[Aurornis]

> Responsibly (test it first!). Not too much. Just a couple times a year.

MDMA fans will argue this on the internet, but MDMA use (even without polydrug abuse) is associated with cognitive deficits in memory and learning. There’s a lot of experimental evidence showing it has damaging effects on neurons.

The damage done by a drug like this wouldn’t necessarily be obvious or even at the level to pass the threshold of significance in a scientific study after one or a couple doses. However, there isn’t much debate even among drug users that taking MDMA frequently produces some profoundly debilitating effects on long-term users.

I think everyone should be aware that it’s very likely that each MDMA dose is incurring some level of damage that is either long-term or potentially permanent. A couple sessions at moderate doses might not produce strictly significant effects but it’s amazing how quickly people go from “a couple times per year on special occasions” to having 20-30 exposures over a decade or two, which starts putting them beyond even the inclusion criteria for most light use studies that were performed.

EDIT: Also note that using DIY testing supplies on your pills is great practice and necessary in the age of fentanyl, but it’s not definitive. The only real way to test is to ship some of your pills off to one of the groups that tests for free and wait months for the results. Pills can contain multiple substances. There is a problem right now where one of the “research chemical” manufacturers has produced a large batch of a compound that is normally used for lesioning (damaging) serotonin neurons in lab studies. It has recreational effects, though, so it’s being sold as a drug. There’s concern that vendors will start mixing it into pressed pills to cut them with an active substance.

[otherme123]

Meanwhile, taking a couple of beers daily for decades doesn't make anyone raise a brow, you can even find people that says it's good for your heart, according to some doubtful study from the 90's.

In some of those studies you might be referring (e.g. DOI: 10.2174/1874473711306010008) say that MDMA users score worse in memory, but better in depression and anxiety, and equal on cognitive or mood. Of course what makes the headlines is that MDMA is bad for memory, no mention to the positive effects. And of course, the narrative would be that if you take MDMA a couple of times per year, soon you won't even remember your own name.

[Aurornis]

> Meanwhile, taking a couple of beers daily for decades doesn't make anyone raise a brow

There are a lot of people bought into the idea that ~1 drink a day is beneficial due to the flawed studies like you pointed out.

But most people who keep up with things know better. My primary care doctor gives a reminder that drinking is not healthy despite what some old headlines claimed (even though I rarely drink).

Even the podcasters seem to have caught on, with many emphasizing that no amount of alcohol is beneficial and even 1 drink per night consumed consistently over time has damaging effects.

There is a lot of backlash when podcasters get too close to these subjects. I remember when Huberman touched on the topic of marijuana and Reddit was up in arms. Huberman isn’t great at scientific accuracy (to say the least) but he was directionally correct. Many people didn’t want to hear it, though.

People like to think their drug of choice is the safe one. They cherry pick a few studies that agree and choose to dismiss anything that doesn’t.

[sireat]

Sure alcohol is not healthy.

Unfortunately, neither is oxygen.

Now you will say that we need oxygen and can survive without alcohol. But then again, we do not have a Faustian bargain of choosing to abstain of all the fun things in life and living for 200 years.

The elephant in the room is that no matter how healthy a life style you live, we presently have no way to reverse a rapid decline in quality of life around 85-90 culminating in complete collapse ages 100-110.

And those are absolute best case scenarios!

My illusion of being in control of your destiny was shuttered when Jack LaLanne - https://en.wikipedia.org/wiki/Jack_LaLanne died at 95.

You can have a great quality of life until mid 80s by leading a moderately healthy lifestyle provided you do not get cancer.

After that we are a loss on how to prolong our lives.

I would almost welcome if Larry Ellison would prove us wrong in 10-15 years at least there would be theoretical hope. We'll see about Peter Thiel as well, but I will not be alive to see his experiments.

[Retric]

There’s a huge difference between living to a healthy 85 and having major cognitive / physical issues at 65 and symptoms well before then. Yes you’re guaranteed to have significant physical decline by 85, but the baseline isn’t static you can still be more physically capable than an un athletic 30 year old.

So we’re talking roughly an extra 30%!

