced comas and such.
I've never personally done ketamine, but what these studies fail to take into account is the simple fact that for most of these classes of compounds, the subjective psychological experience is the entire mechanism of useful action, and looking purely at the physiological side is missing the forest for the trees. Unfortunately, delving into the subjective with double blinding is damn near impossible, since the whole point of blinding is to remove the subjective aspects of the study.
I know my DMT trips have been so potent of an experience, that if you took that out of the picture and just left the physical aspects, it would be little more than vasoconstriction and elevated heart rate, and I fail to see how that would do anyone any therapeutic good.
Terribly misleading link-bait headline. The authors were specifically trying to determine whether the hallucinogenic effects are related to the antidepressant effects, so they blunted the hallucinogenic effects by applying ketamine while under general anesthesia. They found that in that case, there was no effect on depression. So the study showed that the hallucinations are a key part of the depression treatment, not that ketamine is no better than placebo. But now I’m sure that this will be cited by people in shitposts based on the title. Science should know better.
Isn't it widely known already that these drugs help resolve negative memories? The computer obviously needs to be on in order for the routine to execute..
For all practical purposes, peer review is mostly useless today.
More often than not, it's either:
-a cursory glance by someone who doesn't have time to care
-a highly detailed critique from someone who will either be scooped or proven wrong, so they're looking for any reason to reject the paper, good or bad
-a grad student who puts in the effort but probably still lacks the experience for a good review
And if peer review actually was useful then the false cure for MS [0], arsenic-based life [1], or vaccines-cause-autism [2] would all be DOA and never been published in major journals to so much PR fanfare. Heck, most of Retraction Watch wouldn't be a thing [3].
> But it’s a problem for researchers running double-blinded clinical trials, as participants can usually tell whether they have received ketamine or a placebo. [...] The scientists gave the volunteers ketamine or saline as placebo right after they were put under anesthesia, but before their surgery, essentially blinding them to any psychedelic or dissociative effects.
That's a genius way to avoid unblinding. All psychoactive treatment trials have this problem: placebo controlled studies rely on patients not being able to distinguish whether they are in the test group or the control group. I hope future studies (say, for psilocybin) can also use this study design.
If I did drug trials for pain killers this way, would it give any useful data?
Depression and pain are subjective. Personally, I think removing the subjectivity from the trial voids the trial. It is a clever design, but it really just proves the benefit is in the experience and not the physical mechanism.
Having amnesia (forgetting whether they had a trip and whether they were in the treatment group) would probably be better than anesthesia induced unconsciousness. Though I don't know whether short term amnesia can be easily induced.
Pain has subjective parts but it is not merely subjective. You can measure how much effect ibuprofen or tylenol has, even with someone knocked out. You can see pain on an mri, even with someone knocked out.
Am I missing something blindingly obvious here? I would have assumed that the therapeutic effects of a strong mind-altering substance relies on being conscious to, you know, experience the effects.
Saying "It didn't work while the subject was asleep so therefore must be placebo" is just a bizarre position to take.
Imagine if a study stated "Cognitive Behavioural Therapy found to be ineffective on unconscious patients".
The trip is very short, but the effect as a useful antidepressant has to last a lot longer. It's not clear why the trip itself would have anything but short term effects on depression.
Readit News
Maybe it's the trip that helps.
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.
"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.
'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.
Deleted Comment
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)
On one side it showed me (after a long time) how you can be very empathic for all people around you and also reminded me or showed me how really good happiness feels.
And while the effects lasted a little bit for 1-2 weeks, it also is something I know I could do again if I like to.
This definitely gave me an additional/new viewpoint.
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.
The trip is (also) the chemistry!
(FYI, you mean to use the word “propel” in place of “propulse” above… they aren’t synonymous, surprisingly.)
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/10.1101/2023.04.28.23289210v... [2] 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.
[1] https://www.theonion.com/study-dolphins-not-so-intelligent-o...
This is such a stupid study, 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.
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.
https://slatestarcodex.com/2019/03/11/ketamine-now-by-prescr...
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.
