[HN Gopher] Psychedelics are challenging the standard of randomi...
___________________________________________________________________
Psychedelics are challenging the standard of randomized controlled
trials
Author : chapulin
Score : 125 points
Date : 2024-06-03 22:45 UTC (1 days ago)
(HTM) web link (www.theatlantic.com)
(TXT) w3m dump (www.theatlantic.com)
| ThePowerOfFuet wrote:
| https://archive.ph/l3GtQ
| neonate wrote:
| https://web.archive.org/web/20240603195140/https://www.theat...
| s4mw1se wrote:
| 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.
|
| 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.
|
| It's bittersweet though because it also is proof of how much
| progress we lost over those decades.
|
| 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...
|
| 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).
|
| 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)
|
| One of Strassmans patients years ago said on DMT that these
| entities could share more with us if we learn to make extended
| contact.
|
| 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.
|
| 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.
|
| Psychedelics are 100% challenging the gold standard. Whatever the
| that is lol.
| r2_pilot wrote:
| And people experiencing DTs from alcohol withdrawal say
| nonexistent entities are present too. The brain is merely
| capable of processing its inputs based on the laws of physics,
| and considering the complexity of a functioning mind, we
| shouldn't be too surprised when abnormal inputs cause abnormal
| outputs, nor should we necessarily hold much stock in the
| matter. Certainly, though, the tales are interesting if nothing
| else.
| BriggyDwiggs42 wrote:
| We don't have any way of determining whether these
| experiences are purely generated by the brain, and it's not
| smart to claim it's one way or the other without further
| evidence.
| JumpCrisscross wrote:
| > _it's not smart to claim it's one way or the other
| without further evidence_
|
| It's perfectly smart to claim Hoffman did not make "contact
| with external entities on a trip (eyeball with wings)" with
| zero evidence because the _status quo_ is not having
| conversations with eyeballs with wings. Herego, the burden
| of proof is on the eyballs-with-wings guy.
| mistermann wrote:
| Anyone who makes a claim has a burden of proof.
|
| _If I 'm on The Truman Show, could someone please spill
| the beans_?
| deepvibrations wrote:
| Yet we still work on the assumption that consciousness
| arises within space-time...
|
| Disappointing the burden of proof is not deemed necessary
| in this case!
| r2_pilot wrote:
| For what it's worth, I don't have evidence that you are
| conscious (and I never can; your qualia of the concept of
| the color red and your other internal world-state
| representations are solely yours, assuming you are not a
| P-zombie). For the record, I also do not make magic
| claims of free will nor assume there are laws outside
| known physics. If you wish to call in dark matter as a
| potential agent of causal change, then you can propose
| your theories backed by evidence and we'll continue as
| the evidence leads. But as far as my own existence, well,
| cogito ergo sum and all
| mistermann wrote:
| > Yet we still work on the assumption that consciousness
| arises within space-time...
|
| What role is the "yet" playing here, to indicate
| contradiction to my comment?
|
| And without it, I'm not sure what the point of the
| comment would be.
|
| This whole comment section is so confusing.
| r2_pilot wrote:
| Actually, the people who are making the claim that the
| hallucinations are external entities are asserting a
| position. And with a quick application of Hitchens' Razor,
| that which is claimed without evidence can be dismissed
| without evidence.
| telotortium wrote:
| They _do_ have evidence - their own experiences! It's not
| very convincing evidence, to be sure, but as the
| replication crisis shows, even "objective" evidence can
| fail to be convincing or demonstrative for various
| reasons.
| sdenton4 wrote:
| ... The replication crisis does not - I repeat, does not
| - lower the standard for acceptable evidence in the
| sciences.
| telotortium wrote:
| First, the replication crisis, or at least its
| recognition, should if anything raise the standard for
| acceptable evidence.
|
| More pertinently, I am talking here on a purely social
| and practical level. You seem to have taken it as a moral
| statement.
| cheeseomlit wrote:
| We communicate with other people and entities in dreams as
| well, and they seem completely convincing during the
| experience. While its not impossible for the self-
| replicating machine elves from the 5th dimension to
| actually exist, I think its more likely they're reflections
| of our psyche or something like that
| BriggyDwiggs42 wrote:
| Of course it's more likely, I'm just arguing we shouldn't
| dismiss the possibility just because it sounds silly
| before we've studied it thoroughly.
| r2_pilot wrote:
| > before we've studied it thoroughly.
|
| I don't know about you, but I have studied reality pretty
| extensively over the years. I have yet to come across
| evidence that I would submit to a court of law regarding
| the existence of winged eyeballs, or other products of a
| hallucination. Having said that, several lawyers seem to
| be submitting such hallucinations in court thanks to AI,
| so maybe that technology can help us investigate this
| possibility of extracorporeal entities.
| Aloisius wrote:
| People totally blind from birth taking hallucinogens don't
| see entities which strongly suggests they're not real.
| delecti wrote:
| I agree the entities probably aren't real, but an equally
| supported hypothesis would be that you need to _see_ the
| entities to "see" the entities.
| Aloisius wrote:
| Except some people who lost their vision late in life
| _can_ experience them.
| yosame wrote:
| Because they still have a developed (if atrophying)
| visual cortex to generate the visual hallucinations.
| tsimionescu wrote:
| That is easy to check if you measure the amount of light
| reaching the eyes of the patient while the experience is
| happening. Without even checking, I am already quite
| confident that no extra light will be reaching their eyes
| because they took some drug, but it's easy to measure.
| lupire wrote:
| This makes no sense.
|
| You are constantly being bombarded with sensory phenomena
| that your nerves detect but your brain ignores. For
| example, you smell almost nothing, nearly all the time,
| despite being able to smell those scents occasionally,
| such as when you move to a different environment.
| Changing your brain somehow to notice those phenomena
| would not change the physical phenomena.
| telotortium wrote:
| Not a parsimonious explanation - more likely, the visual
| cortex needs to be trained in order to see anything, even
| in the mind's eye.
| spacetimeuser5 wrote:
| >>People totally blind from birth taking hallucinogens
| don't see entities
|
| So these people do not trip at all on hallucinogens?
| Sounds like rather improbable. ~70% of what you call
| "visual experience" is driven by non-visual cortices,
| like anterior cingulate, for example. And even before the
| visual cortex, even on the thalamus level, the thalamus
| receives up to ~60% of top-down connections from non-
| visual cortices. You do not need to literally see
| anything in order to get the information about it. Get
| your potato, monkey.
| tsimionescu wrote:
| Of course we do, what do you mean? We can obviously check
| if there is anyone else in the room, with various
| instruments, and if there isn't, we obviously know for
| certain that the experience was purely generated by the
| brain. What else could it even be?
| mistermann wrote:
| Is it scientific consensus that an absence of evidence is
| proof of absence?
|
| And even if so: is it necessarily true?
|
| PS: did you notice you're using the same methodology
| "believers" use: _it 's obvious_?
| tsimionescu wrote:
| Give the extreme level at which we understand the basic
| functioning of the physical world (the Standard Model),
| yes, absence of evidence for a phenomenon that would
| contradict this model constitutes evidence of absence of
| such a phenomenon.
|
| That is, since the only possible known interactions that
| the brain could pick up are electrical in nature, and
| given that no external electrical field changes are
| observed, that constitutes evidence that no external
| signal is being received by the person. The weak and
| strong forces don't work at such distances, so they are
| out of the question, and gravitational waves or neutrinos
| are far too weak to be detected by our brains, and
| impossible to make so targeted that only a single
| individual would receive the signal.
|
| Now, is it conceivable that a different fundamental
| interaction that mammalian brains can detect but that
| none of our experiments have ever found could exist? Yes,
| but it is so extraordinarily unlikely that it can be
| dismissed out of hand, absent any proof. And the memories
| of people experiencing hallucinations are _certainly_ not
| proof.
| TeMPOraL wrote:
| I'll add to it that there's a wide range of documented
| cases of humans experiencing all sorts of weird phenomena
| when their brains are being physically poked at. A drug
| chemically circuit-bending your brain therefore seems
| much more likely explanation than opening it to perceive
| an extra dimension of reality.
|
| --
|
| [0] - https://en.wikipedia.org/wiki/Circuit_bending
| mistermann wrote:
| > ... constitutes evidence of absence of such a
| phenomenon.
|
| Mostly everyone prefers that easy version of the
| question, but that isn't the one I asked.
|
| The one I asked is:
|
| Is it scientific consensus that an absence of evidence is
| _proof_ of absence? ( "proof" vs "evidence")
|
| (Note also my question was about _scientific consensus_ ,
| but you are welcome to choose either version.)
