What is wrong with the MDMA available today? - v2

[unodelacosa]

I can confidently say none of you have EVER consumed MDMA synthesized in that manner lol, myself included.

Well of course not; it’s a novel synthetic route.

Any of us may have had near-pharmaceutical-grade MDMA though, the thing precluding it from being “pharmaceutical-grade” is the technical lack of “cGMP compliance” owing to MDMA’s current outlawed, Schedule I status. But I read through the whole synthesis, and it’s not too far from practices I was accustomed to as well as others in The Hive era. Ultimately the Grignard is formed and Propylene Oxide is added before oxidation to the achiral ketone, MDP-2-P. After testing for impurities, they reductively aminate the ketone using … (sigh) Methylamine (of course). And this along w/methanol, the ketone previously made, Sodium Hydroxide, and Sodium Borohydride are refluxed together before work-up. Gee, that sounds hella familiar…

The novelty of this route is mostly that its starting precursor is not a DEA / FDA Listed precursor (yet) – 5-bromo-1,3-benzodioxole Check it out (bold mine):

“MDMA is not a particularly complex molecule, and many synthetic pathways have been reported. Most begin from either safrole or piperonal, which are highly regulated and consequently difficult to obtain; for the sake of convenience and efficiency, we elected to avoid these. We identified 5-bromo-1,3-benzodioxole, which does not appear on any geopolitical entity’s list of controlled substance precursors, as a useful starting material for our synthesis. The 1,3-benzodioxole moiety appears in a variety of natural products, including oils, spices, and traditional plant-based medicines.”​

That route is purely something to patent in my eyes.

More than that, though…It’s deliberately meant for large-scale, cGMP-compliant manufacturing of MDMA starting from an affordable and readily available/plentiful, novel precursor in anticipation of further upcoming phase trials and mass market release.… It’s not just “purely something to patent”. That would be Merck patenting MDMA in the 1920’s for no real reason.

The yields kind of bite though. “Acceptable” is what they said, but I like being a bit more north of 50%.

Soon as I saw the word “grignard” I knew this wasn’t a route you’d see in many clandestine labs.

The equipment for testing at each phase of the synthesis, the specialized distillation equipment, the rotovap, a few specific solvents (e.g.: 2-propanol), inert atmosphere, these things are uncommon but not unheard of (LSD chemists need some of these things). But the Grignard isn’t exactly a secret. Just pulling from Rhodium’s archive on the Erowid…

• grignard.aminoethylation.html
• grignard.formylation.html
• grignard.formic.html
• grignard.notes.html
• dmt.indole.grignard.html

Clandestine labs running a Grignard have definitely been seized in the past. Not to be argumentative, and your point that it’s uncommon in most underground labs is correct, no doubt. But then, that’s not saying much since most kitchen chemistry labs are laughably bad, poorly constructed and/or dangerous as all fucking get-out.

The exceptions to this though can be quite impressive.

 

[G_Chem]

“that’s not saying much since most kitchen chemistry labs are laughably bad, poorly constructed and/or dangerous as all fucking get-out..”

Exactly Na you’re right Grignards are not beyond the capability of all clandestine labs but most. I’ve seen enough talk of them on the Hive to believe but an LSD chemist and an MDMA chemist are too different things. MDMA labs are often as you describe.

Regardless, that route has little to do with the discussion here beyond maybe the fact it’s reduced via Sodium borohydride. I bring that up cuz I noticed while scouring the hive ages ago that MDMA made via that reduction often tended to be lackluster from the reports of a few bees. I guess as I’ve said before it doesn’t matter what route is used if it’s pure enough.


So off topic to this, I’ve been thinking more of the possibility that safrole (either residual or intentionally added after synthesis as a signature) may have potentiating properties. It’s a potent and indiscriminate inhibitor of many CYP enzymes.