[shlant]

it is concerning how many people do not understand the VAST difference in quality of life and physical/mental ability over the age of 50 between someone who takes decent care of themselves and someone who doesn't. So many times I've heard people, in the face of making healthier choices, respond with "why would I want to live longer anyways, I'm going to be old and decrepit!". Very sad perspective.

[reverendsteveii]

tw - drugs, addiction, overdose, severe illness, death tldr - I was this dude until I got to see how things turned out for someone with the same attitude roughly 30 years older than me

I was one of those "Here for a good time, not a long time" people in my twenties. Booze, drugs, parties, shows, "Why would I wanna skip all of this just to go to the gym and pretend to run?" After a few years of partying like that you assume the hangover is the worst thing that'll happen and you'll bounce back after two days. But the universe had a gift for me: my uncle, who was about 35 years older than me, had the same attitude. I watched his addiction progress from "he just likes to have fun" to "sure he drinks too much but underneath it he's a good guy" to a point where his family was making him sleep in the garage. The whole time this was happening he was "Here for a good time, not a long time".

It took him over a year to die, once they determined that the liver and kidney damage was beyond mitigation or repair. I got to take care of him, as I lived with my mom (his sister) and his nuclear family had kicked him out after he pulled a gun on his daughter for coming home pregnant. In that year, he lost motor control, couldn't walk and could barely talk. Once I watched him try to tip his head back to drink from a glass of water and his head just kept going backward until he fell over. Only one of his three kids bothered to visit him. It was the one he pointed a gun at. He forgot her name.

Did you know that organ failure has a distinct smell to it? It's ammonia and engine coolant, saccharine sweet but with just a hint of rot. Our whole house smelled like that for the last few months. Those miasma months were spent helping him to the bathroom and explaining to him that he's at Vicki's house, Vicki is his sister and no he can't take his truck and go to the bar because he doesn't have a truck anymore and his license is revoked. He spent the last week of his life in someone else's bed, howling in pain and terror.

I, otoh, got my shit right. I'm not entirely sober but neither do I party like I used to. The bargain I made with myself is that I can do drinks with friends a maximum of twice a month, and I can't ever do drinks alone. I've been able to stick by that for several years now, even after the overdose death of my brother (who was another one who never saw the sense in anything other than maximum immediate fun). I take two fifteen-twenty minute workout breaks per day, one for weights and one for cardio. I've lost 25% of my body mass, I can bench press my dad and I'm actually having a much better time than when I was having a good time all the time. He was in his fifties when he died. I'm 40 now, and while he had already started his decline at 40 I'm stronger and more capable than ever. And I don't even have to tell myself "no" very often. Usually it's just "That's enough for now".

Maybe one day I'll be old and decrepit, but I won't be middle-aged, decrepit and hated by everyone I know. To me that's such a good deal I can't imagine why anyone would turn it down.

[reverendsteveii]

>My illusion of being in control of your destiny was shuttered when Jack LaLanne - https://en.wikipedia.org/wiki/Jack_LaLanne died at 95.

Can we deep dive into that statement? To me, at a glance, LaLanne's life looks like one that began out of control, then he took control of it and through doing more or less what everyone recommends (high protein, high fiber diet low in sugars and carbs with a bunch of exercise every day) he got exactly what one would expect (a life well past the mean life expectancy and with a relatively high quality of life even into his 90s, even being able to do his normal workout routine before he died). Unless you took him literally when he said "I can never die" that feels like an overwhelming confirmation that diet and exercise are key parts of a long, healthy and happy life.

[verisimi]

I personally do not find the idea of endless life in this world appealing at all. I don't even get the desire to live to 100+, nevermind 200. I tend to think that the 'longevity desire' is prompted within oneself when one is not living according to whatever-it-is one thinks one should really do. The rat race is compelling sure, one needs money etc, but that is not the entire purpose of life. Perhaps some seeking/introspection is needed to make life meaningful.

[jajko]

Happy people are generally OK with going anytime, grateful for every moment and experience and only want to have closest ones taken care of. Unhappy ones, especially when its something deep and hard or impossible to tackle, want more and more, like they could somehow fix things in future or cover them up enough to finally arrive at that point they'll never arrive anyway.

Project it to some extremes and its easy to see why sociopathic dictators and billionaires (which most if not all of them are) would love to see significant life prolongation, of course only theirs. One of the biggest threats to near future mankind as it is IMHO, imagine 300 years of rule of pos like puttin' for example.