|
| > That is, since the only possible known interactions
| that the brain could pick up are electrical in nature
|
| This seems "off" to me..."the only know to be possible"
| seems perfectly logical, whereas your wording almost
| sounds like you determine how Mother Nature runs the
| show. Granted, that's how it intuitively seems, but
| still. Regardless, for clarity: are you asserting that
| the final answered has been reached here, in fact?
|
| Still outstanding (for bonus points):
|
| >> And even if so: is it necessarily true?
|
| >> PS: did you notice you're using the same methodology
| "believers" use: it's obvious?
|
| For your troubles, an extra bonus question:
|
| Did atoms exist before they were discovered to exist?
| Dylan16807 wrote:
| Nothing can really be perfectly proven, so go away if
| that's the only standard you will allow discussion of.
|
| > Did atoms exist before they were discovered to exist?
|
| We were certainly able to detect atoms before we figured
| out the exact details.
| BriggyDwiggs42 wrote:
| We need to account for the odd similarity of experience
| across users, which leads to two most probable
| explanations. First, the brain generates the experience,
| and the patterns are a consequence of structural
| similarities across human brains. Second, these entities
| actually exist somehow and we can't yet observe them with
| our modern instruments. I certainly think that the first
| is more likely, but I think we need to do more work to
| reduce the probability of the second, likely by recording
| the brain activity similarities we would expect to see if
| it were a generated experience or by finding a number of
| individuals who don't have the same experiences. We can
| also have people undergo extended trips, as is being
| tested currently, and see if the characteristics of the
| entities or the world indicate a generated experience. My
| only point was that, since this is a matter that depends
| entirely upon subjective conscious experience, a
| phenomenon we lack tools to measure and understand
| somewhat poorly, and since this substance is majorly
| understudied, it isn't smart to simply assume that the
| first explanation is the correct one.
| tsimionescu wrote:
| The second "explanation" requires a fundamental upending
| of basic physics research that is confirmed to higher
| degrees of accuracy than any direct experience we have
| ever had. The first explanation, while slightly handwavy,
| perfectly fits all established models of physics,
| chemistry, biology, neuroscience, and psychology.
|
| I think even mentioning the second explanation is
| entirely splitting hairs. It's like reminding everyone
| that physics can't rule out that God could have created
| the world with its apparent 8 billion year history 2
| hours ago.
| BriggyDwiggs42 wrote:
| Actually yeah I think you're right.
| lupire wrote:
| This is called Bayesian reasoning, BTW, and you
| subconsciously do it all the time. Your entire life would
| be almost completely incomprehensible otherwise.
| jonathankoren wrote:
| This is an absurdly credulous take. If we took this face
| value, then we'd have assume that Carl Sagan really did
| keep an invisible flying dragon his garage.[0] This
| position is the exact opposite of rational thought.
|
| Say it with me, "Extraordinary claims require extraordinary
| proof."
|
| Even famed psychonaut, and inventor of the self-
| transforming machine elves meme, Terance McKenna said the
| only way to prove that it wasn't all in your head was to
| ask the elves a question that was easily and objectively
| verifiable, but you didn't know the answer.
|
| He couldn't do that. He said so. He still publicly said
| that he believed they were real transdimensional
| intelligences, but he made no qualms about the fact that he
| had no proof, they're just a hallucination was very real
| possibility. (They are.)
|
| [0] https://en.wikipedia.org/wiki/The_Demon-
| Haunted_World#Dragon...
| Karunamon wrote:
| The extraordinary nature of a claim or its proof is by
| nature a subjective one.
| spacetimeuser5 wrote:
| >>Say it with me, "Extraordinary claims require
| extraordinary proof."
|
| Let's be honest with it. So someone is experiencing the
| self-transforming machine elves. Please provide the exact
| description of neuronal circuitry (numbers of neurons,
| network architectures, interconnectivity patterns,
| amounts of neurotransmitters used, spike patterns and the
| resulting EEGs etc) which generates this exact
| experience. Ask a distinguished professor of
| neuroscience. Use integrated information theory, emergent
| properties, quantum collapse in microtubules, whatever
| currently established paradigm - and provide the exact,
| 100% comprehensive and full description of the brain
| state that presumably generates this exact experience,
| also allowing to differentiate from all other experiences
| like just "machine elves", "non-self-transforming machine
| elves" or elves with any other properties. Or just begin
| with the 100% comprehensive and full description of the
| brain state/circuitry generating the taste of vanilla,
| which would be distinctly differentiable from the
| state/circuitry generating a taste of chocolate or
| garlic.
| nathan_compton wrote:
| I think the preponderance of evidence points strongly to
| these phenomena being purely mental - in particular the
| vast majority of conscious behaving entities which we
| encounter on a regular basis are physical objects with
| certain properties (having a brain is the big one) and what
| we know about physics, biology, computation, and
| neuroscience makes a pretty compelling case that the
| physical object in question (the brain) is intimately,
| probably one to one, connected with the phenomenon we
| identify as the entity. It would be very strange if we
| found evidence of _non-material_ entities given this
| context. And in the case of the self-transforming machine
| elves we very clearly have a compatible alternate
| hypothesis: they are generated by the brain which we are
| mucking around in with chemicals which are known to disrupt
| its behavior.
| mythrwy wrote:
| I think you may have touched on the actual lesson of
| psychedelics:
|
| "I think the preponderance of evidence points strongly to
| these phenomena being purely mental"
|
| Agreed. Along with all phenomena anyone experiences in
| general.
|
| We all create reality strictly in our heads which
| corresponds, with varying degrees of accuracy, to
| external phenomena.
|
| We like to think this is not the case and we are in
| possession of "objective fact", or maybe we are not at
| this moment, but objective reality certainly is out there
| and we are on track to get it.
|
| But maybe it's really just mental abstractions all the
| way down. All the way down into the earliest evolutionary
| days of perceiving distinction between light and dark.
|
| We cannot see certain wavelengths of light for example.
| But butterflies can. So when I look at a flower with UV
| markings and a butterfly looks at the same flower, who is
| right? How much more "information" is available about
| (for instance) this flower if we could only perceive it?
| How much magnesium is in it? How about if we couldn't see
| things that were not static for more then a day just like
| we can't see sub-millisecond motion with our eyes and
| have to measure it with instruments? Would the flower
| even exist for us in casual every day life at that point?
|
| We have monkey eyes for the most part. We see what a
| highly evolved monkey would need to see, no less, no
| more. This in my opinion is what is so startling (and
| potentially therapeutic) about psychedelics. It awakens
| us to the fact that perception, which we firmly believed
| to be unassailable reality, is just perception and there
| exists the possibility to think about things in new ways,
| to create a new reality in a manner of speaking.
| yieldcrv wrote:
| So, I think that is too dismissive, while I think the
| psychedelic proponents are too exuberant
|
| Basically, I don't think the categorization matters. Like are
| these entities things always here and perceived if we access
| a certain plane, or are these mere configurations and
| figments of our brain that can be repeated. To me, thats not
| important. Its important if the reconfiguration of the brain
| is useful, therapeutic, repeatable, what side effects are
| there, whats going on with people predisposed to
| schizophrenia that psychedelics seem to exacerbate
| permanently. What's going on with floaters/HPPD.
|
| Can LSD be refined for the parts that are useful for us, or
| do we simply slap fine print about potential side effects for
| those with a family history of schizophrenia on it like ....
| _every other FDA approved drug_.
|
| I think fawning over something in the 1950s is juvenile, when
| there probably are advances possible since then to that
| substance.
|
| But I would like it to at least reach parity with Big
| Pharma's designer drugs with clinical trials and listed side
| effects, instead of just anecdotes percolating rave
| communities.
| s4mw1se wrote:
| Rave communities? This is from research and patient panel
| interview that was hosted after the publication. Minus the
| hoffman stuff.
|
| https://pubmed.ncbi.nlm.nih.gov/37897244/
|
| https://www.youtube.com/live/Myq_Hc_39aI?si=qnJ8UhOztRjshEk
| f
| yieldcrv wrote:
| I was replying to r2 about the path they had taken the
| discussion, which was no longer about the article
|
| but you knew that. consider reading it again with that
| interpretation if you didn't know that.
| mbesto wrote:
| > we shouldn't be too surprised when abnormal inputs cause
| abnormal outputs, nor should we necessarily hold much stock
| in the matter.
|
| While my scientific mind wants to agree with you, that same
| scientific mind can't help but wonder...why similar
| experiences are being triggered on totally unrelated
| people.[0]
|
| [0]- https://health.howstuffworks.com/wellness/drugs-
| alcohol/dmt-...
