9 ms·
MDMA-assisted therapy for PTSD: A randomized, placebo-controlled phase 3 trial
- notamy 3y ago> 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.
- prashp 3y agoBut also > Seven participants had a severe treatment emergent adverse event (TEAE) (MDMA-AT, n = 5 (9.4%); placebo with therapy, n = 2 (3.9%)).
- notamy 3y agoYep! I do wish they clarified what exactly that means; perhaps I just missed it in my quick read.
- speed_spread 3y agoSounds like what the common raver would qualify as a "bad trip".
- boppo1 3y agoI don't think MDMA is really in the business of bad trips.
- the_gipsy 3y agoYea, 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.
- morkalork 3y agoSure, 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..
- heavyset_go 3y agoYou 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.
- rexpop 3y agoMany 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".
- d1lanka 3y agoMeh. 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.
- heavyset_go 3y agoMDMA was discovered as an intermediate in the synthesis of a completely unrelated substance. No one designed it.
- rendx 3y agoMDA is a naturally occurring precursor to MDMA and was traditionally used in Root Beer. https://en.wikipedia.org/wiki/Sassafras_albidum https://en.wikipedia.org/wiki/Sassafras_albidum
- heavyset_go 3y agoMDA is not naturally occurring
- tmpX7dMeXU 3y agoOK. 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!”
- hentrep 3y agoThey detail this in the supplementary materials: https://static-content.springer.com/esm/art%3A10.1038%2Fs41591-023-02565-4/MediaObjects/41591_2023_2565_MOESM1_ESM.pdf https://static-content.springer.com/esm/art%3A10.1038%2Fs415...
- theptip 3y agoSee table 2: https://www.nature.com/articles/s41591-023-02565-4/tables/2 https://www.nature.com/articles/s41591-023-02565-4/tables/2
- carimura 3y ago2 in the placebo group.
- deleted 3y ago[deleted]
- RadixDLT 3y agodupe: https://news.ycombinator.com/item?id=37524353 https://news.ycombinator.com/item?id=37524353
- dang 3y agoThanks! 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 https://news.ycombinator.com/newsfaq.html) and there are past explanations at https://hn.algolia.com/?dateRange=all&page=0&prefix=true&query=by%3Adang%20multiple%20dupe&sort=byDate&type=comment https://hn.algolia.com/?dateRange=all&page=0&prefix=true&que... if interested.
- mountainriver 3y agoOverall 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.
- Alupis 3y ago> 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.
- andrekandre 3y ago>> 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. i'm not really familiar with scientific writing, but why would that be insane language to use? what would be better?
- singingfish 3y agoI'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
- johndhi 3y agoNot really. Research almost entirely paused until the last few years.
- singingfish 3y agoaah research impeded by morality police, understand now, thanks
- Alupis 3y agoThat 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.
- theptip 3y agoNo, 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.
- tmpX7dMeXU 3y agoHah. 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.
- 3y ago
- randomNumber7 3y agoEven 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.
- deleted 3y ago[deleted]
- ethanbond 3y agoIf 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.
- carimura 3y agorave massage circles?
- ethanbond 3y agoExactly. Just gotta work The Truth out through the fingertips
- randomNumber7 3y agoIts 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...
- deleted 3y ago[deleted]
- fshbbdssbbgdd 3y agoI’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.
- ethanbond 3y agoYeah 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.
- johndhi 3y agoRick 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.
- TylerE 3y agoMy 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.
- Aurornis 3y agoThis 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.
- hinkley 3y agoIf 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.
- DrKavorkian 3y agoNature 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
- sowbug 3y agoMDMA 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.
- deleted 3y ago[deleted]
- derefr 3y ago• 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.)
- tysam_and 3y agoIf 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.
- Aurornis 3y agoAs with all of these studies, it’s important to remember that this isn’t evidence that taking MDMA by itself is therapeutic. The therapy sessions are the primary treatment in this study and the MDMA is being explored as an adjunct to therapy. 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.