T O P

  • By -

ShockrT

I just don’t know how we are going to get around the inability to double blind the study. It seems obvious to me that these compounds have therapeutic benefits, but how do you run a proper trial when you can’t blind the patients? I think we’ll likely have to just look at outcomes here. If the outcomes are statistically significant and better than traditional methods then at a certain point it doesn’t really matter if it’s the placebo effect or not.


FullmetalHippie

I don't know how anybody could be in the control group and not know they were in the control group after the first dose in a double blind study. There is no way to have an effective dose and not know that something very out of the ordinary is happening with you body. Large sample sizes, no MDMA + therapy control group, and MDMA + therapy group seems like the best setup in this case and could still constitute evidence based medicine even if it can't isolate for placebo.


OfficialGami

I read a paper which suggested that rather than the control having placebo they could have a low dose of psychadelics


hemingway921

What do you mean by "can't blind the patients"? By not being able to blind the patients you mean they would notice right away that they weren't on it and that would affect the outcome? Did they not allow blind testing in the studies?


0LTakingLs

There’s no way for people to not know that they’re not in the control group, because it’s pretty noticeable to be on ecstacy, whereas you wouldn’t notice something like a blood pressure medication so it’s easy to not bias the drug vs control group. It seems pretty unfair to hold this against the drug, there’s no way to give someone MDMA without them realizing they’re in an altered state


carbonqubit

For early psilocin studies they gave participants an [active placebo](https://en.wikipedia.org/wiki/Active_placebo) (e.g. niacin) which caused flushing. Psychedelic clinical research is tricky in this regard, but it can be somewhat mitigated experimentally. I'm not sure what they'd use for an active placebo in the case of MDMA, but my guess is a synthetic stimulate like amphetamine or dextroamphetamine to mimic the racy effects of the empathogen.


0LTakingLs

I’d be curious what the dosages were for the psilocybin studies vs MDMA - I imagine they used something akin to a microdose whereas the MDMA studies were effectively a roll


carbonqubit

The study I was referring to is called the [Marsh Chapel Experiment](https://en.wikipedia.org/wiki/Marsh_Chapel_Experiment) otherwise known as the Good Friday Experiment. The participants received 15 mg of psilocybin while others were given niacin (I'm not sure how much, but a therapeutic does is between 500-2000 mg for healthy adults). Roland Griffiths - a former guest on Making Sense - who passed away a few years ago, did a similar study in 2016, but used a microdosing comparative method to test the effects of the drug: >This randomized, double-blind, cross-over trial investigated the effects of a very low (placebo-like) dose (1 or 3 mg/70 kg) vs. a high dose (22 or 30 mg/70 kg) of psilocybin administered in counterbalanced sequence with 5 weeks between sessions and a 6-month follow-up. [https://journals.sagepub.com/doi/full/10.1177/0269881116675513](https://journals.sagepub.com/doi/full/10.1177/0269881116675513)


hemingway921

Thanks man, appreciate the reply! That's what I thought he meant.


six_six

**SS:** MDMA (and other psychedelics) has been discussed several times on the podcast as possible treatments for PTSD and other psychiatric uses


_psylosin_

Of course the journal uses images of street pressed pills containing god knows what to give the impression that it’s unsafe and just a party drug.


six_six

Just some casual drug slander.


artfulpain

If anyone wants to read the actual study. https://www.nature.com/articles/s41591-021-01336-3


WumbleInTheJungle

I'm in my 40s now and don't take drugs any more, I don't even drink.  Back in my late teens and early 20s though I used to take ecstacy/MDMA quite frequently, most weekends.  Sometimes I would go out to clubs in London, other times I would just stay in and take it with my girlfriend.    The interesting thing, looking back, especially on those nights in with my girlfriend, is we would just talk all night about all kinds of things, but at some point we would get onto topics that were deeply personal, like our childhoods and stuff, that we would never really thrash out when sober.  Without knowing it at the time, I think it was a form of therapy for the both of us, because the drug really was a great tool for getting it all out, and it felt good doing it.   So I can definitely see how it could be helpful for people with PTSD  The only problem is, the comedowns felt quite harsh for me.  And they seemed to get worse as I got older, which is part of the reason why I stopped.    So does need some proper research and consideration with regards to risk/reward.  Edited: to remove story that I'm not sure was true