| r2_pilot wrote:
| Here's a simpler explanation that fits the facts. Humans
| are practically genetically identical, are raised in
| roughly similar cultures with similar expectations of
| reality, and are being dosed with drugs generally assumed
| to be chemically similar (in this case) paired with the
| experiences that are reported. So while it's imperative to
| keep an open mind, it's also important to keep it closed
| enough that your brains don't leak out.
| KennyBlanken wrote:
| Mass media tends to follow a lot of common themes and often
| they are proxies for other general societal attitudes? Many
| of us grew up reading at least some books in common?
|
| Interplanetary aliens always being more developed than us
| (and usually hostile) is a direct proxy for xenophobia to
| people from other countries.
|
| Ever wonder why there's so much hand-waving about
| immigrants stealin' our jerbs?
| chiefgeek wrote:
| Just curious if you've tried psychedelics?
| ASalazarMX wrote:
| Not OC, and I've never tried psychedelics, but even a
| strong fever will make you hallucinate, and I've had a
| couple of those. You mind closes up into itself, and the
| world it creates, while extremely simplistic, feels very
| real.
| r2_pilot wrote:
| SWIM may or may not have confided to me experiences with a
| variety of compounds purported to induce a wide range of
| subjective internal experiences upon their various methods
| of consumption. At any rate, I've certainly read (and
| donated to) Erowid.
| cmilton wrote:
| Did any of your subjective internal experiences create
| objective results?
| tweezy wrote:
| I will say prior to experiencing this myself I felt 100%
| certain that what you said is the truth. It just makes sense.
|
| Now that I've had these experiences, I'm more like 90%
| certain that what you said is true. These experiences add a
| certain humility to the way I experience the world.
|
| So in all likelihood, molecules like dmt will bind to certain
| serotonin receptors in the brain that cause strong and
| repeatable distortions in the visual field (even with eyes
| closed).
|
| The human mind is great at picking out patterns and assigning
| meaning to them based on our experiences. So that shifting
| pattern in my visual space kinda looks like a face, I'm going
| to assign trickster machine elf to that visual pattern.
|
| More likely than not that's what's going on. But there is
| probably some value in experiencing that.
|
| Having said all that, the subjective experience of living
| that is very different. This feels incredibly real. As crazy
| as it sounds, it genuinely feels like blasting into a hyper-
| dimensional space and encountering a population of sentient
| entities.
|
| That feeling is so real, that it leaves just the tiniest gap
| of "hmm, maybe I don't know everything after all. Maybe
| there's more to this story than I could've previously
| comprehended".
|
| All to say is that while you're most likely right, I think it
| could be healthy to acknowledge that you're not definitely
| right. And leaving some room for uncertainty and exploration
| could prove beneficial, even for the skeptics among us.
| cthalupa wrote:
| I've done DMT a handful of times, and experienced the
| "entities" in several of them. After the trips ended I did
| not have any particular feeling that these entities were
| real, though the experiences were strange in a way that was
| quite wonderful.
|
| One trip lacked any of these entities, but the time dilation
| is something that I still contemplate today, a decade or so
| later. It literally felt like hundreds or thousands of years
| had passed, with clear memory of all sorts of mundane days,
| etc., along with more memorable ones, particularly in the
| days following the trip. It had a pretty profound impact on
| my worldview, particularly in the few months following it,
| though those memories faded faster than real memories would.
| Feeling like I had lived for so long did make a lot of my
| day-to-day worries seem far less significant.
|
| Also not anything I ascribe to any sort of mystical or extra-
| planar root-cause, but the ability for the brain to invent
| such a huge quantity of information over a ~15 minute trip is
| crazy to me, in the "man brains are weird" sense.
| colechristensen wrote:
| Yes hallucinating higher powers making contact with plans for
| the subject to make the world better is... a consistent but
| rarely encountered feature of the human brain. Go read the
| descriptions of angels in the Bible and it reads just like
| somebody tripping.
|
| One of the reasons hallucinogens are dangerous is that there's
| a risk that users will believe in their hallucinations and try
| to start cults.
|
| Timothy Leary was one of these drug-induced zealots and he
| among others were the reasons LSD et al got banned in the first
| place. They wanted to overthrow society and implement a quasi-
| religion based on the drugs.
| JumpCrisscross wrote:
| > _all reported that these were beings of a higher intelligence
| and felt that they were external_
|
| "Jaynes asserts that consciousness did not arise far back in
| human evolution but is a learned process based on metaphorical
| language. Prior to the development of consciousness, Jaynes
| argues humans operated under a previous mentality he called the
| bicameral ('two-chambered') mind. In the place of an internal
| dialogue, bicameral people experienced auditory hallucinations
| directing their actions, similar to the command hallucinations
| experienced by many people who hear voices today. These
| hallucinations were interpreted as the voices of chiefs,
| rulers, or the gods" [1].
|
| Basically, the hypothesis that humans as late as the ancient
| Greeks were sort of schizophrenic [2]. (To be clear, it's a
| hypothesis, not science.) But it's neat to think of drugs like
| DMT reverting (converting?) us to that bicameral state.
|
| [1] https://www.julianjaynes.org/about/about-jaynes-
| theory/overv...
|
| [2] https://en.wikipedia.org/wiki/Bicameral_mentality
| anigbrowl wrote:
| Sorry to see you're being downvoted. _Origin of
| Consciousness_ is a masterpiece, even if it 's wrong.
| hattmall wrote:
| Are you saying that speaking to external beings while tripping
| is potentially a treatment for mental health?
|
| I mean yeah, that's what it feels like when you really trip and
| sometimes it can be really exciting, sometimes it's interesting
| and feels informative, and sometimes it's completely terrible.
|
| The best feeling in the world is when you remember that you
| took drugs and the people telling you that you are stuck on a
| foreign planet in cold and darkness away from everyone you know
| for eternity aren't real, that the sun is in fact coming up and
| you are just on earth in your friends backyard.
|
| I have a really hard time thinking anyone that proposes
| tripping as a viable solution to true mental health problems is
| a serious person.
|
| There's basically two camps of people in that arena, and it's
| people that haven't done many drugs, and people that did too
| many drugs.
| TeMPOraL wrote:
| > _Are you saying that speaking to external beings while
| tripping is potentially a treatment for mental health?_
|
| "External" but really just products of your brain, and yes, I
| could see how this would be helpful. Taking such drugs seem
| like giving a whack to the brain to the point you enter a
| kind of "debug mode"; perhaps some issues that you can't
| normally untangle are accessible directly in that mode. At
| the very least, you get to poke at your internal state from
| angles normally not available to you, so some of your mental
| blocks could shake loose and fall back into place.
|
| (I wouldn't know, I never took anything like it or had any
| similar experiences, but that's what I gather from reading
| countless stories and reports of those who did.)
| micromacrofoot wrote:
| if we were to dramatically oversimplify it, we could say that
| these drugs grant someone a perspective that they were unable
| or unwilling to achieve through their typical thought
| processes
|
| it's not hard to imagine why sometimes that can be helpful,
| and we can try to optimize towards "usually helpful" -- but
| sure they could also be harmful or plain useless
| cthalupa wrote:
| The vast majority of people report their experiences with the
| DMT "Machine Elves" as being positive. Very few report the
| experience as being negative, and I have very very very
| rarely heard of a bad trip in the same vein that you see
| occur a significant amount of the time with shrooms and LSD.
|
| Not all of my DMT trips involved these other entities, but
| when they did, they frequently had something to show me or
| say to me. These things weren't "new" knowledge - how could
| it be? I don't believe these are actually external entities -
| but instead things that on some level I knew to be true, but
| had trouble internalizing and operating on. These experiences
| helped integrate that knowledge from something I understood
| on a conceptual basis to something I could actually put in
| practice. One of my first serious long-term relationships
| ended when I was cheated on, and it resulted in me having
| some serious trust issues in relationships after that. I
| "knew" that this is a risk in relationships, but that people
| CAN be faithful, and that allowing these trust issues to
| fester would almost certainly directly result in
| relationships failing because of them. That didn't stop me
| from doing the things that I knew I shouldn't. A DMT trip
| with some experiences related to this didn't teach me
| anything new, but after I found it significantly easier to
| move past those trust issues and become a much better partner
| in relationships.
|
| If I had to guess, something about being exposed to this
| information in such an altered state of conscious can allow
| for you internalize it when you otherwise struggle in your
| normal state of being.
|
| > I have a really hard time thinking anyone that proposes
| tripping as a viable solution to true mental health problems
| is a serious person.
|
| This seems likely to be a personal bias. There is a lot of
| real-deal research from serious people showing promising
| results.