(Granting Equal Liberty, a non-delegable inalienable right that's not granted to Congress by the US Constitution either).
/? Are diet and exercise more effective than pharmaceuticals (and talk therapy) https://www.google.com/search?q=are+diet+and+exercise+more+e...
Personally I have used it at home, and at a treatment center. There is no difference in the antidepressant properties, whether someone was helping me administer it in a medical setting, or not. The antidepressant properties do not relate to the effects of simply being in a clinical trial.
I strongly believe the antidepressant properties arise from the psychedelic/dissociative experience, and not directly from the physical effects. I'm not terribly surprised that ketamine may not produce strong antidepressant effects if the patient is not conscious.
Anyone looking to read more about ketamine antidepressant properties should read "The Ketamine Papers: Science, Therapy, and Transformation" by Phil Wolfson, M.D., and Glenn Hartelius, Ph.D.
It’s really not uncommon for some trials to fail to differentiate from placebo when it comes to depression studies. That doesn’t make this study “rubbish”, it just shows that you need to examine the body of evidence rather than cherry-picking studies that appear to match the outcome you want while dismissing those that say the opposite.
Ketamine is a temporary boost for some people, but it has also been overhyped in recent years. The single biggest downside is that it’s not a long-term solution. The duration of the antidepressant effect is relatively short (days to weeks) and the antidepressant effect appears to diminish with repeated dosing.
It can be a great help for suicidal patients or for getting traditional treatment started, but it’s not a singular solution to depression for most people.
Ketamine prescribing also got out of control fast. I traveled to a city where Ketamine clinics were advertising on the radio and billboards and competing with coupons and discounts and exaggerated promises of efficacy. Reddit and other forums are also filling up with stories of people who think their ketamine “stopped working” because they weren’t properly informed that it was a temporary effect for most people that needed to be combined with traditional therapy. Way too many clinics and influencers looking to ride the hype train without honestly assessing the situation.
But this study doesn't say the opposite. It fails to show an effect. That's different from proving the absence of an effect. Every Ph.D. student in an empirical field learns this in their first year. I'm surprised this study gets so much attention.
You can make a study verifying that a pound gold and a pound feathers accelerate downwards at the same speed in a vacuum, and perhaps you messed up the vacuum, so they actually fall with different speeds in your study. Doesn't prove gravity is messed up. You just failed to prove that it's not. Can have many reasons. Same with this study.
I have a partner who has been prescribed Ketamine for the last 3 years. I firmly believe that the drugs ability to rebuild neural pathways and thus work around / resolve damage to be the only reason why partner is still alive today, and is now ready to return to work after so many years and such a brutal road.
In Australia, being prescribed Ketamine is very difficult, and thus very uncommon. While I do not believe it should be opened up to everyone, my experience over the last few years makes me a massive fan of the drug for specific situations.
Doing studies isn't bad in itself, of course they will produce conflicting outcomes and need to be studied as a large body of evidence.
Yes, it cannot be used as a long-term solution. It's more of a fast-acting effect and has been over-hyped beyond its capabilities.
My immediate reaction was just that their conclusion ("has no short-term effect on the severity of depression symptoms" and what the co-author said in the linked article) is not reasonable to draw based on the study they designed, because they failed to consider whether the therapy needed a conscious patient or not.
Is there any singular solution to depression for most people?
(Of course you can argue they are not using enough K at the 0.5 mg/kg mark, because disccociation starts at 1 to 3 mg/kg per StatPearls.)
Dissociation isn’t necessary for the antidepressant effect, according to studies. In fact, many of the more responsible clinics target longer duration, lower peak dose infusions for this reason.
That's incorrect, it actually produced larger antidepressant effects (50% response rate and 40% remission [1]) than when the patient is conscious (40% response rate and 30% remission according to a large meta-analysis [2]).
[1] https://www.medrxiv.org/content/10.1101/2023.04.28.23289210v... [2] https://pubmed.ncbi.nlm.nih.gov/35688035/
But that large response had nothing to do with ketamine, as the non-ketamine group had the same or higher response.
