> 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.
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.
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]
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 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
> 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.)
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.
Readit News
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.
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.
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.
Moderna's mRNA-4157 is a current example of this: https://jakeseliger.com/2024/04/12/moderna-mrna-4157-v90-new..., although it may be held up by lack of manufacturing capacity as well.
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.
Probably how faith healing works.
And yet I feel better.
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.
The FDA often approves cancer drugs without a phase 3 randomized trial. In fact, most new cancer drugs are approved without a phase 3 trial.
Just taking a random cancer drug from this list: https://www.fda.gov/drugs/novel-drug-approvals-fda/novel-dru...
"The efficacy of IMDELLTRA was evaluated in Study DeLLphi-301 [NCT05060016], an open-label, multicenter, multi-cohort clinical trial....A total of 99 patients received IMDELLTRA..."
This is a new small cell lung cancer drug approved via a phase 2 study that didn't have a control arm and wasn't blinded. This is pretty typical.
> one can see it in tumor response and comparison to known KMCs.
Anything measured by a human can be biased by knowledge that a patient received a treatment, including tumor response (often blobs on a screen from a FDG PET/CT scan.)
RCTs are the gold standard. We don't need to start chipping away at the rigorous standards we have in place to accurately measure the value that a medicine offers.
What we can do - and are doing right now - is do a risk-benefit analysis and allow drugs to be approved with a weaker set of data so that patients with a life-threatening illness can get access earlier.
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)
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.
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.
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.
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.
While my scientific mind wants to agree with you, that same scientific mind can't help but wonder...why similar experiences are being triggered on totally unrelated people.[0]
[0]- https://health.howstuffworks.com/wellness/drugs-alcohol/dmt-...
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.
"Jaynes asserts that consciousness did not arise far back in human evolution but is a learned process based on metaphorical language. Prior to the development of consciousness, Jaynes argues humans operated under a previous mentality he called the bicameral (‘two-chambered’) mind. In the place of an internal dialogue, bicameral people experienced auditory hallucinations directing their actions, similar to the command hallucinations experienced by many people who hear voices today. These hallucinations were interpreted as the voices of chiefs, rulers, or the gods" [1].
Basically, the hypothesis that humans as late as the ancient Greeks were sort of schizophrenic [2]. (To be clear, it's a hypothesis, not science.) But it's neat to think of drugs like DMT reverting (converting?) us to that bicameral state.
[1] https://www.julianjaynes.org/about/about-jaynes-theory/overv...
[2] https://en.wikipedia.org/wiki/Bicameral_mentality
When will these entities share something truly useful, like the design for a working cold fusion reactor, or a cure for Alzheimer's?
Also, people really need to know that while a psychadelic trip can be healing and mystical, it can also go like this:
https://www.reddit.com/r/DMT/comments/gb9ar0/dark_dmt_trip_r...
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.
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.
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.
I read some of the guy's book. It's a trip.
If those external entities were real, we wouldn't need to wait for science, some shaman would just go to the spirit realm and get told about bacteria.
A great point.
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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.
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.
"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.)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9577917/
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9710723/
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
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.
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."
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There have been no RCTs on parachutes or bulletproof vests. Volunteers welcome.
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).
Instead, they should figure out a way to induce it more consistently.
But the benefit of removing placebo effect in a study is that you find things you can add on top of placebo effect.
Dead Comment
https://en.wikipedia.org/wiki/5-HT2A_receptor