Pharmacology Methylone is better than MDMA change my mind

[4DQSAR]

Certainly - one needs to be careful with AMT and particularly 7-methyl AMT. Upjohn's research revealed that the addition of that 7-methyl increases it's monoamine release and reuptake activity by an order of magnitude.

Did you know that in the late 1980s when MDMA was finally brought under legal control in the US, someone spotted that AET was still legal AND commercially available? The individual in question actually sold AET AS MDMA and by all accounts, nobody realized he had misrepresented the product. After his eventual arrest, he was able to fight his case in court and be found not guilty. Not deterred he went straight back out and carried on. Arrested again he was informed by the judge that IF he was ever caught selling AET again, he WOULD be convicted of several civil offences.

But the irony is that the makers had noted how unexpectedly popular AET was with a handful of customers (the guy using multiple names/bank accounts) and the put the price up x10!

I LOVE the fact that the guy had managed to find a loophole. I'm all for loopholes rather than breaking the law.

Now here is the thing. The CsA laws instituted in the US deal with SPECIFICALLY the indole nucleus and use Markush descriptions to make all derivatives of tryptamine automatically illegal. BUT that doesn't cover modifications to the indole. Now I certainly wouldn't want to test that in a court but the CsA laws also specifiy that an analogue mus possess 'similar or more potent' activity than a NAMED drug.

So here is my question. If you synthesize a compound that is chemically related to hallucinogens BUT is an entactogen, is it controlled by the CsA laws? Again, not one I would wish to test but I didn't write the laws and clearly whoever did.... wasn't expert in the field.

Remember when someone was selling the benzofuran analogue of 5-MeO DMT? I forget the name they used and reports weren't great but to the best of my knowledge, it was never actually controlled.

Most nations use caselaw so if someone is found not guilty, defence councils can cite the case as part of the defence. My guess is that is why VERY FEW people have ever gone to court if they were accused of breaking the UK's PSA laws. Sadly nobody repoerted on the cases but it's my impression that the CPS has decided to offer defendants extremely leanient sentencing to avoid it winding up in a court room. Because the moment one person is found not guilty, that opens the door to a defence.

I don't KNOW the above, it's just my impression. IF anyone knows more, I would love to hear about it.

 

[4DQSAR]

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You can see how (S)-AMT is a substructure of LSD but as we know, only one of the four enantiomers of LSD is psychoactive. So my simple logic was to test if AMT likewise was optially active. It IS. That done a simple referral to both the Roussel-UCLAF and Upjohn patents.

People have asked why (R)-7-methyl AMT hasn't turned up as an RC, especially given it's relatively high potency and similarity to MDA and MDMA. The answer is simply that the intermediate 7-methyl-1H-indole-3-carbaldehyde is difficult to make and once you resolve the product, you end up having to throw half if it away. IF someone were to offer 1-(7-methyl-1H-indol-3-yl)propan-2-one, a chiral reductive amination would make it facile.

BUT on reflection, it's SO potent that the racemate has a window where it's active as an entactogen BUT not psychedelic. Problem is, if someone takes a second dose and EVERYTHING changes ;-)

 

[Deleted member 576750]

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You can see how (S)-AMT is a substructure of LSD but as we know, only one of the four enantiomers of LSD is psychoactive. So my simple logic was to test if AMT likewise was optially active. It IS. That done a simple referral to both the Roussel-UCLAF and Upjohn patents.

People have asked why (R)-7-methyl AMT hasn't turned up as an RC, especially given it's relatively high potency and similarity to MDA and MDMA. The answer is simply that the intermediate 7-methyl-1H-indole-3-carbaldehyde is difficult to make and once you resolve the product, you end up having to throw half if it away. IF someone were to offer 1-(7-methyl-1H-indol-3-yl)propan-2-one, a chiral reductive amination would make it facile.

