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Where did all the real mephedrone go?

The original legal high mephedrone is reported to be different to the mephedrone that came after the ban, in both positive and negative effects. Could it have been a different drug altogether?

 

For people who remember the MDMA drought of 2009/2010, the memories aren't always good. Mephedrone had filled the vacuum and it was cheap, easily available, and (for a time) legal. It was also too moreish, stank like cat piss, and had a host of nasty side effects, which made many people long for the return of MDMA. 

And yet for many others, the days of mephedrone are increasingly remembered through the warm haze of nostalgia. According to people on online drug forums, most of the mephedrone that's been produced since the ban has been a weaker, less euphoric substance that isn't on the same level as the pre-ban stuff, regardless of how much they consume.

Everywhere mephedrone is discussed, one can find messages like this:

"I just wish it was as good as it was back in the day. Doing that first line was the best feeling whatsoever, completely unmatched. No matter how good the stuff is these days it just don’t feel the same."

"I believe the pre-ban mcat all came from one factory in China that, because of its poor cleaning practices, produced mcat with a lot of impurities remaining.[1] It was these impurities that were actually responsible for the impossible God-like euphoria that people experienced."

"The pre-ban/post-ban argument isn't irrelevant. There is a difference between the two. Comedowns were brutal, yes. But I remember some incredible 3-day sessions where you'd be feeling just as good on day 2 as day 1, and still going strong on day 3."

These are all real messages that have appeared on popular online drug forums. Also, the sheer number of such messages makes them hard to ignore. The recently closed Dream Market forum—a darknet forum dedicated to the world's biggest darknet market—had a long-running mephedrone megathread with over a million views, making it the most viewed thread on the forum. Much of the discussion was taken up with theories as to what made the pre-ban stuff so good, with members using the term "pre-ban quality" to describe the holy grail of mephedrone, to which all post-ban mephedrone is compared.

However, not everyone agrees.

"Why are you not receiving the same effects that I do?" one post reads on the Dnstars forum. "I get ALL the 2009 effects with the 4-MMC that is around today in 2019. Eye wobbles, euphoria, palm sweats, body sweats, chatty, warm lovey feelings."

"Pre-ban doesn’t seem any different to a lot of people, only people on forums," another reads. "Every one of my mates I give some to says ‘it is just how I remember it, totally the same like 2009.’ They can’t actually believe it is still around."

"Is it not a lot more likely that nostalgia and a damaged serotonin system play a huge part in it rather than some mythical lost ingredient?" one post reads on Reddit. "Find good meph and it's still one of the best euphoric stims, great for long dirty sessions even better if u have someone to fuck."

Clearly, some people aren't convinced that pre-ban drone was anything special or different. However, they seem to be in the minority.

 

So, what's going on here?

 

It's a complicated mess. For starters, one can't deny that tolerance affects us all. People who've been hammering stimulants for years will attest to the fact that the drugs can lose some of their magic over time, or can even stop working altogether.

Not to mention that most people who took mephedrone before the ban are now in their late twenties or early thirties, and consequently have lower levels of the brain chemicals serotonin and dopamine caused by diminishing hormone levels.

Then there's the fact that mephedrone is derived from cathinone, a chemical that degrades very quickly. Although there are no direct studies on the degradation of mephedrone in a plastic bag, mephedrone is very unstable in body fluids stored at room temperature or refrigerated.[2] This may be significant, as before the ban, the factories that made mephedrone had direct links with the headshops and street dealers. Coupled with huge demand, this meant that the drone flew off the shelves as soon as it landed. Since the ban, with much less demand and less direct links between supplier and dealer, some of the drone may not be as fresh.

Add to this memory, expectations, nostalgia, placebo…all of which would account for most differences between pre-ban and post-ban.

However, this does not in any way explain two things.

1. The difference in onset of effects.

The initial rush of pre-ban was reported to occur within 1-2 minutes or less when snorted (a report from Erowid.org says it took 30 secs to come up) and that rush would hit you like a truck. Post-ban, according to newbies and veterans alike, takes around 5-10 minutes to start taking effect, and has a slower, more subtle build-up.

