Recently, there have been a few nasty developments in the world of legal highs. I was contacted by this week by GMTV and Radio 5 Live, asking for an interview about the “new” legal high Ivory Wave causing a stir. Unfortunately, I couldn’t give any interviews for various boring reasons and could only give a bit of advice over the phone/email, so I thought I’d write a post about it now I’ve got the time. Also, The UK’s old friend JWH-018 seems to be causing some trouble over the pond, having been linked a couple of deaths in Indiana. Finally, our government have made some more noise about the “problem” of legal highs which makes no difference for a good year or so and will only make matters worse when they manage to cobble some new legislation together eventually.

Ivory Wave

Ivory Wave has been around for at least a year, and before that, it was called Vanilla Sky. Guess what? It’s always been notoriously dodgy. In a quest to pump out the strongest ever “party powder”, its makers sacrificed safety for a marketing angle.

Earlier this year, the Irish government had a number of legal highs analysed including Ivory Wave and found that it contained MDPV (methylenedioxypyrovalerone), and lidocaine. Lidocaine is a local anaesthetic, added to numb your nose, both to dull the pain of snorting the other stuff and to make it more like cocaine. This isn’t news though – a load of similar products around before the cathinone ban contained it. MDPV on the other hand is worrying.

MDPV appears to be a dopamine and noradrenaline reuptake inhibitor, delivering plenty of stimulation but little in the way of euphoria. The vast majority of similar products available before April’s cathinone ban contained either mephedrone (4-methylmethcathinone) or a fluorinated analogue such as 3-fluoroumethcathinone. While these were also very stimulating, they delivered a much loved euphoria as well, so why would the makers of Ivory Wave depart from the norm and go for a subjectively worse compound instead? Because they just weren’t potent enough enough to earn Ivory Wave its reputation as the strongest legal high available.

A typical dose of mephedrone or similar analogue for a new user would be around 50 – 100mg, while a typical dose of MDPV is around the 5 – 10mg mark. Sure, at that dose, the effects of MDPV don’t seem like much compared to mephedrone et al, but when people are used to cheap cocaine or the majority of similar legal highs, they rack up their usual sized line and hoover up far more than an equivalent dose of MDPV. As a consequence, users were frequently terrified and unable to sleep for days on end. Well done, Ivory Wave, you truly are the strongest!

On April 16th, 2010, the UK passed legislation banning a huge number of compounds, including mephedrone, all common available derivatives including MDPV and a shitload of theoretical compounds that haven’t been made yet. Despite the original incarnation of Ivory Wave falling under the banning stick, on August 10th, there was a lot of fuss about legal highs including Ivory Wave hospitalising 22 people around the Edinburgh area, so what’s going on?

Well, firstly, just because MDPV got banned, it doesn’t mean the manufacturers couldn’t stick some new legal chemical in there and call it the same thing. I’m sure you’ve all seen a packet of crisps or a chocolate bar with “New improved recipe!!!!11″ plastered all over the packaging – this is the same sort of thing. Of course, it’s not as innocent as that – these are psychoactive substances we’re talking about – but it’s nothing extraordinary. Products like Charge+ or Beanz pills have changed their ingredients before, so that’s what I expected had happened with Ivory Wave.

That doesn’t appear to be the case. Several websites selling the stuff now claim both that Ivory Wave is no longer for sale in the UK, suggesting it still contains MDPV, and that Ivory Wave found in the UK at the moment is fake. This leaves us with several possible scenarios.

1. Ivory Wave available in the UK is the same stuff it’s always been, and has been illegally imported.
2. Ivory Wave available in the UK is fake, but still contains MDPV. If this MDPV had to be illegally sourced or manufactured, it’s more likely to be impure, and these impurities are doing some damage.
3. Ivory Wave available in the UK is fake, but still a new product with new, legal and dangerous chemicals in, trying to capitalise on the original Ivory Wave’s reputation

At first glance, it looks like we can ignore the first one. If it’s been around for ages, why are we only hearing about it now? Well, before the cathinone ban, Ivory Wave was definitely the strongest, but nowhere near the most enjoyable or popular product, so people tended to steer clear of it. However, when the ban came into effect, and somehow Ivory Wave was still around,  lots of people looking to find a “mephedrone replacement” would have stumbled across it. This spike in popularity makes scenario #1 as plausible as the rest, so for now, it’s anyone’s guess.

If you find any new information making one of these scenarios more likely, please let us all know!

For now, I’d advise anyone to steer clear, especially the stuff in red foil packets as that’s the type most frequently mentioned in the myriad forum posts on the topic.