BUT on reflection, it's SO potent that the racemate has a window where it's active as an entactogen BUT not psychedelic. Problem is, if someone takes a second dose and EVERYTHING changes ;-)

LSD is a really interesting compound to me, it has that same pharmacophore as tryptamines but the structure is rigid and typically has far greater affinity than any tryptamine off the top of my head

I think the rigidity keeps it in a more optimal configuration for binding, and possibly imparts some metabolic resistance

 

[Shinji Ikari]

I liked methylone a lot in 2009/2010. I grabbed a 10g bag just before it was banned in the UK and haven't encountered it since. It's more forgiving than MDMA but I definitely had a good long bout of the sads at the end of that binge.

I don't know what the benefit over MDMA would for therapeutic use. I'm terms of effects it's just MDMA but less and I don't think MDMA is generally considered to be neurotoxic when taken on its own at normal doses. Methylone is only "safer" when you're abusing it (and it'll still pickle your brain when you smash it, can confirm) which is kind of moot in a therapeutic context.

I still like methylone though. Would love to see it make a comeback. I can't see that ever happening though. It's rise in popularity to begin with coincided with a global MDMA drought and with real MD readily available nerds like us are the only ones who would ever seek it out.

 

[4DQSAR]

What I found most interesting was overlaying LSD with the NBOMe compounds. That ortho methoxy benzyl moiety PERFECTLY overlays the diethylamine moiety of LSD. Even the lone-pairs of the oxygen align. The 2,5-dimethoxy overlays the N of the indole and encompasses the 5-MeO of the more potent tryptamines. The 4 (para) substitution of the PEAs/NBOMes perfectly overlays, you guessed it, the 7 position of the indole ring.

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It's really difficult to explain a 3D structure using a 2D image but I've drawn LSD and underneath it a compound that is half way between LSD and the NBOMe. What I can't do is show the benzene ring of the NBOMe rotated by 90 degrees as all you would see is an edge. But the two classes overlay and what is extremely useful is that it highlights the key moieties.

In essence the diethyl is merely space-filling with a hydrophobic group. As you know there are quite a few other amides that are also active and the key thing that all possess is an ability to fill the same pocket.

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I realize that the above is the BEST explaination of what 7-methyl AMT actually DOES. It perfectly overlays p-methyl amphetamine. As you noted, it's very important to carefully test to confirm the safety profile of 7,a-DMT (7, alpha dimethyl tryptamine) but in essence, it's a reasonably selective serotonin reuptake inhibitor. 7-methyl AET WAS tested by Upjohn but was shown to possess MAOI activity. I discussed this with David Nichols a few years ago and he mentioned that the reason the alkyl was made longer was to suppress 5HT2a affinity BUT he also noted that the longer alkyl chain was a core reason for the compound having significant MAOI activity.

I would be prepared to bet that even racemic 7,a-DMT will have a window between it's entactogen activity and it's psychedelic activity given that it's seratogenic activity is an order of magnitude larger than AMT but I underline the fact that unlike MDMA, increasing the dose would significantly alter the subjective effects.

It just seems crazy to me that a simply VAST number of different tryptamines have become RCs but the only indole substitution is the 5 methoxy...

 

[4DQSAR]

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I ABSOLUTLY promise this is my last word on the topic.

3-Methoxy-4-methylamphetamine - Wikipedia

en.wikipedia.org

More accurately, 7,a-DMT overlays the above compound. While the Wikipedia entry is for the raecmic compound, I am prepared to bet that one enantiomer is responsible for 5HT2a affinity, the other for seotonin modulation. Nichols produced the compound he abbreviates a MME. Page 304 states:

'Racemic MMA proved to be as potent as MDMA or (+ )-MBDB in drug discrimination assays in rats trained to discriminate MDMA or (+ )-MBDB, respectively. Surprisingly, both enantiomers of MMA had nearly identical potencies, similar to the racemate, in substitution tests in ( + )-MBDB-trained rats. Perhaps most exciting was the finding that MMA lacked serotonin neurotoxicity.'

