What is wrong with the MDMA available today? - v2

[unodelacosa]

@indigoaura @snmfmy Yeah the media has poisoned the terms "meth", "methamphetamine", "MDMA", "methylenedioxy", and even the word, "amphetamine", which itself is "alpha-methyl-phenyl-ethyl-amine".

And then there's "dextroamfetamin" to try to disguise amphetamine 'salts'. You can retool methamphetamine into being α,n-dimethylphenethylamine (DMPEA), or n-methyl-dexedrine works. Safrylamine I think was used at some point for 3,4-MDA and Methsafrylamine was MDMA according to this nomenclature.

Good find with that study, @indigoaura – it just ended last month. Nice one! Thanks for sharing.

I think I got that right but I might not be right.

Seemed right to me. Very German. That's why chemical names tend to be one, long, compound noun.

 

[PsychedelicSummer]

I’d like to return to a question I’ve harbored a long time now that some chemists are active in the tread. From my reading, the main hypothesis regarding what causes this MehDMA appears to be that it’s due to some synthesis byproduct which may be related to either bad starting material; bad synth or a combination thereof. Though I’ve never been able to let go of the isomer hypothesis.

So I’d like to ask anyone of you knowledgeable chemists (Locking at for example unodelacosa & vash445) say if any of the 6 mass equivalent isomer of MDMA below can be made with a different precursor than what’s used to produce MDMA? A precusor that's not controlled?

2,3-MDMA
2-(3-methoxyphenyl)-N-methyl-3-butanamine
2-(4-methoxyphenyl)-N-methyl-3-butanamine
p-ethoxymethamphetamine
p-methoxy-m-methylmethamphetamine
2-(2-methoxyphenyl)-N-methyl-3-butanamine

(Pictures and information regarding identification of the above mentioned molecules here: https://www.researchgate.net/public...d_isobaric_substances_using_fast_LC-ESI-MS-MS)


And 2 more general questions:

Does anyone know anything about the effects of any of these isomers?

Anyone has any idea of how to get anyone to do an analysis of some tested MehDMA as described in the paper above?

 

[snmfmy]

I’d like to return to a question I’ve harbored a long time now that some chemists are active in the tread. From my reading, the main hypothesis regarding what causes this MehDMA appears to be that it’s due to some synthesis byproduct which may be related to either bad starting material; bad synth or a combination thereof. Though I’ve never been able to let go of the isomer hypothesis.

So I’d like to ask anyone of you knowledgeable chemists (Locking at for example unodelacosa & vash445) say if any of the 6 mass equivalent isomer of MDMA below can be made with a different precursor than what’s used to produce MDMA? A precusor that's not controlled?

2,3-MDMA
2-(3-methoxyphenyl)-N-methyl-3-butanamine
2-(4-methoxyphenyl)-N-methyl-3-butanamine
p-ethoxymethamphetamine
p-methoxy-m-methylmethamphetamine
2-(2-methoxyphenyl)-N-methyl-3-butanamine

(Pictures and information regarding identification of the above mentioned molecules here: https://www.researchgate.net/public...d_isobaric_substances_using_fast_LC-ESI-MS-MS)


And 2 more general questions:

Does anyone know anything about the effects of any of these isomers?

Anyone has any idea of how to get anyone to do an analysis of some tested MehDMA as described in the paper above?

I think I actually made a few posts about this particular paper in this thread.

If I remember correctly, the techniques were developed to distinguish between MDMA and the 17 isobaric substances after drugs were seized by law enforcement.

 

[snmfmy]

Could it be your PERIOD.

This is tongue in cheek but I don't think most of the people on this board realize that when a woman's on her PERIOD, Stimulants are much LESS stimulating than the two weeks prior.

"However, with psychomotor stimulant drugs, such as amphetamine and cocaine, responses to the drugs were greater during the follicular, compared to the luteal, phase of the cycle. These findings suggest that, consistent with certain pre-clinical findings, circulating levels of ovarian hormones influence the central effects of stimulant drugs in women."

https://www.sciencedirect.com/science/article/abs/pii/S037687160500400X?via%3Dihub

Remember very small doses of hormones prevent ovulation.