2. Some of the side effects that pre-ban meph caused.

The comedown from pre-ban meph was known to be particularly bad, even for those who were used to the typical MDMA hangover. People commonly reported insane anxiety and depression, near enough suicidal, for days on end. Though post-ban meph is hardly free of a comedown, the best stuff these days is reported by meph veterans to be much more forgiving – and while everyone's biochemistry is different, it's a general rule that comedowns get worse as we get older, not better.

Pre-ban was also known to cause some weird side effects, including numbness and discolouration in certain parts of the body. A 2010 Mixmag survey found that 15% of people had reported cold or blue fingers, which have also been reported by people on online drug forums. However, not once have these symptoms been reported off of post-ban. This all implies some kind of difference.

While the pre-ban debate has been relentless and has resulted in numerous bloated forum threads, it has never been gotten to the bottom of. And almost 10 years on from the ban, the debate rages on.

So, is there any evidence that pre-ban mephedrone was chemically different to the mephedrone produced today?

Yes and no.

Though mephedrone was first synthesized in 1929, its earliest recorded widespread production was in 2007 by the Israeli company Neorganics, which sold it under the product names Neo-dove, Sub Coca, and Spirit. As with most legal highs, no description of the exact constituents of any of these products was offered on their website. However, a chemical analysis of four Neorganics products was posted on the Bluelight forum in November 2007. Test results showed that while Spirit contained only mephedrone, Neo-dove and Sub Coca both contained caffeine, ethylcathinone and phthalimidopropiophenone in addition to mephedrone.

Ethylcathinone is a stimulant drug that acts similar to amphetamine. Phthalimidopropiophenone is not an active stimulant, however, it’s believed to be potentially capable of acting as a prodrug for cathinones when ingested, meaning it might improve how mephedrone is absorbed by the body.

It's possible that this mix of chemicals worked synergistically to produce effects that were stronger than the bulk of post-ban mephedrone. Despite the test results clearly showing that two of the Neorganic products contained more than just mephedrone, as word got out that mephedrone was the drug in these capsules responsible for the high, it's possible that some people were led to believe that's all the Neorganics range contained.

However, this can only explain a small minority of cases at most. The Neorganics range was discontinued in January 2008 after the Israeli government made mephedrone illegal. It wasn't until 2009 that mephedrone became increasingly popular in the UK and other parts of Europe, and was being sold on websites as 'research chemicals', 'plant food' and 'hoover freshener.' If in March 2009 there were fewer than 10 online vendors of the drug, by June, new sites opened almost weekly, offering a choice of products that purportedly contained mephedrone. And not all of them were a pure product.

"I was reading all the thread and didn’t find a word about Crystallus," a Dnstars user called Cartel wrote. "Maybe you remember that in 2006-2009, this powder was sold in every open net source. It was real fire and it was…MCAT with bk-MDMA (methylone) mix."

"Yes, gives more euphoria and lasts longer," Cartel continued, "dose was less (as far as I remember) but comedowns were much worse than from pure 4-MMC (mephedrone). At that time there were no tests to check the substance to know exactly what you were taking, but at the shop’s menu it was explained. It was in the form of very small sparkling crystals."

Cartel's memory is likely off by a year or so, as Crystallus didn't appear until 2007/2008; however it can't be verified. The makers of these legal highs are impossible to track down now, probably dead from their own poisonous concoctions or on an island testing out the latest unclassified research chemicals.

However, there is some evidence to support Cartel's statement.

In 2009-2010, police from all over Europe seized big quantities of psychoactive substances mainly in powder form, mostly from headshops and individuals. These included samples of mephedrone as well as unidentified white powders. Many of these products were analysed and their contents were summarised in a 2010 Europol–EMCDDA report.

In general, it was not uncommon to find mephedrone in combination with other synthetic cathinones – i.e. methylone, butylone and ethylcathinone.

Based on these findings, it's likely that Crystallus and other cathinone mixtures were sold in bulk to headshops and individuals all over Europe. Many of these products were surely sold on as 'mephedrone' to a naive client base, in the same way that pills containing MDMA and other stimulants are frequently sold as 'ecstasy' by street dealers.

Could it be that many who miss pre-ban mephedrone actually miss its mix with methylone?

In many ways it seems entirely plausible.