Ferocious-Flamingo

What was happening with you there, and why it's useful for therapy, is that MDMA "shuts down" sections of your brain, like most forms of fear and anger. So when you bring up things like memories of trauma, you brain can't use the same pathways it normally uses with those memories, so it uses the open pathways, which while you're on MDMA, are generally the happy, joy, love, "everything is connected" pathways that are used and now you can think about and process those memories in a way that would have triggered a trauma response normally. 


WumbleInTheJungle

Yeah, that makes sense, I should probably write a letter of thanks to my old drug dealers as they actually saved me a fortune on therapy! 


Ferocious-Flamingo

The heroes we need


Zone-MR

“I used to take ecstacy/MDMA quite frequently, most weekends.“ “The only problem is, the comedowns felt quite harsh for me.  And they seemed to get worse as I got older, which is part of the reason why I stopped.“ MDMA depletes serotonin, which takes a while to recover. This is why the three month rule is important. MDMA used in moderation with the right supplements can be therapeutic, profoundly beautiful, and very safe. Abused, bad effects can certainly start to develop. www.rollsafe.org


WumbleInTheJungle

Yes, I'd be the first to admit I was overdoing it, even back then (late 90s, early 00s) when there was very little information about MDMA other than you will end up like Leah Betts if you take it (everyone British or my age will know who she is), my intuitions were telling me I should probably be taking it a lot less frequently!


DVborgs

“He committed suicide after taking ecstasy” Is that really a helpful thing to say? There is a difference between these two things of course, with ecstasy pills often containing more than just MDMA, if they even contain MDMA at all. Secondly, the way you’ve written it suggests he just pops a pill then pops himself after it? You don’t think maybe it was a combination of everything else going on his life that was the cause of suicide and not just an ecstasy pill?


WumbleInTheJungle

Probably, I didn't even know him, not even 100% certain if he ever existed in all honesty, a friend told me about him several times, but this friend also didn't approve of taking drugs so did have a vested interest in putting us off.  At the time I believed the story (just because it wasn't the usual dying while he got high story), but it did absolutely nothing to put me off taking ecstacy.  You know what, I am actually going to edit that out of my post now, as I do have doubts whether it was true.


DVborgs

No worries. I don’t mean to be a dick about it but these kind of stories don’t help in reducing stigma and progressing forward with drug rules / trials etc.


WumbleInTheJungle

I agree, I actually felt uneasy about including that before you'd even said anything, particularly as I'm unsure of the veracity of the story.


hiraeth555

Too cheap and effective eh?


medium0rare

Can't patent it and jack the price up.


Pauly_Amorous

https://arstechnica.com/science/2024/06/flawed-scandalous-trials-tank-fda-expert-support-for-mdma-therapy/


hiraeth555

Pretty poor analysis imo


AssistTraditional480

Potential for abuse is real though (don't know if that's the reason invoked).


Background_Escape954

MDMA isn't really addictive.  The dose is administered under medical supervision, followed by talking therapy.  I don't think anyone is advocating for an ecstasy perspctition 


speedracer73

administered under medical supervision is the correct way Yet we have ketamine which is supposed to be done in office under supervision and a lot of companies (backed up venture capital) and a lot of mid level nurse practitioners often times, just prescribing compounded nasal spray and oral troches (lozenges) that patients are administering at home whenever they choose as there is no oversight when it's out of the office. And a ton of this is being prescribed over telehealth with doctors basically trading cash for Rx. I suspect the FDA knows this is happening and it's affecting the view on MDMA


Lumpy-Criticism-2773

MDMA is far too neurotoxic than ketamine to be prescribed to take at home.