How much could very small changes in other hormone systems in men and women affect the response to MDMA which is a psychostimulant amphetamine?

Once again there are known physiological processes that are known to be evident and extant in MDMA users and the general population that could result in mehMDMA responses.

But we're still searching for the magical interfering boogeyman molecule that nobody knows actually exists and nobody knows what dose would be responsible.

And all the while millions of people around the world are blasting off with MDMA.

Just go look at drugsdata.org

 

[snmfmy]

"Chronic administration of THC prevents the behavioral effects of intermittent adolescent MDMA administration"​

Chronic administration of THC prevents the behavioral effects of intermittent adolescent MDMA administration and attenuates MDMA-induced hyperthermia and neurotoxicity in rats - PMC

Most recreational users of 3, 4-methylenedioxymethamphetamine (MDMA or “ecstasy”) also take cannabis, in part because cannabis can reduce the dysphoric symptoms of the ecstasy come-down such as agitation and insomnia. Although previous animal ...

www.ncbi.nlm.nih.gov

Now they're not sure why, but it seems that chronic administration of THC to rats, to model daily chronic THC use in humans. Apparently blunts the serotonin and dopamine release caused by MDMA.

Does that mean that smoking weed (and now that's ridiculously strong weed that wasn't there before the mehMDMA) all the time for months or years on end is responsible for your mehMDMA experience?

It's a little scary to think that modulation of cannabinoid 1 and 2. Receptors by long-term consumption of cannabis at high levels of THC could result in a dampening of response to MDMA, but apparently It happens in rats.

 

[PsychedelicSummer]

Hormones has been discussed at length before, does not fit in to plenty of experiences described in this thread nor does the MehDMA effect only affect women. Any relationship between THC and MehDMA would obviously have been discovered a long ago. BTW, I'm not a woman.

 

[ĐmantuNJofra]

to the fundamental question just in this thread:

Nothing it is good if you are not stupid, speaking general

and before was bettter thing is just doesn't make sense well I guess I'm not a commerciall one

 

[snmfmy]

Hormones has been discussed at length before, does not fit in to plenty of experiences described in this thread nor does the MehDMA effect only affect women. Any relationship between THC and MehDMA would obviously have been discovered a long ago. BTW, I'm not a woman.

Why do you assert it would have been discovered long ago? It's only been within the last 10 years that such ridiculously potent marijuana and THC derivatives and distillates has been readily available.

10 years ago it wasn't commonplace to find 25 to 30% THC content in marijuana.

In fact, in 2012 the average THC content of marijuana was only 12%.

We know that it takes a certain level of neuroreceptor agonism or antagonism to actually make morphological changes significant enough to disrupt the neurotransmitter system to any real degree. Consumption of two to three drinks of alcohol regularly with meals rarely instigates the morphological changes to GABA receptors and the upper regulation of glutamate receptors that instigates withdrawal. However, once the consumption exceeds 6 to 8 units of alcohol every day alcohol withdrawal syndrome is seen upon abstinence.

We have no idea What the break point for THC morphological changes to the cannabinoid receptors that would reduce the effects of MDMA in humans are, but there's evidence that it happens to rats. The dampening effect may only happen transiently.

And since the number of people that are affected by this mehMDMA is literally minuscule compared to the number of people that consume MDMA all the time. Whatever is causing the effect is something exceedingly rare.

I don't think anyone that's in the "the MDMA is different" or "there is something else in the pill" groups of mehMDMA proponents has kept records detailed enough to discount potential confounding factors like you assert in your response.

Many other steroid hormones like pregnenolone and allopregnenolone modulate neurotransmitters and affect dopamine release and can also blunt the response to THC.

Since steroid levels are known to fluctuate significantly due to stress, nutritional status, and other variables, there's no way to determine whether the subjective response to MDMA is affected in certain people by these transient changes in steroid levels.

