MDMA-assisted therapy for PTSD: A randomized, placebo-controlled phase 3 trial(nature.com)
nature.com
MDMA-assisted therapy for PTSD: A randomized, placebo-controlled phase 3 trial
https://www.nature.com/articles/s41591-023-02565-4
109 コメント
I’m skeptical that a placebo control for MDMA can be valid. The effects of MDMA are pretty noticeable. The study actually asked participants if they thought they were on MDMA, and most answered correctly.
If the participants can tell, it somewhat defeats the purpose of having a placebo control group.
If the participants can tell, it somewhat defeats the purpose of having a placebo control group.
If you start with people who know what MDMA feels like, I suspect you're sunk for the reasons you state.
But if for instance the placebo were niacin... niacin makes most people feel funny. If you don't know what MDMA or a niacin flush feels like, you might just know something is happening but not what.
And then you test people who don't experience niacin flush with or without a placebo to make sure that niacin isn't a therapeutic chemical.
But if for instance the placebo were niacin... niacin makes most people feel funny. If you don't know what MDMA or a niacin flush feels like, you might just know something is happening but not what.
And then you test people who don't experience niacin flush with or without a placebo to make sure that niacin isn't a therapeutic chemical.
Blinding isn’t just about the patients - It’s about the therapy providers as well. We would like to think they’d provide the same treatment regardless of what the patient received but over-eager researchers tend to get more excited about the active group and provide them more attention and enthusiasm.
Niacin isn’t a great placebo these days because it’s not the 70s any more and people going into these studies will probably Google what to expect from the drug. Also Niacin is short acting and makes people itchy and uncomfortable, so it’s not really compatible with therapy.
Niacin isn’t a great placebo these days because it’s not the 70s any more and people going into these studies will probably Google what to expect from the drug. Also Niacin is short acting and makes people itchy and uncomfortable, so it’s not really compatible with therapy.
Isn’t that why many psychiatric experiments engage in some misdirection?
Talked to a therapist at the MAPS conference who said that the way you know a patient is in the trial is about halfway through their therapy session, they inevitably say, "But enough about me, how are YOU doing??"
That is the most MDMA thing ever.
My understanding is that in trials like this they’ll usually use a benzodiazepine as the control. Not psychedelic, but psychoactive enough that a drug-naive person wouldn’t know for sure what they were on.
This was not an active placebo study. The placebo group did not receive any medication.
Benzodiazepines would not be an appropriate active placebo anyway as they are a sedative, not a stimulant. They would also be expected to interfere with the therapy because they impair memory and alertness, so that’s a no-go.
Benzodiazepines would not be an appropriate active placebo anyway as they are a sedative, not a stimulant. They would also be expected to interfere with the therapy because they impair memory and alertness, so that’s a no-go.
It's a control. A baseline. That's the whole point. And especially with the therapy trials they're running, its not like it'll hurt people to have been given a placebo (unlike if you were to say, trial an HIV antiviral with a placebo)
Yeah this is going to be hard with all the psychoactive substances, but really we shouldn't discard placebo effect as "not real," especially for disorders that we already know are highly mediated by beliefs (about the self or the world). Reliably and persistently mutating those beliefs toward an actually improved life seems perfectly fine to me.
Right, but if you observe a high enough effect size, it’s in some sense irrelevant whether there was a placebo arm. If somehow there is a reliable d=0.4 placebo effect, then that is just as good as if the drug “really works”. To be clear on magnitudes, there was a something like 70% increase in the treatment effect vs. therapy+placebo.
Indeed what does it even mean for the cure to be “just in your head” or “a placebo” if condition is purely psychological, the trauma is resolved, and there is no remission? It’s a very different game vs. a mechanistic acting drug which either does or does not reduce cholesterol or whatever.
Indeed what does it even mean for the cure to be “just in your head” or “a placebo” if condition is purely psychological, the trauma is resolved, and there is no remission? It’s a very different game vs. a mechanistic acting drug which either does or does not reduce cholesterol or whatever.
I would be surprised if that wasn't a glaring point for them, but you do control as best as you are able to.
This should be the second of two Phase III studies, which are pretty rigorous. Some drugs are just very hard to make a valid control for.
Some studies also use a drug placebo and a control group with a combination of interventions, or little to none at all, as best as I understand.
One can use statistics afterwards to help bolster claims of efficacy if a sham/placebo group is difficult to source.
This is my best understanding of the matter.
This should be the second of two Phase III studies, which are pretty rigorous. Some drugs are just very hard to make a valid control for.
Some studies also use a drug placebo and a control group with a combination of interventions, or little to none at all, as best as I understand.
One can use statistics afterwards to help bolster claims of efficacy if a sham/placebo group is difficult to source.
This is my best understanding of the matter.
Rick Doblin has some talking points on this that I found fairly compelling... but now I can't find them. Basically that their trial is as good as you can do given that.
Why not use another group taking an amphetamine in addition to one taking an inert placebo?
As effective as that might be in terms of a proper active control group, it does not seem terribly ethical to give amphetamines to patients with PTSD without any medically sound reason to do so.
That and you’d have to correct for undiagnosed ADHD which suddenly improved with a course of amphetamines.
> There were no deaths or serious TEAEs [treatment emergent adverse event]. These data suggest that MDMA-AT reduced PTSD symptoms and functional impairment in a diverse population with moderate to severe PTSD and was generally well tolerated.
But also
> Seven participants had a severe treatment emergent adverse event (TEAE) (MDMA-AT, n = 5 (9.4%); placebo with therapy, n = 2 (3.9%)).
> Seven participants had a severe treatment emergent adverse event (TEAE) (MDMA-AT, n = 5 (9.4%); placebo with therapy, n = 2 (3.9%)).
