What is wrong with the MDMA available today? - v2

[dth103]

Hey guys. I felt the need to briefly chime in on this and express my gratitude for those exploring the 'mehdmda' phenomenon. I myself have experienced this, my recent experiences have been of the crystal 'molly' variety in SF, a far cry from the 'mints' of my hometown Chicago.

I do have one question, which I'm sure has probably been asked or explored, given the manic anxiety of those affected: Could the impurities or changes to the synth be a possible cause of the 'LTC'?

 

[unodelacosa]

So ingest just means to take in, it doesn't imply an ROA

For really? Maybe you’re right. Well certainly there’s validity to your claim from a descriptivist view and considering the Latin root means “to carry” (gerere), perhaps this is really the case. Dictionaries seem to generally say “especially by mouth” though, and can we agree that “digest” and “ingest” both contain this root? So also we agree then that “digestion”, when not used metaphorically, refers to what happens post-oral-consumption? Idk, to me, you can inject, insufflate, inhale, or ingest. ¯\_(ツ)_/¯ Anyone else care to chime in here?

Regarding drug dependency and compulsive behavior pattern disorder, we’re not gonna see eye-to-eye because you already believe in the made-up theory of what’s called “addiction”. Did you know the World Health Organization created that term in, I think it was 1958? They were attempting to categorize drugs according to their potential for causing harm from dependency. The word itself is sort of asinine in that it literally means “spoken for”, sharing etymology with words like “dictionary” and “dictate”. It’s an absurd metaphor that smacks of ignorance and a lack of scientific understanding and sophistication. Within five years, they attempted to remove the term from the surrounding lexicon but it was too late and too powerfully sensationalist to stop by then.

So here we are in 2021 with people using the term addiction with grave tones, and simultaneously people flippantly saying shit like, “omg, these potato chips are addicting”, or like, “I’m so totally addicted to this YouTube channel!” The term is rendered impotent to me by these facts, and I can’t help but think it contributes to the problem more than it helps people who would be better off using the medical terms “[drug] dependency”, “tolerance”, and then in the behavioral sciences sense: “compulsive behavior pattern disorder”. In my humble opinion, these things should be addressed separately, and conflating the issues with an outdated term from the 1950s is, honestly? Dangerously irresponsible. But so few people I talk to who have drug abuse problems seem to know anything about this, so it’s just unfortunate and no one’s real fault.

Oh and don’t worry, I’m not upset or anything to hear your predictable opinion of me, and I’m not saying that to be rude or offensive; but I was absolutely expecting this response. You’re not the first person “in recovery” with whom I’ve conversed. I’m quite sure you’re intelligent, well spoken and well read, someone people admire for their worldly experiences, even as much to call you “Drug Jesus”, and all this even though you’re still fairly young, I suspect.

These are all good things, and I’m sure there are ppl in your life who are proud of you for getting a grip on your drug abuse problems before you did something severely catastrophic. That kind of “close call” with oblivion, as it were, is a powerful experience and a potent source for a certain self-righteous attitude that is very tempting to assume when confronted and confused by reality. By definition, not all drug use = drug abuse. Rehabilitation lingo won’t tell you this though. It’s a lot easier if you simply believe the problem lies in the drugs themselves instead of in the user. For example, the belief that no one can use crystal meth without becoming a strung out mess who ruins everything in their life is based on the premise that there is a quality imbued to the drug magically rendering it this way. Logically though this is blaming an inanimate object.

It’s very easy to project your issues onto others, but I acknowledge this cuts both ways. Have you ever heard the expression: when you have a hammer every problem looks like a nail?

From your perspective it’s a lot easier to run with the “addiction recovery” view of the world, applying it willy nilly to everyone you see using drugs you failed to use correctly. I mean it’s fine; I’m not trying to call you out or shame you for it. I’ve got my own shortcomings. For example: I’m fucking terrible at being drunk, so I generally nurse one beer or something if I’m in a social situation requiring a bit of drinking. Otherwise my drinking “snowballs” into massive, idiotic, angry, drunken intoxication, and well to be quite honest it’s embarrassing and not a good look. I’ve learned this and I avoid it now. However, it doesn’t mean I simply assume no one else is capable of responsible alcohol intake. I just know the limits of my own relative parameters, and I acknowledge what my drug skills are and aren’t. I leave the heavy drinking to others.