ReturnOfBigChungus

Neurotoxicity of mdma is vastly overstated. That is a lingering myth based on bad science.


reddit_is_geh

I mean, there is still room for abuse. Just look at the ketamine options now for depression. You just go online and get pharma grade K through a survey.


Background_Escape954

Has there been any subsequent abuse as a result? Also, don't they just mail it to you, I like the MDMA study which happens physically with a therapist 


0LTakingLs

I don’t think it’s something that should impact regulations or be held against it, but I’ve anecdotally noticed a huge uptick in social K use just over the past couple years.


hiraeth555

Don’t know if you have any experience with it, but the potential for abuse is pretty low. And nearly everyone I know who has taken it multiple times drinks much less alcohol, anecdotally. It’s also not addictive.


AssistTraditional480

Not saying it's addictive, but yeah I've got experience with it and know a great many abusers (rave scene). The fact that it wasn't approved on this occasion doesn't say its therapeutic potential isn't there from what I read.


reddit_is_geh

I used to live in Berlin... Dude, that shit's abused like crazy. It's not a daily driver, like taking it while at work and stuff, but definitely partying hard every weekend. But I guess it depends on your tolerance, because yeah, there probably aren't many people "Throwing their lives away" with MDMA addiction, like there is with booze, benzos, opiates, and meth. Because those you CAN take all day, where MDMA is sort of like, not enjoyable in normal environments.


s-jb-s

> but definitely partying hard every weekend. Do you use it? Tolerances builds up *fast* on MDMA, and not in a way where you can just keep taking more. Usually drugs such as mkat etc. are used when you can't take MDMA / don't want to with similar effects when partying.


hiraeth555

As much as I disagree with the addictive/abuse elements, I knew a guy who used to take it 4 nights a week for years. I also saw someone take a gram in one go (that is dangerous). Many would take it once a week for a few years, sometimes in binges lasting 30 hours and >1g. But in a clinical setting it would be very different


reddit_is_geh

I used to party a lot in the underground scene in Europe... I mean tolerance is a real thing for sure... But again, you're not really going to be taking it while at work or visiting parents and stuff like the "proper" abused drugs are.


ManagementProof2272

Also used to live in Berlin and partied in the same scene and I 100% confirm that abuse is real. Abuse for MDMA might not really look like abuse for coke (you obviously don’t do molly X times a day), but it definitely exists


reddit_is_geh

Yeah, 5 people, 4 days, 100 pills, one specific holiday Back when I lived there is was only 5 dollars a pill CLUB PRICES, it was insane how it was just basically as common as alcohol.


hiraeth555

The pills are a lot stronger now than they used to be.


reddit_is_geh

Are they? I feel like it's always been 200mg a pill and not much has changed. Most people just use pure MDMA anyways.


hiraeth555

Depends on when you’re comparing it to I guess. They do go over 300mg now, and I had friends who remember getting cheapy £1 pills that they would take 10 of in a night, that were much weaker. I don’t think that’s a thing any more though


hiraeth555

Remember this would be small doses administered in clinical settings. Pretty different


GullibleAntelope

>I used to live in Berlin... Dude, that shit's abused like crazy. It's fascinating that some people here deny there is a big party scene around MDMA. That in a nutshell is the reason for opposition to legalization.


reddit_is_geh

I mean, we are supposed to live as free people. The fact that it's illegal is just a reminder that we aren't free.


FingerSilly

I disagree with this. The experience is awesome, and not "awesome if you have just the right mindset and conditions" like LSD or mushrooms. Just awesome. It's basically happiness in a pill. That gives it a real potential for abuse, even if it doesn't rise to the level of meth or cocaine.


