> 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.
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.
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.
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.
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.
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...
> 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.
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...
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?
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.
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.
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?
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.
Is it really much different to, say, looking at food and getting hungry, or looking at someone naked and getting aroused? While these are more immediate and conscious experiences, its clear that something as simple as looking at things can affect our biochemistry.
I take your point - you're right maybe there isn't anything that much more different.
But it feels a lot more different because the two examples you used are very clear and direct stimulus-response pairings. See food, get hungry (and get ready to digest)
See mate, get aroused, genitals get ready.
But a hormonal response is weird because:
- you see a baby then your body makes you more nurturing
- testosterone has all kinds of health implications on a longer time frame, it affects decision making, strength, muscle growth etc etc
So the fact that the body has been preprogrammed to alter our mind when we see (our?) baby is kind of impressive. Would be interesting to know if it's all babies or just our own. Do male midwives or fathers of adopted children see the same T drop.
Not to mention that T is also such a sought after hormone that understanding (and controlling) this response could be quite helpful
> Cognition is such a handwave IMO - what's the biochemistry behind that?
Hormones are chemical messengers. They exist to relay messages between different organs and tissues. An organism is constantly sampling its environment and adjusting its internal state to optimize survival and reproduction. Within this framework, it is not at all surprising that cognition interacts with hormones; in fact, it would be kind of surprising to find a biochemical pathway that is entirely independent of cognition.
A good example is stress. For those of us in the first world, stress begins as something cognitive, but it is expressed hormonally as increased serum cortisol. All you have to do to change your hormone balance is start ruminating!
Another example is oxytocin. If another human touches you affectionately, you'll see a bump in serum oxytocin. But it depends on your judgment of how affectionate the contact is, which is cognitive.
I appreciate your response here but it's still pretty handwavy.
Ultimately it's pretty easy to sit back and say - well it's just so. Sure we have a flight or fight and pathways towards adrenaline and cortisol. We also have pathways for oxytocin so we like to find a friend/mate. So obviously we'd also have pathways towards wanting to nurture our kids. That's evolution bro - I guess nature and science are pretty obvious and boring after all /s
The response to children is impressive to me because it appears to be highly specific in its stimulus and the ramifications are pretty large.
Our cortisol and adrenaline response is very generic. All kinds of things can trigger it. You can experience adrenaline by jumping out of a plane or gambling at a roulette table. Even in a showdown in poker or playing video games. So the same response has been conditioned towards all kinds of situations when originally it might have been predominantly towards enemies/predators
Likewise for oxytocin we can probably produce oxytocin from cuddling a pet so it's kind of generic in stimulus.
Meanwhile there's a whole slew of specific responses that men and women have towards babies that I personally find fascinating in their specificity. Maybe because I'm just ignorant but I'm excited for the future when we may be able to understand how a bunch of senses (visual, aural, olfactory) convert into specific neural signals which the body is preprogrammed (how?) to then produce a specific response (via what biochemical pathways) to induce a hormonal response. Which incidentally have pretty wide ranging physiological consequences in the case of testosterone.
I’m unsure why the downvotes, but it would be an interesting study whether there is an adaptation for lower testosterone to encourage fathers to be more nurturing and less aggressive to their offspring. Ie, is there a plausible and measurable explanation for why the t-drop is evolutionarily advantageous.
Who knows. I did a postgrad in medicinal chemistry and I was always amazed at how we scaled up from tiny molecules/proteins into this crazy emergent system. Yet at the individual molecule level there was still so much we couldn't understand from a holistic first principles point of view.
At the time IIRC computer simulations would struggle to model like more 12 water molecules solvating something accurately.
So building up from that atomic level up to proteins into a full physiological system always seemed like magic to me and it's always felt like we didn't really know anything.
Coming back to the t response it would be interesting to know if anything else accidentally triggers it. Eg is it just babies that triggers the response? Only our baby? What about adopted babies or babies of family members? Can other cute things trigger it?
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
My vote as well. Proximity and "stickiness" to the mother. Likely not a thing if the father moves on to the next region/town after sireing a child. I think back to the isolated humans encountered by the British when working on their rocket programs. Basically groups of women that men moved between, impregnating. Move into a group, kill a child or two and/or fight other males, impregnate someone and move on. I overlay this behavior whenever I try to figure people out.