When people reminisce about pre-ban mephedrone, they all attest to the exact same thing; that it felt more on the MDMA side; more euphoria, nicer body feelings and more empathy in comparison to what came after the ban. The effects of methylone are actually said to be broadly similar to MDMA, although with a higher tendency to redose. Methylone is also known to cause gurning, a side effect of pre-ban meph that for some reason is less pronounced with post-ban (if pre-ban made you look like you'd done 20 pills, post-ban makes you look like a respectable raver).

The only problem with this theory is the claim that pre-ban meph kept working for days on end with almost no diminishing effects, whereas methylone is known to have rapidly diminishing returns. However, this would not necessarily rule the theory out. If a person takes multiple drugs, each drug could alter the effects of the others, often in an unpredictable way.

Still, others aren't convinced.

"Pre-ban 4-MMC was not a methylone mix," a reply reads on the Dnstars forum. "There was a mix available in pre-ban days called Bubbles. But it was nothing like pre-ban meph on its own."

Indeed, while legal highs such as Bubbles can explain why the effects of actual pure mephedrone today seems different to some people, it's not the full story.

In 2010, an obscure study from the University of Sunderland analysed 6 samples of mephedrone. One sample was donated by BBC Radio North East and the rest were purchased from websites www.flowerpowerfeeder.co.uk, www.ordermephedrone.co.uk, www.mrmeph.com, www.mephedrone2u.com and www.fastmephedrone.co.uk.

All six samples contained 2 impurities at levels <0.02% w/w. Only one sample contained another impurity at 0.31% w/w.

Those are remarkably low levels for a street drug. Although the impurities are unknown, they are likely to be unreacted precursor chemicals, according to Mark Parkin at the Department of Forensic Science and Drug Monitoring at King’s College London. Indeed, the researchers from the University of Sunderland concluded that these impurities aren't likely to be the reason for some of the severe adverse effects that have been reported. And let's be honest, it likely doesn't explain the stronger positive effects too.

In fact, almost every analysis performed on mephedrone before the ban shows a similar high purity.[3] [4] [5] However, these tests would not necessarily detect isomers, which play an important role in determining the effects of a drug.

Like many street drugs, mephedrone can exist as two isomers, R and S, which are molecules that are chemically similar but not identical. In other words, the R-isomer of a drug will not necessarily behave the same way as the S-isomer of the same drug when taken by a person. It could be said that each isomer is like a different drug.

Gregg and Baumann (2014) have shown that the S-isomer of mephedrone is more serotonergic, which would confer MDMA-like properties; while the R-isomer is known to be more stimulating.

Could it be that the manufacturing of mephedrone before the ban resulted in the S-isomer being 100% synthesized? This would line up with what people have said about post-ban lacking those lovely, gooey serotonin effects. It sounds almost too perfect.

Unfortunately, there is no evidence for this.

Analysis of mephedrone purchased from the internet before the ban found it was racemic, a 50/50 mixture of isomers. [5] Analysis of mephedrone found at a UK festival in 2014 and in UK wastewater, as well as multi-kg seizures of the mephedrone precursor 2-bromo-4’-methylpropiophenone, indicates that post-ban mephedrone is also racemic.[6] [7] [8] [9]

"There is only one sample of meph I tested before the ban, but taking into account all the other cathinones I tested, I am almost sure that all these chiral compounds are traded as racemic mixtures," says Martin Schmid, a scientist who helped identify mephedrone in samples seized by police. "Trading as a pure isomer would be very cost intensive and it does not make any sense, since in many cases we still do not know which of the two is the eutomer (the isomer with the desired pharmacological activity)."

Indeed, Gregg and Baumann's study didn't appear until 2014. The idea that underground chemists were synthesizing a pure isomer without even knowing which one had the most recreational value, is so absurd that we can rule it out completely.

I was baffled. If mephedrone today was chemically the same as it was before the ban, why did it look, smell, feel so different?

 

There was one man who could help.

 

Dr. Zee is the Israeli chemist credited with discovering mephedrone in 2004. Once Chinese suppliers learned how to make it themselves, the drug was flooded into Europe as a cheap legal high (and the rest, as they say, is history).

Mephedrone is not a drug discovery that Dr. Zee is proud of. A self-styled 'psychonaut', his goal is to learn about self and reality by transcending normal consciousness, an area of effects where mephedrone came up short. "It only had recreational value," he says from his office in Amsterdam. "And it was too moreish…you can't just take some and then stop. If someone can do that, that person deserves a medal."