Furthermore, I believe that the majority of proponents of the mehMDMA movement discount any potential interference from widely consumed substances and therefore don't investigate potential confounding substances.

For example, inhibition of the norepinephrine transporter reduces the subjective drug high of MDMA

"Reboxetine reduced the effects of MDMA including elevations in plasma levels of NE, increases in blood pressure and heart rate, subjective drug high, stimulation, and emotional excitation"

Norepinephrine transporter inhibitors and their therapeutic potential - PMC

The norepinephrine transporter (NET) is located in the plasma membrane of noradrenergic neurons, where it functions to take up synaptically released norepinephrine (NE). The NET thus serves as the primary mechanism for the inactivation of ...

www.ncbi.nlm.nih.gov

I have never heard anyone state that norepinephrine release is necessary for the subjective high from MDMA yet it clearly is.

How many everyday substances inhibit NET to enough of a degree that the subjective effects of MDMA are reduced somewhat.

---

"In the presence of Ro4-1284, MDMA-mediated horizontal hyperlocomotion was delayed and attenuated, whereas rearing activity was abolished."

Vesicular Monoamine Transporter 2 and the Acute and Long-Term Response to 3,4-(±)-Methylenedioxymethamphetamine - PMC

3,4-(±)-Methylenedioxymethamphetamine (MDMA, Ecstasy) is a ring-substituted amphetamine derivative with potent psychostimulant properties. The neuropharmacological effects of MDMA are biphasic in nature, initially causing synaptic monoamine release, ...

www.ncbi.nlm.nih.gov

There are only a few specifically designed VMAT2 inhibitors. However, It was recently found there are many non-selective beta adrenergic blockers that inhibit VMAT2, as well as ziprasidone. These include carvedilol, salmeterol (advair), and formoterol(foradil)

Advair and foradil are prescribed to millions of people for asthma control.

Inhibition of VMAT2 by β2-adrenergic agonists, antagonists, and the atypical antipsychotic ziprasidone - PMC

Vesicular monoamine transporter 2 (VMAT2) is responsible for packing monoamine neurotransmitters into synaptic vesicles for storage and subsequent neurotransmission. VMAT2 inhibitors are approved for symptomatic treatment of tardive dyskinesia and ...

www.ncbi.nlm.nih.gov

How many other pharmaceuticals or everyday substances have some level of inhibition on VMAT2 but are unknown because there were never any assays done to assess it?

After all, we're not talking about complete abrogation of the effects of MDMA. We're talking about some reduction enough to say that the MDMA really wasn't that good.

 

[snmfmy]

Then there's also the fact that MDMA instigated dopamine release is modulated by a cross talk between serotonin and gaba receptors. MDMA inhibits nigral gaba release which disinhibits striatal dopamine release, however, it increases gaba release in the VTA which inhibits dopamine release in the nucleus accumbens. This is all moderated also by MDMA actions on 5HT2A/C receptors.

If GABA release can differentially impact dopamine release in areas of the brain, what would a substance that blocks the action of MDMA on GABA receptors do?

Nobody knows because it hasn't been investigated yet, or at least I haven't found a paper that looks at gaba antagonism or GABA agonism with respect to the subjective effects of MDMA.

Lastly, I'll give an anecdote of my own. Gabapentin at 1600 mg a day drastically reduces the subjective effects of MDMA and mushrooms. After a few weeks of no gabapentin, the response to MDMA and mushrooms returned to what was expected.

 

[snmfmy]

I wonder if any of the mehMDMA crowd is where that supplementation of 5-HTP at 5 mg. Per kilogram in non-human, primates reduces binding potential of a highly selective 5HT1B radioligand to the same degree as administration of MDMA.

BPND values were significantly decreased in several examined brain regions after administration of amphetamine (range: 19–31%), MDMA (16–25%) or 5-HTP (13–31%).