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.
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).
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.
> 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.
Not always, you can see effects from open placebos, where you tell the participant that they're getting a placebo but placebos have been clinically proven to reduce pain.
It even seems to work when you warn participants in the consent docs that you may lie to them (authorised deception).
I agree that it's probably a broader effect than just sugar pills, it should probably be called expectancy effects.
Benedetti et al have done a load of work on recovering surgical patients that suggest that many, many drugs (including valium) mostly work based on these kinds of effects. Its a fascinating field (and what I did my PhD on).
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.
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).
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.
That's true, but I'm not sure such a link has ever been established. Is there any study that has found measurable variance in cancer or infection outcomes based on differences in mental outlook?
In short, yes! Mental outlook has a big effect on outcomes. It won’t cure you, but it will improve your physical outcomes.
This is the meta analysis they refer to:
Rozanski A, Bavishi C, Kubzansky LD, Cohen R. Association of optimism with cardiovascular events and all-cause mortality: a systematic review and meta-analysis. JAMA Netw Open. 2019;2(9):e1912200. doi:10.1001/jamanetworkopen.2019.12200
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.
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.
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.
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.
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.
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.
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.
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).
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.
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.
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.
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.
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.
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.
'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.
Hilariously, this works even if the patient is aware of the placebo effect. I'm on antidepressants (first time in my life) since two weeks ago. I feel MUCH better already. But the drug I'm taking starts working at least 4 weeks after therapy starts. There was not a single trial where it performed better than placebo during a shorter timeframe.
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.
> 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.
"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.
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)
Furthermore, RCTs just identify the substances that have positive effect on the largest subgroup of the studied group (which 'coincidently' is what the Pharma Mafia is most interested in). But we are all individuals, differing in genetic, epigenetic, foreign organisms, metabolism. The near only value the RCTs have to an individuum is to determine the substance(s) which most probably have an effect.
Memorably, someone in the UK recently dismissed over 100 studies because they didn’t perform double blind RCT. Which is hilarious when you consider the studies were about gender affirming/reassigning treatments.
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.
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.
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.
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.
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.
> 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]
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.
Totally unrelated is relative (ha ha). We are all the same species after all. Why wouldn't we respond similarly to similar inputs? Especally with something very different to our everyday experiences.
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?
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.
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.
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.
> 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.
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
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.)
>>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.
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
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.
People don't see self-replicating machine elves if they have no idea who Terence McKenna is.
Ultimately, these are easily programmed experiences by people good at creating mythology. The more pseudoscientific one makes the mythology the better too of course or at least some loose connection to pseudoscience.
If we just say elves then it is obviously ridiculous. Self-replicating machines sounds STEM enough.
That was McKenna's brilliant con-artistry. Painting a STEM varnish on centuries old bullshit that no one would have bothered reading about otherwise.
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.
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.
And what evidence do you actually have for your position? Your position is tailored to make subjects better taxpayers, rather than understanding how the brain/mind actually works. That's ok, than just assert this, that it is just a position amongst an infinity of other positions, rather than claiming that your position is the ultimate truth.
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.
>>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.
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.
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.
The claim was that some external entity was communicating with the people taking DMT. However, others in the room did not detect that entity, so it can't be made up of normal matter, or at least not at normal sizes. It is possible that the entity detected the person taking DMT somehow and started contacting them from far away, but then an instrument could detect the change after the DMT is consumed.
The alternative is that the entity is communicating in some way that is neither electromagnetic nor gravitational nor the weak or strong interactions, which would require new physics, and it would also require some explanation of why our brains would have evolved to capture this fifth force of nature that somehow doesn't have any measurable effects outside of DMT.
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?
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.
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.
This is called Bayesian reasoning, BTW, and you subconsciously do it all the time. Your entire life would be almost completely incomprehensible otherwise.
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.
> ... 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?