JWH-018

JWH-018 was the main synthetic cannabinoid found in Spice and similar products in the UK last year. Here’s a couple of posts and comment threads here for some background:

• JWH-018, Spice & Me
• JWH-018 Toxicology
• Synthetic Cannabinoid Discussion
• Smoking Mix Discussion

A large number of synthetic cannabinoids (along with GBL, BZP and related piperazines) were banned on December 28th, 2009, but remained legal in the US, where the market has exploded just like it did here before the – the only difference is over there, the most popular brand is K2 rather than Spice.

Well, that was the only difference until very recently. In May, the smoking of K2 was “linked” to two deaths in Indiana – a rather odd situation indeed! It seems there’s no conclusive evidence available to say that K2 actually caused these deaths – it could be the same as all those people that apparently died of mephedrone over here who didn’t actually take it (Eg, Gabbi Price). However, just because we’ve been consistently lied to by the British press, it would be unwise to immediately rule out the other possibility – that K2 is somehow killing these people. As it happens, we’ve also got some more evidence right here on this blog that supports that conclusion: this guy reports vomiting blood after oral ingestion of JWH-018.

Here’s what I think. JWH-018 is safe, at least in the short term, so it’s not responsible for what we’re seeing. I reckon we’ve got a harmful contaminant or impurity left over from the synthesis which is causing all the damage. If there was a bad batch going round, it would also help to explain why those two deaths are both in Indiana, although I’m not sure where that commenter hails from.

Unfortunately, once again, this is all speculation, but it’s speculation based on all the evidence we have available. Fortunately, David Kroll, who’s forgotten more pharmacology than I know, has arrived at that same conclusion – contamination. Be sure to check out his post for links to the original stories, more detail and more speculation.

If you come across any more stories or bad batches, let us know!

For now, I’d advise those in the US to avoid any new brands popping up, avoid K2 in Indiana and, if you’re buying pure JWH-018, avoid it like the plague if it doesn’t exactly resemble the previous batches you’ve bought.

Post from: Synchronium

A Look At Legal Highs

You Might Be Interested In:

• Should Mephedrone Be Legal?
• Mephedrone: The Facts
• Meen Green!
• Synthetic Cannabinoid Discussion
• Mephedrone Banned On Friday 16th April
• The ACMD’s Mephedrone Report Part II
• The ACMD’s Mephedrone Report Part I
• Legal Highs & Terrorism
• Mephedrone Cat
• Top 10 Reasons Why Legal Highs Should Stay Legal

Dangerous Drugs, England And Wales
Dangerous Drugs, Scotland
The Misuse of Drugs (Amendment) (England, Wales and Scotland) Regulations 2010

Made
31st March 2010

Laid before Parliament
1st April 2010

Coming into force
16th April 2010

The Secretary of State makes the following Regulations in exercise of the powers conferred by sections 7, 10, 22 and 31 of the Misuse of Drugs Act 1971(1).

In accordance with section 31(3) of that Act the Secretary of State has consulted with the Advisory Council on the Misuse of Drugs.
Citation, commencement, interpretation and extent

1.—(1) These Regulations may be cited as the Misuse of Drugs (Amendment) (England, Wales and Scotland) Regulations 2010 and shall come into force on 16th April 2010.

(2) In these Regulations “the 2001 Regulations” means the Misuse of Drugs Regulations 2001(2).

(3) These Regulations extend to England, Wales and Scotland.
Amendment to the 2001 Regulations

2. The 2001 Regulations shall be amended as follows.

3. In Schedule 1 (which specifies controlled drugs subject to the requirements of regulations 14, 15, 16, 18, 19, 20, 23, 26 and 27)—

(a) in paragraph 1(a), after “methcathinone”, insert—

“4–methylmethcathinone”;

(b) after paragraph 1(l), insert—

“(m) Any compound (not being bupropion, diethylpropion, pyrovalerone or a compound for the time being specified in sub–paragraph (a) above) structurally derived from 2–amino–1–phenyl–1–propanone by modification in any of the following ways, that is to say—

(i) by substitution in the phenyl ring to any extent with alkyl, alkoxy, alkylenedioxy, haloalkyl or halide substituents, whether or not further substituted in the phenyl ring by one or more other univalent substituents;

(ii) by substitution at the 3–position with an alkyl substituent;

(iii) by substitution at the nitrogen atom with alkyl or dialkyl groups, or by inclusion of the nitrogen atom in a cyclic structure.”.