https://bitnest.netfirms.com/external/DrugDes.Disc/9.299

Pihkal notes:

'Some years ago a report appeared in the forensic literature of Italy, of the seizure of a small semitransparent capsule containing 141 milligrams of a white powder that was stated to be a new hallucinogenic drug. This was shown to contain an analogue of DOM, 3-methoxy-4-methylamphetamine, or MMA. The Italian authorities made no mention of the net weight contained in each dosage unit, but it has been found that the active level of MMA in man is in the area of 40-60 milligrams. The compound can apparently be quite dysphoric, and long lived.'

Now my point here is that Shulgin does not claim to have tested MMA and rather than a 3-methoxy, 7,a-DT has pyrrole ring of the indole system that places a nitrogen over the spot where the 3-methoxy would sit. Now it's simply impossible to extrapolate the subjective effects of 7,a-DMT but as I have previously mentioned, it appered to be significantly more potent than MDMA so one presumes more potent than MMA. I believe the key to this is that the aromatic indole system keeps the bioisostere of the methoxy planer to the benzene ring in the same way that bromo butterfly keeps the system planer.

So has the PEA homologue ever been made? No would appear to be the answer. I thought I had heard of 'hemi fly' compounds but no.

 

[Allylbenzene]

I thought I had heard of 'hemi fly' compounds but no.

Here's one:

2C-B-5-hemiFLY-α6, also known as BNAP, is a serotonin receptor modulator of the phenethylamine and FLY families related to the psychedelic drugs 2C-B and DOB. It is a cyclized phenethylamine with a partial ergoline- or LSD-like chemical structure. Its tricyclic structure mimics the A, B, and C rings of LSD.

2C-B-5-hemiFLY-α6 - Wikipedia

wikipedia.org

 

[4DQSAR]

I would stick to the indole or as synthetic complexity is lower. If you noted, I carefully ensured that the stereoisomerism of the compounds I showed was clear. But with two chiral centres, that means 75% is waste, Maybe there is a chiral synthesis, but I don't imagine that researcher would care. Yeild need only be 'enough'.

Plus I was sort of highlighting that enantiomers that were MDMA-like rather than psychedelic.

 

[pcplease]

I would say that it is "superior" only if it provides you more of the effects you desire from MDMA. It was medicinal for me and when released I used a little bit most days as it provided me good antidepressant effects and a focus/clarity I'd never felt before. I'd tried many, sometimes in success, by then. Coke is too scatterbrained and euphoric, MDMA is very safe in moderate use.

I did not moderate my use when i had all three MDxx readily available the previous decade. MDxx has its place for sure in therapy, M1 may even be superior for certain people especially as an adjunct. It is chattier and may promote more communication between couples.

 

[HealingEnergy14]

Some really neat research coming out around methylone recently. Studies show that it works when administered alongside SSRIs, it is better tolerated than MDMA with less ADRs, more stable cardiovascular readings, less off target effects with little binding to tested GPCRs, less depletion of serotonin for less risk of neurotoxicity, and likely less neurotoxic metabolites (this one is my own assumption feel free to write it off)

Frontiers | Methylone is a rapid-acting neuroplastogen with less off-target activity than MDMA

Background: Post-traumatic stress disorder (PTSD) is a highly prevalent psychiatric disorder that can become chronic and debilitating when left untreated. Av...

doi.org

I highly recommend reading the recently papers mentioned in the intro, particularly the human trials and the FST with SSRI coadmin and comparison

Methylone is wayyy better for parties and talking to people! I loved that drug in the early 2010's. There certainly was a comedown but it was considerably less than the MDMA that was around at the the time imo.

I can't understand why 4-MMC is supposedly (I have never ordered, tried or tested it) available on the darkweb but methylone isn't. Methylone was far superior in my eyes.

Oh well.

 

[4DQSAR]

@HealingEnergy14 - YMMV. It's not as if methylone wasn't known of in 1988 but it was MDMA that was what everyone wanted.