Yep! I do wish they clarified what exactly that means; perhaps I just missed it in my quick read.
They detail this in the supplementary materials: https://static-content.springer.com/esm/art%3A10.1038%2Fs415...
Sounds like what the common raver would qualify as a "bad trip".
I don't think MDMA is really in the business of bad trips.
You can definitely have a bad time on it that's akin to a bad trip, especially if you're hashing out trauma with a therapist while on it.
Many people have had bad trips on MDMA. I don't know where this reputation comes from, but it's common to have extremely intense and unpleasant emotions, sensations, or thoughts. Anxiety, agitation, muscle tension, sweating, and/or chills are all documented effects of the drug.
For a dozens of anecdotes, just search "MDMA bad trip".
For a dozens of anecdotes, just search "MDMA bad trip".
Meh.
What's your source?
Yes, those things can of course happen, but they're very rare and in the minority.
It is absolutely NOT common to have a "bad" experience with a drug that is chemically designed to make you feel incredible via serotonin depletion.
What's your source?
Yes, those things can of course happen, but they're very rare and in the minority.
It is absolutely NOT common to have a "bad" experience with a drug that is chemically designed to make you feel incredible via serotonin depletion.
OK. Firstly, people in academia don’t even talk like this (“what’s your source!”). Secondly, you’re fighting anecdotes with anecdotes, which is fine, except you’re trying to pull the ladder up after you.
You’re coming across as an MDMA fanboy and the way that you’re approaching the conversation will have if anything a negative impact on “the cause”.
MDMA wasn’t ‘designed’ to do anything. It happens to do something. I’m surprised that you’re even phrasing it this way because MDMA fanboys tend to obsess over the lore of its discovery.
I have been present for bad MDMA trips. One of these people has C-PTSD (putting aside the controversy about its existence), and had a C-PTSD-related bad trip, which seems highly highly relevant to this topic.
I’ve done a bunch of MDMA. I’m certainly going to do a bunch more throughout the rest of my life. I’m not going to kid myself about it being perfect. I’m not going to kid myself about the fact that over a large enough population even “improbable” adverse reactions are meaningful. Nerds that do drugs are so often insufferable because they’ll try to intellectualise what’s essentially “God I love drugs and they’re great!”
You’re coming across as an MDMA fanboy and the way that you’re approaching the conversation will have if anything a negative impact on “the cause”.
MDMA wasn’t ‘designed’ to do anything. It happens to do something. I’m surprised that you’re even phrasing it this way because MDMA fanboys tend to obsess over the lore of its discovery.
I have been present for bad MDMA trips. One of these people has C-PTSD (putting aside the controversy about its existence), and had a C-PTSD-related bad trip, which seems highly highly relevant to this topic.
I’ve done a bunch of MDMA. I’m certainly going to do a bunch more throughout the rest of my life. I’m not going to kid myself about it being perfect. I’m not going to kid myself about the fact that over a large enough population even “improbable” adverse reactions are meaningful. Nerds that do drugs are so often insufferable because they’ll try to intellectualise what’s essentially “God I love drugs and they’re great!”
MDMA was discovered as an intermediate in the synthesis of a completely unrelated substance. No one designed it.
MDA is a naturally occurring precursor to MDMA and was traditionally used in Root Beer. https://en.wikipedia.org/wiki/Sassafras_albidum
MDA is not naturally occurring
Yea, it's just not gonna happen with a controlled dosage under supervision. People that over dose (as in take too much, not dying) can have a bad trip at least for an amount of time.
Sure, maybe under a controlled environment where candidate selection is a thing. I've seen some wild reactions in people who turned out to have undiagnosed bipolar disorder or border line personality disorder at the time. They all got diagnosed and treated at a later date so hooray for them. But goddamn, the serotonin dump from even a moderate amount of mdma triggered some intense episodes of mania. Hell, I bet you could use it as a means of diagnosis; it was so obvious in retrospect. Group of friends, chill environment, everyone taking about the same amount, good quality stuff and one person just losing their shit afterwards. Makes you suspect there's something not quite right with them..
2 in the placebo group.
I've been hearing about this for a long time - probably since the late 1990s, so I'm surprised to see that it seems only in the last couple of years that there are phase three trials. I would imagine that the safety profile of MDMA is already well understood / fairly well researched in the 1950s and 1960s
MDMA was first synthesized in 1912 by Merck. Merck and US Army did several animal trials in the 1950s, but by the end of the decade MDMA was shelved and thought to have no therapeutic benefit. It wasn’t until Sasha Shulgin rediscovered it in 1976 that its therapeutic benefits were discovered, at which point therapists and psychiatrists began quietly using it for psychedelic assisted psychotherapy. In July 1984 the DEA proposed making MDMA a Schedule I controlled substances, which led to outcry from practitioners who requested the DEA hold hearings to provide testimony on MDMA’s therapeutic benefits. While these hearings were ongoing, the DEA used its emergency scheduling authority in May of 1985 to place MDMA in Schedule I.
Animal efficacy and human safety trials of MDMA began in the late 1980s, and the first FDA-approved, placebo controlled, double blind phase I study was published in 1996.
Animal efficacy and human safety trials of MDMA began in the late 1980s, and the first FDA-approved, placebo controlled, double blind phase I study was published in 1996.
Not really. Research almost entirely paused until the last few years.
aah research impeded by morality police, understand now, thanks
That may not necessarily be the reason. It could simply be until recently nobody believed there could be positive medical uses for MDMA specifically. Not all recreational drugs have legitimate medical uses, or are better than existing medically prescribed drugs.
After our current opioid crisis, it's not unreasonable to assume research on opioid medical usage will decline or stop - outside what has already been studied, for example.
After our current opioid crisis, it's not unreasonable to assume research on opioid medical usage will decline or stop - outside what has already been studied, for example.