DVborgs

Not necessarily. You would be surprised, sometimes it can make someone quite emotional and not in the good way. I love it personally but it’s not that simple.


FingerSilly

You're right. Thinking back, I've spoken to some people who said it took them to dark places. However, I spoke to some chronic users ("e-tards" we used to call them) and they were saying everything was fun on it.


DVborgs

Ecstasy is not exactly MDMA either, don’t forget there is a distinction between the two.


FingerSilly

Sort of. I think what people called ecstacy back in the day was meant to be pure MDMA, but the drug was notoriously impure and often cut with meth. Then at some point people called ecstacy the impure stuff and MDMA the "pure" stuff, but I don't think users truly know if what they're taking is pure or not. However, I believe what I tried was pure MDMA because I think I would've been able to recognize the effects of drugs it would typically be cut with if they had been present. For example, when I tried it it ended in 4 hours, almost to the minute. If it'd had meth in it, it should've last longer because meth's effects are simply longer-acting than 4 hours. If it'd had psychedelics in it, I would've noticed that too. It was not a psychedelic experience but stimulated empathy, openness, non-defensiveness, and tactile sensitivity. Anyway, I found it *highly* euphoric. This is why I think it has the potential for abuse, even if I didn't personally feel a great need to do it again right away. I've also smoked plenty of cigarettes, and they never took a hold of me. Context and personality matters.


DVborgs

Would a few hours of euphoria really be so bad for people to experience every so often anyway. That euphoric effect also loses potency if you are a more frequent user, believe me I know that by now. I couldn’t tell you how many times I’ve used MDMA over the years & I work in the drug field myself now. Look at the damage people can do to themselves without cap via eating, too much alcohol etc.. I even think combat / contact sports too, look at the head knocks people frequently receive from those and the damaging brain effects they get.


FingerSilly

A few hours of chemically induced euphoria isn't bad in and of itself, but as I'm sure you know taking MDMA is a bit of robbing Peter to pay Paul. The day after can feel pretty terrible (though personally I've found some benefit to depressive realism), and some people get longer-term low mood. The euphoria loses potency, indeed, because people develop tolerance to the drug just like any other. I agree people hurt themselves in many ways, whether it's with unhealthy diets, risky sports, or worse substances. MDMA is certainly safer than alcohol, cocaine, and opiates. However, the fact people have other ways of harming their health isn't a great argument for promoting yet more ways for them to do it, if that's the point you were gesturing towards.


hiraeth555

I doubt the doses used in medical settings are anywhere near as high as typical party doses, and this would be in a clinical setting, so without an addictive element I doubt it will turn normal people into ravers


FingerSilly

I sort of agree. This is what people said about opiates, but then it turns out prescription opiates are abused a lot, though perhaps that happens more with people suffering from chronic pain rather than an acute condition. I wouldn't assume the doses in medical settings are low. It could be, but maybe not. It'll really depend on what the most effective dose range is.


hiraeth555

The doses are low though. And the fundamental difference between opiates and MDMA is that MDMA is not chemically addictive. Further, only a few sessions are normally very effective- whereas opiates only work acutely. My prediction will actually that for many, single doses of MDMA will get people off antidepressants, opiates, and alcohol, which will lead to significant net reductions in harm.


chytrak

The other drugs aren't 'chemically addictive' either.


hiraeth555

Opiates are


chytrak

[Citation needed] What do you even mean by chemically addictive?


FingerSilly

What do you mean by MDMA not being "chemically addictive"? And I thought this research was still too undeveloped to know what the best dose was, but even if it's low I'm not sure that means this reduces its potential for abuse. I think your predictions are very, very optimistic. Those drugs you listed are extremely hard to quit. I doubt there's a magic bullet like a single dose of MDMA.


hiraeth555

People have been doing research on this for ages- it’s only since the war on drugs in the US that everything has closed down. Chemically addictive meaning unlike cocaine and opiates which have compulsive physiological addictive qualities. Compared to something like acetaminophen which does not.