Different people like different stuff. I could sit in a room with a tonne of cocaine for a year and not even be tempted to have even a line. I loathe it. But it would seem I am in a minority.

 

[Shinji Ikari]

I can't understand why 4-MMC is supposedly (I have never ordered, tried or tested it) available on the darkweb but methylone isn't. Methylone was far superior in my eyes.

Can confirm. It isn't the same as the pre ban stuff, it's usually yellowish shards rather than the fluffy white powder I remember from 2009, but it's no less fiendy.

Would love to see methylone make a comeback too but I think it's been lost to time. I did bump into someone on reddit a few years ago who claimed to be selling it and one of the mods in the MDMA and 2C-B sub endorsed the guy and said it was legit but I didn't take the punt. I've never seen a DW vendor stocking it.

It's not as if methylone wasn't known of in 1988 but it was MDMA that was what everyone wanted.

There was a time around 2008-9 I think when most of the 'MDMA' going round in the UK was methylone. After the saffrole ban and before the PMK route emerged. I wrote a little bit about it in my dissertation as a sort of intermission chapter while transitioning from discussing drug enforcement in the 90s to the emergence and expansion of the legal highs scene, which was sort of a product of the MDMA drought.

Different people like different stuff. I could sit in a room with a tonne of cocaine for a year and not even be tempted to have even a line. I loathe it. But it would seem I am in a minority.

Same here not a fan. Took quite a lot in my early 20s but I've hardly had it since save for a few isolated incidents where I was offered a bump at a social or whatever.

Whoops I rambled.

 

[nznity]

I think mdma is one of the most dangerous drugs out there mentally. Have been preaching this for years. After shooting it, I had a crippling headache for months

That's cardiovascular system damage.

 

[4DQSAR]

Same here not a fan. Took quite a lot in my early 20s but I've hardly had it since save for a few isolated incidents where I was offered a bump at a social or whatever.

Whoops I rambled.

Mate, whatever you write is worth reading.

Have you even politely refused a line? The next thing the person offering the line ALWAYS seems to exclaim is 'but it's FREE' as if I thought they would hand be a bill later. So now I apologise and thank them explaining that my medication precludes my using it.

UK law does not have a statute of limitations which is a shame, because something akin to what I said actually happened. When it was picked up I pointed out it was all present and they should weigh it to confirm. They just said 'no need - why do you think I asked you? Because I don't NEED to check'.

See, I can digress with the best of them.

I used to know people involved in the MDMA supply chain in The Netherlands and to the best of my knowledge, while the price of PMK did go up a lot, the response was to put less into each pill and often add a dash of speed. I mean Doves circa 1988 were always 125mg and quite accurate in that detail. By 2002 that was down to 75mg (plus speed) and as far as I know, it dropped so much that people were taking 5-6 over an evening.

But methylone was being sold in Dutch 'smart shops' disguised as 'Explosion - room odourizer'. They just dissolved it in water and added vanilla extract. It was funny because WE all knew but for whatever reasons, nobody in law enforcement spotted it for YEARS. The Dutch are the masters of disguising stuff.

 

[Sixx_Psychonaut]

Methylone triggered a 2 year long bout of extreme acute depression in me and anecdotally has done the same in several other people I know.

I know yada yada research this anecdotes that sample size controlled environment double blind blah blah blah

But I'm telling you this is a known phenomenon

Are you talking about post acute withdrawal syndrome due to regular long term use?

 

[Shinji Ikari]

ave you even politely refused a line? The next thing the person offering the line ALWAYS seems to exclaim is 'but it's FREE' as if I thought they would hand be a bill later. So now I apologise and thank them explaining that my medication precludes my using it.