Opioids cause me to have stomach problems, massive nausea and a constant feeling of motion sickness. I find more euphoria from benzos than painkillers anyway, and I’ve tried plenty of various opioid drugs. I think it’s personal enzymology and individual variances in neurotransmitter saturation profiles that owe to these differences such as e.g.: why opioids don’t do much for some ppl like yours truly, but others barely catch a whiff of opium and they turn into an extra from the movie Trainspotting.

We may have to agree to disagree, but I want people to know: you can use drugs responsibly through dedication to harm reduction techniques and a reasonable amount of self-discipline. “Addiction” is made-up monkey garbage, and it is definitely not a disease. That’s just a sad cop-out. The aspects to consider are tolerance and dependency, which have a direct 1:1 link. Practice tolerance control and you have dependency control as well. It’s fairly easy, unless you’re compulsive. I want to expound on that but first let me just point out that I’m not directing this broader stuff about my thoughts on dependency vs addiction at you @Zuda as much as I am in general putting this alternate theory of addressing drug abuse issues out there, though I also recognize how off topic this is. So to pull it all together, here we go...

So if you’re compulsive, first piece of advice for you is: fucking stop it. You’re not a child, and if you are still a child, you have no business complaining about drugs you’re too young to use in the first place. If you’re an adult, you have no business being so impulsive, but if you’re between 18-25, this is understandably more difficult due to physical limitations in your brain’s anatomy. We’re not done developing our brains until about 25 years of age. The centers of the frontal lobe responsible for impulsiveness, procrastination, time management, and other mature/responsible aspects of our personality continue developing a full seven years after we legally hit adulthood. And I honestly think we continue evolving beyond that, maybe less in a physical sense and more in a dataset kind of way.

But I’ve read our brains gradually produce more MAOs as we get older. And so I think it’s entirely possible that the reason so many people consider MDMA from their past to be better than MDMA from their present is because: when you’re younger and still fairly fresh to rolling and tripping, MDMA really kicks you in the fucking face. There’s probably a certain window for most people when it will really be the best feeling in the world and after that it’s still pretty good provided you manage your expectations and you learn to enjoy being exactly where you are instead of obsessing over where you aren’t. I hope that makes sense to someone else.

Maybe I’m addicted to writing longAF diatribe responses on drug discussion forums. </ramble>

 

[unodelacosa]

Which is why I cannot see this discussion existing if all MDMA is original and equal.

“Original”, what do you mean by this? Pure MDMA will always be pure MDMA in the scientific sense. What someone calls “pure MDMA” in the black market drug trade is not always being given a truthful name. Meaning: it is not always pure, and so there is much interest in ascertaining what these impurities, active cuts and fillers really are, and subsequently what they do in the pharmacodynamic sense.

All I’m urging anyone to do is to remain open-minded and skeptical of all theories until they can be objectively proven by a few double-blind studies that have replicable, mutually consistent results. Personally I don’t see enough in the literature to warrant a deeper investigation into the theory that MDDMA is the sole culprit for an alleged decline in MDMA quality among some but not all anecdotal reports online.

There are so many other explanations. And but ppl say “Yeah but this is MDMA tested by IEC and they’re saying it’s pure but it’s still not the same!” But I’m thinking hang on, they can’t even detect MDDMA because they don’t have the fucking analytical standard? What kind of shit is that?

Kinda shakes my faith in their ability to accurately discern what’s in a sample of MDMA.HCl sent to them, and I strongly still suspect adulterants are to blame for maybe 90% of the cases where ppl think MDMA isn’t what it used to be. Fundamentally at least, this is phrased incorrectly. MDMA will always be MDMA as it’s incapable of being anything else, the same way carbon will always be carbon, oxygen will be oxygen, H, N, so on and so forth. But what drug dealers call MDMA, or Molly, Mandy, Sassy, Suzy Thundertussy whatever, that has variations depending on cuts, impurities, potentiators, inhibitors, etc.

Over two decades ago I wanted to ensure I had a reliable source for MDMA, and they say if you want something done right you gotta do it yourself. That idiom is not always true of course but regardless, I manufactured my own for a while, which I do not recommend trying unless you 100% have the legal authorization to do. Obey the law, and if these actions become permitted in the future or you find yourself in a permissible jurisdiction regarding this matter, then probably one of the surest ways you would have would be to synthesize your own MDMA, mastering purification techniques and analytical skills so as to assure quality production, and then you can take the new Pepsi challenge with your home brew family jewel molecule Molly, and the so-called “MDMeh”.

