[patrec]

Here's a citation for a drug Shulgin is famous for:

> MDMA provides an immediate enjoyable feeling by stimulating the release of neurotransmitters, such as dopamine and serotonin in the brain. Unfortunately, abnormal regulation of the brain neurotransmitters, as well as the increased oxidative stress causes damage to the brain neurons after the MDMA exposure.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7878040/

[netizen-936824]

All of those studies are either in rats or mice or are in vitro. A lot of the mice and rat studies can't be translated to humans because they have significantly different metabolisms and researchers use entirely different dosages than humans do in the wild

>MDMA has been administered to approximately 1,700 human subjects with only one serious adverse reaction.

https://maps.org/mdma/

There are currently human studies of MDMA. These would probably not be moving forward if they found "brain frying" although I appreciate your willingness to read abstracts

[mythrwy]

Just curious if you have been around people who take a lot of MDMA (I don't know what the "abuse" threshold is) or you have yourself.

It does "something" to your cognitive abilities that is not beneficial. I don't know how permanent it is. Probably recoverable in most cases?

Maybe not using 3 time a year (or whatever) but multiple times per week for months on end yes, it makes a person get "funny in the head". I've seen it with more then one person.

I'm not anti drug nor denying therapeutic use (makes sense) but I'm fully convinced from observation MDMA is not risk free or harmless, especially when used to excess. Yes, anecdotal. But just a word of advice for whatever it's worth.

[agency]

I don't think even the most hardcore pro-drug advocates would claim that using MDMA multiple times per week is ever safe, but is there any evidence that that kind of abuse is remotely common? On average taking ecstasy is safer than riding a horse [1], and if you really just love to get fucked up and don't care about burning a hole in your brain, why not just graduate to straight-up meth?

[1]: https://en.wikipedia.org/wiki/David_Nutt#%22Equasy%22

[mythrwy]

I don't know how common that kind of usage is. This was a group of people I hung with back in the 90's.

The dangers of riding a horse are immediately apparent and it's easy to link cause and effect. Additionally the damage from a bad horse ride (unless you hit your head) are more likely to be physical trauma, a broken leg etc.

The (possible) negative effects of a drug on cognition are more subtle and harder to attribute.

Again, I'm not anti drug at all (especially legally speaking).

It's just, what I saw and I feel I should relate it as a bit of a cautionary tale. I am convinced overuse of MDMA has a negative effects on the kind of cognition that allows a person to plan, link cause and effect, think abstractly and that kind of thing. It's not a scientific study, just what I believe from observation.

[svnt]

Here is how I think about it: your cognitive processes are accustomed to certain biochemical biases. You’ve grown and developed your brain in response to stimuli under a certain set of conditions.

One set might be jacked adrenals due to your propensity for epic soundtracks and caffeine or chocolate consumption.

Another set might be alcohol and social feedback.

If you spend a lot of time in these states, your unbiased function diminishes because you are optimizing for a different chemical bias.

If you are not so far gone, or are exceptionally motivated or introspective, you can integrate those experiences, and it might expand your awareness. If you can’t, or don’t, it might increase your function while using but reduce your sober function. This effect will increase as you spend more and more time ‘high’: you are transitioning function within your own constrained cognitive capacity to a different bias.

[netizen-936824]

So you're kinda on the right track. What happens is that we have a specific range of regulation that our neurotransmitters and receptors etc fall into based on our genetics which could be a bit modified through epigenetic means.

That range of regulation is what we drift towards when we start adapting to an exogenous compound (some drug) that is consistently present through repeated dosing.

Considering that information, we do adapt to become "normal functioning" (according to the previously mentioned genetics) and it becomes more difficult again when we suddenly remove the drug (again forcing us out of that range that our genetic regulatory mechanisms would like us in)

During periods that we are using the exogenous compound we can form new habits driven by changes made by the drug which can stick around after removal, as removal of the drug won't suddenly undo many of the synaptic changes that occurred. I think this is what we can call the integration of experiences and I think that long term potentiation is a big factor in those changes (which is a pretty neat topic on its own, I'd recommend reading about LTP if you want to understand some of the mechanisms of learning)

[zasdffaa]

> multiple times per week for months on end yes

that is not use but abuse, and I'd expect bad consequences.

[netizen-936824]

That sums it up very succinctly, thank you.

[eurasiantiger]

Overdosing on MDMA can cause serotonin syndrome, which can cause neuronal death due to excitotoxicity.

[Terry_Roll]

And thats the come down after popping a pill or two at some rave in the middle of field in Essex. Fortunately the body doesnt stop making new brain cells provided one's diet is adequate.

I was surprised to learn the US Military resurrected MDMA in the 50's and then in the 70's Prof Alex Shulgin got hold of it. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3931692/

Other country's handled it differently. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6435835/

But it does lend credence to the conspiracy theory that the British security services started flooding the football terraces to reduce the football hooliganism that was blighting the British isles, as "documented" by later films like Football Factory starring Danny Dyer and many more.

Still without it, would the world have what the US call EDM and what others call the Rave culture?

[jaminal]

This is very likely false; a myth perpetuated from the war on drugs combined with people taking unknown, untested substances in recreational settings.

If they experienced serotonin syndrome it was quite easy to just point at the reported seratonergic substance that had been ingested (and which also may not have been present at all, depending on the source).

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5931730/

[eurasiantiger]

The worst cases are likely from interplay with other medications or simply overheating.

However, the same is repeated in literature about plain methamphetamine, not just methylene-dioxy-methamphetamine, so I would not entirely trust the current state of science on this.

[jaminal]

It’s repeated for lots of medications where it could never happen. SS is widely misunderstood even in the medical community.

I trust specific doctors who specialize in psychedelic medicine and psychiatry who have deep understanding of the metabolic pathways and pharmacokinetics of these substances.

https://www.pharmacytimes.com/view/serotonin-syndrome-myths-...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8820588/

[netizen-936824]

Overdose on many substances is bad and can damage neurons if it crosses the BBB. That's not saying anything special about entactogens/empathogens/psychedelics

[eurasiantiger]

I agree.