The title is misleading though, unfortunately. What the study found is that Ketamine-while-unconscious is no better.
That is exactly what they are saying in the study. No better than placebo means Ketamine does not cure depression. If ketamine cured depression it would work in every case.
Increasing serotonin receptor density trough Ketamine use may relieve depression, but so can being cared for.
Your beliefs do not matter, biology matters. And it may in fact be that your "strong beliefs" in ketamine are why it helps you.
When it comes to mental health we also have these big umbrella categories (depression, schizophrenia) that are made up of groups of illnesses. Schizophrenia has so many different causes, and thus different treatments, that viewing it as a single illness can actually be problematic.
Anyways, my point is that what you're saying makes no sense at all.
> If ketamine cured depression it would work in every case.
Depression can have many different causes, and people have many different biological variables, so it should not be surprising that a given treatment isn't 100% effective.
There are many example of this in the real world. With your logic, one might say: the sars covid-19 virus doesn't cause illness because some exposed people showed no symptoms. The families of the dead people would disagree.
I am sharing my personal perspective, alongside the fact that controlled studies have proven it is one of the most effective treatments known to exist.
Nobody thinks ketamine cures depression, it is one treatment.
Dead Comment
Anyone who talks in such terms shouldn't have their opinions on medicine listened to. There's a reason that medicine typically sticks to such terms as QALY (quality adjusted life year) and other such terms to produce the best outcomes in a resource constrained environment.
By your reasoning, many things are "life savers", but not every intervention is equal, is it?
> Anyone who talks in such terms shouldn't have their opinions on medicine listened to.
Criticizing hyperbole by using hyperbole is a questionable strategy.
All this shows is that ketamine while under general anaesthesia is not more efficacious than placebo. Ok then. This just seems like a failed attempt to introduce better blinding to me. I'm not convinced it sheds any light on the mechanism by which ketamine is effective.
[1]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3992936/
Things similar to this have been used as treatment in the distant past of psychiatry as well, when ethics was nowhere to be found. Induced comas and such.
So maybe Ketamine does nothing and people just feel better when someone cares for them.
Anyway in the absence of an objective measure of depression everything seems to be on a loose footing
I know my DMT trips have been so potent of an experience, that if you took that out of the picture and just left the physical aspects, it would be little more than vasoconstriction and elevated heart rate, and I fail to see how that would do anyone any therapeutic good.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5999402/
If these are accurate does it make sense for them to be entirely inhibited by general anesthetic?
Thank you very, very much to the author for saying this
More often than not, it's either:
-a cursory glance by someone who doesn't have time to care
-a highly detailed critique from someone who will either be scooped or proven wrong, so they're looking for any reason to reject the paper, good or bad
-a grad student who puts in the effort but probably still lacks the experience for a good review
And if peer review actually was useful then the false cure for MS [0], arsenic-based life [1], or vaccines-cause-autism [2] would all be DOA and never been published in major journals to so much PR fanfare. Heck, most of Retraction Watch wouldn't be a thing [3].
[0] https://www.statnews.com/2017/11/28/multiple-sclerosis-paolo...
[1] https://phys.org/news/2012-07-scientists-nasa-arsenic-life-u...
[2] https://retractionwatch.com/2011/01/06/some-quick-thoughts-a...
[3] https://retractionwatch.com/
sounds like an ideal reviewer, tbh
So "yet to be peer reviewed" means the study paper is closer to "random generated garbage text" than to "important insight".
That's a genius way to avoid unblinding. All psychoactive treatment trials have this problem: placebo controlled studies rely on patients not being able to distinguish whether they are in the test group or the control group. I hope future studies (say, for psilocybin) can also use this study design.
Depression and pain are subjective. Personally, I think removing the subjectivity from the trial voids the trial. It is a clever design, but it really just proves the benefit is in the experience and not the physical mechanism.
Saying "It didn't work while the subject was asleep so therefore must be placebo" is just a bizarre position to take.
Imagine if a study stated "Cognitive Behavioural Therapy found to be ineffective on unconscious patients".