Serotonin concentration enhancers at clinically relevant doses reduce [11C]AZ10419369 binding to the 5-HT1B receptors in the nonhuman primate brain - Translational Psychiatry

The serotonin (5-HT) system plays an important role in the pathophysiology and treatment of several major psychiatric disorders. Currently, no suitable positron emission tomography (PET) imaging paradigm is available to assess 5-HT release in the living human brain. [11C]AZ10419369 binds to...

www.nature.com

Reduced binding potential usually equates to reduce action of an agonist on the receptor. Reduced action of MDMA at 5HT receptors would equate to reduced subjective effects.

And now we have the second identified effect of 5-HTP supplementation that would directly reduce the subjective effects of MDMA.

"In the presence of elevated levels of 5-HTP, the enzyme AAAD is engaged primarily in serotonin production, at the detriment of catecholamine production. Subsequently, 5-HTP supplementation in the absence of adequate L-DOPA or L-tyrosine will result in diminished concentrations of the catecholamines."

The Relationship Between Serotonin and 5-HTP

5-Hydroxytryptophan (5-HTP) is a naturally occurring amino acid produced from the essential amino acid L-tryptophan. 5-HTP is the precursor for neurotransmitters, which are chemicals that transmit a nerve impulse across neuronal gaps that are called synapses. These neurotransmitters include...

www.news-medical.net

So not only does 5HTP, pre-load or pre-supplementation reduce the binding potential and therefore the action of MDMA at 5-HT receptors, it also reduces the levels of dopamine and norepinephrine in the brain (because of competitive displacement of AAAD enzyme), which would reduce the subjective effects of MDMA.

I'm glad I never preloaded 5-HTP.

 

[🔥highonfire🔥]

It works alot when you're young then it stops from tolerance, then you quit, try again a few years later, get bunkish, quit for almost 10 years, search better get real deal, try a few times and notice the reduction in experience due to tolerance, then use conservatively, never more than twice a year to keep the magic.

 

[unodelacosa]

I’d like to return to a question I’ve harbored a long time now that some chemists are active in the tread. From my reading, the main hypothesis regarding what causes this MehDMA appears to be that it’s due to some synthesis byproduct which may be related to either bad starting material; bad synth or a combination thereof.

This is not a singular thing that can be easily accounted for, this anecdotal phenomenon, which could be caused by anything from placebo, to underestimating set & setting, from one particular impurity introduced during a poorly executed synthesis to an imposter drug being used to swap in for MDMA 100%, and ppl on this thread incl. the OP have been thrown off because Energy Control Spain is running a scam just shy of being easily proven, and they hide behind plausible deniability.

Most likely the answer is all of the above. The actual cause in a particular case does not collapse down into reality until needed. It's quite the feline friend of Schrödinger's…

Though I’ve never been able to let go of the isomer hypothesis.

It's not a bad one. These are (mostly) all valid causes for a subpar experience with what was marketed and sold as 'MDMA.'

So I’d like to ask anyone of you knowledgeable chemists (Locking at for example unodelacosa & vash445) say if any of the 6 mass equivalent isomer of MDMA below can be made with a different precursor than what’s used to produce MDMA?

Well of course.

A precusor that's not controlled?

There are myriad ways of getting to 3,4-MDx, though in the end the majority of the time it comes down to reductive amination of MDP-2-P (the intermediate ketone aka: PMK).

2,3-MDMA

This is a stimulant only, not an empathogen, you know…Check out the extensions and commentary on PiHKAL entry #100 for MDA.

2-(3-methoxyphenyl)-N-methyl-3-butanamine
2-(4-methoxyphenyl)-N-methyl-3-butanamine

Where are you getting these from? EDIT: Oh, I looked at the paper you shared. If anything it underscores the challenges and difficulty of accurately identifying chems in a compound matrix born from illicit production.

p-ethoxymethamphetamine

I guess you mean p-ethoxy-n-methamphetamine? Sounds like it's probably unpleasant and not super likely to spin out from a MDMA synthesis.

p-methoxy-m-methylmethamphetamine

and I assume you mean 4-methoxy-3,n-dimethylamphetamine. Probably another 'dirty'-feeling CNS stimulant. I know that clandestine MDMA chemists sometimes use too much heat when isomerizing Safrole into Isosafrole. It ends up breaking up the 3,4-methylenedioxy ring and their end product winds up being, in some unknown portion, 3,4-dihydroxymethamphetamine. This possibly accounts for some of the Meh experiences. There is no one solid boogeyman.