David Hanson
Minister of State
Home Office
31st March 2010

Let’s take a look at this and try and make some sense of it shall we?

(a) in paragraph 1(a), after “methcathinone”, insert—

“4–methylmethcathinone”;

First off, mephedrone (4-methylmethcathinone) is explicitly mentioned to appear after methcathinone, which is already class B. I suppose we knew that much was going to happen already, so onto the more complicated stuff…

(b) after paragraph 1(l), insert—

“(m) Any compound (not being bupropion, diethylpropion, pyrovalerone or a compound for the time being specified in sub–paragraph (a) above) structurally derived from 2–amino–1–phenyl–1–propanone by modification in any of the following ways, that is to say—

This means that any cathinone derivative described by any of the following paragraphs will also become class B. Like the cannabinoids banned last December, this ban doesn’t list a tonne of individual substances, but instead covers a wide range of actual and theoretical substances by detailing possible alterations to the original cathinone structure. Here they are:

(i) by substitution in the phenyl ring to any extent with alkyl, alkoxy, alkylenedioxy, haloalkyl or halide substituents, whether or not further substituted in the phenyl ring by one or more other univalent substituents;

This first part covers modifications of the phenyl ring, or “round bit” of the cathinone structure (R4). Unfortunately, this covers a massive range of compounds, including Mephedrone (alkyl), Methedrone (alkoxy), Methylone, Ethylone, Butylone & MDPV (all alkylenedioxy) and flephedrone (halide; also includes the 3-F isomer) .

(ii) by substitution at the 3–position with an alkyl substituent;

This covers the addition of a carbon side chain of any length on the carbon atom just before the nitrogen atom (usually referred to as the alpha carbon).  All the compounds listed in Annex A,  Appendix 1 of the ACMD’s report include a chain of at least one carbon long (alpha methylation), but by not specifying the length of this “alkyl substitute”, this also covers  existing compounds with longer alpha side chains such as pentylone and MDPV as well as any potentially interesting theoretical compounds.

(iii) by substitution at the nitrogen atom with alkyl or dialkyl groups, or by inclusion of the nitrogen atom in a cyclic structure.”

The final nitrogen atom present in cathinone has two available places to add stuff. One or both of these could be a carbon chain (alkyl or dialkyl), or a single carbon chain could form a ring by starting and ending at this nitrogen atom (the “cyclic structure”), which is what this part covers. Examples include ethcathinone (alkyl – a single carbon chain), n,n-dimethylcathinone (dialkyl – two carbon chains) and MDPV (includes the cyclic pyrrolidinyl structure).

I know that’s still quite technical, but hopefully what I’ve written is a little clearer than the original text. Feel free to ask questions in the comments though!

The gist is, all the popular cathinone derivatives mentioned by name above will become class B on Friday 16th, as well as a great deal of the more esoteric ones. One compound not included in this ban is naphyrone, currently marketed as Energy-1 or NRG-1. Unfortunately, I hear it’s rather shit and also not particularly safe, but the ACMD are already looking into banning that for next time. That’s pretty much it for cathinones in the UK then. I feel like we should all go out and get commemorative T-shirts or something…

On a more serious note, for those previously law abiding citizens who have developed a psychological addiction to mephedrone, you have two choices: continue buying lower quality stuff at an inflated price from a regular drug dealer or find some help. Luckily, Drug-Forum.com has a great Recovery and Addiction section that you should definitely check out.  You’re also welcome to post your stories and progress in the comments under this post.

Post from: Synchronium

Mephedrone Banned On Friday 16th April

You Might Be Interested In:

• The ACMD’s Mephedrone Report Part II
• The ACMD’s Mephedrone Report Part I
• Should Mephedrone Be Legal?
• A Look At Legal Highs
• Shaun The Sheep
• Mephedrone Cat
• Mephedrone Update
• Mephedrone: The Facts
• Nutt Sacked Episode III – Revenge Of The Schizoids
• Nutt Sacked Episode II – Attack Of The MPs

I’ll probably write a few comments about the entire report in my next post, whenever that may be. Anyhoo…

Annex A. Recommendation For The Generic Control Of The Cathinone Derivatives

Scope of a generic definition

The ACMD here set out recommendations on the range of compounds that should be included in a generic definition for the control of cathinone derivatives under the Misuse of Drugs Act 1971.

It was proposed that the scope of compounds covered by generic control should be much wider than the 6 ring substituted compounds listed in Table 1 (annex A) and wider than the 10 compounds reported to the EMCDDA since 2006.