Proof and strong evidence are the same thing in my view of the world, for everything outside of pure mathematics. Of course, this means that even a previously "proven" fact can turn out to be wrong later on. But the alternative is that "proof" simply doesn't exist, as nothing about the physical world can be "proven" to the extent that 2+2=4 can be.
And yes, atoms have of course always existed. As the other poster points out, even before we could even understand the concept, we could detect them. Cats can detect them.
The thing about this posited entity that makes me so certain it is not an external phenomenon (or, if you prefer being mathematically pedantic, that gives me such a high degree of confidence that the probability of that is very very low) is that it is not detectable at all in many other experiments you can run. None of our finest instruments would pick up any increase or decrease in the physical quantities they can measure in the room with the person on psychedelics, if we were to waste money looking for this signal. And then, if they don't, then how could the brain of this person pick up such a weak signal? Why would it even have evolved to be able to detect this fifth fundamental force if it's so weak it can't even be detected by devices that are affected by a single atom passing them by?
"The" alternative is an interesting way to "think".
Psychedelics are a hell of a drug. So too is culture, and the conditioning of consciousness that comes with it. It starts the day you were born, and it never stops. This indoctrination is like the background noise of a city....you've never experienced it not being there, so you don't even notice it.
Many here seem to disagree with you, at least if one interprets their words literally. It's hard to know what they mean they since getting anyone to answer a question directly is typically not possible.
> ...so go away if that's the only standard you will allow discussion of.
What does "if that's the only standard you will allow discussion of" refer to?
>> Did atoms exist before they were discovered to exist?
> We were certainly able to detect atoms before we figured out the exact details.
Did atoms exist before they were discovered to exist?
No obligation to answer the question that is asked, just thought it would be fun to see if you have the ability.
> What does "if that's the only standard you will allow discussion of" refer to?
The way you blocked out everything else in the post to reiterate your question, which they had already answered fine unless you are doing the thing I accused you of, in which case I reiterate: go away
> Did atoms exist before they were discovered to exist?
Hmm, I think you misunderstood my previous answer. I'll try again.
We knew about the existence of atomic matter since humans have been a species, with overwhelming amounts of evidence. There is no "before" in that sense.
(If you mean "before humans and the concept of science existed" then the answer is yes but it has no relevance to a question of whether science is missing anything.)
> The way you blocked out everything else in the post to reiterate your question...
"Blocked out"? I didn't block out anything, I quoted specific text. Quoting specific text in no way disallows discussion of other things, which is what you accused me of.
> ...which they had already answered fine...
No, they answered a question more to their liking - they didn't answer mine at all. They, like many others, seem to have an aversion to discussing certain aspects of reality, so they chose to opt out of the conversation, a right which you too have.
> in which case I reiterate: go away
Why? Are there certain aspects of reality that you have an aversion to being pointed out? Well, simply click the X in your browser window and all this harshness can disappear.
> Hmm, I think you misunderstood my previous answer.
I understood it perfectly well, it is a highly predictable response to that class of prompt, one of three or so responses.
> We knew about the existence of atomic matter since humans have been a species, with overwhelming amounts of evidence. There is no "before" in that sense.
Humans knew about the existence of atomic matter since they've been a species?
>>> The concept of the atom that Western scientists accepted in broad outline from the 1600s until about 1900 originated with Greek philosophers in the 5th century BCE. Their speculation [1] about a hard, indivisible fundamental particle of nature was replaced slowly by a scientific theory supported by experiment and mathematical deduction.
Could you possibly share even one piece of evidence of this (you don't even need to link to it, quoting it from memory is fine, provided you include some detail)?
It sounds like I broke your prediction if you're this confused.
Atomic matter is right there and everywhere. We didn't know about the structural details of atoms, but we knew about the bulk effects.
When the topic of discussion is signals that no current equipment can measure, there are some pretty direct analogues that might be convincing in some ways, but when it comes to something as fundamental as atoms, we were only ever lacking nuance in our knowledge. Signals like that would be a lot bigger than nuance, and our physics experiments leave a lot less room for it.
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.
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.
>>And in the case of the self-transforming machine elves we very clearly have a compatible alternate hypothesis: they are generated by the brain
And what is the actual evidence for this alternate hypothesis? 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.