| tsimionescu wrote:
| It's quite common, though poorly understood, for the brain to
| have surprisingly consistent hallucinations in response to a
| particular substance. Just like seeing the same sort of
| entities on DMT, people in accute alcohol withdrawal almost all
| report hallucinations of small-ish vermin (e.g. rats, snakes,
| mice, cockroaches). It seems pretty clear that these substances
| each produce their own particular kind of input to the brain
| that then gets interpreted by the very similar neural circuitry
| we all have to the same kind of memory/experience.
|
| I wonder if this type of thing will actually end up helping
| neuroscience research as well, seeing as how some of these
| substances seem to push higher level concepts than what is
| typically easily induced in an fMRI. If they turn out to be
| safe for human use, they should be usable in this setting as
| well.
|
| And yes, of course an entity your brain is hallucinating
| "knows" about your memories. It's you talking to yourself.
| qbxk wrote:
| it seems like you're a bit too comfortable with thinking that
| just because the hallucinations are hallucinations they must
| be useless. alcoholics see snakes and rats and vermin, and
| that's not very much help to anybody. but all these
| psychedelic folks are hallucinating higher orders of
| intelligence that understand their trauma and can help them?
| hallucination or not, seems like a useful thing to have
| access to. far more than shadows of snakes, for sure
| andrewflnr wrote:
| They didn't imply the hallucinations were useless. Rather
| the opposite in fact.
| tsimionescu wrote:
| As the other commenter pointed out, I'm not at all claiming
| they are useless. I actually think it's more likely than
| not that the hallucination itself is what is having the
| therapeutic effect, that it's not a side effect at all. And
| even if that's not true, I think it's still very wise for
| the one experiencing it to engage with the hallucination.
|
| All I'm saying is that none of this makes it even slightly
| remotely possible that it is anything other than a
| hallucination.
|
| And note: they are not hallucinating a higher level of
| intelligence, they are hallucinating a way to accept their
| own trauma in the form of an entity that appears more
| intelligent. Just like when writers create a super-
| intelligent alien in a movie, they don't actually create
| something more intelligent than humans.
|
| Now, if they were seeing an entity that explained new ways
| of solving partial differential equations to them, then I
| would say that the external entity hypothesis merits some
| investigation.
| slfnflctd wrote:
| I'm deeply appreciative of the voice of reason in these
| discussions. My parents raised me in a demon haunted
| world, and having access to the intellectual tools which
| brought me out of that world fills me with gratitude
| toward those who helped make them widely available and
| continue to do so.
| adammarples wrote:
| I have had dreams where I listen to songs and marvel at
| the incredible skill of the songwriter, and sadly accept
| that I could never have 1/10th of that skill. It was a
| surprise for me to reflect back on the dream and realise
| that of course because it was my dream I was in fact the
| song writer too, somehow also able to listen to it with
| no idea what would come next. The mind is a fascinating
| thing.
| sdenton4 wrote:
| Was the song actually that good, or did your brain simply
| tickle the 'appreciation for incredible beauty' neurons
| while playing back some Nickelback memories?
| andrewflnr wrote:
| I'm pretty sure I've experienced both, actually.
| Occasionally bits of it, melody or words, will survive in
| my memory that I think are actually good, if only I could
| reconstruct the rest of it. Other times I'm pretty sure
| there was nothing actually there.
| lupire wrote:
| The bit you remember might be great. The part you don't
| remember might never have existed. I've often "solved"
| problems in semi-lucid sleep, by brainstorming an idea
| and pursuing it, but when I push, the idea doesn't makes
| sense, or is meaningless, not just wrong.
| adammarples wrote:
| Almost certainly the latter. But how would I know...?
| amenhotep wrote:
| The trick is that you're not just generating the song;
| you're generating the experience of listening to the
| song. Much more efficient :)
| mistermann wrote:
| For clarity: is this to say that it is a fact that these are
| simpy hallucinations, nothing more?
| tsimionescu wrote:
| It is a fact that they are experiences in your brain and
| not communication with an entity of any kind outside your
| brain.
|
| The word "hallucination" sometimes has some negative
| connotations that suggest they are deceitful or useless
| experiences that you should ignore and forget. I'm not
| trying to say that at all. I do think it's quite possible
| that any therapeutic effect is entirely due to these
| experiences, and, if so, they should be encouraged, not
| ignored.
| mistermann wrote:
| To you, what is the meaning of "fact" and "is a fact"?
|
| What, specifically, separates a "fact" from a "non fact"
| in this specific context?
| adammarples wrote:
| What possible answer do you think there could be to this
| question? Facts are true statements. Questioning what
| your interlocuter thinks a "fact" is isn't going to move
| the debate forward in any useful way.
| mistermann wrote:
| > What possible answer do you think there could be to
| this question?
|
| There are a few different classes/categories you'll see,
| but not many.
|
| > Facts are true statements.
|
| Do (non-specialized, as in _scientific_ facts) facts
| require a proof, or not? And if not....
|
| > Questioning what your interlocuter thinks a "fact" is
| isn't going to move the debate forward in any useful way.
|
| _Perhaps_ (is that future you see _the real thing_?), it
| may provide value though.
| tsimionescu wrote:
| A fact is something which generally agrees with the
| accepted body of scientific knowledge, even if it
| challenges specific assumptions. A non fact is something
| that blatantly contradicts this body of knowledge without
| any credible new evidence.
| mistermann wrote:
| > A fact is something which generally agrees with the
| accepted body of scientific knowledge, even if it
| challenges specific assumptions.
|
| Is there a difference between a fact and a scientific
| fact (from a Philosophy of Science perspective)?
|
| > A non fact is something that blatantly contradicts this
| body of knowledge without any credible new evidence.
|
| Can you cite anything authoritative that supports this
| claim?
|
| _And_....are "fact" and "non fact" the only two
| options?
| krzat wrote:
| There is psychological approach called internal family system,
| it explains personality as collection of entities that
| cooperate unaware of each other. Perhaps some drugs disturb
| this to such extend that it feels like there are multiple
| people in consciousness.
|
| If those external entities were real, we wouldn't need to wait
| for science, some shaman would just go to the spirit realm and
| get told about bacteria.
| vwoolf wrote:
| And also the argument that people have demons in them:
| https://www.astralcodexten.com/p/book-review-the-others-
| with....
|
| I read some of the guy's book. It's a trip.
|
| _If those external entities were real, we wouldn 't need to
| wait for science, some shaman would just go to the spirit
| realm and get told about bacteria._
|
| A great point.
| lupire wrote:
| People with DID and schizophrenia feel this way.
| optimalsolver wrote:
| >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
|
| When will these entities share something truly useful, like the
| design for a working cold fusion reactor, or a cure for
| Alzheimer's?
|
| Also, people really need to know that while a psychadelic trip
| can be healing and mystical, it can also go like this:
|
| https://www.reddit.com/r/DMT/comments/gb9ar0/dark_dmt_trip_r...
| cthalupa wrote:
| This person did an insanely high dosage of DMT. Most people
| can hit "breakthrough" levels at 20-30mg, and I rarely hear
| of even experienced DMT users taking more than 50mg. 100mg
| for someone on their first real trip isn't something anyone
| should do - and from their general attitude towards tripping
| solo when knowing they aren't in a great mental place, it
| doesn't seem like they're particularly experienced with
| shrooms or lsd, either.
|
| I wouldn't cautious people against social drinking to the
| point of getting a buzz just because getting blackout drunk
| is often an unpleasant experience.
| MacsHeadroom wrote:
| > The DMTx participants all reported... that these were beings
| of a higher intelligence and felt that they were external.
|
| This is not true. I know multiple DMTx participants and many
| report that the beings are conjurations of their own
| subconscious, i.e. very much "internal."
| Animats wrote:
| That's been true of other drugs with strong noticeable effects.
| Not a new problem.
| jseliger wrote:
| 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:
| https://jakeseliger.com/2024/01/29/the-dead-and-dying-at-the....
| We have Kaplan-Meier curves for fatal diagnoses. We know what
| happens (the tumors grow and metastasize. One doesn't need
| elaborate phase 3 RCTs to figure out if there'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: https://atelfo.github.io/2023/12/23/biopharma-from-
| janssen-t...
|
| Moderna's mRNA-4157 is a current example of this:
| https://jakeseliger.com/2024/04/12/moderna-mrna-4157-v90-new...,
| although it may be held up by lack of manufacturing capacity as
| well.
| david_shi wrote:
| 100% agreed. "RCT's are the gold standard" doesn't make them
| gospel.