No, the war on drugs was definitely the reason, and it was stated as such at the time. They were doing PTSD research with veterans in the 70s and the feds shut it down even though it was clearly promising.
Hah. People have believed in this for some time. MAPS has been around for a while. What you mean is, not the right people, and now we are back to morality policing.
Overall seems positive, some interesting pieces:
> The only measured exploratory covariate with a significant interaction with treatment was lifetime history of SSRI use, which was associated with improved efficacy of MDMA-AT (P = 0.02; Supplementary Table 5). Covariates significantly impacting the main effect were sex assigned at birth and baseline Beck Depression Inventory (BDI)-II score; female sex assigned at birth and baseline BDI-II score ≥23 were both associated with improved outcomes irrespective of treatment assignment (P < 0.05).
This is an interesting outcome, particularly the SSRI usage
> Eight participants (MDMA-AT, n = 7; placebo with therapy, n = 1) experienced cardiac TEAEs, which included palpitations (MDMA-AT, n = 5 (9.4%); placebo with therapy, n = 1 (2.0%)) and tachycardia (MDMA-AT, n = 2 (3.8%)); all were mild.
Seems a bit concerning, but I have little to measure this against.
> superiority of MDMA-AT over SSRIs cannot be assumed without a direct comparison
I feel as though this should be done. Even though the results are promising they come with a significant safety risk for the participants who are essentially at the mercy of the administrator and could be easily subject to abuse.
That being said, for people with severe PTSD this is surely a godsend. Maybe we can mitigate the safety issue other ways.
> The only measured exploratory covariate with a significant interaction with treatment was lifetime history of SSRI use, which was associated with improved efficacy of MDMA-AT (P = 0.02; Supplementary Table 5). Covariates significantly impacting the main effect were sex assigned at birth and baseline Beck Depression Inventory (BDI)-II score; female sex assigned at birth and baseline BDI-II score ≥23 were both associated with improved outcomes irrespective of treatment assignment (P < 0.05).
This is an interesting outcome, particularly the SSRI usage
> Eight participants (MDMA-AT, n = 7; placebo with therapy, n = 1) experienced cardiac TEAEs, which included palpitations (MDMA-AT, n = 5 (9.4%); placebo with therapy, n = 1 (2.0%)) and tachycardia (MDMA-AT, n = 2 (3.8%)); all were mild.
Seems a bit concerning, but I have little to measure this against.
> superiority of MDMA-AT over SSRIs cannot be assumed without a direct comparison
I feel as though this should be done. Even though the results are promising they come with a significant safety risk for the participants who are essentially at the mercy of the administrator and could be easily subject to abuse.
That being said, for people with severe PTSD this is surely a godsend. Maybe we can mitigate the safety issue other ways.
> That being said, for people with severe PTSD this is surely a godsend.
This seems a bit of a premature statement. The long term usage affects of MDMA use can be very costly, and I suspect long term use of something that provides artificial "feel good" emotion will have a tremendous downside for people who are already struggling with normality.
> sex assigned at birth... female sex assigned at birth
As an aside - in a scientific article, this is insane language to use and really calls into question the assumptions and conclusions.
This seems a bit of a premature statement. The long term usage affects of MDMA use can be very costly, and I suspect long term use of something that provides artificial "feel good" emotion will have a tremendous downside for people who are already struggling with normality.
> sex assigned at birth... female sex assigned at birth
As an aside - in a scientific article, this is insane language to use and really calls into question the assumptions and conclusions.
> in a scientific article, this is insane language to use and really calls into question the assumptions and conclusions.
Springer Nature would appear to disagree with your assertion.
"Authors should use the terms sex (biological attribute) and gender (shaped by social and cultural circumstances) carefully in order to avoid confusing both terms. Article titles and/or abstracts should indicate clearly what sex(es) the study applies to. Authors should also describe in the background, whether sex and/or gender differences may be expected; report how sex and/or gender were accounted for in the design of the study; provide disaggregated data by sex and/or gender, where appropriate; and discuss respective results. If a sex and/or gender analysis was not conducted, the rationale should be given in the Discussion. These guidelines apply to studies involving humans, vertebrate animals and cell lines."
https://www.springernature.com/gp/policies/book-publishing-p....
Springer Nature would appear to disagree with your assertion.
"Authors should use the terms sex (biological attribute) and gender (shaped by social and cultural circumstances) carefully in order to avoid confusing both terms. Article titles and/or abstracts should indicate clearly what sex(es) the study applies to. Authors should also describe in the background, whether sex and/or gender differences may be expected; report how sex and/or gender were accounted for in the design of the study; provide disaggregated data by sex and/or gender, where appropriate; and discuss respective results. If a sex and/or gender analysis was not conducted, the rationale should be given in the Discussion. These guidelines apply to studies involving humans, vertebrate animals and cell lines."
https://www.springernature.com/gp/policies/book-publishing-p....
Your citation actually furthers my point. We are not discussing the logical notion of Gender here.
The point of these studies is that MDMA can improve the efficacy of talk therapy. I don’t think anyone in this space is thinking MDMA will replace traditional anti depressants as a thing you take regularly for an indefinite period of time.
Further, I’d speculate MDMA is not obviously harder on the body than adderall or other stimulants currently legal for ADHD.
Further, I’d speculate MDMA is not obviously harder on the body than adderall or other stimulants currently legal for ADHD.
>> sex assigned at birth... female sex assigned at birth
> As an aside - in a scientific article, this is insane language to use and really calls into question the assumptions and conclusions.
It's not a scientific statement, it's a political statement. It doesn't matter if you agree with that political statement or not - it simply has no business being in a scientific report.
Injecting political ideology into what is supposed to be factual findings is wrong.