Btw MDMA.HCl as well as MDE.HCl, both are bright white when pure. Pure MDA is kinda off-white, eggshell to khaki colored. The hardest I’ve ever rolled was on a combination of MDMA and MDA... and a hot tub, lol. Some experiences are just hard to top, ya know? And I look back on some of the weird triple-stacks that would have everyone mash faced but also tripping moderately and I wonder what all was in those pills back then, but who knows? It could all just be an exercise in futility and it’s difficult to know if this is true.

Let’s assume the root of the problem is in its production and it’s not deliberate cut. Also we’re assuming this is a widespread, significant problem, which I’m not saying it isn’t, nor saying it is, just saying I’m not certain how prevalent the problem actually is. But if we accept all of this, then what’s the proposed solution? How would we reach out to the clandestine chemists of the underground, get their attention and draw it to the flaw in their production process and then ensure that the right fix to the problem is implemented properly and make sure the chemist is incentivized to do so? Ultimately why have this discussion without proposed and outlined solutions for this? (Actually nvm that, academic discussion satisfies well enough)

 

[unodelacosa]

@Zuda and @unodelacosa

I don't have time right now to find a lot of links, but I want to add a quick comment to your addiction debate.

There are significant genetic variables that impact how dopamine is released and the type of reward response that people get from dopamine. This is one reason why ADHD meds allow ADHD individuals to function normally, but would make another person feel "high." Dopamine release and response is a significant factor in addiction. It really is not as simple as you either have discipline or you don't. It is also not as simple as Meth being addictive for everyone.

Some people are going to be very vulnerable to the dopamine reward provided by meth and other people are not. You can have genetic testing done that will show you which mutations you have and whether you are likely to be highly influenced by dopamine rewards. I don't think either one of you truly knows what it is like to be the other, because you probably have brains that are wired very differently.

For some people, discipline will allow them to use meth responsibly and not in an addictive fashion, but for other people, that is not possible. It is truly dependent on individual brain chemistry and your dopaminergic system.

Yeah I’m fully aware of this and I’ve stated before that self-disciplined meth use is not for everyone. Similarly, ethanol consumption isn’t for everyone; I feel like it brings out bad qualities in my personality for example. So I avoid it, but I don’t cast aspersions on others who manage drinking much better than I do.

Others might not do well on coke, or meth, or whatever. So they should probably avoid their problem substances but take caution not to assume everyone else has to avoid their particular triggers, so to speak. I’ve never said self-discipline is all it ever takes every time, and I’m well aware of the genetic predisposition to the compulsion problem commonly called addiction. But I also believe culture and community play a significant role here, and I feel compelled to share an alternative theory that cautions people not to fall into the psychological trap of “addiction”culture particularly when the word itself is a blunder by the WHO from the 1950s.

It’s still a vital point well worth bringing up here though.

EDIT: btw, yes I am totally aware of the impact monoamines have on MDMA, and I’ll have to look it up later, but also I’ve read papers explaining how impurities formed as side products to amphetamine and methamphetamine can actually have an opposing pharmacological action and that when isolated, confirmed CNS depressing effects can be observed. It wouldn’t surprise me if this were true of 3,4-methylenedioxy substituted amphetamine-class drugs too, even if their activity profiles differ quite a bit from more general stimulants.

 

[psy997]

Please keep the non MehDMA research related discussion out of this thread. I am not interested whatsoever in reading discussions of linguistics unrelated to our research here, nor the merits or lack thereof of low dose amphetamines, opioid use, etc.

 

[Negi]

I started rolling in the late 90s; half a white dove and I was in love

Rolled periodically until 2005, then took an 11 year hiatus. My close friend sourced some mdma crystal for me and I must confess, I too, was under the impression the "magic" was no more. It wasn't a bad experience, just not what i remembered from the years prior. Came across some red bulls over a year ago and once again, enjoyable but nowhere near the same effect or intensity. Fast forward to last weekend in orlando, stumbled across the red Supreme presses with glitter in them. Tested them, instantly smoked and fizzed, turning from dark purple to black in about 3 seconds.