| Aurornis wrote:
| > 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:
|
| RCTs for mental health conditions are a completely different
| situation. The short-term placebo response rate for cancers is
| not high (obviously) though the influence of unblinded trial
| operators making subjective analyses can be a problem.
|
| Many mental health conditions, on the other hand, have
| unbelievably high placebo response rates over the duration of a
| short trial. The magnitude of the placebo response is almost
| hard to believe in certain studies.
|
| The placebo effect can be a problem for approving new drugs as
| some times the placebo group improved so much that there isn't
| much room left for the active drug to improve beyond that. This
| is a problem of study design and rating systems that is
| difficult to solve.
|
| Unfortunately, some study operators use this fact to their
| advantage by omitting placebo group. Without a placebo group,
| it's not obvious that the drug is actually doing anything
| better than placebo, of course.
| BurningFrog wrote:
| > * Many mental health conditions, on the other hand, have
| unbelievably high placebo response rates over the duration of
| a short trial*
|
| Probably how faith healing works.
| vitiral wrote:
| If someone could explain how "the placebo effect" is not
| just "scientifically proven faith healing" I'd love to hear
| it.
| otherme123 wrote:
| Placebos doesn't heal. They just seem to relief some
| symptoms typically self reported, like pain, but the
| underlying cause is still there.
| Xymist wrote:
| The tricky thing about that (which isn't false, per se)
| in the context of mental health is that "relieve some
| self reported symptoms" can actually be sufficient
| treatment. As with many sorts of pain, if the patient
| feels better, _they are better_ in a meaningful sense.
| Whether it's "real" is sort of beside the point,
| especially if the problem is that they are (for example)
| too miserable to do normal life things that would stop
| them being miserable and the placebo is sufficient for
| them to feel as if perhaps they could.
| lukas099 wrote:
| Also, relief of emotional discomfort can help the patient
| adopt more behaviors that are associated with positive
| changes in mental health, such as exercise and pursuing
| social engagements.
| Uehreka wrote:
| Not necessarily. The placebo effect is the kind of thing
| where you might have trouble at first telling if your
| symptoms are improving or if you're just having a "good
| day" or an "easy week", and that confusion can even last
| a month or two during which you're over-observing your
| internal state and feeling hopeful that "maybe this is
| what getting better feels like". But in the long term you
| often figure it out.
|
| I had a placebo effect recently when switching ADHD
| medication to get around the shortages. For a couple
| months I thought there was a chance my new meds might
| actually be better, they definitely felt different (and
| still do). But six months in it's clear to me that I'm
| struggling with productivity more than I was before I
| switched (though less than when I was off meds).
|
| I'm just one guy, but I'd guess this is why doctors don't
| just prescribe placebos all the time as actual therapies
| (well, that and they'd lose credibility which would then
| destroy any remaining placebo effect).
| QuantumGood wrote:
| Warts are overall very responsive to placebos.
|
| My M.D. father, family practice in the army, later a
| pathologist, would do what he had learned from other
| doctors: Put some dye in toothpaste, put it on the
| wart(s), bandage it, talk about what a miracle cure it
| was etc. He said it worked the few times he tried it.
| Modified3019 wrote:
| FYI, food dyes are not inherently inert, and are capable
| of having antifungal, antiviral, and/or antioxidant
| effects. Quick examples:
|
| https://link.springer.com/article/10.1007/s10068-011-0002
| -0
|
| https://www.purdue.edu/newsroom/releases/2020/Q3/new-
| approac...
|
| The pigments fungi produce are so _essential_ to their
| survival, they can't defend against pathogens when they
| are gene edited to stop producing them.
|
| Toothpaste is also far from an inactive substance, there
| are definitely plausible mechanisms at play with the
| toothpaste and dye mix that could help suppress/resolve a
| wart. It would be worth a study, though I'm not sure what
| one would use to try and achieve a truly inert placebo
| for comparison without first figuring out what doesn't
| work.
| sugarkjube wrote:
| Nothing to do with placebo, it's the covering that did
| the trick, not the talk about miracle cure.
|
| (I discovered this myself when I was a kid, any proper
| airtight cover is likely to get rid of it, YMMV)
| collyw wrote:
| Stress negatively affects the outcome of patients, why
| couldn't the opposite be true?
| TrevorJ wrote:
| Mental health conditions _are_ typically defined by a
| collection of symptoms though, aren 't they? I am not
| suggesting there is no underlying cause, but our ability
| to detect and quantify that cause is lacking, so defining
| disorders based on a collection of symptoms is what we
| are mostly left with in many cases.
| tsimionescu wrote:
| It varies a lot. For many conditions, like cancers, the
| placebo effect is basically random noise (cancers
| sometimes just reduce or go away on their own, regardless
| of treatment or even of the appearance of treatment ; we
| don't know the natural rate of this, because it's
| unethical to not treat people who you know have cancer).
| In addition, in non-blind trials, there is a "placebo
| effect" that amounts to mistakes or lies by those
| involved in the research in favor of a positive outcome.
| This is not a real effect in patients at all, just an
| artifact in the reported data.
|
| Then, for conditions linked to our psyche, including pure
| psychological conditions but also things like pain, blood
| pressure, heart rate, nausea, and some others - the
| placebo effect is more real, but usually temporary. Some
| people who have been living in some amount of despair at
| their condition experience a positive surge of hope once
| treatment starts, and they can ignore the pain, or feel
| some push to get out of their depression, or calm their
| anxiety which was exacerbating, say, the high blood
| pressure etc. This effect almost always tapers off if the
| treatment is not doing anything more fundamental.
|
| Coupled with the fact that we don't understand how
| psychological disorders work at the chemical level at
| all, especially in relation to the conscious mind and
| interventions on that (e.g. therapy, but also various
| religious practices), this means it's very hard to
| account for this without a double-blind RCT.
| vitiral wrote:
| The problem as I see it is that all medicine is
| fundamentally trying to find effective scaffolding on the
| human body, triggering it's own ability to heal. A
| surgeon can't repair a corpse. What causes the body to
| heal itself more effectively? I would think this is
| brutally difficult to study, since it's all subjective.
| Zababa wrote:
| I think part of medicine is that, but part of medicine is
| trying to keep you alive despite your body. Or maybe what
| I'm arguing here is the "body healing itself". But for
| example, if you have autoimmune disease, or allergies,
| you want the body to slow down and take it easy because
| it's harming itself.
| vitiral wrote:
| sure. How effective is faith/placebo at curing those
| conditions I wonder?
| disgruntledphd2 wrote:
| > they can ignore the pain,
|
| Just to note that on pain specifically, belief that one
| has been administered a drug can cause the body to
| synthesise painkillers. This has been most rigorously
| demonstrated by the fact that these painkilling effects
| are suppressed by naloxone (an opioid antagonist).
| burnished wrote:
| Fascinating
| taeric wrote:
| I'm fairly convinced this is not much different than the
| way that your body will prime itself if it knows you have
| an alarm going off at a given time. I don't have the
| paper anymore, but it was shown that your hormone profile
| will change with just the knowledge of an alarm. Similar
| results have been found for other drugs and using cues to
| the body so that it will prime them itself.
|
| I'd love to read more on how this links to the powers of
| ritual and general routines. Specifically, if I'm not
| misremembering, it isn't just "belief that one has been
| administered a drug", but it has to be a drug that you
| have had before. Or that you have seen work on someone
| else. Just taking sugar pills does nothing. Taking sugar
| pills that you thought were the aspirin pills you took
| last time you were sick can cause the body to react.
| dr_dshiv wrote:
| The placebo effect is not a single thing. That is, there
| are ways of amplifying the effect and minimizing the
| effect. For maximum effect, treatments ought to be
| designed to take advantage of the placebo effect to the
| extent possible. That's because placebos have low side
| effects and are often very effective. However, this
| creates some challenges -- how do you test which placebo
| effect works best? What do you use as a placebo? It's not
| that hard, really -- just use a placebo with less of a
| placebo effect.
|
| Niacin was used as the placebo for Timothy Leary's Good
| Friday experiment [1], where he randomly dosed catholic
| monks on psilocybin. Unlike a sugar pill, Niacin creates
| some facial flushing -- so you do feel something. But it
| would be very clear eventually that you didn't get the
| psilocybin. But that doesn't negate the findings of the
| experiment.
|
| [1] https://en.wikipedia.org/wiki/Marsh_Chapel_Experiment
| tsimionescu wrote:
| Sure, for those conditions that have subjective
| components (e.g. pain, mood) or where there is more or
| less direct conscious control of the condition (e.g.
| heart rate, BP), you can vary the strength of such
| effects.