Considering his discovery was made over 15 years ago, I wonder if his memory of them days is a bit hazy. I start out by telling him how mephedrone has changed in appearance over the years. The Chinese pre-ban stuff usually came as a fine white powder or small sugar-like crystals. Once mephedrone was banned in 2010, production switched over to India and that's when the tan/beige-coloured rice shards made an appearance.

Before I can ask my question, Dr. Zee interjects: "That's 4-MEC. That's not mephedrone. Mephedrone does not create rice shards."

"Aha."

4-MEC is a drug that bears a chemical resemblance to mephedrone and has been marketed alone or in mixtures with other substituted cathinones. Because of its structural closeness, it may have been identified as mephedrone in tests that cannot differentiate between the cathinones.

"The slight difference in the shape of the molecule made 4-MEC crystallize as elongated crystals, which people would call the rice shards," Dr. Zee says. "You can take the elongated crystals and grind them down so that they look like a powder, but it's impossible to take 4-MMC and make it crystallize into elongated crystals because we don't have control at the molecule by molecule level."

I'm somewhat surprised as I hadn't seen anyone say the uniform rice shards weren't *actually* mephedrone. Most people just said they were more on the stimmy-side and lacked the sheer euphoria that the Chinese stuff had. Besides, the rice shards only dominated the market for a few years after the ban. Thanks to drug testing labs like Ecstasydata, we know that most post-ban mephedrone is really mephedrone and not something else…yet most people say the effects are "lacking."

As a man of science, Dr. Zee has little time for subjective opinions. There is simply no data set for this type of information, and the way it has been collected makes it very difficult to analyse. However, he admits that some of the adverse effects pre-ban meph caused are suggestive of a chemical difference. "I remember the photos of the blue knees and everything. It is a curious thing. But in all of my years of working in the Netherlands I've never encountered it once in that country. It's always been reported from the UK. And why? I don't know."

Indeed, none of the old-school meph users in my home city of Aberdeen had experienced those symptoms either, even though 2-3 day binges were the norm. However, a Dundonian friend of a friend used to get "blue fingers and purple palms" along with his pals off the pre-ban stuff. Curiously, his supply came not from the internet but from a guy who apparently created the compound (or the mixture) called Bubbles. It really adds weight to the idea that people experiencing these symptoms were getting a cut product. Or maybe they were just freaky symptoms pre-ban meph caused.

Certainly, it's not just the appearance of mephedrone that has changed since the ban; the smell has changed too. Most post-ban meph has only a light smell, usually described as bleach or vanilla-like. However, the Chinese meph smelled so strong that you could smell it from a mile off, and that smell poured out of your body for weeks afterwards. The smell was usually described as cat piss and burnt circuit boards.

"I would say piss," Dr. Zee says, remembering the smell. "It was also yellowish sometimes, which also kind of prompts the mind to think of pee. The smell came from the solvents."

This interests me as my research had suggested the smell was due to lazy finishing methods. So, if Chinese pre-ban was solvent-laced mephedrone, could the solvents have affected absorption? Maybe this could have caused the intense rush that people reported.

"I don't think the solvents do affect absorption," Dr. Zee says. "As the powder passes through the mucus membrane whether it's in the gut or in the sinuses (depending on whether you swallow it or insufflate), the entire crystal structure whether it contains solvent or not is broken down into individual molecules. You don't have anything save individual molecules coursing through the bloodstream or through the brain fluid for that matter. So, the solvents or any contamination is treated differently from the active itself."

It's another theory ruled out. However, Dr. Zee believes that the smell does indeed have something to do with why pre-ban felt so different to some people.

"That is a psychological effect. If you read the literature about the Pepsi challenge: if you put the Coca-Cola in a blue cylinder and the Pepsi cola in a red cylinder, you'll see that people make more mistakes. They guess wrongly more often than if you put both drinks in a white cylinder. So, it shows that the priming of the mindset plays a role in the experience that you have from the drug," he says.

"With pre-ban, my customers sold it to websites and stuff, and some of them would actually ask for the pissy stuff. I was surprised to find in 2008 that I ran a batch and it was super clear and with big crystals, and people didn't want it. Because they didn't recognise it visually."