[bdangubic]

no X, no beer - you get to live to be 100 :) except you know, boring as shit :)

[Centigonal]

There is also evidence linking some common pharmaceuticals to long term deficits in memory and cognition.

Diphenhydramine (Benadryl/OTC Sleep Aids) use is associated with an increased risk of dementia [1], while benzodiazepines like Xanax and Ativan are strongly associated with long term cognitive deficits [2]. Taking many drugs is a cost-benefit analysis, and it's important to be informed about the possible consequences before diving in.

[1] https://www.health.harvard.edu/blog/common-anticholinergic-d...

[2] https://academic.oup.com/acn/article-abstract/33/7/901/47349...

[distances]

> Meanwhile, taking a couple of beers daily for decades doesn't make anyone raise a brow

That totally raises eyebrows I'd say. I like beer as much as the next person, but nobody I know pretends that daily beers would be fine, healthy, or even acceptable. The only person that I know of who likely drinks ~daily self-identifies as an alcoholic.

[otherme123]

I avoid alcohol like the plague. I'm spaniard, and I can assure you that there are a lot of people that takes one glass of wine with each meal (something that qualifies you as an alcoholic in medical terms). In the summer, beer is king, and I would say half the population takes at least a bottle (33 cl / 12 fl.oz.) daily, as a substitute for water (luckily, zero-alcohol beer is also on the rise). Wouldn't be unheard that you drink wine or beer at lunch and then go to work until 6pm.

Alcohol consumption is totally normalized here. In fact, the only socially valid reason to not drink at a party or celebration is that you are driving later. That's my experience at least.

[distances]

True that this surely is very much culture dependent.

I'm also from Europe but a bit higher up, and grew up in a party drinking culture. It wasn't an issue if you were drunk twice a week as long as those were the designated party days, Friday and Saturday, and Sunday was reserved for the unavoidable hangover.

Alcohol with food wasn't too common so drinking alone on other days heavily hinted towards losing control.

[carlmr]

>Alcohol consumption is totally normalized here. In fact, the only socially valid reason to not drink at a party or celebration is that you are driving later. That's my experience at least.

It's a bit sad, but it's a reason I pick the car sometimes. To have an excuse for not drinking.

[chrisdhal]

I think this may be generational. I'm GenX and growing up it was no big deal for my parent's generation (yes, the boomers) to have a drink a night. Even among people of my generation now it wouldn't be uncommon. Probably less than before, but I don't think anybody would think twice about a beer or a drink per day would be any big deal.

[investa]

Raises my eye brow, even before watching Huberman. A week of drinking everyday makes you feel shit.

[serjester]

I would love to see some studies on this because everything I've seen is either rats that were exposed to truly insane doses (10X more than a human would take) or among long term, heavy users (weekly).

I don't necessarily doubt that there's some level of brain damage going on, but the extent is poorly understood and likely over exaggerated.

[Aurornis]

> because everything I've seen is either rats that were exposed to truly insane doses (10X more than a human would take) or among long term, heavy users (weekly).

These studies get emphasized by MDMA proponents because they find them easiest to argue against.

Many of the arguments are based on flawed logic, like taking rat mg/kg numbers and translating directly to human mg/kg numbers. This isn't how drugs are scaled to animal doses (see https://pmc.ncbi.nlm.nih.gov/articles/PMC4804402/ if you want to understand) so it leads to a lot of claims that studies are giving insane doses when they may not be.

Honestly this game isn't my favorite because someone always comes along to point out why various studies aren't 100% perfect in humans with a large sample size and then tries to suggest that therefore it should all be ignored. If they can't attack the study, they attack the motivations of the authors or insert claims like how the sample group may have been taking other drugs. If that fails, they try to claim that the drug users may have had those deficits to begin with, which led to the drug use. It goes on and on.

Here's one random study where abstinent users had decreased memory scores. The decrease scaled relative to how much of the drug they recalled using: https://pubmed.ncbi.nlm.nih.gov/9855498/ (Opponents will point out one of the authors is hated in the drug community due to past controversy and therefore they won't trust the study)

Here's another one where ex-users showed verbal memory deficits, among other things: https://pubmed.ncbi.nlm.nih.gov/16510479/

It's honestly not hard to find studies like this, but what you won't find is big placebo-controlled gold standard trials with enough dosing to achieve statistical significance. That's because it's not ethical to do so, and therefore it won't happen.