2-(2-methoxyphenyl)-N-methyl-3-butanamine

Yeah it looks like a possible outcome side product during MDMA production. What exactly are you driving at here?

(Pictures and information regarding identification of the above mentioned molecules here: https://www.researchgate.net/public...d_isobaric_substances_using_fast_LC-ESI-MS-MS)

Thanks! Nice find.

And 2 more general questions:
Does anyone know anything about the effects of any of these isomers?

I believe they're generally CNS stimulants mostly if/when active. Have you really search the literature?

Anyone has any idea of how to get anyone to do an analysis of some tested MehDMA as described in the paper above?

Not easily, no. One could invest in a used GS-MS which will set you back at least a few thousand dollars, but it's not what the universities and legitimate labs shell out for new ones. Just a thought.

Now they're not sure why, but it seems that chronic administration of THC to rats, to model daily chronic THC use in humans. Apparently blunts the serotonin and dopamine release caused by MDMA.

Does that mean that smoking weed (and now that's ridiculously strong weed that wasn't there before the mehMDMA) all the time for months or years on end is responsible for your mehMDMA experience?

No, it just means that for rats, but humans are quite different from rats, despite some neurotransmission stuff they have in common, like most mammals. Moreover, on a personal/anecdotal tip, I smoke weed daily and have done so for years with occasional tolerance breaks here and there. Doesn't seem to affect my ability to roll my face off.

In fact, if anything, it kinda feels like MDMA prevents me from getting stoned on THC products just a bit.

It's a little scary to think that modulation of cannabinoid 1 and 2. Receptors by long-term consumption of cannabis at high levels of THC could result in a dampening of response to MDMA, but apparently It happens in rats.

I guess. I'm a little dubious of this study, and anyway, there are likely a lot more factors involved in this than first meets the eye.

Hope that helps a little. Also, try reading this comprehensive report from legendary DEA chemist, Dal Cason, who was friends with Dr. Shulgin, for instance… https://erowid.org/archive/rhodium/chemistry/mda.dalcason.html

 

[Rectify]

What is wrong with the MDMA available now?

I DON'T HAVE ANY!

 

[PsychedelicSummer]

Thank you Unodelacosa!

unodelacosa said:
What exactly are you driving at here?

Well, my thinking comes from me imagining if I were a clandestine chemist, maybe I would have made one of the above isomers and found out that it had MDMA like effects and could be made from an uncontrolled precursor and that GS-MS wouldn't be able to different it from real MDMA. If I remember correctly from the paper I mentioned, it is column chromatography that is need to be of any help.

snmfmy said:
Why do you assert it would have been discovered long ago? It's only been within the last 10 years that such ridiculously potent marijuana and THC derivatives and distillates has been readily available.

I have had MehDMA experiences both using and not using THC. When using THC, I'm after only a certain level of effect (I dislike beeing too stoned). Thus if very potent product, I use only a little. As this thread has many descriptions of groups people having MehDMA experiences, if it only had affected those using THC if would already have been discovered.

I've tried to supplement with booth 5-HTP & NAC, but no difference.

As I've said before, the MehDMA I've taken blocks psychedelics, contrary to real stuff that synergizes with psychedelics (tried with 2C-B, LSD & AL-LAD). I've given MehDMA to people who never had any empathogen, and though they've said it was "OK", no amplification of touch, no heightened empathy, maybe very slight increase in music appreciation, no mega mydriasis. Does give bruxism and urinary retention though.

