3 ms·

Sure, happy to. Here's a meta-study [1] that cites another meta-study showing single use harm. [2] This study [3] shows changes in serotonin patterns seven year

Sure, happy to. Here's a meta-study [1] that cites another meta-study showing single use harm. [2] This study [3] shows changes in serotonin patterns seven years after administration in primates. MisterYouAreSoDumb was a legendary Redditor who frequently commented on the topic of harm. This one's a collection of references and a good TL;DR. [4] It's ten years old now but there's still a treasure trove of material here. Another comment from them that is the beginning of a series. [5] And as I mentioned earlier, the safety protocols required to mitigate the damage are extensive. You cannot rely on users going the distance to have a less-harmful experience. You must assume it's being taken under non-ideal conditions, with plenty of redosing, which is multiplicatively more damaging, as the axon terminals involved will simply run dry. Hope that's helpful. I'm not here to judge. I've also taken MDMA in my youth and quite a lot of it. But I do wish we had these resources available then as we do now so I could have made a more informed decision. My personal, anecdotal, experience is I had a bunch of pretty magical experiences with MDMA in my youth which I've never been able to reproduce since. That was personal confirmation that irrevocable changes had occurred due to use. The internet is chock full of similar stories. [1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181923 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181923 [2] https://sci-hub.se/https://pubmed.ncbi.nlm.nih.gov/12869661 https://sci-hub.se/https://pubmed.ncbi.nlm.nih.gov/12869661 [3] https://www.jneurosci.org/content/jneuro/19/12/5096.full.pdf https://www.jneurosci.org/content/jneuro/19/12/5096.full.pdf [4] https://www.reddit.com/r/Drugs/comments/15ix0s/comment/c7mvi4i/ https://www.reddit.com/r/Drugs/comments/15ix0s/comment/c7mvi... [5] https://www.reddit.com/r/DrugNerds/comments/13lp0b/mdma_neurotoxicity_part_1_metabolites/ https://www.reddit.com/r/DrugNerds/comments/13lp0b/mdma_neur...

cthalupa 3y ago
Thanks! These are interesting. Couple of notes I made from my first perusal. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181923 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181923 They point out that they showed neurotoxicity in animal studies with doses higher than those typically for recreational users. In studies of human users, they did find evidence of brain structural alteration, but no large-scale cognitive impairment of clinically relevant proportions. Fairly significant evidence of impact to memory. https://www.jneurosci.org/content/jneuro/19/12/5096.full.pdf https://www.jneurosci.org/content/jneuro/19/12/5096.full.pdf They chose dosages for MDMA here that are extremely high. 80-120mg is the standard recreational dose with anything above 150mg being considered high, but the dosage they chose would be the by-weight equivalent of a 160lb person taking 340mg of MDMA. This looks intentional - they say in the study the selected a dosage that was known to cause brain lesions. The sci-hub study references a species-specific dose scaling chart that explains some of this, but it also disclaims that the science of the dose scaling is disputed. I'm not super sure what to make of it - it stands to reason that too much of anything can be dangerous, but it doesn't seem like the science is close to being settled on whether or not these dosing differences make sense. I haven't yet had a chance to go through all the references from the reddit post, but I'll work through them. I think it's pretty compelling evidence that there is risk in taking MDMA long term, or in very high dosages on more acute timescales. I don't know that what I have read so far counters the science in the meta-study I linked around more moderate use, since that did draw primarily on observational studies that included imaging of human users. I'm no expert, though, and hopefully no one reading this is taking my understanding of the science as anything resembling authoritative. It does further highlight a lot of the potential risks in taking street drugs, though - you never know the actual potency or chemical composition of what you're being sold. >My personal, anecdotal, experience is I had a bunch of pretty magical experiences with MDMA in my youth which I've never been able to reproduce since. That was personal confirmation that irrevocable changes had occurred due to use. The internet is chock full of similar stories. Hmm. There's a lot of experiences I found magical at one point in time that I've never been able to reproduce, none of them related to drugs. I think it's hard for humans to disentangle their perceptions from the novelty of new experiences, the impact of their mental state, point in life, etc. etc. At any rate, thank you again for the wealth of information.

cthalupa 3y ago

Thanks! These are interesting. Couple of notes I made from my first perusal. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181923 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181923 They point out that they showed neurotoxicity in animal studies with doses higher than those typically for recreational users. In studies of human users, they did find evidence of brain structural alteration, but no large-scale cognitive impairment of clinically relevant proportions. Fairly significant evidence of impact to memory. https://www.jneurosci.org/content/jneuro/19/12/5096.full.pdf https://www.jneurosci.org/content/jneuro/19/12/5096.full.pdf They chose dosages for MDMA here that are extremely high. 80-120mg is the standard recreational dose with anything above 150mg being considered high, but the dosage they chose would be the by-weight equivalent of a 160lb person taking 340mg of MDMA. This looks intentional - they say in the study the selected a dosage that was known to cause brain lesions. The sci-hub study references a species-specific dose scaling chart that explains some of this, but it also disclaims that the science of the dose scaling is disputed. I'm not super sure what to make of it - it stands to reason that too much of anything can be dangerous, but it doesn't seem like the science is close to being settled on whether or not these dosing differences make sense. I haven't yet had a chance to go through all the references from the reddit post, but I'll work through them. I think it's pretty compelling evidence that there is risk in taking MDMA long term, or in very high dosages on more acute timescales. I don't know that what I have read so far counters the science in the meta-study I linked around more moderate use, since that did draw primarily on observational studies that included imaging of human users. I'm no expert, though, and hopefully no one reading this is taking my understanding of the science as anything resembling authoritative. It does further highlight a lot of the potential risks in taking street drugs, though - you never know the actual potency or chemical composition of what you're being sold. >My personal, anecdotal, experience is I had a bunch of pretty magical experiences with MDMA in my youth which I've never been able to reproduce since. That was personal confirmation that irrevocable changes had occurred due to use. The internet is chock full of similar stories. Hmm. There's a lot of experiences I found magical at one point in time that I've never been able to reproduce, none of them related to drugs. I think it's hard for humans to disentangle their perceptions from the novelty of new experiences, the impact of their mental state, point in life, etc. etc. At any rate, thank you again for the wealth of information.