[serjester]

I appreciate you dropping those.

In https://pubmed.ncbi.nlm.nih.gov/9855498/ the average dose was a staggering 440mg a month (multiple rolls a month) with a sample size of 24 people. This is definitely falls under "heavy" usage and even then it's hard to disambiguate correlation vs causation in such a small, underpowered study.

The average participant in your second study, https://sci-hub.ru/10.1177/0269881106059486, had again taken an average of 800 lifetime doses. These are insane amounts and do not remotely reflect the average user.

Here's a meta study for example that found no long term impact among more realistic users - https://pmc.ncbi.nlm.nih.gov/articles/PMC3053129. I haven't looked into this in a long time, so I ran a deep research query, and for typical usage (<50 lifetime doses, months between sessions) there seems to be very little evidence of structural or functional harm.

[1] https://chatgpt.com/s/dr_6817cd9ce85081918c7d55fa9a28c654

[tpm]

> why various studies aren't 100% perfect

You have to agree the presented studies are very far from 100% perfect, you just chose to believe them. That is your choice but you shouldn't force this choice on others.

> what you won't find is big placebo-controlled gold standard trials with enough dosing to achieve statistical significance

Would they be really needed if MDMA really was the killer drug you are making it to be? Because for alcohol (or heroin) abuse it's not that hard to get statistical significance from observation studies on population - a combination of large number of people abusing alcohol and its large negative effects. Where are similar studies for MDMA proving your claims?

[kin]

Same, any existing study I've read follows abuse-level or Chronic usage. Would love to know affects of recreational usage.

I'd imagine such a study would be quite difficult because so many things could affect your results: sleep, diet, age, alcohol, covid, etc.

I know nothing about this but I feel like the technology exists to scan your brain before and after to see neuron damage. I just want to know if a single use causes permanent brain damage and to what extent.

[magicalhippo]

Like those old "mobile phones are bad for you" studies, where they effectively cooked rats in microwave ovens and found out that wasn't healthy for them.

[valec]

dosed reasonably (~125 mg with no redoses), ideally at lower ambient temperatures, and ideally with an SSRI at the end of perceptible effects to stop MDMA to keep circulating through the neuron and causing oxidative stress, you will quite literally see 0 axonal damage. maybe some neurotransmitter depletion, but this is only temporary.

PCA yes that is concerning but I would be extremely surprised if it ended up in the MDMA supply chain. MDMA is made cheaply at quantities several magnitudes higher than research chemicals. it's much more likely PCA will be sold as a cut for others RC's -- especially as a part of those dreadful cathinone soups labelled "3-mmc" these days

[Aurornis]

> you will quite literally see 0 axonal damage.

There is absolutely no scientific backing to support such an absolute claim.

The animal studies using SSRIs worked because they dosed the SSRIs before the MDMA. By occupying the serotonin transporter the MDMA is prevented from entering the neurons, which prevents the damage.

Taking an SSRI afterward might do something for the very tail end of the dose, but that's after most of the action and therefore most of the damage. You can't get all of the recreational effects, then block the transporter afterward and expect the same protection.

SSRIs are also potentially dangerous with MDMA due to the possibility of serotonin syndrome.

There have been numerous recipes floated around in drug circles for combating the neurotoxicity but they’re extrapolations and hypotheses, not firmly supported concepts.

[el_nahual]

What is the best resource for "safer" MDMA consumption? (Like, which SSRI to take and at what dosage).

Also, isn't mixing SSRIs and MDMA a huge no-no, given the potential for a serotonin storm/serotonin syndrome?

[cess11]

You should avoid SSRI:s adjacent to MDMA use. The hypothesis is that by blocking the serotonin transporter you'd avoid dopamine getting reabsorbed into serotonin vesicles, but there is very little evidence that this would work and there are obvious risks.