Let me tell all of you, by far the best pills I've ever rolled on in my life. The first half was pure bliss, better than I could have imagined. Pure euphoria, happiness in abundance and I had perma googly eyes. Rolled for 3 hours and dropped the other half. I was mangled for another 3 hours, grinding my teeth and massaging anything with a heartbeat east of the Mississippi. I inquired later where the pills were sourced from, to learn they were from the Netherlands. Makes sense, I guess.

Its not you. Its the quality of the drugs and synthesis used. The magic is still there, if you're lucky enough to find good mdma.

What doses of crystal MDMA had you tried? It's interesting you had such a great experience considering how almost everyone in the thread has found the mass market high dose Dutch pills to be meh.

 

[EntheoDjinn]

Side note: did you know that magic, wish-granting "genies" share etymological roots with the word "Djinn" both referring the demons. You see, a genie in a lamp is actually a demon,

No I didn't. I thought it was a good name too, but now knowing it's got that extra meaning it's even better. Thank you .

Apparently eating/drinking K is even more bad news on the bladder, so not to be recommended as a full-time hobby.

 

[diaphon]

Now, I am trying to get more information on how much would need to be present to impact the transporters.

@indigoaura I think you've hit upon a really interesting mechanism here. The paper you cited (Sandtner et al 2016) implies that there are 2 binding sites on the serotonin transporter - one is a high affinity agonist site, and the other is a low affinity inhibitory site. MDMA only binds to the high affinity site, but MDDMA can bind to either.

If the kinetics work in the normal way, then when MDMA and MDDMA are both present the MDMA will preferentially bind the high affinity site forcing MDDMA to bind to the low affinity site. So it's not only the amount of MDDMA that determines the inhibitory effect - it's also how much MDMA is occupying the preferred binding sites.

In other words, a little MDDMA on its own will not have an inhibitory effect, but that same little bit of MDDMA in the presence of a lot of MDMA will. Since MDDMA has this weird dual-mode binding pattern, the two molecule soup will behave in more complex ways than you'd predict based only on independent concentrations.

Anyway, that's how I read the paper. It's a good one, thank you for sharing it!

 

[indigoaura]

Dear Indigo Unfortunately we only have data from in-vitro assays. From these I estimate that for MDDMA to interfere with MDMA action it ought to be present in a percentage of 20 and higher. Due to possible differences in the pharmacokinetics of these two compounds the situation could be different in vivo. Greetings Walter

This is the latest reply from Sandtner. Of course, we do not know how much MDDMA was in my sample, because International Energy Control could not quantify it. However, they did identify that just under 80% of the sample was MDMA. So, there is 20% unaccounted for, in that analysis, and it is possible that a large portion of that is MDDMA.

I have multiple emails out to IEC right now. As I said before, there is a language barrier and that makes conversation a bit challenging. I am still planning to purchase the standard and send in additional samples, but am waiting for them to tell me how much they are going to charge me for all of that.

@unodelacosa - You are new to the thread, and relatively new to Bluelight. I am not sure how much of the original 300+ page thread you read. However, after reviewing quite a bit of published research, it is clear to me that the GCMS analysis that is being done by harm reduction labs is not sophisticated enough to identify all contaminants and byproducts. This is especially apparent when you read paper after paper of top scientists struggling to correctly identify synthesis byproducts and constantly trying new analytical methods to improve accuracy.

Even the Energy Control website states in no uncertain terms that precision is not their goal.

Trying to balance speed, precision and cost is a constant area of development for labs, and increasing one usually requires a trade-off from the others. At Energy Control, like most other harm reduction organizations, our goal is not to be as precise as possible, but to reach as many people as possible, and provide them with useful information to help them make safer choices. Unlike a professional lab, this means that slight trade-offs are made in the amount of detail given if that means an even bigger improvement in cost or speed can be made.

I don't say any of this to be negative towards harm reduction labs, as they provide a valuable service. But anyone who thinks that they are getting 100% accuracy and precision from GCMS testing at harm reduction labs is misinformed. From what I have read, it seems that law enforcement can identify synthesis byproducts in nearly all street samples, so clearly information is being left out when your result is simply "MDMA."

You said,

"Personally I don’t see enough in the literature to warrant a deeper investigation into the theory that MDDMA is the sole culprit for an alleged decline in MDMA quality among some but not all anecdotal reports online."