The scope should include all cathinone derivatives that have been found in seizures and collected samples together with compounds that have not been encountered but have misuse potential. This includes cathinone derivatives with and without ring substituents and with side chains longer than those usually encountered in the phenethylamine drugs.

The scope should also include any substances known or believed to be pro-drugs, i.e. substances that are metabolised to a known active substance (for example GBL is converted in the body to GHB).

The generic definition should not include those substances already controlled under the Misuse of Drugs Act, i.e. diethylpropion (Class C), cathinone (Class C), methcathinone (Class B) and pyrovalerone (Class C). Finally the definition should not include any substances, e.g. bupropion, that are ingredients of legitimate pharmaceutical products or that have other legitimate uses.

The structure of cathinone derivatives is represented by the generalised structure below:

Figure 1: Generalised structure of cathinone derivatives
where,

The phthalimido group has so far only been encountered in the compound α-phthalimidopropiophenone. This substance has been found in a capsule in combination with 2-fluoromethcathinone and in capsules containing a mixture with 4-methylmethcathinone, N-ethylcathinone, and caffeine.

The reason for adding α-phthalimidopropiophenone is not clear. It may have been added deliberately, perhaps as a pro-drug for cathinone, but there is no information about its pharmacology or metabolism. This substance is also an intermediate in the synthesis of cathinone and N-alkyl derivatives of cathinone. It could therefore be present unintentionally as a residue of an intermediate, the product of a failed chemical synthesis, or even the miss-labelling of an intermediate.

In addition to compounds with the generalised structure in (Figure 1, Annex A) the phenyl ring can be replaced with a naphthyl ring (e.g. Figure 2, Annex A) or with a thiophene ring. The naphthyl analogue of pyrovalerone (Figure 2, Annex A) is available on the Internet and is being retailed as “NRG-1”. These compounds cannot easily be included in a generic definition for the cathinone derivatives having the generalised structure in Figure 1, Annex A, but they could be controlled as named substances or by one or more separate generic definitions. The ACMD intend to review these substances and provide further advice at a later date.

Figure 2: Naphthyl analogue of pyrovalerone

The systematic chemical name for the structure in Figure 2, Annex A is 1-(2-naphthyl)-2-(1-pyrrolidinyl)-1-pentanone and alternative names include naphthylpyrovalerone, naphyrone and O-2482.

Appendix I, of this Annex includes all the cathinone derivatives, with the general structure in Figure 1, Annex A, that have been encountered in seizures and collected samples, substances that are already controlled, ingredients of known pharmaceutical products, substances available via the Internet and substances that are listed in Wikipedia. However, the market for cathinone derivatives is still evolving and new substances will continue to appear.

Many cathinone derivatives are mentioned in patents for pharmaceutical applications but the only known non-controlled cathinone derivative with a marketing authorisation appears to be bupropion, an ingredient of ®Zyban.

Some cathinone derivatives are mentioned in patents for non-pharmaceutical applications.

A structure-based search of the 12th Edition of the Merck Index (1996), carried out previously by Dr Les King, found no contentious compounds.

Interestingly, a recent patent (WO PCT 2010006196) relating to water purification membranes mentions the compound in Figure 3 below, which is closely related to methylone (bk-MDMA). This compound would be included within a generic definition since the term methylenedioxy can have two meanings. However, compounds analogous to those in Figure 3, Annex A are unlikely to have any commercial uses.

Figure 3: 3,4-methylenedioxy-N-methyl-β-keto-amphetamine

Structure Activity Relationships

Cathinone derivatives have a range of effects (e.g. stimulant, empathogen and antidepressant).

The cathinone derivatives without ring substituents (e.g. diethylpropion, methcathinone, buphedrone, N,N-dimethylcathinone) are mostly stimulants.

Most of the cathinone derivatives encountered as legal highs are ring substituted compounds with a secondary amino group (R2 = methyl or ethyl and R3 = hydrogen) or with a cyclic amino group (NR2R3 = pyrrolidino group or phthalimido group). These substances are primarily stimulants, with varying degrees of empathogenic effects (i.e. similar in effects to MDMA). Ring substituents (R4) have included alkyl, alkoxy, methylenedioxy and halide.

The side chain substituent (R1) has mostly been a single alkyl group. However there are examples with allyl (an alkenyl) and propargyl (an alkynyl) groups and also examples with a second alkyl group attached to the same carbon atom as R1, but these compounds are not within the proposed scope.