SSRI:s will give you a strong tolerance against serotonergic drugs and it will take a long time to lower that tolerance, months, maybe a year or two. As far as I know it hasn't been studied scientifically but I've seen people get quite uncomfortable experiences from MDMA and 5-HT2a-psychedelics (LSD, psilocybin, mescaline, those) after being off SSRI medication for several months, that I amateurishly attribute in part to downregulation of serotonin sensitivity.

A more acute risk is MAO inhibitors, which are sometimes prescribed as antidepressives. You're more likely to suffer acute damage or die from a combination of MDMA and an MAOI than with an SSRI, though neither is a good idea.

The Bluelight forums are a decent source of harm reduction advice, https://www.bluelight.org/community/forums/. Be aware that some participants in the discussions have problems with risky or abusive use, or give bad advice. Stickied guides tend to be of high quality, however.

[_bin_]

Nope. https://pubmed.ncbi.nlm.nih.gov/16472832/

2mg/kg dose, so ~160mg for an adult human. More importantly rat to human is usually a 6ish HED factor so that’d be <30mg. In reality metabolism, brain volume, etc all matter but this is not an even remotely safe drug.

Also taking SSRIs near MDMA administration is one of the worst pieces of what is doubtless intended as harm reduction advice I’ve ever seen. You don’t hand people a recipe for serotonin syndrome because of a small scale rat test or two.

[valec]

> Also taking SSRIs near MDMA administration is one of the worst pieces of what is doubtless intended as harm reduction advice I’ve ever seen. You don’t hand people a recipe for serotonin syndrome because of a small scale rat test or two.

you have a deep understanding of releaser pharmacology if you state this. don't take it from me though--matthew baggott, one of the leading researchers studying enactogen pharmacology recommends doing this exact thing

[_bin_]

Okay, I looked at Baggott's work a little more. Here are my primary concerns:

1. He's talking his book to a certain extent. This is his life's work and he runs a company in this space (though a B corp) so he will have a bias here. That's fine overall, as it may help balance people unfairly biased against psychedelics, but it's worth remembering. I'm not saying this to impugn his character so much as to point out everyone has biases, and someone in his position likely has strong ones, even if partially-founded.

2. He believes an SSRI alleviates negative symptoms, but we don't know it does more than alleviate the comedown. It appears his endpoint was cognitive performance post-use, not long-term damage that may appear once off the SSRI.

3. This doesn't touch the dopaminergic risks of amphetamines, which are substantial.

A few exploratory bits of research into one potential way to alleviate the acute effects post-administration don't translate to an established method to use this in a remotely-safe fashion.

[amanaplanacanal]

Likely all amphetamines are neurotoxic the same way MDMA is, but we still use them for many things, including adhd. As a wise man once said, the dose makes the poison.

And as we know alcohol is carcinogenic and there is no known safe dose, but people still drink.

[cess11]

One of the main hypotheses is that concurrent release of neurotransmitters can cause dopamine to be reabsorbed into serotonin vesicles where the 'wrong' MAO enzyme breaks it down, releasing hydrogen peroxide.

Another hypothesis is that the human serotonin systems, specifically the prefrontal cortex, are relatively young and not evolved to take a beating, unlike the 'fight-and-flight'-related dopamine systems.

One indication that this might be the case is differences between people that use amphetamine regularly through nasal or oral routes compared to people using MDMA in a similar manner, where the latter group typically suffers more obvious neuronal damage faster. Amphetamine needs to be taken at very high doses to affect the serotonin transporter, so you'd typically see this in users mainlining lots of it.

As far as I know you don't see the same mental and neuronal risk profile with e.g. 6-APB and similar benzofurans that David Nichols lab produced in the nineties, as with MDMA. They are also not as subjectively rewarding and 'fun' as MDMA, indicating that the dopamine release plays an important part in this regard.

'The dose makes the poison' is usually credited to Paracelsus, late 1400s, early 1500s. Whether he should be considered wise is a matter of debate, Francis Bacon disagreed and argued against Paracelsus and the rosicrucians that did consider him to be.

Edit: Should probably add that methamphetamine is a much more potent serotonergic agent than amphetamine, and in some societies 'amphetamine' or 'amphetamines' tend to actually mean meth because that's what's available to them.