I've very seldom taken a second sample of the at least 10 different batches I've bought from DN in northern Europe over at least 5-6 years. That's because I don't like the effect. Of real MDMA I've taken in total 1,2 g well spaced out and I do get a clear MDMA effect from as little as 80 mg. Of todays MehDMA I only get more side effects if I increse from 120 mg (my weight is 70 kg).

 

[AlsoTapered]

Just jumping up a few posts. I have it on reliable authority that 3,4-methylenedioxy phenmetrazine is inactive. MANY years ago when it was legal to do so, someone I know had a sample made. It was inactive. But then I don't know if they validated the sample by sending a bit for NMR/GC-MS. But it was someone who I believe knew his stuff.

Possibly this is of value because it suggests that active conformation of MDMA isn't as it appears. MDMC is active so the O isn't responsible for the lack of response.

Anyone know if 3,4-MD methylphenidate was ever produced? I wouldn't imagine it would work but don't KNOW for sure.

 

[🔥highonfire🔥]

Do isomers play a big role in phenethylamines? Is that the reason there seems to be 2 separate dosage ranges for DOC?

 

[snmfmy]

and I assume you mean
No, it just means that for rats, but humans are quite different from rats, despite some neurotransmission stuff they have in common, like most mammals. Moreover, on a personal/anecdotal tip, I smoke weed daily and have done so for years with occasional tolerance breaks here and there. Doesn't seem to affect my ability to roll my face off.

In fact, if anything, it kinda feels like MDMA prevents me from getting stoned on THC products just a bit.


I guess. I'm a little dubious of this study, and anyway, there are likely a lot more factors involved in this than first meets the eye.

Yes but are you taking gram levels of distillates, gummies, vape juice, dabs, like we know people are doing?

Are you Regularly smoking 30% THC marijuana because that's what's on the market now?

mehMDMA is not widespread and with the exception of known low content and the pills that tested different. I've never had a mehMDMA experience. Nobody that I have ever met has had one.

And the vast majority of people, even on this board continue to have fire experiences on MDMA.

I don't expect any of the causes eye proposed to apply to the average person.

That's why I don't believe that it's an impurity because it would be widespread and affecting everyone.

Remember, it's a very very small percentage of people that are complaining of this. Their idiopathic response to some level of THC could easily be causing this syndrome and the majority of people would be fine.
And as far as cannabinoid receptors modulating dopamine and serotonin receptors well, here's a nice paper that doesn't have to do with rats. It details the afferent interplay between the endocannabinoid, dopaminergic and serotonergic systems.

The following quote gives you an idea about what's in the paper:

"Indirect and polysynaptic modulation of 5-HT neurons by CB1 receptors." (Figure 3)

Modulating the neuromodulators: dopamine, serotonin and the endocannabinoid system

Dopamine, serotonin and endocannabinoids are key neuromodulators involved in many aspects of motivated behavior, including reward processing, reinforcement learning and behavioral flexibility. Among the longstanding views about possible relationships ...

www.ncbi.nlm.nih.gov

 

[Parabolan]

I got mine reagent tested 5 different times, to show that it's pure MDMA. I know there's a lot of shit out there, but that doesn't mean that there's no good MDMA out there.

 

[snmfmy]

I got mine reagent tested 5 different times, to show that it's pure MDMA. I know there's a lot of shit out there, but that doesn't mean that there's no good MDMA out there.

Reagent testing even using five reagents can't show it is pure. I guarantee that I can find you lots of substances that have no reaction to those five reagents.

If you're saying you can have a reasonable certainty that it doesn't contain a particular adulterant, that may be a reasonable statement.

 

[Parabolan]

Reagent testing even using five reagents can't show it is pure. I guarantee that I can find you lots of substances that have no reaction to those five reagents.

If you're saying you can have a reasonable certainty that it doesn't contain a particular adulterant, that may be a reasonable statement.

Well, I know it's decent MDMA. A buddy of mine rolled balls on 80mg of it, and he's experienced.