In scientific writing, such as studies like this - just the facts please. Anything else opens questions about motivations, conclusions, etc.
Injecting political ideology into what is supposed to be factual findings is wrong.
In scientific writing, such as studies like this - just the facts please. Anything else opens questions about motivations, conclusions, etc.
> In scientific writing, such as studies like this - just the facts please.
But those are just very precise facts? Clarifying that they refer to "female sex assigned at birth" is strictly less ambiguous than "female".
But those are just very precise facts? Clarifying that they refer to "female sex assigned at birth" is strictly less ambiguous than "female".
Alupis is simply trying to help out Science in an objective and apolitical way by pointing out that some phrases can rile people up into hooting and hollering. Phrases like “assigned female at birth” can, to use an empirical term, “whip one up into a real doozy of a tizzy” that can only be quelled by posting. Anything that might trigger Poster’s Rage is definitionally Not Science because scientific words do not make people “get all flustered”
The very fact that you are this "riled up" about a plainly obvious statement such as I have made here only serves to validate my position.
Take a look at your statements and tell me you are arguing from a scientific standpoint and not one from your own personal political ideology. You cannot, in good faith, make this claim.
Take a look at your statements and tell me you are arguing from a scientific standpoint and not one from your own personal political ideology. You cannot, in good faith, make this claim.
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Nobody stood around and just made up a sex for a newborn soviet job-assignment style, making the language "assigned at birth" inaccurate from a scientific standpoint. From a scientific standpoint, Female and Male are clearly defined.
I will not engage any further in a political debate about this subject here. My point was political ideology statements should not be in scientific writing because they are political, the language changes with the political climate, and the language is imprecise. People reading scientific writings 100 years in the future should not have to wonder what political climate the paper was written in.
Scientific writing should not be a product of it's date and political climate.
I will not engage any further in a political debate about this subject here. My point was political ideology statements should not be in scientific writing because they are political, the language changes with the political climate, and the language is imprecise. People reading scientific writings 100 years in the future should not have to wonder what political climate the paper was written in.
Scientific writing should not be a product of it's date and political climate.
Male and female are clearly defined (not really, but let's assume for the arguments sake).
Intersex people exist, and they are impossible to identify without them telling you about it.
So these people are really "assigned" a gender at birth.
They might not be a huge amount of the population, but they exist.
So why not use "assigned at birth"? It includes them and doesn't hurt anyone at all.
I'd ask you to reconsider, whether the authors made a political statement, or whether you made this a political statement by yourself. Because I read it and not a single political thought crossed my mind...
> making the language "assigned at birth" inaccurate from a scientific standpoint
That's a strawman argument about semantics ("assign" in English does not always mean "soviet-style"), which I'm not going to bother engaging with.
> Scientific writing should not be a product of it's date and political climate.
By virtue of using language, it virtually always is. For example, the common/acceptable way of referring to ethnicities changed over time. It's virtually impossible in anything involving humans to have language (and therefore scientific language) not evolve over time.
> From a scientific standpoint, Female and Male are clearly defined.
And how do you distinguish the "scientific" female and male from the "colloquial" female and male, without leaving it ambiguous according to the "political background" of the reader? Or rather, what if, in a purely hypothetical future English, "female" and "male" refer unambiguously to the gender people identify as? It seems like you would like scientific writing to conform specifically (and only) to what you consider acceptable language _right now_, and are not actually particularly interested in accessibility to future readers.
That's a strawman argument about semantics ("assign" in English does not always mean "soviet-style"), which I'm not going to bother engaging with.
> Scientific writing should not be a product of it's date and political climate.
By virtue of using language, it virtually always is. For example, the common/acceptable way of referring to ethnicities changed over time. It's virtually impossible in anything involving humans to have language (and therefore scientific language) not evolve over time.
> From a scientific standpoint, Female and Male are clearly defined.
And how do you distinguish the "scientific" female and male from the "colloquial" female and male, without leaving it ambiguous according to the "political background" of the reader? Or rather, what if, in a purely hypothetical future English, "female" and "male" refer unambiguously to the gender people identify as? It seems like you would like scientific writing to conform specifically (and only) to what you consider acceptable language _right now_, and are not actually particularly interested in accessibility to future readers.
> It's not a scientific statement, it's a political statement.
This is a good point. Once a scientific term becomes politicized by its usage outside of clinical settings, it ceases to be scientific.
For example, weight has become politicized so when you read something like “7lb 5oz infant” in a study you can just throw the whole thing in the trash because the researcher has clearly gone Woke.
This is a good point. Once a scientific term becomes politicized by its usage outside of clinical settings, it ceases to be scientific.
For example, weight has become politicized so when you read something like “7lb 5oz infant” in a study you can just throw the whole thing in the trash because the researcher has clearly gone Woke.
In scientific writing Mass is usually referenced instead of Weight, because weight changes depending where you are, even on the same planet (being a measurement of gravitational force).
You are making my point even stronger... and weight being political is news to me.
You are making my point even stronger... and weight being political is news to me.
> Mass is usually referenced instead of Weight
You’re telling me buddy! People actually think that doctors weigh babies and write down the numbers they see on the scale when everybody really smart knows they measure infant Mass by measuring their liquid displacement and multiplying it by the density of the standardized homogenous baby slurry provided by NIST.
It’s like dang John Stewart in every delivery theater I tell you what
You’re telling me buddy! People actually think that doctors weigh babies and write down the numbers they see on the scale when everybody really smart knows they measure infant Mass by measuring their liquid displacement and multiplying it by the density of the standardized homogenous baby slurry provided by NIST.
It’s like dang John Stewart in every delivery theater I tell you what
You are attempting to be funny and dismantle my argument by locating holes. However, unfortunately for you, these misguided political jabs only strengthen my argument.