More often than not, yes. Of the occasions I have accepted over the last few years it's usually (always?) been a close friend when I've known the gear is clean and I've been in safe surroundings. For anyone else I generally just politely say that I'm already full

I used to know people involved in the MDMA supply chain in The Netherlands and to the best of my knowledge, while the price of PMK did go up a lot, the response was to put less into each pill and often add a dash of speed. I mean Doves circa 1988 were always 125mg and quite accurate in that detail. By 2002 that was down to 75mg (plus speed) and as far as I know, it dropped so much that people were taking 5-6 over an evening

Interestingly enough my first experience with "doves" from from a legal high stall at a music festival in 2007 and I expect the would have been one cathinone or another. Brand recognition huh?

I remember pouring through old newspapers when I was researching the fallout from the Leah betts 'overdose' and there was an article from the mirror c1995 comparing various different presses and their subjective effects with doves being classed as a good all rounder favoured by beginners.

The same article also featured an interview with a supposed 'dealer' who claimed it was common practice to cut pills with guitar polish and rat poison as a way to maximise profits. They didn't elaborate on how adding rat poison to pills served to bolster their repeat business. As far as drug reporting was concerned back then they really did make it up as they went along. Not to say they don't now but looking back on those old articles now you really do have to suspend all disbelief to read through them without bursting out laughing.

I used to know people involved in the MDMA supply chain in The Netherlands and to the best of my knowledge, while the price of PMK did go up a lot, the response was to put less into each pill and often add a dash of speed. I mean Doves circa 1988 were always 125mg and quite accurate in that detail. By 2002 that was down to 75mg (plus speed) and as far as I know, it dropped so much that people were taking 5-6 over an evening

makes sense but before my time. The first time I took MDMA (or a pill, rather) was in 2006 and I only needed one. Like seriously, for a year after that roll whenever I walked in the pub everyone would greet me by explaining "IT'S SO LOVELY!!!"

I never quite lived it down. But from that I infer that the quality of pressed pills c2006 was probably quite good.

Mate, whatever you write is worth reading

Questionable statement but all the same. I enjoy your posts too.

Edit: typo

 

[love_child]

3mmc is trash I tried it and felt absolutely nothing. Just burned the hell out of my nose.

 

[4DQSAR]

@Shinji Ikari - I'm NOT proud of this but as you may know, the pill that 'killed' Leah Betts was an Apple™ and when the police confirmed they were good, EVERYONE in Bristol was after them. But the shameful bit? All around Bristol large ads of poor Leah lying in a coma were put everywhere to warn people. The next night someone (and it wasn't me or anyone I knew) drove around Bristol spraypainting the word 'lightweight' onto her forehead.

I laughed - but now, I'm ashamed that I did.

We ALL know that it was NOT MDMA that killed Leah but bad advice. She had read that rehydration was important and indeed it is - if you are dancing. But the poor girl drank over 7L of water in less than 90 minutes, drove her body into dilutional hyponatremia, cerebral edema and her heart stopped. Tragic, but lying to defend a political position only ever loses trust.

Some people have asserted that her father, a former police inspector, was somehow involved in the 'Essex Boys' murders. I don't think so. I DO think that the police look after their own and given that the two people sent down were convicted largely on the testimony of a police informer, that is a little concerning. The two found guilty were also bang at it so all an informant would have to do is tell one gang of bad lads a big buyer was on and give the time and place... then tell another gang of bad lads where to ambush. Could be the same person.

I have said this forever. If you ever come across someone who feels the need to be tooled up, leave, don't look back. Don't regret having bounderies.

Or as William S. Burroughs put it 'Watch whose money you pick up'.

 

[MedicinalUser247]

I'm just surprised that there isn't a Beta-Methoxy-MDMA. https://ibb.co/ynSMB9g7

 

[MedicinalUser247]

I'm just surprised that there isn't a Beta-Methoxy-MDMA. https://ibb.co/ynSMB9g7

Though this one does exist. https://en.wikipedia.org/wiki/3C-BOH Whether you prefer Methylone or MDMA I really think it comes down to your own choice of Drugs you feel like taking.