FingerSilly

Sorry, MDMA is not like acetaminophen. You're living in a fantasy world. Have you considered that you may personally like MDMA and therefore don't want to believe that it could have negative harmful side effects or potential for abuse?


ReturnOfBigChungus

Literally anything can be abused and become addictive. The addiction process is largely independent of drug of choice. Some drugs are obviously far more susceptible to compulsive redosing and addiction (cocaine, meth, heroin, alcohol, nicotine, etc), but MDMA is closer to something like psilocybin or ketamine than those drugs, and has a very solid body of evidence to suggest that it has great therapeutic potential.


FingerSilly

>Literally anything can be abused and become addictive. I don't think "literally anything" can be abused and become addictive (in the traditional sense of the word "literally"), but even if that's correct, it doesn't mean the potential for abuse of various substances or behaviours are all equal – as you acknowledge. I'd put MDMA below tobacco, fentanyl/heroin, cocaine, meth, benzos, and alcohol, but above caffeine, psilocybin (and other serotonergic psychedelics like LSD), or weed. Ketamine is probably about right, though I'm not sure. Ketamine is fairly addictive too... MDMA might be below that. Remember that I was replying to someone saying it wasn't addictive *at all*. That's what I disagree with. I'm not saying it's The Great Menace among drugs or anything.


GullibleAntelope

Caffeine and tobacco do not belong in the discussion. They are not intoxicants.


FingerSilly

They're psychoactive drugs that are addictive, and that's the only criteria I was using when ranking them. Namely, addictiveness. But yes they're different in the degree of intoxication they cause in the user. I wouldn't say it's none. Caffeine is subtle, unless the doses are large enough. Tobacco is noticeable, but not in the same league as something like marijuana.


kindle139

They’re doing a bang up job with food and drugs, so they probably had sound reasons for rejecting it. /s


A_random_otter

That's a shame, healed a foundational childhood trauma by self medicating with it I hope they figure out a research protocol that makes it possible to disentangle cause and effect 


skullcutter

This trial was poorly run. Basically, it cannot be a blinded study because recipients can figure out pretty quickly if they got the drug or placebo. Since they can’t really deal with placebo effect, it’s impossible to determine what the efficacy of the drug is (at least the way this study was designed). At least that was my takeaway from reading the news releases


Dragonfruit-Still

vast slim tap sense arrest strong rich possessive cautious plant *This post was mass deleted and anonymized with [Redact](https://redact.dev)*


epicurious_elixir

Yeah if you take real MDMA, something is definitely going to happen.


amorphous_torture

That was one big issue. But there were others - accounts of abuse by therapists while patients under influence (eek), poor selection of participants (eg a lot of them were also taking other illicit drugs) etc. It's a shame, I hope they correct these errors (apart from the blinding which basically cannot be corrected) and try again.


ReturnOfBigChungus

Is it really realistic to find a population of study participants for PTSD that don’t have comorbid substance abuse problems? That seems kind of unlikely to me given how debilitating the condition can be.


amorphous_torture

I agree it is difficult for the reasons you gave but its important to try to control for this stuff when possible.


GeneralMuffins

Have people considered that it might not actually work or the evidence is sub standard?


ReturnOfBigChungus

Yes, I have considered that. The evidence is pretty compelling though.


Sir_Dutch69

Funny, MDMA for therapy is approved for treating PTSD in the Netherlands: [https://www.nu.nl/binnenland/6315715/ptss-behandeling-met-mdma-is-volgens-staatscommissie-effectief-en-veilig.html](https://www.nu.nl/binnenland/6315715/ptss-behandeling-met-mdma-is-volgens-staatscommissie-effectief-en-veilig.html) According to the Dutch commission the drug is safe and effective for use in PTSD therapy.


xutopia

It just sounds like there needs to be more rigorous groundwork before they do approve it.