I notice batches that look fairly clean to the eye with nice crystal structure and clarity but still have the tiniest hint of safrole to be the best. I wonder if that residual safrole is inhibiting CYP enzymes enough to change the effect.

The batches that can bring about rolls where 7-8hrs later I’m not rolling exactly but still in a positive upbeat mindset. Those all seem to smell of safrole. Batches that don’t often end more like 3.5-5hrs.

-GC

 

[indigoaura]

Nice post! Current Good Manufacturing Practices (cGMP) = excellent shit. Really cool read, and I‘m impressed with their new starting point, eschewing preparation from safrole for an even simpler compound – thought it makes me realize this likely has something to do with the difficulty in procuring Safrole in 2022.

@F.U.B.A.R. is right vis-à-vis the word “recipe” here, which isn’t something any self-respecting chemist would likely say about a novel cGMP synthetic route they published, ya know? Breaking Bad was a fun show and all, but I cringed whenever they’d say “let’s cook.”

Not that I personally give a shit, mind you, and this is clearly an informal setting here, not an academic journal discussion forum with only chemical engineers and pharma-geeks, but considering how serious your approach to this thread and overall topic is, this is something to keep in mind when/if you’re pitching a proposal to some university or lab or whatever. It’s better to stay in good habits, and I’m sorry if I seem like a dick for pointing this out; I’m not trying to call anyone out, and you likely know this point…

And if I didn’t care, I wouldn’t say anything, but I care enough, @indigoaura, pseudonymous though you are, to bring up the point both for you and anyone who might find it useful.

Man, this kind of nitpicking is ill-placed and unnecessary and brings down the vibe of this thread.

I was speaking informally to an audience of Bluelighters in a casual manner. It was meant to be said with some excitement, like "Yee Haw! MAPS shared their recipe!"

I know the difference between academic language and casual language, and I also know how to adjust language accordingly, depending on purpose and audience.

I realize tone does not often come through as intended, so perhaps you felt it was a serious use of the word recipe, or that I felt it was academic (I did not).

 

[indigoaura]

Some early quotes from the article that stood out to me:

Most of these clandestine syntheses are well-documented, both by anonymous chemists, in online forums, and by forensic scientists, who often identify clandestine production methods by their distinct impurity profiles.

This quote acknowledges and reinforces that different starter compounds will result in unique impurity profiles.

Compound 11 is synthesized via the bromination of benzodioxole with NBS; analysis of multiple batches, from a range of suppliers, indicated that the only significant impurities present in the batch are 5,6-dibromo-1,3-benzodioxole and succinimide, which is insoluble in Compound 11 and consequently present in only very trace amounts. We additionally screen for the presence of 4-bromo-1,3-benzodioxole, which would likely present separation challenges during production, but we have never observed this isomer in the starting material. At the levels observed, neither of the two significant impurities interfered with the downstream chemistry.

Does this imply that other starting materials do have impurities that would interfere in downstream chemistry and/or present separation challenges? That is the inference I feel can be made here.

 

[unodelacosa]

Man, this kind of nitpicking is ill-placed and unnecessary and brings down the vibe of this thread.

Just trying to look out. Don’t be so crestfallen.

I was speaking informally to an audience of Bluelighters in a casual manner.

To be fair, we all have oscillated a bit between formal and informal language in this thread. I’m not calling you out, just offering some clarity on a minor point someone else was teasing you about in good nature.

It was meant to be said with some excitement, like "Yee Haw! MAPS shared their recipe!"

And it was just injecting a little levity to the conversation over a minor verbal technicality.

I know the difference between academic language and casual language, and I also know how to adjust language accordingly, depending on purpose and audience.

Not everyone on here may know this difference though, and I sometimes post/respond for the sake of the community more so than for the direct sake of whichever particular post to which I’m responding. No offense was intended.

I realize tone does not often come through as intended, so perhaps you felt it was a serious use of the word recipe, or that I felt it was academic (I did not).