[_bin_]

There are a lot of possible mechanisms:

- mitichondrial inhibition

- hyperthermia

- excitotoxicity for DA at least

- hyperthermia speeds up redox cycling of dopamine quinones

- more quinones due to all your dopamine unprotected by vesicles

- metabolic impairment means harder to regenerate NADPH/make glutathione

- probably others I can’t remember at the moment.

You may notice many of these “synergize” in a way that’s particularly bad for the user.

It’s really not worth touching for anyone outside a clinical setting.

[cess11]

Someone else said that all amphetamines are likely to be neurotoxic the same way MDMA is. I responded that they don't have to be.

Why did you take this as an invitation to do a purely theoretical exercise in listing possible mechanisms for neurotoxicity? At the very least you ought to have anchored your reasoning in actual risky MDMA use, what people actually do, instead of just ranting out words that could scare a layperson. I.e. behaviours that are common, like combining MDMA with alcohol, or dopaminergic psychedelics like LSD and 2C-B, or forgetting to drink water, or whatever that isn't pseudo-academic stuff like 'sped up redox cycling of dopamine quinones'.

I also think you should have taken the time to show that you have an understanding of why millions of people disagree with you. In my opinion it would also be prudent to compare the risks you see with other neuronal risks, like living in an environment with ICE exhausts or having kids and suffering sleep deprivation for years on end or just plain old poverty. The latter is shown to, on average, have detrimental effects on the brain that can be clearly visible in medical examinations, unlike sporadic, responsible use of MDMA.

[_bin_]

This is a weirdly defensive answer. I didn't attack you personally, I brought up well-founded risks.

Your suggestions, while interesting, don't remove these risks. Yes, certain types of abuse make it worse: dosing higher, polydrug abuse, hot environments, and dehydration are all ways to damage your brain further. However, use of MDMA in an ideal sense probably still causes some level of damage.

https://pubmed.ncbi.nlm.nih.gov/16472832/

2mg/kg dose, so ~160mg for an adult human. More importantly rat to human is usually a 6ish HED factor so that’d be <30mg. In reality metabolism, brain volume, etc all matter but this is not an even remotely safe drug.

This isn't a "purely theoretical exercise", most of those are established mechanisms of amphetamine toxicity. This isn't "listing possible mechanisms", this is sharing salient info of risks of which possible abusers (given the nature of the thread and discussion so far) should be aware.

I'm sure as heck not "ranting out behaviors that would scare a layperson". Most of what I listed is pretty comprehensible with a grasp of high school chem and bio. Most of the information for this is freely available online. The information we have should scare a layman out of use, and probably someone with a greater background, too.

Whatabout-ing with sleep deprivation or similar doesn't make sense to me either. Did I say that was good or healthy? Bad things stack. Your body doesn't keep a record where it says "you've accumulated 10% damage from an un-fun cause like exhaust or sleep deprivation, so now you get to experience 5% damage from a fun cause like molly." That's just a really weird way of thinking about this.

People are within their moral rights to run the risk but I don't understand this defensiveness that it's somehow a good or smart risk to run for the average case of abuse.

[cess11]

It's as if you didn't read my comment. I said nothing about risk mitigation.

I find it unethical to try to scare people away from recreational drug use, for several reasons. One being the inherent distrust of their ability to form their own opinions, another the kind of linguistic gatekeeping involved where scientific information is withheld through the use of professional or academic vocabulary, and yet another that I don't believe that it works, in my experience it has more often than not the opposite effect and enables or fuels harmful behaviour.

Where do you live, is it actually true that they teach neuroscience in highschool there or did you just make that up? Or do you think one can do a risk assessment from your comments without having a scientific understanding and mental model of the nervous system in general, and the central nervous system in particular?

We know from a lot of informal experimental data that sporadic, responsible MDMA use is, on average, very safe. It's likely to be safer than a long term weed habit, which carries a risk of damaging the heart and things like bronchitis, besides the contamination risks which are relatively hard to test for.

Also, it's not "whatabout-ing". Without a frame of reference the risks you bring up are meaningless to most people and useless in regards to policy. To judge whether you want to take the strictly neurotoxic risks involved in dancing on MDMA you'd need to understand how it compares to other factors in your life. In practice few people go about it in this way, however, and for good reason because the immediate risks involved in going to roll at a rave like party are of a quite different nature. Things like traumatic injury from a fall or sexual abuse or financial harm or the psychological effects of mistaken intimacy with strangers or somesuch.