You don't need a perfect account to have a reasonable account. You've set up an absurd standard which essentially no knowledge could reasonably meet. I'm not a distinguished neuroscientist, but I've published papers in neuroscience and while we certainly can't provide a full account of the precise details of these brain states, the balance of the physical sciences, including neuroscience, leads me to strongly favor the "machine elves aren't real" hypothesis.
Sorry, dude, but your behavior can be formally comparable to a grandma's at a bazaar selling potatoes rather than someone with a slight quest for fundamental science. Obviously her potatoes are the best, *just because* they're reasonably the best and reasonable resources have been invested in them, and all other potatoes are absurd.
Here're the schematics of some modern computer electronics [1], [2]. Every element, every connection is described in detail and in place. Is this absurd?
Under the hood you consider the brain a similar type of computing machine, a bit more complicated, but fundamentally it should be the same. So the relevant schematics should be available.
Yet, instead of acknowledging that in order to obtain 90% of information I requested with modern neuroscience methods a person should be effectively dead or brain damaged, you just call it absurd. So have a reasonable way to the bazaar.
Recent advances in physical science [3],[4] have effectively shown that local realism is false. And there is a corpus of research in neuroscience, which I won't discuss here, as well as developed instrumentation and theory in physics (like field theory) which can allow to test these alternative hypotheses, rather than just bluntly stick to one's important subjectively reasonable opinion.
If you are an expert on how the brain generates what's reasonable and unreasonble, do you have queues of developers, chemists, mathematicians, any other types of technologists, who are developing technologies which actually contribute to human civilization, obviously using their brains for this and asking your recommendations on how to tune their technology generation engine(=brain) to generate more and faster? I doubt that even Huberman has any.
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.
There is a huge difference between believing "perception is possession of objective fact" and "its mental abstractions all the way down," but I think a reasonable appraisal of the world makes both almost certainly equally wrong. My assertion that the machine elves are mental phenomena should not be taken to mean that I think everything is, which I think is a pretty silly idea.
When we perceive something, anything, it comes to us strictly as a mental (or emotional or sensational if you like) projection.
In other words, our perception is inevitably subjective and personalized.
Now most of us can agree on many things, but this is because we have the same frames of reference (as modern humans etc). Under normal circumstances we have similar mental models and similar perceptive facilities which given similar phenomena produce agreement.
But this agreement doesn't doesn't necessarily tell us what a phenomena actually "is" in objective fact, nor give us all available information about the phenomena. It only means we agree on a picture of objective reality (which is important for our species) and that our mental models more or less work to guide us around. But that in no way implies we are, nor are necessarily capable of being, in full possession of actual objective reality.
If we were an gnat 1/2 mm in length with a 3 day lifespan and many less neurons we would probably perceive things very differently. Or (as a thought experiment) if we were Lord God of the universe, immortal creator of time and space.
Point being, all reality we experience goes through our minds, our experiences, our filters and the picture at the end corresponds roughly with something we call "objective reality".
This isn't to bash on objective science nor promote superstition or argue for the objective physical existence of machine elves either. Some models and perceptional frameworks work better then others when you are trying to survive as a species and rational measurable science is pretty powerful tool. But sometimes, maybe especially with therapy issues it could be useful to back up and remember we have a frame of reference. It can be changed to some extent.
When someone sees a "machine elf" yes they are hallucinating, we can agree on that and we sober people don't see the elf nor can we measure it with instruments so it's reasonable to say it's simply a mirage or a mental trick.
But is there perhaps some underlying "reality" to machine elves that is translated as a "machine elf" because what the hell else could you call it? Maybe not an external sentient being, but part of a collective unconscious we share as humans? Or maybe (less probably imo) there is more sentience in the universe then we currently understand? I don't really know, but that so many people have similar experiences is interesting and perhaps worth exploring to better understand what we as humans are underneath this superficial top floor of consciousness.
I'm not saying that machine elves definitely don't exist and I'm certainly not saying that my collection of things I think are true are objectively true. I'm simply saying that from my point of view its very unlikely that machine elves being real is the explanation for people reporting interactions with machine elves.