Firstly, I didn’t bring it up, someone else did. Secondly, the distinction is important because drug war propagandists like to say shit like “Look at the ingredients that go in meth! You mix up cough medicine with battery acid, ammonia, concrete cleaner, nail polish remover, match sticks, anti-freeze and more toxins! It can’t be healthy for you with all those chemicals in it!” having no idea—or deliberately ignoring—how organic chemistry actually works.

It’s not a buzzkill, just relax. It’s only semantics, a small linguistic thing. It’s kinda like how you don’t call a Certified Massage Therapist “a masseuse” generally, as the word may connote a sex worker in some people’s minds, a confusion professional CMTs seek to avoid. Or lesser-known actors are sometimes a little offended when they’re called “an aspiring actor”, because most often they are in fact working actors, you’ve just never heard of them, so “aspiring actor” is a bit of a backhanded compliment. Don’t call an “interior designer” an “interior decorator”; they’re different. An optometrist is not the same thing as an ophthalmologist. And so and so forth.

Idk, fuck it; I was just trying to help. No need in taking offense when none was intended, same as I take no offense to the phrase “cooking drugs”, I thought I wanted to make sure people know it annoys some clandestine chemists, but no good deed goes unpunished … Either way, great find; thank you for sharing the article.

 

[F.U.B.A.R.]

I’m not calling you out, just offering some clarity on a minor point someone else was teasing you about in good nature.

Just to offer some further clarity, I wasn't teasing @indigoaura I honestly didn't notice she'd used the word 'recipe' - it was just a joke aimed at clandestine cooks...

 

[Mjäll]

So an innocent joke became a failed excuse for a nitpick

Sometimes things work, sometimes not

Btw i think this whole topic is silly so everyone feel free to redirect all your spite at me :D

 

[Rectify]

The Simulation Won't Have MDMA.

 

[vash445]

I can confidently say none of you have EVER consumed MDMA synthesized in that manner lol, myself included. That route is purely something to patent in my eyes. Soon as I saw the word “grignard” I knew this wasn’t a route you’d see in many clandestine labs.

I’m hitting a festival in 3wks, I’ll see what’s about.

-GC

I'm pretty sure a very similar route was in strikes "how to Build" MDMA section wayyyy back in the day it's nothing novel... I also wouldn't doubt it hasnt been done. everything just needs to be really dry.

1. The 1,2-methylenedioxy- benzene is selectively brominated with N-bromo- succinimide to form 4-bromo- 1,2-methylenedioxybenzene.
2. The 4-bromo-1,2-methylenedioxy- benzene is reacted with Mg to give the Grignard adduct (R-MgBr), and coupled with allyl bromide to form safrole.
   
   Seems the difference is a 2-propanol substituent via ring-opening addition between the same aryl Grignard reagent used to synthesize safrole, above, and 1,2-propylene oxide

Synthesis of Safrole - [www.rhodium.ws]

 

[unodelacosa]

"Compound 11 is synthesized via the bromination of benzodioxole with NBS; analysis of multiple batches, from a range of suppliers, indicated that the only significant impurities present in the batch are 5,6-dibromo-1,3-benzodioxole and succinimide, which is insoluble in Compound 11 and consequently present in only very trace amounts. We additionally screen for the presence of 4-bromo-1,3-benzodioxole, which would likely present separation challenges during production, but we have never observed this isomer in the starting material. At the levels observed, neither of the two significant impurities interfered with the downstream chemistry."

Does this imply that other starting materials do have impurities that would interfere in downstream chemistry and/or present separation challenges? That is the inference I feel can be made here.

Yes but only because this is true of impurities in general, it doesn't necessarily imply anything about the compound in question nor the impurities that may or may not be produced via a particular synthesis. Although, we know from history that indeed this is the case – other impurities brought in via different syntheses will produce signature byproducts, some of which can and will interfere with the downstream chemistry (EDIT: with respect to MDMA synthesis).