Having fried a piece out of n thousand axon terminals isn't really a concern to most users, and compared to the drudgery of everyday life it likely feels like a low price to pay for many people. To convince them that this should be their primary concern requires another strategy from you..

[neilv]

> I think everyone should be aware that it’s very likely that each MDMA dose is incurring some level of damage that is either long-term or potentially permanent.

In school, I knew a very smart person who got into drugs, especially MDMA. They later got clean, but when they got brain imaging done for some reason, a doctor who looked at it said they could tell the patient had done a lot of MDMA. Reportedly, the damage was visible on the imaging, and it was characteristic.

I'm sorry that my friend had to learn the hard way, and I'm glad that I was always too scared of drugs to try any myself.

[Teever]

What is your friend doing now?

[neilv]

They're doing OK now, and working in tech.

They seemed potentially on a less-common career trajectory before they got derailed. But of course people's lives take turns for all kinds of reasons, so who knows whether they could've had a different life.

[reillyse]

Not to be rude but gunna have to call BS on this.

I don’t think MDMA usage shows up like this on brain scans, it’s not even like brain scans are that accurate and that nothing else could cause a scan to look bad.

This smacks of very anecdotal “this is your brain on drugs” energy.

[mx7zysuj4xew]

Sounds a lot like the "LSD orange" story that gets told over and over

[neilv]

I relayed what my friend said that the doctor said.

I'm sure that a doctor commenting on imaging knows vastly more about the topic than I do. And probably more than you do.

Or are you asserting that I'm BSing, friend was BSing, doctor was BSing, or doctor had been fed BS?

[reillyse]

So at this point there is a chain of three people who we have to believe and honestly you’ve left out whatever doctor was doing the imaging - usually a radiologist looks at the imaging and interprets it.

Unless they were doing a scan for “does my brain look like I took a bunch of ecstasy” the probability of the radiologist saying “it looks like the patient did a shit ton of ecstasy is close to zero” .

Secondly there is no characteristic markers for ecstasy use - it doesn’t leave a big X on the brain. This idea is like thinking somebody could look at an xray of a broken bone and name the person who caused the damage.

Lastly the story has the characteristics of a normal BS anecdote , with the allusion to authority (a doctor told me!) and it just so happens to dovetail really well with your life choices and validates you. So yea whiff of BS off this one.

[neilv]

To me, my friend (who's always been sincere) saying that a doctor told them something, is more credible than some random person saying that the chance a doctor actually told them that is close to zero.

[yibg]

This is why using anecdotes to determine truth is not reliable.

[yobid20]

So I was a heavy user. Every weekend, up to 5 pills a night, for years through college and into early 20s. This was back in the late 90s early 2000s. Now I am in my 40s. Top rated software engineer by my peers, sharp as hell, getting even sharper every year as my knowledge still grows, described as a true 10x expert engineer because of how much I do and code circles around everyone else. I am not saying this to brag. My point is simply that if there were some sort of permanant damaged cognitive effects, it never affected me like that. I never had any negative side effects ever. Or perhaps there was and I could have been the next Einstein but damaged myself to be where I am now. Guess I'll never know. I havent done again since I was around 22 or 23. It just stopped being enjoyable to me and everyone else I knew had already moved on past the party phase of their lives.

Also, a weird coindidence, during the heaviest usage phases, those were also my highest grades during college.

Do I regret using it so much? Not really. That was probably the happiest I've ever been in my entire life. I have very good memories , some of the best I've ever experienced. Often I think back I wish I could go back and do it again. Being an adult and getting old simply just sucks.

[dingnuts]

> it's amazing how quickly people go from “a couple times per year on special occasions” to having 20-30 exposures over a decade or two

a couple times a year is 20 exposures over a decade. were you trying to demonstrate an escalation? did you mean 20 over a year?

[airbreather]

Following on from my earlier post in this topic about LSD, we also had more than a couple of years where it was pills, pills and more pills, every weekend.

By this time most people I knew were working, serious work (with serious pay), so it was heavy on for the weekend, but then an enforced 5 days/nights off to work (gotta pay for your habits).

I never really had suicide Tuesdays, or the various variants of it, usually managed to get some food or calories into me during the weekend, probably the worst of it was just the sleep deficit.