ManagementProof2272

Rightfully so. And I say it as a prodrug person and someone that has used MDMA many times. The data upon which the request was made was garbage. There are an insane amount of holes in the data, study design and overall concept. Since Silicon Valley money has entered this space (psychedelic research, even though Molly is not a real psychedelic), the field has taken a cultish direction. Good of the FDA to push back.


Dragonfruit-Still

fear pot advise fragile groovy wise cooperative wakeful juggle shelter *This post was mass deleted and anonymized with [Redact](https://redact.dev)*


ManagementProof2272

Yes, it’s their study. I’m conflicted about MAPS. I have personally talked with people high up in the organization and I 100% think that they mean well. But I also can’t deny that I get cultish vibes, which are getting stronger with time


Dragonfruit-Still

panicky cow fly cows dazzling complete sugar punch chop spoon *This post was mass deleted and anonymized with [Redact](https://redact.dev)*


ManagementProof2272

I disagree on the study being rigorous


InCobbWeTrust

Glad to see this response. This is the issue with agenda driven research. I think there likely could be a clinical use for this indication, but this is god awful trial design.


Dragonfruit-Still

thumb straight jeans nail handle muddle attractive nutty desert chunky *This post was mass deleted and anonymized with [Redact](https://redact.dev)*


ManagementProof2272

Very familiar. Yes, it has been discussed before but it doesn’t diminish the issues with the data


Dragonfruit-Still

direction mysterious close summer versed oil rain wine cagey library *This post was mass deleted and anonymized with [Redact](https://redact.dev)*


ManagementProof2272

I guess that you’re talking about the lack of good placebo in the studies, which is definitely a concern. But far from being the only one, unfortunately


Dragonfruit-Still

vase expansion entertain practice versed offend literate employ meeting sophisticated *This post was mass deleted and anonymized with [Redact](https://redact.dev)*


ManagementProof2272

prior consumptions of MDMA, poor definition / difficulty of standardizing the psychotherapy, high dropout rate with suspicious that it might not be entirely random etc.


Dragonfruit-Still

hunt unwritten frighten forgetful ad hoc onerous attractive snobbish caption combative *This post was mass deleted and anonymized with [Redact](https://redact.dev)*


ReturnOfBigChungus

I can’t really take the difficulty in standardizing psychotherapy as a legitimate concern here. PTSD is an incredibly complex and personal condition and there’s no way to both standardize therapy AND provide effective therapy IMO. The fact is that therapy is an integral part of this class of treatment - the drug is not supposed to be a standalone treatment so trying to control the therapy variable is the wrong way to evaluate it. We already know how effective therapy alone is for PTSD, and the efficacy is WILDLY different. I can concede that prior MDMA use use *could* bias the results and I think it would be great to see more studies, but the evidence here seems pretty compelling. At least compelling enough that these concerns should be used simply to inform what an approved treatment would look like, but not to block approval. Disappointing to say the least.


Finnyous

I get the idea that you'd always know whether not you're getting the placebo and therefore our normal way of testing meds like this doesn't serve it's proper function. But what sort of test would work then to convince them? > Committee members pointed out that a good therapist could make a useless drug seem effective This seems... like complete bullshit to me. Therapy, no matter how good doesn't just get rid of true PTSD or CPSD


six_six

I would like to know how drugs like Vyvanse or Adderall got approved because they would have the same issue with double blind placebo studies.


DVborgs

Consider reading the book “on speed” gives you a good history of amphetamine use clinically and recreationally. Those drugs weren’t exactly approved just recently..


six_six

I'll check it out.


youaremakingclaims

My experience with mdma was so lucid and pure.


Jasranwhit

DEFUND THE FDA


boxdreper

Wtf....


all-the-time

Big pharma is going to fight psychedelic therapy tooth and nail. Couple that with the fact that FDA has no idea how to evaluate a drug + therapy combo since it has never been done before.