 

[Biscuit]

Whilst I don’t want to rehash this unnecessarily, the German article that analyzed the enantiomeric ratios, is this the only study or release of data of this kind in recent years that we know of? It is a shame that they did not publish the identity of the pills tested because I’d be very interested to know if any of these included some of the mega dosed but thoroughly underwhelming pills.

The image of the various pills which has been posted together with this link (see Negi post page 52) seem to be only of pills that do not seem to be recent presses at all. Is that of another similar but older study or are these the pills the German study tested? I just want to be sure that the article is beyond reproach and that the pills which were analysed were on the market at the time and included some of the mega dosed pills, given that this article seems to be the singular foundation for discounting the isomer theory completely.

No doubt the derisive comments will follow from some but for my mind, I just want to be sure, and once I am, I’m happy to move on from this possibility.

 

[G_Chem]

Whilst I don’t want to rehash this unnecessarily, the German article that analyzed the enantiomeric ratios, is this the only study or release of data of this kind in recent years that we know of? It is a shame that they did not publish the identity of the pills tested because I’d be very interested to know if any of these included some of the mega dosed but thoroughly underwhelming pills.

The image of the various pills which has been posted together with this link (see Negi post page 52) seem to be only of pills that do not seem to be recent presses at all. Is that of another similar but older study or are these the pills the German study tested? I just want to be sure that the article is beyond reproach and that the pills which were analysed were on the market at the time and included some of the mega dosed pills, given that this article seems to be the singular foundation for discounting the isomer theory completely.

No doubt the derisive comments will follow from some but for my mind, I just want to be sure, and once I am, I’m happy to move on from this possibility.

I’ve theorized that domestic German product is superior to many other countries for a number of reasons. First if we look at the average milligram quantities used they’ve stayed at or below 120mg despite other countries seemingly taking more and more. They also are country full of smart competent chemists.

It’s unfortunate that study took place in Germany because before it ever came out I was speaking of Germans possibly having better than average domestic product.

-GC

 

[Negi]

Whilst I don’t want to rehash this unnecessarily, the German article that analyzed the enantiomeric ratios, is this the only study or release of data of this kind in recent years that we know of? It is a shame that they did not publish the identity of the pills tested because I’d be very interested to know if any of these included some of the mega dosed but thoroughly underwhelming pills.

The image of the various pills which has been posted together with this link (see Negi post page 52) seem to be only of pills that do not seem to be recent presses at all. Is that of another similar but older study or are these the pills the German study tested? I just want to be sure that the article is beyond reproach and that the pills which were analysed were on the market at the time and included some of the mega dosed pills, given that this article seems to be the singular foundation for discounting the isomer theory completely.

No doubt the derisive comments will follow from some but for my mind, I just want to be sure, and once I am, I’m happy to move on from this possibility.

The table that included photos of pills was from a someone's PhD thesis about pills sized on Malta between 2006 and 2011. I'll email the lead author of the Germany study about the dosages and shape/design of the MDMA pills in their study.

I’ve theorized that domestic German product is superior to many other countries for a number of reasons. First if we look at the average milligram quantities used they’ve stayed at or below 120mg despite other countries seemingly taking more and more. They also are country full of smart competent chemists.

It’s unfortunate that study took place in Germany because before it ever came out I was speaking of Germans possibly having better than average domestic product.

-GC

Based on police & seizure information, I would be skeptical that a significant degree of the total MDMA market is "domestic" in Germany. Unless the German labs simply never get busted, most MDMA labs appear to be in Belgium and the Netherlands. Even the information about busts of major German drug dealers specifically mentions MDMA being transported in from NL.