|
| But in many other conditions, you can't, because that
| kind of placebo effect is just noise. For example, you
| can't vary the effectiveness of placebo effects in
| antibiotics studies (though you may be able to reduce
| certain side effects like headache or nausea).
| dr_dshiv wrote:
| Well, you can if there is a mental connection to the
| immune system. E.g. attitudes toward life and toward
| disease seems to affect outcomes in cancer patients. And
| placebos can affect that.
| llamaimperative wrote:
| It is but it's a very finicky treatment.
| ziddoap wrote:
| Faith healing has _heavy_ religious tones. Yet not
| everyone who responds positively to a placebo is
| religious. So, it feels sort of weird to call the placebo
| effect some form of faith healing.
| protonfish wrote:
| I guess it depends on how you define _religion_. I think
| that we can have faith in anything - science, your
| doctor, etc. that could work in a similar fashion to
| religious faith.
| burnished wrote:
| This is specious. Religion is clearly centered around the
| spiritual and physical beliefs about the world and the
| practices of a specific group.
|
| Trusting your doctor is usually more along the lines of
| an educated guess due to the necessity to act without
| perfect information.
| vitiral wrote:
| That was the point of the question. Wouldn't you say
| "placebo" has _heavy_ intellectualizing overtones?
| ziddoap wrote:
| No, I wouldn't.
| vitiral wrote:
| Why not when you feel the opposite about "faith healing"?
| Zababa wrote:
| I think part of it is regression to the mean. Like, your
| body heals itself naturally from many things. Say you get
| a cold. For most people at some point it'll heal. If you
| have a group of people with the cold, and try to
| determine how effective vitamin C or zinc or
| COLDKILLER777 is, you can't just give it to them and say
| "look, they're healed", because they would heal
| naturally. You have to prove that they feel less symptoms
| or heal faster than people in the same circumstances that
| don't receive the same molecule.
|
| I also remember some similar stuff for back pain and
| surgeries. In that context people were seeking treatment
| when their back issues peaked, and the question was, when
| you take the cohort of people that had back surgery and
| the cohort of people that didn't, did the back surgery
| make a difference? Because some people healed naturally.
|
| I don't know if this is true in that specific context,
| but to take a more pedestrian one, I've had lots of small
| cuts, burns and things like that during my life, and they
| all healed.
| somenameforme wrote:
| The placebo effect controls for all of these factors, and
| is entirely real. It's the reason placebo control groups
| exist in the first place. If the placebo effect was just
| statistical noise, then you could _greatly_ simplify
| trials by just taking a random group of people as the
| control, and do away entirely with trying to hide from
| both patient and technician who is taking the drug -
| because it wouldn 't matter at all.
|
| You can see the opposite effect with the less well known
| nocebos [1]. People can experience objectively measurable
| side effects (such as bloating) that are in no way
| associated with a treatment, but that a patient believes
| to be a side effect. It can even be fatal. The article
| references aboriginals who will 'curse' one another
| resulting in the victim rapidly dying, because he
| believes so strongly that he is going to die! A similar
| thing in contemporary medicine has been observed with
| those who receive a fatal prognosis of cancer with them
| ending up dying long before there is any way the cancer
| could have killed them.
|
| [1] - https://en.wikipedia.org/wiki/Nocebo
| djtango wrote:
| Isn't that amazing? That we can help people extraneously
| without having to administer chemicals which have a
| nonlocalised effect on our bodies.
|
| There's still so much to learn I recently heard that new
| fathers see a reduction in testosterone. How does having a
| baby chemically alter a man!? What's the stimulus and
| mechanism for that...
| whythre wrote:
| Pheromones from the pregnant mother seem like a good
| candidate for the reason behind Low T...
| edmundsauto wrote:
| As a recent father: low sleep.
| djtango wrote:
| I can't really refute this but I suspect based on the
| body of research on this study, the drop must be a lot
| more than just sleep deprivation. There are plenty of men
| who work long hours and have poor sleep but I don't
| believe the drop in T is as remarkable as that post
| partum
|
| How about the science behind how a baby's crying
| stimulates milk production.
| llamaimperative wrote:
| Again cognitive.
|
| These are only challenging you because you're assuming
| cognition cannot affect hormones/chemical systems but we
| _know_ otherwise.
| djtango wrote:
| Not really challenging me, I'm more marvelling at the
| fact that as giant bags of proteins, we're able to look
| at our baby and our testicles decide that it's the time
| to stop doing what they do most of the time.
|
| Cognition is such a handwave IMO - what's the
| biochemistry behind that? What's the signalling mechanism
| by which our brain does that? Does that mean with the
| right external brain signals we can turn off T
| production?
|
| The implication of cognition having control over the
| body, which you assert is so well known, is that if we
| can achieve more control over our cognition we can
| achieve biochemical control of our body. So the bene
| gesserit is less fiction than we like to think?
| borski wrote:
| "Mind over matter" is not a colloquialism for no reason.
| It doesn't work all the time, but to say it never does is
| a mistake.
| disgruntledphd2 wrote:
| I think that (as with many of the problems of the modern
| world ;P) it can all be blamed on Descartes.
|
| The notion of dualism is profoundly problematic in a
| bunch of ways, but the biggest problem with it is that it
| created generations of scientists who ended up believing
| that consciousness and body experience are completely
| separate, which is a little ludicrous when you think
| about it.
| nonameiguess wrote:
| This plus added stress, likely poor nutrition, missed
| exercise, a whole lot of things happening to new fathers
| that can lower measured serum testosterone. Whether or
| not it matters is an entirely different matter. Headline
| bloodwork numbers don't mean much out of context, and
| most of the outcomes you'd actually care about (athletic
| performance, muscle retention, general feeling of
| wellbeing and energy level) are all impacted by the same
| things whether or not testosterone is lowered. The one
| thing that might matter separately is sperm production,
| but if you care about being maximally able to get your
| wife pregnant again immediately after she gives birth,
| you can get that tested separately.
| llamaimperative wrote:
| Why couldn't it just be cognitive? Your endocrine system
| is not totally isolated from your cognition.
|
| It's fairly apparent how fathers amped up on testosterone
| could be worse for offspring survival than those who have
| a drop, so the evolutionary pressure is pretty clear,
| then the mechanism is readily explained by "they know
| that they have a child."
|
| How does adrenaline get released when you see a dangerous
| situation with merely your eyeballs?
| BurningFrog wrote:
| This seems very much like a mechanism that would be
| favored by evolution, not an accident of circumstance.
|
| I have no clue _how_ that mechanism migh operate, of
| course. I realize that makes this comment less
| persuasive, but so be it.
| djtango wrote:
| The evolutionary advantage of it is fairly apparent - but
| understanding how we can control our own body chemistry
| without pharmaceutical intervention is of great interest
| to me.
|
| It's a silly example but what if you could combat age
| onset testosterone decline with brain exercises or by
| watching an hour of UFC everyday. I'd take that in a
| heartbeat over hormone therapy if it worked
| collyw wrote:
| The placebo effect is as powerful as many prescription drugs.
| It amazes me that scientists generally dismiss it rather than
| actually study it intensely. It's well known that stress can
| negatively affect your physiology, so I see no reason not to
| think that the opposite could be true.
| darepublic wrote:
| Hence why magical thinking can be useful sometimes (or at
| least that's what I tell myself wishfully)
| bigyikes wrote:
| Can you say more? Does "magical thinking" mean religion,
| or something else? I'm actually curious.
| darepublic wrote:
| Can mean believing things will be OK, or events will
| somehow spare you, whatever the reason. Whether it's
| because of religious conviction, you've grown a lucky
| beard, had a happy dream the night before, etc. Even
| while being somewhat conscious of the irrationality of
| such beliefs they sometimes can be of help I feel. Also
| when music inspires / motivates you I feel like it stirs
| up a similar effects to a strong magical belief.
| burnished wrote:
| 'Everything happens for a reason' is a pretty common
| example of magical thinking that you might be more
| familiar with. Basically when someone favors a magical
| principal over cause and effect when describing the
| world.
|
| I don't think it would make sense to say religion in
| general is magical thinking, a lot of religion can be
| moral or legal precepts or an explanation of the world
| that is rooted largely in cause and effect. There is
| clearly some magical thinking at play when you get into
| specifics but personally I'm not sure where we would say
| it enters play: is the belief in a final tallying magical
| thinking when it is justified by the belief that there
| exists an entity capable and willing? Not sure.
| refurb wrote:
| > One doesn't need elaborate phase 3 RCTs to figure out if
| there's a good shot that a treatment is working....The existing
| system raises costs and causes people to die while waiting a
| decade or more for exciting treatments
|
| The FDA often approves cancer drugs without a phase 3
| randomized trial. In fact, most new cancer drugs are approved
| without a phase 3 trial.
