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Psychedelics are challenging the standard of randomized controlled trials

144 点作者 chapulin12 个月前

14 条评论

ThePowerOfFuet12 个月前
<a href="https:&#x2F;&#x2F;archive.ph&#x2F;l3GtQ" rel="nofollow">https:&#x2F;&#x2F;archive.ph&#x2F;l3GtQ</a>
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CogitoCogito12 个月前
&gt; How do you study mind-altering drugs when every clinical-trial participant knows they’re tripping?<p>Are there really no protocols for research in which participants can tell whether they have received a certain drug or not? I mean sure I think that double-blind is best for research, but are there really not other cases in which they deal with the patients knowing?<p>Edit:<p>&gt; By striving to cleave the drug’s effects from the context in which it’s given—to a patient by a therapist, both of whom are hoping for healing—blinded studies may fail to capture the full picture.<p>Okay I see the issue is that patients not being blind to the treatment is (thought to be) necessary for the treatment to work. Okay yeah so that means it&#x27;s hard to make the participants blind in anyway. Still I&#x27;m surprised there aren&#x27;t approaches to deal with this. Of course it might mean by definition double-blind trials aren&#x27;t possible, but then again maybe that&#x27;s not always appropriate. I can see the pandora&#x27;s box being opened by allowing drug studies to bypass these restrictions though so I guess I see why people don&#x27;t like it.<p>Later in the article:<p>&gt; In an email, an FDA spokesperson told me that blinded RCTs provide the most rigorous level of evidence, but “unblinded studies can still be considered adequate and well-controlled as long as there is a valid comparison with a control.” In such cases, the spokesperson said, regulators can take into account things like the size of the treatment effect in deciding whether the treatment performed significantly better than the placebo.
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jseliger12 个月前
RCTs are fine but the obsession with them is overwrought and counterproductive. My own drum to beat on this is regarding clinical trials for fatal diagnoses like cancer: <a href="https:&#x2F;&#x2F;jakeseliger.com&#x2F;2024&#x2F;01&#x2F;29&#x2F;the-dead-and-dying-at-the-gates-of-oncology-clinical-trials&#x2F;" rel="nofollow">https:&#x2F;&#x2F;jakeseliger.com&#x2F;2024&#x2F;01&#x2F;29&#x2F;the-dead-and-dying-at-the...</a>. We have Kaplan-Meier curves for fatal diagnoses. We know what happens (the tumors grow and metastasize. One doesn&#x27;t need elaborate phase 3 RCTs to figure out if there&#x27;s a good shot that a treatment is working; one can see it in tumor response and comparison to known KMCs. The existing system raises costs and causes people to die while waiting a decade or more for exciting treatments: <a href="https:&#x2F;&#x2F;atelfo.github.io&#x2F;2023&#x2F;12&#x2F;23&#x2F;biopharma-from-janssen-to-today.html" rel="nofollow">https:&#x2F;&#x2F;atelfo.github.io&#x2F;2023&#x2F;12&#x2F;23&#x2F;biopharma-from-janssen-t...</a><p>Moderna&#x27;s mRNA-4157 is a current example of this: <a href="https:&#x2F;&#x2F;jakeseliger.com&#x2F;2024&#x2F;04&#x2F;12&#x2F;moderna-mrna-4157-v90-news-for-head-and-neck-cancer-patients-like-me&#x2F;" rel="nofollow">https:&#x2F;&#x2F;jakeseliger.com&#x2F;2024&#x2F;04&#x2F;12&#x2F;moderna-mrna-4157-v90-new...</a>, although it may be held up by lack of manufacturing capacity as well.
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s4mw1se12 个月前
LSD was expected to be the holy grail of mental health treatment in the 40s and 50s before it was made illegal by the U.S. and the rest old the world following in the united states foot steps.<p>I’m very grateful that we are starting to see research really pick up steam and public companies like MindMed pushing for FDA approval with MM120.<p>It’s bittersweet though because it also is proof of how much progress we lost over those decades.<p>Not to discredit PTSD and Mental Health research, but just to expand on how much we don’t know about our mind and what these chemicals really are…<p>DMTx had its first round of clinical trials, where participants have extended experiences in DMT hyperspace and all share common hallucinations (i.e talking to other lifeforms).<p>What’s interesting is that these experiments are showing us how our brain models the world. Unlike freebase N,N-DMT which is a short lived rocky experince. These patient reported and the data showed that after the first few minutes on DMTx things started to normalize (the brain started modeling their world better)<p>One of Strassmans patients years ago said on DMT that these entities could share more with us if we learn to make extended contact.<p>Albert Hoffman the inventor of LSD also said he had contact with external entities on a trip (eyeball with wings) and said that it told him that they chose him to discover LSD for the sake of humanity.<p>The DMTx participants all reported that these entities knew about their life and their traumas and helped them process these all in different ways. They all reported that these were beings of a higher intelligence and felt that they were external.<p>Psychedelics are 100% challenging the gold standard. Whatever the that is lol.