 

[Negi]

Just went to email and remembered that I had already corresponded with the main author. I can't remember if I posted this in the thread.

my email:

Hello Mr Losacker,

I was excited to discover your paper "Determination of the enantiomeric composition of amphetamine, methamphetamine and 3,4-methylendioxy-N-methylamphetamine in seized street drug samples from southern Germany", specifically the section on seized MDMA samples. Research on clandestinely produced MDMA frequently omits data on it's enantiomeric composition, so your paper was very useful as an indicator that the more recent synthesis methods and precursors used to produce MDMA (PMK-glycidate, etc) still result in a racemic product.

On the topic of recent MDMA synthesis methods, were you able to identify any of the substances that made up the remaining 9.9% of the crystalline MDMA samples? There has been some online speculation that recent MDMA precursors and synthesis methods might be producing positional isomers or other closely related substances that would remain in MDMA at the retail level. Have you see any indication of this in the samples that you have tested?

As an aside, that you very much for publishing this paper as open access, so that the knowledge in it could be freely shared across the world.

Regards,

[Name]

Their response:

Dear [Name],

I am glad to hear, that our resaerch is already attracting interest. Since MDMA in Germany originates from the only Netherlands, it can of course not be excluded, that in other countries non-racemic quantities may be obtained. But I think you have a deeper knowledge of the current international situation...

As the method section says, quantification was not done by myself but in the LKA Mainz. They do this mostly for legal reasons for the drug dealer. As far as I know, they only detect the main additional ingredients, such as bulking agents (eg. lactose), but not minor by-products.

Best regards
Moritz

So it sounds like they never had access to the raw samples so they wouldn't be much help for knowing the dosage in the pills. They do indicate though that they believe all of the MDMA samples came from the Netherlands. This was also noted in the paper.

 

[G_Chem]

Just went to email and remembered that I had already corresponded with the main author. I can't remember if I posted this in the thread.

my email:


Their response:


So it sounds like they never had access to the raw samples so they wouldn't be much help for knowing the dosage in the pills. They do indicate though that they believe all of the MDMA samples came from the Netherlands. This was also noted in the paper.

He also states you may have deeper current knowledge, so I’ll take that all with a fat grain of sea salt.

Still cool shit you messaged him though, not often we see the researchers own words on the subject.

-GC

 

[Tranced]

“that’s not saying much since most kitchen chemistry labs are laughably bad, poorly constructed and/or dangerous as all fucking get-out..”

Exactly Na you’re right Grignards are not beyond the capability of all clandestine labs but most. I’ve seen enough talk of them on the Hive to believe but an LSD chemist and an MDMA chemist are too different things. MDMA labs are often as you describe.

Regardless, that route has little to do with the discussion here beyond maybe the fact it’s reduced via Sodium borohydride. I bring that up cuz I noticed while scouring the hive ages ago that MDMA made via that reduction often tended to be lackluster from the reports of a few bees. I guess as I’ve said before it doesn’t matter what route is used if it’s pure enough.


So off topic to this, I’ve been thinking more of the possibility that safrole (either residual or intentionally added after synthesis as a signature) may have potentiating properties. It’s a potent and indiscriminate inhibitor of many CYP enzymes.

I notice batches that look fairly clean to the eye with nice crystal structure and clarity but still have the tiniest hint of safrole to be the best. I wonder if that residual safrole is inhibiting CYP enzymes enough to change the effect.

The batches that can bring about rolls where 7-8hrs later I’m not rolling exactly but still in a positive upbeat mindset. Those all seem to smell of safrole. Batches that don’t often end more like 3.5-5hrs.

-GC

Would any of these be the same CYP enzymes that cause differing breakdown of MDMA > MDA, causing a more MDA like experience for some people?

I honestly think I maybe have/don't have them. A couple of hundred milligrams of DXM seemed to cause a gram+ experience, I trip off enough MDMA, and it still works for me... etc.

 

[F.U.B.A.R.]

So an innocent joke became a failed excuse for a nitpick

Sometimes things work, sometimes not

Btw i think this whole topic is silly so everyone feel free to redirect all your spite at me :D

Why is it silly? It's an extremely valid topic of conversation as far as I'm concerned...