I don't necessarily think it is the sole culprit for all reported anecdotes of MDMA decline. More likely, there are many combinations of factors at play. In his 2005 paper, Pifl identified other monoamine inhibiting byproducts totally unrelated to MDDMA. However, I am surprised you think that it does not warrant investigation, as it has popped up now several times throughout the thread. It was identified as the potential culprit for a second peak in NMR results, it was identified in someone else's lab sample, and now it is identified in my lab sample. IMO, all possible leads warrant investigation.

Let’s assume the root of the problem is in its production and it’s not deliberate cut. Also we’re assuming this is a widespread, significant problem, which I’m not saying it isn’t, nor saying it is, just saying I’m not certain how prevalent the problem actually is. But if we accept all of this, then what’s the proposed solution? How would we reach out to the clandestine chemists of the underground, get their attention and draw it to the flaw in their production process and then ensure that the right fix to the problem is implemented properly and make sure the chemist is incentivized to do so? Ultimately why have this discussion without proposed and outlined solutions for this? (Actually nvm that, academic discussion satisfies well enough)

I cannot speak for everyone else in this thread, but here is what I would personally like to see:

1. Through analytical testing, I would like to conclusively identify that synthesis byproducts are present in my samples.
2. I would like to know what they are.
3. I would like to develop a straight forward way to separate them from MDMA.
4. I would like to test the MDMA once those byproducts have been removed and see if it is improved or not.
5. If this corrects the problem, I want to inform other people of how to clean their product.
6. Also, inform harm reduction labs of what is going on and see if they can find a way to report on the impurities in a more reliable fashion.

I think that if harm reduction labs begin reporting on this issue, then perhaps the clandestine labs will adjust in response. If not, then at least the end user would have some knowledge and options for improving their product.

 

[indigoaura]

@indigoaura I think you've hit upon a really interesting mechanism here. The paper you cited (Sandtner et al 2016) implies that there are 2 binding sites on the serotonin transporter - one is a high affinity agonist site, and the other is a low affinity inhibitory site. MDMA only binds to the high affinity site, but MDDMA can bind to either.

If the kinetics work in the normal way, then when MDMA and MDDMA are both present the MDMA will preferentially bind the high affinity site forcing MDDMA to bind to the low affinity site. So it's not only the amount of MDDMA that determines the inhibitory effect - it's also how much MDMA is occupying the preferred binding sites.

In other words, a little MDDMA on its own will not have an inhibitory effect, but that same little bit of MDDMA in the presence of a lot of MDMA will. Since MDDMA has this weird dual-mode binding pattern, the two molecule soup will behave in more complex ways than you'd predict based only on independent concentrations.

Anyway, that's how I read the paper. It's a good one, thank you for sharing it!

Thanks for explaining this in such a straight forward way. Yes, it seemed to me like the MDDMA almost has super-powers as far as the transporters are concerned.

 

[Imadoofus]

What doses of crystal MDMA had you tried? It's interesting you had such a great experience considering how almost everyone in the thread has found the mass market high dose Dutch pills to be meh.

I initially started with moderate doses of the crystal, and while it was enjoyable, it was never full-on rolling. I experimented with larger doses, but could never really reach that old school magic of days before. The redbulls I had last year tested out good with reagents, but it was definitely the mehdma. I took 4 of those over a 12 hr period and my brain was completely fried the next day, with a massive headache to boot.

The supreme pill was absolutely delicious, so much I made an account to share my experience on the topic. Ive been coming to this forum for years and never posted.. When I started enjoying mdma again after all those years of abstinence, I was convinced I had abused it too much when I was younger because that magic was gone. Even crystal that tested out amazing didn't provide it, nor did good pills. 1 supreme had me rolling so hard I chewed my lips up pretty bad, and I've never done that. I wanted to dance, hug and share my soul. It was a divine experience, especially since it caught us all off guard. There was 6 of us and we all agreed it was the best pill we've ever had. Ever. And coming from me, thats a lot to say. There was even a sweet, beautiful after glow several days later that kinda just lingered. 1 pill did that, and I'm used to consuming several a night. Im intentionally going to wait a few months before I do them again, just to relish the anticipation of knowing the magic isn't lost and the keys to heaven are still floating around.

 

[indigoaura]

There have been significant changes to the MDMA amounts in pills as shared by Drugs Data. Something may be changing with manufacturing, because I am seeing more and more pills dosed around 130 mg instead of 200+ mg.