It started to taper off when children started arriving, as the double hit on sleep deficit, even if all the other problems and responsibilities could be managed, was just a killer.

I would argue that no noticeable cognitive decline occurred, I have worked 30 odd years in a highly demanding profession demanding abstract thought and the ability to deal with lots of details and join dots others may not see. So I think I would notice if I was fried.

One thing was, pretty early on, I got on to the concept that most drugs are buy now, pay later. And that if you were going to do something that was going to vastly increase the rate of consumption of certain precursor chemicals in the mind and body, to preload heavily to avoid depletion burn out.

So I had a standard stack of supplements we almost always would take first. Maybe why I never really had the Monday/Tuesday crashes many seemed to, as well.

[zolbrek]

What supplements did you take?

[airbreather]

Chellated magnesium made a big difference, plus tryptophan and l-tyrosine, vit c and SAME.

SAME is interesting, when US was handing out prozac the EU was doing SAME, for similar efficacy and way less side effects. Most countries it is OTC.

[getpost]

> everyone should be aware that it’s very likely that each MDMA dose is incurring some level of damage

I think this is overstating the risk in supervised clinical usage, depending on what you mean by "some level of damage." It's possible that a single alcoholic beverage may induce some level of damage, but that is irrelevant for most drinkers. A more realistic comparison might be the risk associated with surgical anesthesia, which is significant, but that doesn't mean surgery should be necessarily avoided. There are always risk/benefit tradeoffs, and the MAPS research has focused primarily on MDMA use after other therapies have failed.

The MAPS Investigator's Brochure[0] acknowledges that, while preclinical studies in animals have shown serotonergic neurotoxicity at high or repeated doses, there is as yet no consistent evidence of neurotoxicity in controlled clinical settings with limited dosing. The report characterizes high-, medium-, and low-level risks. No high-level risks were identified, and medium-level risks are mainly cardiovascular and psychological.

[0] https://maps.org/wp-content/uploads/2023/04/MDMA-IB-15th-Edi...

[pipes]

Used far too much of it from 18 years old to as about 30 years old. I think it has played havoc with my short term memory. It has certainly made my work much more difficult. If I could change anything in my past it would be this. I'm pretty much playing my career on hard mode because of this.

[Dlemo]

Light studies have different expectations on their numbers and doesn't mean crossing that is a health risk.

For me, MDMA was definitely a crazy positive experience. It def helped against my depression in sense of letting me experience and remembering the experience something I haven't known existed before.

[blast]

If it's ok to ask: what was it that you experienced that you hadn't known existed before?

[Dlemo]

At the moment of taking it, a huge amount of empathy and happiness.

After that the memories of that day and feeling

[blast]

Wow. And thanks. I don't mean to pry, but did this make you want to take it repeatedly?

I ask because I've seen people get in trouble this way. They have a first experience which is amazing and then get into chasing it.

[qoez]

Thank you for being the necessary but resposible buzzkill in conversations like this

[mx7zysuj4xew]

There's nothing necessary about it, if anything it just lowers the signal to noise ratio

[mx7zysuj4xew]

I don't know where you get your facts from but every issue you brought up has either been thoroughly debunked (cognitive deficits) or borders on sensationalism (fentanyl)

[HaZeust]

Was about to call my old dealer; cheers

[owenversteeg]

Something I see a lot these days, what with modern scientism and all, is that even a tiny amount of $x causes permanent damage. You hear it about everything, from sunlight exposure to alcohol to sleep deprivation to red meat consumption. Most of the studies, of course, are an amusing combination of poor study design, funding bias and/or p-hacking, but occasionally a well-designed independently funded study by honest people slips through. Typically these studies will show the effect size so small as to be negligible. For example the Nature study about alcohol consumption shrinking brains showed an effect size over a lifetime of drinking equivalent to a fraction of the brain shrinkage that occurs over a normal year. Statistically significant? Yes. Practically significant, and enough to outweigh any benefits? Ehh...

But the larger problem is that the slabs of thinking meat that we inhabit are the most complex system in the known universe, and it is usually impossible to understand the effects of a single chemical. I wrote about this here a few months ago: https://news.ycombinator.com/item?id=42326209