I thanked Dr. Zee for his insights. But I couldn't shake the feeling that I was still missing a piece of the puzzle. I was tempted to call him again and ask about the solvents, temperature and stirring rate of his original process, but I don't. It was so long ago and I doubt he'll remember. Besides, even with my puny understanding of chemistry, I know that these are just different ways of making the same thing. And from a chemical point of view, that end product is either 4-MMC or it is not.

However, there is an area of chemistry where all these variables come into play.

Polymorphism is the ability of a substance to exist in more than one crystalline form, due to various conditions in the crystallization process (solvent effects, level of supersaturation, temperature, change in stirring conditions, etc.)

In fact, polymorphism is very common amongst drugs and is responsible for differences in many properties like absorption, bioavailability, toxicity.[10] This could go a long way in explaining the initial rush of pre-ban meph, as well as the increased potency and adverse effects.

Or maybe not.

All this talk about mephedrone will be unfathomable to some people. To them, mephedrone was just a substitute for real drugs. It wasn't that good.

But whatever you think of the stuff, it goes to show that the quality of street drugs can be highly variable, and why it's never just as simple as getting a pure product. It also goes to show just how subjective the effects of drugs are, for myriad reasons, and why the relationship between buyer and dealer is eternally at odds.

Perhaps the truth with the pre-ban debate lies somewhere in the middle. Though the initial rush of pre-ban meph was arguably stronger, one can't help but think that any other positive differences are exaggerated by most people. Certainly, mephedrone isn't the only drug to have an ongoing debate around its quality. One can witness the debate about the distinction between MDMA produced via PMK or Safrole; where old timers are saying that MDMA is not as good as it was in the late 90s and before, regardless of how much they consume; even though there should be no difference in effect. Perhaps it's human nature to view our past through rose-tinted glasses; and when our pupils were huge and dilated, those glasses get rosier still.

Let's leave the last word to KingOfTheTing, a Dnstars user, whose message put things into perspective:

"You had to try it to know, and if you didn’t try it you won’t understand as meph today does still produce good effects, just not to the same degree as the legal stuff. People are fast enough to cite how good the effects were, but mostly forget to mention the whole host of nasty side effects that came along with it."

"Maybe realistically, we are better off without it."

 

 

References


[1] Power M (2013) From Chinese factory to UK households – realities of the trade in legal highs. [online] Available at: https://www.theguardian.com/society/2013/may/09/chinese-factory-trade-legal-high 

[2] Johnson RD1, Botch-Jones SR (2016) The stability of four designer drugs: MDPV, mephedrone, BZP and TFMPP in three biological matrices under various storage conditions. Journal of Analytical Toxicology.

[3] Motbey CP, Karanges E, et al (2012) Mephedrone in adolescent rats: residual memory impairment and acute but not lasting 5-HT depletion. PLoS ONE. 

[4] European Monitoring Centre for Drugs and Drug Addiction and EUROPOL (2010) Europol-EMCDDA joint report on a new psychoactive substance: 4-methylmethcathinone (mephedrone). European Monitoring Centre for Drugs and Drug Addiction and EUROPOL, Lisbon. 

[5] Gibbons S, Zloh M. (2010) An analysis of the 'legal high' mephedrone. Bioorganic and Medicinal Chemistry Letters.

[6] Castrignano E, Mardal M, et al (2017) A new approach towards biomarker selection in estimation of human exposure to chiral chemicals: a case study of mephedrone. Sci Rep.

[7] Castrignano E, Yang Z, et al (2018) Enantiomeric profiling of chiral illicit drugs in a pan-European study. Water Research.

[8] International Narcotics Control Board (2016) Chapter III. Extent of licit trade in precursors and the latest trends in precursor trafficking [online] Available at: https://www.incb.org/documents/PRECURSORS/TECHNICAL_REPORTS/2016/PARTITION/ENGLISH/2016PreARr_E-Extent_of_licit_trade_in_precursors_and_the_latest_trends_in_precursor_trafficking.pdf

[9] International Narcotics Control Board (2019) Precursors and chemicals frequently used in the illicit manufacture of narcotic drugs and psychotropic substances [online] Available at: http://www.unis.unvienna.org/pdf/2019/INCB/Precursors_without_annexes_E_ebook.pdf

[10] Lu J, Rohani S (2009) Polymorphism and crystallization of active pharmaceutical ingredients (APIs). Current Medicinal Chemistry.

 

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