A birth certificate is not a scientific writing. A study of the affects of MDMA on PTSD is.
A birth certificate is not a scientific writing. A study of the affects of MDMA on PTSD is.
> A birth certificate is not a scientific writing. A study of the affects of MDMA on PTSD is.
I’ll cheers to that! It is important that we do not include words like “assigned female at birth” in any scientific writing because
I’ll cheers to that! It is important that we do not include words like “assigned female at birth” in any scientific writing because
Take a breath and calm down. Triggered is supposed to be a meme, not reality.
I’m sorry seeing those Woke Words in a Science just make me so hopping mad. It’s like if they use those words and people read them, then the words will make science more or less… what I’m trying to say is they’re so bad, and nothing made of Science could make me feel this way. The only way to do anything with all this discomfort I feel from the Words when I see them online is post in the comments, it’s literally the way we’ll save society writ large
There are many social aspects to the "male" and "female" experience in society, it helps to separate those out from congenital physiology. For example, living as a woman often entails responsibilities of caregiving, housekeeping, and/or "social reproduction." Certain "emotional labors" are also relegated to women's roles, such as calendaring and keeping in touch, but none of these are safely assumed to have derived from congenital sex.
Expectations of eg emotional stoicism in men preclude eg certain platonic intimacies that are common among women. Gendered relationship norms significantly influence our mental and physical health. It would be unscientific to presume they were physiologically congenital. For that reason, it makes sense to refer to study participants by their "sex assigned at birth," rather than presuming any overlap between socialized gender and congenital sex. Remember, in scientific inquiry, precision is key.
Expectations of eg emotional stoicism in men preclude eg certain platonic intimacies that are common among women. Gendered relationship norms significantly influence our mental and physical health. It would be unscientific to presume they were physiologically congenital. For that reason, it makes sense to refer to study participants by their "sex assigned at birth," rather than presuming any overlap between socialized gender and congenital sex. Remember, in scientific inquiry, precision is key.
Please don’t paint your obvious naivety re gender as scientific enlightenment. This is real populist Ben Shapiro reasoning and I’d really hope that this community is above it. The reality is that esp. when we are talking about mental health it is important to be specific about the nature of a sex/gender breakdown. Could it be a question of hormones? Socialisation? The author/s are using concise language in a scientific publication and because of your naivety and typical software developer undeserved sense of transferable expertise, you are claiming it as superfluous, when it isn’t. Please consider that maybe you are wrong, and not everyone else.
You seem to be conflating gender with sex?
You are aware of intersex/chromosomal conditions and “gender assignment” treatments at birth right? “Sex assigned at birth” is a well-defined empirical label.
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Thanks! but on HN, we don't count reposts as dupes if the story hasn't had significant attention yet. This is to give good stories multiple changes at getting attention.
This is in the FAQ (https://news.ycombinator.com/newsfaq.html) and there are past explanations at https://hn.algolia.com/?dateRange=all&page=0&prefix=true&que... if interested.
This is in the FAQ (https://news.ycombinator.com/newsfaq.html) and there are past explanations at https://hn.algolia.com/?dateRange=all&page=0&prefix=true&que... if interested.
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Even as someone who has used this recreational, I'm very sceptical about mdma for medical treatment.
I have seen smart people needing professional help for a very long time after using this too often. And too often is already every second weekend, because the body needs so long to restore the serotonine.
But maybe they are using very little doses? I can still not believe that taking this regularily is a good idea.
Edit: Sry for not reading it carefully enough to find the dosage.
Still 120-180 mg with only one month in between is a lot.
I have seen smart people needing professional help for a very long time after using this too often. And too often is already every second weekend, because the body needs so long to restore the serotonine.
But maybe they are using very little doses? I can still not believe that taking this regularily is a good idea.
Edit: Sry for not reading it carefully enough to find the dosage.
Still 120-180 mg with only one month in between is a lot.
If only there were some mechanism by which we could separate people's personal vibes and anecdata from actual scientific understanding... perhaps a series of clinical trials?
History will look unkindly upon people who kept these substances out of the hands of people who need them because "I knew a guy once who did too much street MDMA and went stupid."
Honestly, adopting that position in the face of a well-designed Phase 3 RCT showing such strong results is pretty much actively evil as far as I'm concerned. People are suffering. People are blowing their brains out after combat; people are afraid to get in their cars after accidents, or walk outside or have sex after being raped, and you're like "ehh Idk I knew a guy." Come on.
History will look unkindly upon people who kept these substances out of the hands of people who need them because "I knew a guy once who did too much street MDMA and went stupid."
Honestly, adopting that position in the face of a well-designed Phase 3 RCT showing such strong results is pretty much actively evil as far as I'm concerned. People are suffering. People are blowing their brains out after combat; people are afraid to get in their cars after accidents, or walk outside or have sex after being raped, and you're like "ehh Idk I knew a guy." Come on.
Its not like "I know a guy". Its like common knowledge for people who do this stuff that it seriously fucks you up if you do this too often. Its like 100% guaranteed.
I would not take this every day for a month even if you offer me a years salary.
Every medic who thinks this is a good idea should do the self test in my opinion. The same goes for giving ritalin to kids, but that is a different story...
I would not take this every day for a month even if you offer me a years salary.
Every medic who thinks this is a good idea should do the self test in my opinion. The same goes for giving ritalin to kids, but that is a different story...
> Its like common knowledge
Why don't you just say folk wisdom? Commonly rumored? Calling something "knowledge" doesn't make it such. The entire point of science, and the reason it's so ridiculously hard, is that common knowledge is so frequently wrong.
> I would not take this every day for a month even if you offer me a years salary.
Then don't? No one is asking you to, nor is this trial nor the proposed line of treatment anything like this.
> Every medic who thinks this is a good idea should do the self test in my opinion.