|
| Just taking a random cancer drug from this list:
| https://www.fda.gov/drugs/novel-drug-approvals-fda/novel-dru...
|
| _" The efficacy of IMDELLTRA was evaluated in Study
| DeLLphi-301 [NCT05060016], an open-label, multicenter, multi-
| cohort clinical trial....A total of 99 patients received
| IMDELLTRA..."_
|
| This is a new small cell lung cancer drug approved via a phase
| 2 study that didn't have a control arm and wasn't blinded. This
| is pretty typical.
|
| > one can see it in tumor response and comparison to known
| KMCs.
|
| Anything measured by a human can be biased by knowledge that a
| patient received a treatment, including tumor response (often
| blobs on a screen from a FDG PET/CT scan.)
|
| RCTs are the gold standard. We don't need to start chipping
| away at the rigorous standards we have in place to accurately
| measure the value that a medicine offers.
|
| What we can do - and are doing right now - is do a risk-benefit
| analysis and allow drugs to be approved with a weaker set of
| data so that patients with a life-threatening illness can get
| access earlier.
| tsimionescu wrote:
| One thing that doesn't often get appreciated in such
| discussions is that there are a lot of drugs that seem
| promising at first, but fizzle out in larger trials. If drug
| companies had a known pathway to go from positive initial
| results to very expedited approval, even for limited cases, you
| can be absolutely sure that they would game the hell out of
| this system to sell "miracle drugs" to desperate dying patients
| who will pay anything for a chance.
|
| While it's sad and horrible to know that a cure for your
| condition may already exist and be just out of reach, and I can
| imagine the despair at that, I'm not convinced the alternative
| is all that more appealing.
|
| I would also note that it's certainly not, by any stretch, the
| worse injustice in the medical system. For every one patient
| with a terrible cancer that _might_ have survived if allowed
| access to an experimental treatment, there are millions of
| people dying of easily treatable diseases for which we have had
| a treatment for the last hundred years, but who can 't afford
| it.
|
| The existence of a cure for your condition that you just can't
| access for whatever reason is a reality of our system. Caution
| in introducing new drugs is actually one of the more rational
| reasons, that one needs to try to come to terms with.
| collyw wrote:
| Got to remember that there is a great financial incentive for
| trials to come out positive. Who pays for clinical trials?
| eviks wrote:
| There is way too little obsession with them given how much of
| research isn't using/reusing this method
|
| And specifically regarding cancer we also know a lot of very
| extensive drugs fail at reducing mortality
|
| (specifically, as far as I remember, tumor reduction may have
| no connection to mortality for some cancers, so we don't really
| "know what happens" without factual data)
| omginternets wrote:
| A while back I posted a moderately popular comment, which I think
| is equally relevant here.
|
| https://news.ycombinator.com/item?id=37949336
|
| 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.
| panagathon wrote:
| Your intuitions are on the mark.
|
| https://link.springer.com/article/10.1007/s00213-017-4771-x
|
| This study finds that:
|
| > No patients sought conventional antidepressant treatment
| within 5 weeks of psilocybin. Reductions in depressive symptoms
| at 5 weeks were predicted by the quality of the acute
| psychedelic experience.
|
| I think there's another out there with similar findings, that
| the stronger the mystical-type experience induced, the stronger
| the impact on the pathology. I haven't been able to dig it up
| though.
| silverquiet wrote:
| I've had many treatments for depression throughout my life, to
| include trans cranial magnetic stimulation, which I think is
| considered a rather modern second or third line type
| intervention.
|
| Ultimately none of it has mattered much. I went through the
| "Death of God" thing at about seven years old and also acquired
| a condition that causes me chronic pain to this day around
| then. It seems rather natural that that could cause someone to
| be sad.
|
| I suppose at the end of the day, you can't escape modern life
| and you can't create a god where none exists, so we try drugs
| and other tweaks to the brain because it's what we have.
| dbspin wrote:
| My experience is oddly similar. But I do question whether
| existential anxiety about the existence of a deity at age
| seven, is more of a symptom of trauma than a cause. In my
| case I grew up in a dismally religious family, in an
| alienated place, at a time when the disconnect between my
| families belief and the implicit beliefs of modernity were in
| stark contrast. It was fairly inevitable that the
| contradictions would become absurd. I don't see that
| revellation as responsible for my dark worldview though.
| That's likely more mundane toxic family, learned
| helplessness, chronic health related stuff.
| silverquiet wrote:
| I'd say my religious upbringing was a positive experience
| actually, to the point that today I wish I was able to
| believe in it. My brushes with evangelical Christianity
| however are what initially caused me to question the whole
| thing - it's hard to believe that they believe in what they
| say when their actions are so in contradiction with the
| words in their religious texts. That this was so apparent
| to a seven-year-old me is quite an indictment and I think
| explains a lot of the recent secularization of the US.
|
| I do have a possible surgery that may relieve the pain at
| some point and I think that that hope may be about the
| closest thing I have to religion these days.
| tootie wrote:
| Transcendence is 100% a chemical process. So is all cognition
| and perception.
| monktastic1 wrote:
| Your objection is addressed in the comment. See "If you're a
| materialist, you might object..."
| dbspin wrote:
| That's the wrong level of description. It adds little to the
| argument about whether neurochemistry or perception underly
| the efficacy of psychedelic treatments. As a counterpoint -
| human cognition and perception only exist in contexts beyond
| the brain - a perceived world, brain development through
| perceptual stimulation, language acquisition etc. Brain in a
| vat does nothing.
| omginternets wrote:
| Missing the point completely ...
|
| The issue is that not all chemical processes produce
| transcendence.
| monktastic1 wrote:
| A lovely take. For years now, JHU has been emphasizing that the
| benefits of psilocybin are strongly correlated with whether one
| has a "mystical-type experience." My own explorations (long
| ago) strongly bore this out.
| bitcoin_anon wrote:
| I mildly disagree with this on the basis that I've experienced
| lasting antidepressant effects from psychedelics at sub-
| transcendent doses.
| omginternets wrote:
| Well, sure, but we're trying to account for why psychedelics
| work so much better in some cases.
| kaashmonee wrote:
| 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's used as a psychedelic and it's an
| amphetamine.
| neom wrote:
| LSD acts as a direct agonist at the 5-HT2A receptors,
| effectively pretending to be serotonin, whereas MDMA increases
| the release of serotonin and other neurotransmitters, affecting
| several receptor types, but not primarily acting as a direct
| agonist to 5-HT2A receptors.
|
| https://en.wikipedia.org/wiki/5-HT2A_receptor
| nico wrote:
| 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
|
| 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/sellable)
| chemical? Whose interests is the healthcare industry serving or
| protecting?
| tsimionescu wrote:
| You are conflating two things: medical research and the
| practice of medicine. During the normal practice of medicine,
| most doctors do everything they can to harness the power of the
| placebo effect: they reassure the patient, they speak calmly
| and warmly, they encourage religious people to pray, etc.
| Doctors care about a positive outcome, and will take any help
| they can get to achieve it.
|
| In medical research, we are interested in figuring out if a
| particular drug helps for a particular condition. We already
| know that for some conditions, even giving patients a drink of
| water helps a bit. We need to understand if the drug is better
| than that, or if it only appears to help. The placebo effect is
| a baseline of noise in this case, and we need some way to
| filter it out to understand if there is some signal from the
| drug itself. If not, then you might as well give the patients
| some water rather than waste their money on an expensive hard
| to reproduce potentially poisonous substance.
| eviks wrote:
| There is nothing to harness, it's just noise. But also
| homeopathy exist, so the broader healthcare industry is happy
| to feed anyone gullible enough with sugar pills to harness this
| power
| lukas099 wrote:
| Pretty much every intervention that a doctor prescribes does
| "harness the power of the placebo effect". It just _also_ is
| effective beyond that effect.
| aredox wrote:
| Oh, it's already done, it's called homeopathy. And it's a
| striving business, don't worry, the patients'needs are ignored
| just as much.
| mannyv wrote:
| It's amusing that the placebo effect is so strong that they
| needed to create a standard that eliminated it.
|
| Instead, they should figure out a way to induce it more
| consistently.
| lukas099 wrote:
| When you perform a medical intervention that is effective
| beyond placebo, you are also inducing placebo. Drug research is
| just trying to find the most effective treatments, not trying
| to get rid of the placebo effect. Also, I think most doctors
| are happy to let patients have their placebos of choice
| (crystals or herbs or what have you), as long as it doesn't
| interfere with the rest of their treatment.