 

[unodelacosa]

Why is it silly? It's an extremely valid topic of conversation as far as I'm concerned...

I have to agree with @F.U.B.A.R. on that, @Mjäll …

I mean check out the definition of silly for a minute:

sil·ly| ˈsilē | adjective (sillier, silliest) having or showing a lack of common sense or judgment; absurd and foolish: another of his silly jokes | “Don't be silly!” she said. • ridiculously trivial or frivolous: he would brood about silly things.
SYNONYMS foolish, stupid, unintelligent, idiotic, brainless, mindless, witless, imbecilic, imbecile, doltish; imprudent, thoughtless, rash, reckless, foolhardy, irresponsible; mad, erratic, unstable, scatterbrained, featherbrained; flighty, frivolous, giddy, fatuous, inane, immature, childish, puerile, half-baked, empty-headed… British informal daft, dotty, scatty, divvy, dappy; North American informal dumb-ass; ANTONYMS sensible, rational

I can't cosign that. The discussion alone has prompted lots of people to think about chemistry, clandestine operations, the perils and effects of global drug prohibition, the power of placebo, the value of IEC Spain, and so many other relevant topics that dismissing it as silly can't really be what you meant. I'm assuming you were just saying that you're personally not too concerned with the topics in this discussion, right?

 

[Mjäll]

Why is it silly? It's an extremely valid topic of conversation as far as I'm concerned...

That was written mostly to signify that i was aware i was being off topic in this thread. That is, i have no interest in discussing the actual subject and just came in to remark on someone's remark - so feel free to judge me for that.

If i had to explain why i think it's silly i'd simply say i've personally had what matches the description of good MDMA and this complaint about recent MDMA seems to be a narrow phenomenon among people who might aswell just be afflicted by permatolerance or aging brains. But really i have nothing to contribute to the topic. This criticism has been voiced multiple times just in the few parts i've skimmed through.

 

[unodelacosa]

Whilst I don’t want to rehash this unnecessarily, the German article that analyzed the enantiomeric ratios, is this the only study or release of data of this kind in recent years that we know of? It is a shame that they did not publish the identity of the pills tested because I’d be very interested to know if any of these included some of the mega dosed but thoroughly underwhelming pills.

The image of the various pills which has been posted together with this link (see Negi post page 52) seem to be only of pills that do not seem to be recent presses at all. Is that of another similar but older study or are these the pills the German study tested? I just want to be sure that the article is beyond reproach and that the pills which were analysed were on the market at the time and included some of the mega dosed pills, given that this article seems to be the singular foundation for discounting the isomer theory completely.

No doubt the derisive comments will follow from some but for my mind, I just want to be sure, and once I am, I’m happy to move on from this possibility.

Hey mate, just wanted to apologise if I've come across as derisive, it was never my intention but the fault is still entirely mine.

I appreciate you being thorough on this point, but I simply cannot see the dramatic effect difference between MDMA and subpar counterfeit MDMA, or "MehDMA" or whatever, being accounted for purely by enantiomeric ratios, if this were even the case and assuming the phenomenon isn't psychosomatic or similar. However, there is no incentive for drug manufacturers to mess with their initial racemic results, and all major and known methods of producing MDMA produces the racemic blend. I get the argument with PMK-glycidate being chiral, but that would spin off different compounds entirely, not just some goofball configuration of MDMA's optical isomers. But with no easy way of testing this, we're all kinda spinning our proverbial wheels here, aren't we?

who might aswell just be afflicted by permatolerance or aging brains. But really i have nothing to contribute to the topic. This criticism has been voiced multiple times just in the few parts i've skimmed through.

Fair enough and I agree with you on some of that. Personally I still find the phenomenon pretty interesting, no matter what causes it. But then I'm afflicted by a strange curse in which I find far too many topics interesting…