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fl0ki11 个月前
It looks like I get to be the one to comment a classic criticism of RCT absolutism.<p>There have been no RCTs on parachutes or bulletproof vests. Volunteers welcome.
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mannyv12 个月前
It&#x27;s amusing that the placebo effect is so strong that they needed to create a standard that eliminated it.<p>Instead, they should figure out a way to induce it more consistently.
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Animats12 个月前
That&#x27;s been true of other drugs with strong noticeable effects. Not a new problem.
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kaashmonee12 个月前
The title seems a bit misleading. I thought they were talking about LSD or psilocybin. But this is referring to an MDMA-based therapy which I feel is more of a stimulant, or at least is used as one more often than it&#x27;s used as a psychedelic and it&#x27;s an amphetamine.
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nico12 个月前
Really hope at some point the healthcare industry starts trying to figure out how to harness the power of the placebo effect to enhance healing, rather than trying to do away with it<p>I mean, is the goal healing people? Or is it to only heal them if they get better by the direct effect of a (patentable&#x2F;sellable) chemical? Whose interests is the healthcare industry serving or protecting?
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omginternets12 个月前
A while back I posted a moderately popular comment, which I think is equally relevant here.<p><a href="https:&#x2F;&#x2F;news.ycombinator.com&#x2F;item?id=37949336">https:&#x2F;&#x2F;news.ycombinator.com&#x2F;item?id=37949336</a><p>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&#x2F;psilocybin&#x2F;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&#x27;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&#x27;t to say we can&#x27;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&#x27;t the absence of disease; it&#x27;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&#x27;ve pretty systematically dismantled those in favor of a grounded hyper-rationality [1]. As a scientist, I can&#x27;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&#x27;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&#x27;s &quot;God is dead quote&quot;. 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.
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hereme88812 个月前
The title itself is hilarious if you think about it.<p>But in an important note, I don&#x27;t like that I never read of the warnings for psychedelics, like triggering schizophrenia.
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sowut12 个月前
when i was 17 i found out about mushrooms and would take 1&#x2F;8th ounce once a month for about 6 months which culminated in me absolutely convinced i was jesus for about 6 years. good stuff
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spacetimeuser512 个月前
&gt;&gt;By striving to cleave the drug’s effects from the context in which it’s given—to a patient by a therapist, both of whom are hoping for healing—blinded studies may fail to capture the full picture.<p>The amount of monkey types amongst these researchers is spectacular. In the current AI boom, with various RAG and prompt engineering, everyone is striving to maximize context, and no-one would deny that modern AI emulates parts of human mind&#x2F;brain. And context sensitivity of quantum systems is also pretty much obvious.<p>Modern astronomy, for example, can pretty much as well challenge the standard of randomized controlled trials: no one uses experimental planets and galaxies to test their null hypotheses. No engineer would strive to falsify the objects they are developing by deliberately designing non-working engines etc. And this is pretty much considered science.<p>While these &quot;social scientists&quot; are still full of medieval bullshit, so that it is more optimal to commit suicide than use their evidence-skewed medicine, which under the hood by default considers the subjects are either rocks or dead.
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taeric12 个月前
This is the second narrative I&#x27;ve seen recently where folks seem to think they have a strong argument against RTCs. Just, what?<p>Yes, there have been advancements in statistical tools. And we actively know some causal pathways. More, sometimes the expensive randomized trials are just not worth the standard ROI calculations...<p>But, to think that you have found some magic bullet against RTCs shows you don&#x27;t really appreciate why they are so vital. And is usually a sign that you are reading the narrative of someone invested in an outcome.