 

[Zuda]

Oh and don’t worry, I’m not upset or anything to hear your predictable opinion of me, and I’m not saying that to be rude or offensive; but I was absolutely expecting this response.

Let me guess, you've heard it before. Well, I can honestly say that I've never heard somebody say "addiction isn't real" in response before so I guess you win that one. lol

I'd type a lot more but I'm tired today and got stuff to do. All the love

 

[Zuda]

Also, I would love to do a chrome spectroscopy test, but I don't have a machine on-hand. I wonder if there is any rudimentary way of doing that?

 

[Zuda]

Yes, but

Can confirm they definitely used to do this. Pure marketing. This was the large batch commercial brown stuff out of Europe and people doing it on smaller scale here as well. We were talking about this elsewhere, but tree hugging hippie types liked the idea that their "sass" (used to refer to MDA but also to MDMA) came from plants, and so could say that they were taking "natural" drugs (meanwhile the same people loved acid but looked askance at heroin or cocaine. Hmm.) Some of this stuff used to be of very high quality, though, I can attest, in fact it was probably the best MDMA that most people on the scene had access for a number of years. It wouldn't be the first time that the whims of the popular drug culture lead the market astray as to what was really good stuff and what was not. In kind of the reverse of the scenario with the brown MDMA, some of the best LSD I sampled, which was quite pure according to LC/MS, happened to be off-color in solution (this was a case of the phenomenon of very small impurities resulting in large discolorations.) In liquid form, it was shunned as "dirty silver" while it was probably was purer than the "white fluff" that was circulating beside it. Put onto paper, it was, of course, sold as the "white" and all were satisfied.


Ingesting K is mega wasteful compared to parenteral administration but is actually lovely. Doses are northwards of a gram, but who was counting when Indian "pre-fab" K was super cheap in bulk? The oral experience lasts considerably longer, as one might expect, but is qualitatively different too, in ways that are hard to articulate. I'd say that it feels mellower and more akin to a classic psychedelic (albeit of course still being very much a dissociative.)

With regards to the little slapfight about meth, I have to come down with @unodelacosa again, all due respect to @Zuda's experience of addiction. Taking controlled dosages of MA is an entirely different ballgame than smoking bowls and doing lines of commercial product. Even less than 100mg of good product can lead to a great, euphoric experience that even can take on some serotonergic, "rolly" characteristics. The neurotoxicity is only happening when people are taking retarded dosages for days. It's especially absurd (not to say offensive) to accuse another person of being in active addiction precisely because they claim not to be. ("Orr was crazy and could be grounded. All he had to do was ask; and as soon as he did, he would no longer be crazy and would have to fly more missions. Orr would be crazy to fly more missions and sane if he didn't, but if he was sane he had to fly them.") I don't say this to pooh-pooh addiction, I'm in recovery myself, but no, in fact, not everyone who took the same girls to the dance as we did wound up with the clap.

I once had a very dear friend (RIP) who was a very dedicated and prolific polydrug user. Experienced guy, could handle his shit. He was visiting me, and I had to go to work. I left a box of various carefully labelled drugs in his care. He asked me if he could try a little bit of the MA (snow-white, very fine crystals, almost powder.) I said why not. I wasn't worried. It didn't occur to me that he wasn't counting on it being about as pure as it could possibly be. He went ahead and IV'd some eyeballed amount. He absolutely lost his shit and wound up on the inpatient psychiatry service. Sola dosis facit venenum and all that. Really good meth doesn't necessarily have those big crystals so pleasing to the eyes of tweakers. It can, but more often than not those are methylsulfonylmethane or something similar.

I have a million better things to do than have a slap fight. If he doesn't want to realize he's addicted to methamphetamine it's really not my business

 

[indigoaura]

Guys, we have had a really, really hard time keeping this thread on topic and trying to keep the length down. Future readers would really appreciate it if the unrelated debates could be removed to another thread. Debating the nuances of methamphetamine use and/or addiction really belongs elsewhere. It is not particularly related to the topic at hand.

 

[unodelacosa]

@indigoaura I think you've hit upon a really interesting mechanism here. The paper you cited (Sandtner et al 2016) implies that there are 2 binding sites on the serotonin transporter - one is a high affinity agonist site, and the other is a low affinity inhibitory site. MDMA only binds to the high affinity site, but MDDMA can bind to either.