I believe its important to explore these experiences and I think people should do so, both under the aegis of science and less formal self exploration. But in the end we cannot just accept mere perception as naively correlated with reality. The process of connecting perception to reality is one of the great works of human beings and, from where I am sitting, that great work seems pretty definitively negative on machine elves.
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.
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
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.
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.
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.
Was the song actually that good, or did your brain simply tickle the 'appreciation for incredible beauty' neurons while playing back some Nickelback memories?
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.
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.
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.
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.
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.
Mathematical facts could be said to be different, though I think they are still compatible with my definition, so they could be considered a subset. So no, I don't believe there are other kinds of facts that don't match the criteria, though of course you can subdivide the ones that do into all sorts of categories.
And while any positive statement is either a fact or a "non fact", there are plenty of things we don't know the truth of (P=NP? Gravity is quantum?), and something that today seems a fact can be a non-fact tomorrow, though this rarely happens in physics (often, some preconditions just need to be added to make the older "fact" still correct).
I'm not sure what you want me to cite. Why I believe in this definition of "fact"?
Actually, it turns out It's been me who's been wrong this whole time....I googled "fact" and came up with:
------------
fact
/fak(t)/
noun
1. a thing that is known or proved to be true.
2. information used as evidence or as part of a report or news article
------------
I was under the impression that a distinguishing factor of "fact" was Truth, now that I know that mere information is a fact, it explains a whole bunch of what confused me about this world.
-
Even more interesting:
------------
truth
/tro͞oTH/
noun
1. the quality or state of being true.
2. that which is true or(!) in accordance with fact (see above) or reality
> 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.
>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:
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.
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.
Society has already been overthrown with a quasi-religion based on drugs. They're trying to make experimental gene therapy MANDATORY right now. Even though 3 million people mysteriously died after receiving the previous "vaccine".
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.
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.
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.
> 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.)
"Debug mode" is also my favorite way of putting it, and yes it does seem to give me greater access to retrieve memories and discover, re-evaluate, and re-program heuristics I thought were just background constants.
I've also read that some who are quite experienced in lucid dreaming can have conversations with their subconscious by embodiment into a character in their dream. I bet there is a lot of potential utility to be discovered there.
As someone who did a far amount of psychedelics decades ago I can state for certain that not all "tripping" is the same, depending on a variety of factors. LSD is completely different than psilocybin which is completely different than peyote. All of these trips are completely different based on your mental state, your surroundings and the size of your dose (among other things). Given the wide array of mental health problems people suffer, I find it absurd to assert that there it is impossible that psychedelics offer no potential treatment for some of these problems. That isn't to say they are a cure-all, are suitable for treating all patients, or all conditions, but it is to say that there has been very promising research done to suggest that some psychedelics do improve some mental health problems. There has been convincing research done on the treatment of PTSD and alcoholism, and research in this field has really only begun to get off the ground.
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
> One of Strassmans patients years ago said on DMT that these entities could share more with us if we learn to make extended contact.
If you want to hear some really wild stories read Ayahuasca In My Blood: 25 Years of Medicine Dreaming. Such as ayahuasca curing a man who received a bushmaster bite or entities revealing an herbal cure for a woman's liver failure.
> 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."
The study has... let's just say "other methodological problems". But they did do an RCT of parachute use! (The open peer review correspondence is quite fun, too).
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.
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.
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.
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?
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.
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
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.
> 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.
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.
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.
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.
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.
Alan Watts reopened my interest in the metaphysical while deconstructing western mythology. Check out some of his lectures if you're interested in exploring the potential for reviving some of those positive experiences.
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.
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.
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.
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
>>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.
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!
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).
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."
I am not advocating for anything, just exercising my English and typing skills. But you can try measuring more parameters in every person, integrate various findings from science and plan experiment design more carefully.
I have heard about only one startup using AI to facilitate RCTs.
A more optimal option is of course suicide, as the more of these RCT researchers will be out of the game, the more newer and more flexible brains will come in.
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.
This may be a peak HN comment. Calling researchers who are experts in their fields and have dedicated a lifetime towards gaining knowledge and experience in the field are described as "monkey types".
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.