I have a better proposal: how about they do a bunch of solid RCTs on it? That way we get actual information instead of noise.
Why don't you just say folk wisdom? Commonly rumored? Calling something "knowledge" doesn't make it such. The entire point of science, and the reason it's so ridiculously hard, is that common knowledge is so frequently wrong.
> I would not take this every day for a month even if you offer me a years salary.
Then don't? No one is asking you to, nor is this trial nor the proposed line of treatment anything like this.
> Every medic who thinks this is a good idea should do the self test in my opinion.
I have a better proposal: how about they do a bunch of solid RCTs on it? That way we get actual information instead of noise.
> I have a better proposal: how about they do a bunch of solid RCTs on it?
Good but somehow a lot of medics give ritalin to kids. If you would buy some ritalin, and also some speed. Try both and realize it is pretty similiar.
I know someone in his mid twenties who has a tremor in his left hand because he had to take this since the age of 10.
And maybe there are cases where it makes sense. But defenitely not in that amount. Idgaf about what anyone tells me about this.
Good but somehow a lot of medics give ritalin to kids. If you would buy some ritalin, and also some speed. Try both and realize it is pretty similiar.
I know someone in his mid twenties who has a tremor in his left hand because he had to take this since the age of 10.
And maybe there are cases where it makes sense. But defenitely not in that amount. Idgaf about what anyone tells me about this.
I'm also I since guy, so I'm not against what you are saying. Your just twisting my words.
You know the story of mdma? It was developed for medical use...
And I sayd im skeptical of this, because I cannot imagin, that any serious study, considering the risks comes to this conclusion. Unless it literally stops people from suicid. But as far as I know it's more probable to increase this risk so idk.
You know the story of mdma? It was developed for medical use...
And I sayd im skeptical of this, because I cannot imagin, that any serious study, considering the risks comes to this conclusion. Unless it literally stops people from suicid. But as far as I know it's more probable to increase this risk so idk.
But dude, that's the whole point of these studies! It's really hard to know what a given drug does! We should absolutely factor in people's subjective experiences and recreational experiments in terms of deciding whether it's worth investigating something more thoroughly, but once real, high-quality studies are done (especially RCTs), people's recreational experiences hold very little water when they are in conflict with the study.
Yes I also misunderstood the usage. They make a therapy session once a month where the patient gets high before the session.
On the other hand, they dont factor in the body mass of the patient and give everyone the same dosage. That doesnt seem high quality to me. And 120-180mg isn't just a little. Thats at the upper end of what you would take when you go to a party, just for reference. Give this to someone with 60kg body mass and they can have a very bad experience.
On the other hand, they dont factor in the body mass of the patient and give everyone the same dosage. That doesnt seem high quality to me. And 120-180mg isn't just a little. Thats at the upper end of what you would take when you go to a party, just for reference. Give this to someone with 60kg body mass and they can have a very bad experience.
The dosages are discovered and defined by the Phase I trial, also in a very systematic way that is meant to break free of folk wisdom about correct dosages.
> I would not take this every day for a month...
From the article:
The treatment period consisted of three 8-h dosing sessions, in conjunction with therapy, spaced approximately 1 month apart.
From the article:
The treatment period consisted of three 8-h dosing sessions, in conjunction with therapy, spaced approximately 1 month apart.
Thank you and sorry for not reading carfully enough.
It's still a pretty heavy dosage. Most sane ravers would take less with more time in between. But I guess if you stop after 3 sessions it is ok.
They gave everyone the same dosage without considering the body mass.
Then 120mg as initial dosis for someone who has no tolerance is a crazy kick (considering body mass of ~80kg).
It's still a pretty heavy dosage. Most sane ravers would take less with more time in between. But I guess if you stop after 3 sessions it is ok.
They gave everyone the same dosage without considering the body mass.
Then 120mg as initial dosis for someone who has no tolerance is a crazy kick (considering body mass of ~80kg).
Taking multiple "points" (100mg doses) in a single session is extremely common among enjoyers of MDMA.
People don't really build tolerance to MDMA when they use it responsibly.
This is a phase 3 clinical trial, aka the last and most rigorous phase before potential FDA approval. There have already been studies previous to this one that establish safe bounds for dosage of chemically pure MDMA in a clinical setting, many of which are targeted at patients with "no tolerance" (aka drug naïve).
You are clutching pearls pretty hard here. Experimental medicine is not without risks. Apparently 8 whole active study group participants (less than 10%) experienced mild tachycardia, aka fast heartbeat, in a setting full of trained medical professionals with the skills and equipment to handle such events. There was also some sweating and nervousness. Compare that to a moderate to bad episode of PTSD and it's a walk in the park by comparison. This is highly ethical research. Take a breath and carefully read the full study and some of its references, as well as some other ones prior to this phase 3 trial, if you are seriously concerned about this issue.
People don't really build tolerance to MDMA when they use it responsibly.
This is a phase 3 clinical trial, aka the last and most rigorous phase before potential FDA approval. There have already been studies previous to this one that establish safe bounds for dosage of chemically pure MDMA in a clinical setting, many of which are targeted at patients with "no tolerance" (aka drug naïve).
You are clutching pearls pretty hard here. Experimental medicine is not without risks. Apparently 8 whole active study group participants (less than 10%) experienced mild tachycardia, aka fast heartbeat, in a setting full of trained medical professionals with the skills and equipment to handle such events. There was also some sweating and nervousness. Compare that to a moderate to bad episode of PTSD and it's a walk in the park by comparison. This is highly ethical research. Take a breath and carefully read the full study and some of its references, as well as some other ones prior to this phase 3 trial, if you are seriously concerned about this issue.
> Taking multiple "points" (100mg doses) in a single session is extremely common among enjoyers of MDMA.