If the kinetics work in the normal way, then when MDMA and MDDMA are both present the MDMA will preferentially bind the high affinity site forcing MDDMA to bind to the low affinity site. So it's not only the amount of MDDMA that determines the inhibitory effect - it's also how much MDMA is occupying the preferred binding sites.

In other words, a little MDDMA on its own will not have an inhibitory effect, but that same little bit of MDDMA in the presence of a lot of MDMA will. Since MDDMA has this weird dual-mode binding pattern, the two molecule soup will behave in more complex ways than you'd predict based only on independent concentrations.

Anyway, that's how I read the paper. It's a good one, thank you for sharing it!

I took the same message from the paper as well, except I was picking up that the lower affinity site would, at best, slightly inhibit reuptake of 5-HT. But I guess since SSRIs prevent 5-HT from traveling back up the transponder and block the action of MDMA’s massive serotonin release, this could be possible. One would think the timing might prevent this, and maybe it accounts for a “meh” experience rather than no experience.

Well if this is true, then MDTMA, which only binds to the lower affinity site, should have an opposing effect against MDMA as well, right?

 

[indigoaura]

I took the same message from the paper as well, except I was picking up that the lower affinity site would, at best, slightly inhibit reuptake of 5-HT. But I guess since SSRIs prevent 5-HT from traveling back up the transponder and block the action of MDMA’s massive serotonin release, this could be possible. One would think the timing might prevent this, and maybe it accounts for a “meh” experience rather than no experience.

Well if this is true, then MDTMA, which only binds to the lower affinity site, should have an opposing effect against MDMA as well, right?

Based on my understanding, yes.

In any case, the author of the paper has confirmed that if consumed together, the MDDMA would block the action of the MDMA. So, this line of thought is theoretically sound.

There are a lot of monoamine inhibiting compounds. Did you get a chance to review that paper on duloxetine? That paper does such a great job of describing a human study where a monoamine inhibitor was consumed along with MDMA. The charts represent my own "meh" experiences quite accurately.

 

[diaphon]

I took the same message from the paper as well, except I was picking up that the lower affinity site would, at best, slightly inhibit reuptake of 5-HT. But I guess since SSRIs prevent 5-HT from traveling back up the transponder and block the action of MDMA’s massive serotonin release, this could be possible. One would think the timing might prevent this, and maybe it accounts for a “meh” experience rather than no experience.

Given the sophistication of the contributors to this thread I hope I'm not dumbing things down too much if I say that brain networks operate using frequency coding, not binary coding. It's the frequency of transmission that carries the signal, more like a musical tone than like a light switch. So even a slight inhibitory effect on the serotonin transport might alter the frequency of transmission enough to produce a noticeable difference in the experience. It's like having a flat string on a guitar, the instrument doesn't break but the music doesn't sound right. It doesn't take much inhibition to produce that kind of an effect.

And that's consistent with what, to me, is a "meh" experience. It feels like taking MDMA through a thick blanket, like I can feel that the contours of the experience are present but I can't quite get to them. It's very frustrating! Definitely not all-or-nothing. At least, that's what "meh" means for me. It may be (probably is) confirmation bias, but it does feel like there is a true MDMA experience happening somewhere in there but I'm just being prevented from getting to it.

 

[unodelacosa]

@diaphon @indigoaura I wonder if there are any corollaries between MDMA/MDDMA/MDTMA & methamphetamine/dimethylamphetamine/trimethylamp... meaning to say, there’s a good chance that if a chemist could accidentally synthesize MDDMA they could as easily synthesize dimethylamphetamine from phenylacetone as a side product to dl-methamphetamine. I’ll have to check the literature to see if there are any hints of serotonergic inhibition and effects-blockading similar to what may be happening with MDDMA acting as a non-selective serotonin reuptake inhibitor to co-ingested MDMA.

Given that methamphetamine is is fairly potent releasing agent of 5-HT (much more so dopamine and adrenaline, but all the same; meth causes a ~15x larger 5-HT release than its primary amine, amphetamine), this seems like a worthy subject to check into. N,N-dimethylcathinone & methcathinone aren’t serotonergic enough perhaps to expect much... what other drugs are active, secondary amines that feature serotonergic effects and are worthy of investigating into this dynamic? In the case of DMT vs NMT, it’s interesting to note that NMT seems to have a bit of an inhibitory effect on DMT’s primary action, but that could be solely due to logistics I suppose.