| aredox wrote:
| They figured it out, it is called homeopathy and it racks
| millions each year.
| Dylan16807 wrote:
| People do try to figure that out.
|
| But the benefit of removing placebo effect in a study is that
| you find things you can add _on top of_ placebo effect.
| spacetimeuser5 wrote:
| >>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.
|
| 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/brain. And
| context sensitivity of quantum systems is also pretty much
| obvious.
|
| 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.
|
| While these "social scientists" 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.
| nathan_compton wrote:
| I don't really get what you are saying here. RTCs are designed
| precisely to allow one to draw statistical conclusions which
| would be untenable due to confounding effects that would be
| impossible to disentangle otherwise, particularly in regimes
| where effect sizes are small and results are sometimes
| difficult to quantify.
|
| I'm having trouble understanding what you are even getting at
| with comparisons to astronomy, where the absence of controlled
| experiments isn't some grand innovation astronomers cooked up
| but a basic constraint imposed by studying stuff that is light
| years away. Any decent epistemologist would tell you that the
| character of knowledge generated by astronomical observations
| is of a lower quality than that of a RCT. I'm sure some
| astronomers or cosmologists would give their left arm to do a
| randomized controlled trial!
| spacetimeuser5 wrote:
| With astronomy, where the data are mainly derived from
| observations and simulations, no one is spreading alarms that
| it is not science. While with RCTs - and specifically RCTs in
| the filed of human cognitive neuroscience and psychedelics -
| there is all this monkey circus regarding whether placebos or
| psychedelic experiences are real. In human neuroscience ~80%
| of data is derived as well from observations and is
| effectively non-reverse-engineerable, while the hype
| regarding pseudoscience is much higher.
|
| You buy aspirin in a pharmacy and the drug's instruction
| label lists tons of adverse effects - this is obviously a
| seemingly high quality of knowledge resulting from hard work
| in RCTs. Yet, there's absolutely no information predicting
| which exact adverse/beneficial effects will manifest in a
| specific person in a specific state of consciousness - and
| this is the actual empirical level where RCT derived
| information should actually matter and where it is ~50%
| useless (due to lack of context in RCTs themselves).
| nathan_compton wrote:
| I still don't see what you are getting at. It is hard to
| generate good information about the risks and benefits of
| drugs and doing RTCs is very difficult, for the reasons to
| which you refer and others. Are you advocating that we just
| give up on knowing this stuff? That we do large RTCs that
| have the statistical power to characterize more "context"?
| I'm having trouble understanding whether your comment just
| comes down to "getting knowledge is hard and I'm tired of
| people trying to do it."
| chongli wrote:
| _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._
|
| Modern astronomy and astrophysics is just about the most
| rigorous experimental science outside of particle physics.
| Models are developed against simulations and past observations.
| Then new observations are proposed, selected, scheduled, and
| performed. The null hypothesis is almost always based on the
| standard models and can only be overturned by new models using
| new data.
|
| A future observation of some phenomenon "out there" is, in
| principle, no different from a future observation of some
| phenomenon in the lab. We don't call them "experiments" but
| they are every bit as difficult to falsify. Perhaps even
| moreso, since those who collect the data are generally not the
| same people as those who design and test the models. Since data
| is eventually released publicly, anyone is free to re-run the
| simulations and re-test the models against the same data, as
| well as propose future planned observations to test any
| weaknesses in the models.
| CogitoCogito wrote:
| > How do you study mind-altering drugs when every clinical-trial
| participant knows they're tripping?
|
| 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?
|
| Edit:
|
| > 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.
|
| 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's hard to make the participants blind
| in anyway. Still I'm surprised there aren't approaches to deal
| with this. Of course it might mean by definition double-blind
| trials aren't possible, but then again maybe that's not always
| appropriate. I can see the pandora's box being opened by allowing
| drug studies to bypass these restrictions though so I guess I see
| why people don't like it.
|
| Later in the article:
|
| > 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.
| jerf wrote:
| Yes, there are, which honestly makes this entire article
| premise a bit bizarre. Double blind and all that is an ideal,
| not a requirement. It can't be a requirement, because whether
| we can run double-blind or any other kind of study is not
| always a matter of how good we are or how much effort we are
| willing to put in, but a characteristic of the thing we want to
| study, as it is here. It's hardly the only drug where the
| participants can have a pretty good guess whether they're on a
| placebo or not. As just an example off the top of my head, I
| doubt there were a whole lot of chemotherapy testers who
| thought they were vomiting for days and losing their hair due
| to a placebo.
|
| Contrary to frequently-expressed opinion online, we are not in
| fact constrained to running only super-massive-sample-size
| triple-blind preregistered peer-reviewed gold-plated scientific
| studies and only permitted to say we might have an opinion if a
| metanalysis of multiple of those concurs. It's _nice_ when we
| can do that, but the universe is not always so accommodating.
| sigtstp wrote:
| Side-note: I believe in many such cases (cancers and other
| serious diseases), the "placebo" is actually the existing
| standard treatment (not sugar pills), as it would be
| unethical to withhold treatment.
| plasticchris wrote:
| Just find people who have never done any drugs, they will have
| no idea what to expect and the placebo effect will be strong
| enough. I ate a regular brownie once in college (my friend left
| it on my door knob as a nice surprise). I was freaking out for
| a bit, having no idea what a pot brownie was like. Sat down
| next to someone playing wow and asked them to tell me if I
| started acting oddly.
| instagib wrote:
| There has to be some options other than sugar pills for the
| placebo. Niacin that gives a flushing effect. By pill or powder
| for long or short release respectively. Combine that with
| something else or a cocktail literally.
|
| Possibly take another drug that gives you a 'high' at a dose
| which has no effect on the condition under test.
|
| Get enough psychedelic and marijuana users at a focus group for
| a long list of possibly coherent ideas.
|
| I read that they have no way of double blind testing cupping
| because it is painful and visibly leaves marks on your body.
|
| I would put numbing cream on each participant's back, put
| isolation headphones on them, put some pressure on the persons
| back, and then apply a temporary tattoo with an electronic
| bandaid that detects if a person removes the bandaid covering
| the cupping/fake marks.
| hereme888 wrote:
| The title itself is hilarious if you think about it.
|
| But in an important note, I don't like that I never read of the
| warnings for psychedelics, like triggering schizophrenia.
| freeqaz wrote:
| I actually spoke to a doctor about this once during a psych
| eval. You can get screened if you're worried about
| schizophrenia and there are strong indicators that you're
| likely to develop it. (Which would mean to probably avoid
| psychedelics)
|
| In general though it doesn't seem like they will _cause_ it.
| Just accelerate the onset.
| observationist wrote:
| Numerous studies have shown that the overall rate of occurrence
| in drug users is the same as the rate of occurrence in non drug
| users. Drug use causes schizophrenic breaks to happen earlier
| in susceptible individuals. The nature of schizophrenia makes
| the situation a "when" and not "if" question; around 1% of the
| population will have a schizophrenic episode and break from
| reality, regardless of whether they abstain from drugs or not.
| Almost any psychoactive drug can trigger early schizophrenic
| breaks; even caffeine or extreme stress and social trauma can
| be the trigger.
|
| Drug use can result in other forms of psychosis. Psychedelics
| can result in pathological derealization, when the individual
| begins to question everything about their life up to that
| point, becoming vulnerable to any potential model of the world
| that offers plausible answers. Persistent use can detach
| someone from reality, making it hard for them to integrate with
| normal society and maintain a normal, responsible life.
|
| Any drug use should be done responsibly. Harm reduction sites
| and drug safety activists and influencers have provided a huge
| wealth of information. Things that should be taught in school
| can nonetheless be found online, giving you the necessary
| health, use, preparation, and other harm reduction information
| necessary to be a responsible user.
|
| It's awesome that mainstream academia and the medical
| establishment are allowing this research. A better informed
| society will be a safer, healthier society, without the
| misinformation and stigmatized gossip that passed for "drug
| safety" in recent history.
| taeric wrote:
| This is the second narrative I've seen recently where folks seem
| to think they have a strong argument against RTCs. Just, what?
|
| 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...
|
| But, to think that you have found some magic bullet against RTCs
| shows you don'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.
| sowut wrote:
| when i was 17 i found out about mushrooms and would take 1/8th
| ounce once a month for about 6 months which culminated in me
| absolutely convinced i was jesus for about 6 years. good stuff
| mythrwy wrote:
| If you are Jesus, maybe skip the crucifixion part this time?
| sowut wrote:
| turns out everyone is their own personal jesus
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