300mg, especially for someone without prior MDMA experience, is an absolutely unhinged hero dose.
300mg spaced out over the course of 12 hours or so is somewhat less so, but you absolutely will get fewer effects on re-dosing, and fewer the next day as well if you dose again.
That said 120mg should be pretty safe for anyone, but with lower-tolerance or lighter users, could definitely reduce their ability to engage in meaningful conversation or retain any memory of what they discussed.
Which isn't to say they won't come away from the experience feeling warm fuzzies and possibly with significant improvements in their PTSD symptoms, but it does make me wonder if it's a good way to study how much of that is the talk therapy and how much is just the therapeutic effects of the drug
300mg, especially for someone without prior MDMA experience, is an absolutely unhinged hero dose.
300mg spaced out over the course of 12 hours or so is somewhat less so, but you absolutely will get fewer effects on re-dosing, and fewer the next day as well if you dose again.
That said 120mg should be pretty safe for anyone, but with lower-tolerance or lighter users, could definitely reduce their ability to engage in meaningful conversation or retain any memory of what they discussed.
Which isn't to say they won't come away from the experience feeling warm fuzzies and possibly with significant improvements in their PTSD symptoms, but it does make me wonder if it's a good way to study how much of that is the talk therapy and how much is just the therapeutic effects of the drug
MDMA-AT is definitely not taking it regularly. It is done only a handful of times, with pharmaceutical-grade MDMA and no other adulterants, in controlled doses, in a controlled setting. Very different than a Tesla pill at a rave every other weekend.
Ok, not regularly already makes more sense. Still the dosage would be very interesting, and the time interval. I didn't talk about tesla pills, but mdma crystals dosed with a high precision weight according to body mass.
That a tesla pill with 0-300 mg can be harmful is obvious^^
That a tesla pill with 0-300 mg can be harmful is obvious^^
The proposed use is MDMA-assisted therapy. Take a dose, talk to a therapist. Wait a month, repeat. You seem to be imagining people popping the stuff like SSRIs.
Intuitively, this makes a lot of sense. MDMA is a fun drug because of the fact that it makes it basically impossible to feel negative emotion under its effect. PTSD is characterized by extreme negative emotion around a particular trauma, to such an extent that it becomes disruptive to living a normal life. Just talking about the traumatic inducing experience can lead to uncontrolled emotional responses, making it difficult to approach therapeutically. The MDMA acts as a shortcut around that last bit: by blocking the patient from feeling negative emotion while they talk about their trauma, they can re-evaluate it in a more removed way.
Combine that with theories about how we edit memories when we recall them, and you've got a pretty obvious method of action.
It's not intended to be a chronically taken treatment. But the results were pretty massive. That CAPS-5 score they talk about the reduction by 24 points versus therapy alone's 15 is on an 80 point scale, with the bare minimum for PTSD diagnosis at a 12, and "moderate" PTSD being in the 23-35 range.
Compared to most results coming out of the mental illness treatment field, MDMA's looking like a silver bullet.
Intuitively, this makes a lot of sense. MDMA is a fun drug because of the fact that it makes it basically impossible to feel negative emotion under its effect. PTSD is characterized by extreme negative emotion around a particular trauma, to such an extent that it becomes disruptive to living a normal life. Just talking about the traumatic inducing experience can lead to uncontrolled emotional responses, making it difficult to approach therapeutically. The MDMA acts as a shortcut around that last bit: by blocking the patient from feeling negative emotion while they talk about their trauma, they can re-evaluate it in a more removed way.
Combine that with theories about how we edit memories when we recall them, and you've got a pretty obvious method of action.
It's not intended to be a chronically taken treatment. But the results were pretty massive. That CAPS-5 score they talk about the reduction by 24 points versus therapy alone's 15 is on an 80 point scale, with the bare minimum for PTSD diagnosis at a 12, and "moderate" PTSD being in the 23-35 range.
Compared to most results coming out of the mental illness treatment field, MDMA's looking like a silver bullet.
Yes that makes more sense. I can imagine that could work. Do you know how it compares to therapy with hypnosis?
There are multiple psychologist in my family, so maybe thats why im opposed to doing therapy with drugs unless physically necesarry.
There are multiple psychologist in my family, so maybe thats why im opposed to doing therapy with drugs unless physically necesarry.
As other commenters have noted, this is MDMA-assisted therapy. Controlled dose, setting, with supportive professionals.
But one interesting thing to note:
> Least squares (LS) mean change in CAPS-5 score (95% confidence interval (CI)) was −23.7 (−26.94, −20.44) for MDMA-AT versus −14.8 (−18.28, −11.28) for placebo with therapy (P < 0.001, d = 0.7).
The placebo group got better, too! What this means is that therapy for PTSD actually works! It just works better on average with MDMA assistance.
But one interesting thing to note:
> Least squares (LS) mean change in CAPS-5 score (95% confidence interval (CI)) was −23.7 (−26.94, −20.44) for MDMA-AT versus −14.8 (−18.28, −11.28) for placebo with therapy (P < 0.001, d = 0.7).
The placebo group got better, too! What this means is that therapy for PTSD actually works! It just works better on average with MDMA assistance.
You cannot really compare the two use cases. It's like banning morphine because if people used that in parties they would have a heart attack.
I'm not against banning anything. Just considering the side effects you need very hard evidence to justify this.
And I couldnt find exact information about dosage and regularity in the paper...
And I couldnt find exact information about dosage and regularity in the paper...
> And too often is already every second weekend, because the body
The intended therapy is taken several times in a guided sessions, 3 for this study, with a therapist. They aren't just sending people home with a bottle of mdma to take before bed.
The intended therapy is taken several times in a guided sessions, 3 for this study, with a therapist. They aren't just sending people home with a bottle of mdma to take before bed.
Yeah my impression of a therapeutic setting would be an asymptotic progression of a few doses in short intervals with an exponential back-off ending in no further uses or perhaps once a year.
Resets are not a recurring situation. I'd take it as a sign of using the treatment in bad faith.
Resets are not a recurring situation. I'd take it as a sign of using the treatment in bad faith.
> And too often is already every second weekend, because the body needs so long to restore the serotonine.
Get some 5HTP in you.
Get some 5HTP in you.
Nice to learn s.th. xD. I'm probably a bit too old now anywas. I just knew bananas and nuts are good, but not why^^
> I'm very sceptical about mdma for medical treatment.
Data disagrees with you.
I have seen tremendous improvement in quality of life of veterans with PTSD with just a few MDMA assisted therapy sessions.
Data disagrees with you.
I have seen tremendous improvement in quality of life of veterans with PTSD with just a few MDMA assisted therapy sessions.
I couldn't find information about dosage and regularity in the paper.
If it really is just a few sessions with enough time between then im ok with that.
But there should be enough scientific evidence that anything more is very dangerous.
If it really is just a few sessions with enough time between then im ok with that.
But there should be enough scientific evidence that anything more is very dangerous.
>But there should be enough scientific evidence that anything more is very dangerous.
By all means, go find it and report back!
By all means, go find it and report back!
https://en.wikipedia.org/wiki/MDMA#Long-term
Wasnt that hard right. All just anecdotal evidence of course /S
Wasnt that hard right. All just anecdotal evidence of course /S
nobody knows the correct dose because nobody could do the trial
it could be anything in any interval or nothing
we have FDA approved treatments that say “don’t do this for more than 2 years” and at the very least we can make objective choices because the side effects are listed… because those also occurred to an actual human being in a controlled environment
I can’t advocate for ignorance like this
it could be anything in any interval or nothing
we have FDA approved treatments that say “don’t do this for more than 2 years” and at the very least we can make objective choices because the side effects are listed… because those also occurred to an actual human being in a controlled environment
I can’t advocate for ignorance like this
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Nature is the mecca of all science. MDMA will be approved by FDA, that's inevitable. Likely would require special licensing. Clinics will pop up all over the country and it won't be long before “off label” prescriptions will appear. The incidence of PTSD will suddenly rise and before we have a chance to quell the opioid epidemic another epidemic will replace it on the front pages of the news. Meanwhile the smart ones will invest in whichever pharmaceutical company will be the first to patent an SSRI/MDMA combination drug.
“The only thing that we learn from history is that we learn nothing from history.” Hegel
• MDMA is almost anti-addictive — the more often you take it, the less fun it is. MDMA acts on the brain almost as if it by "using up" some scarce resource inside the brain, that only gradually builds back up when not taking MDMA. If you try to take MDMA again the very next day after taking it, you just get a headache. There's a reason you don't hear about "MDMA junkies" the way you hear about heroin junkies.
• SSRIs and MDMA are counteractive; being on SSRIs suppresses the effect of MDMA. (And also, due to this, you can end up with serotonin syndrome on the come-down from MDMA.)
• SSRIs and MDMA are counteractive; being on SSRIs suppresses the effect of MDMA. (And also, due to this, you can end up with serotonin syndrome on the come-down from MDMA.)
MDMA isn't physically addictive. Could be psychologically addictive the way the lottery or Netflix is, but I doubt it's going to be giving oxycodone much competition.
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If you're talking about pairing an SSRI with MDMA, then perhaps you would perhaps be well-served by adding some reticence to the confident assertions made.
That pairing would be like a Clorox + Bleach pairing of the psychotropic world.
There is significant interest in the drug, and the culture largely is focused on appropriate administration measures. This is not a half-baked solution, MAPS has worked on this for decades.
That pairing would be like a Clorox + Bleach pairing of the psychotropic world.
There is significant interest in the drug, and the culture largely is focused on appropriate administration measures. This is not a half-baked solution, MAPS has worked on this for decades.
I don’t know who needs to hear this, but: Taking MDMA you bought off the street and hoping it’s going to cure whatever ails you isn’t even remotely similar to what’s being studied here. MDMA is also well known to produce depressive rebound effects in the following days that can worsen mental health problems if the patient isn’t properly monitored and prepared. (and no, taking some supplements and 5-HTP won’t save you from all the side effects no matter what that guy on the internet claims)
Importantly, both the MDMA-assisted therapy and the regular therapy groups improved over the course of this study. It should go without saying that regular old therapy is and will continue to be the first-line treatment for PTSD. People will debate the relative safety of MDMA all day long, but no matter how you look at it, MDMA will always be more risky than therapy alone. The MDMA group had a 1-in-10 incidence of treatment related adverse events, for example.
Another important piece of context is that true placebo control is impossible in these studies. Patients and caregivers will know which patients received MDMA due to the dramatic effects of the drug. This doesn’t negate the study, but you do have to consider the fact that these patients went into this study expecting to maybe get MDMA with the expectation that MDMA would help them. They would no doubt be either excited or disappointed after realizing which group they were in. This will, unfortunately, impact the results in ways that can’t be measured.
I hope future studies will compare against an active control group. It would be much better to compare, for example, therapy with placebo, therapy with SSRI, and therapy with MDMA. It’s easy to differentiate from placebo, but it’s much harder to find new treatments that outperform existing options.
Another alternative would be to trial an active placebo group. For example, if one group received MDMA and another group received a dose of amphetamine then both groups would know they had received a psychoactive drug with euphoriant properties, but if they were truly drug naive (as asked in the intake screener) then theoretically they wouldn’t be able to tell which group they were in. This would more effectively isolate MDMA’s unique properties, if any, without breaking the blinding as much.