No haloalkyl substituents (e.g. trifluoromethyl –CF3 as found in piperazine derivatives) in the ring (R4) or on the side chain (R1) have been encountered or reported in the literature. However, replacement of the ring methyl group, as in mephredrone, with a trifluoromethyl group is likely to produce substances with similar activities. It is recommended therefore that haloalkyl substituents be included in the generic definition for ring substituents.

Cathinone derivatives with a primary amino group (i.e. no N-alkyl substituents) are rarely encountered, possibly because of their instability. There are only two known examples, bk-MDA (known to substitute for MDMA in rats) and cathinone (a stimulant).

The NR2R3 amino groups reported in the scientific literature have included alkylamino (R2 = alkyl, R3 = H), dialkylamino (R2 =alkyl, R3 = alkyl), the cyclic pyrrolidino group and a large number of other cyclic amines. However, for the pyrovalerone analogues an increase in size of the nitrogen containing ring from a five-membered pyrrolidine ring to a six-membered piperidine ring resulted in a substantial loss in binding potency. There are also examples of N-allyl, N-propargyl and N-cycloalkyl substituents.

The anti-depressant drug bupropion has a tertiary-butyl group on the nitrogen atom and several other substances investigated for their potential as smoking cessation drugs also have a bulky alkyl group on the nitrogen atom, e.g. tertiary-butyl, iso-propyl or cycloalkyl, or the alkyl amino group is replaced by a cyclic piperidino group (a cyclic amino group with 6 membered ring).

Salts, stereoisomers, esters and ethers

Cathinone derivatives with the generalised structure in Figure 1, Annex A, all have an asymmetric α-carbon atom giving rise to R and S stereoisomers.

With the exception of the phthalimido derivatives, all cathinone derivatives have a basic nitrogen atom and can therefore form salts.

There is no definition of esters and ethers in the Misuse of Drugs Act 1971, but from a chemical perspective esters usually only applies to derivatives of acids with a hydroxyl group, and derivatives of alcohols and phenols. Likewise ethers usually only applies to derivatives of alcohols and phenols. On this basis the cathinone derivatives would not form esters or ethers.

However, keto compounds, R1R2C=O, can form ketals, R1R2C(OR’)2, which arguably might be described as a special form of an ether. Ketals of cathinone derivatives have been discussed on drug forums in the context of a pro-drug and are mentioned in the scientific literature, usually as a means of protecting the keto group during chemical syntheses.

Generic definition for the control of cathinone derivatives

The ACMD have considered a number of options for the control of cathinone derivatives, including listing of named substances, several generic definitions and combinations of these approaches.

Taking into account the ACMD’s consideration of the scope, together with structure activity relationships and prevalence of known cathinone derivatives, the following generic definition is recommended:

Any compound (not being bupropion or a substance for the time being specified in paragraph 2.2) structurally derived from 2-amino-1-phenyl-1-propanone by modification in any of the following ways, that is to say,

1. by substitution in the phenyl ring to any extent with alkyl, alkoxy, alkylenedioxy, haloalkyl or halide substituents, whether or not further substituted in the phenyl ring by one or more other univalent substituents;
2. by substitution at the 3-position with an alkyl substituent;
3. by substitution at the nitrogen atom with alkyl or dialkyl groups, or by inclusion of the nitrogen atom in a cyclic structure.

Notes

• the parent compound is cathinone
• “any” is taken to mean one or more

Comments

This is a definition that includes all permutations for the three substitution areas, i.e. in the ring (R4), in the side chain (R1) and on the nitrogen (NR2R3).

• All the cathinone derivatives would be in the same Class which would result in some anomalies for compounds already controlled.
• Includes all the compounds in Appendix 1.
• Includes primary amines without ring substituents (no known examples, except cathinone which is not included within the scope of this definition).
• Includes ring substituted primary amines (bk-MDA is the only example).
• The term “cyclic structure” has a very wide scope (e.g. all ring sizes, all heterocyclic nitrogen compounds and structures with ring substituents).

Appendix 1

Cathinone (Class C) beta-keto-amphetamine Note: only encountered in Khat although it has been encountered as the pro-drug, α-phthalimidopropiophenone (see below)	R1 = Me R2 = H R3 = H R4 = H
α-phthalimidopropiophenone Note: found in products from the Internet	R1 = Me NR2R3 = phthalimide R4 = H
Methcathinone (Class B) Ephedrone α-methylaminopropiophenone	R1 = Me R2 = Me R3 = H R4 = H
N,N-Dimethylcathinone Metamfepramone Dimethylpropion Note: encountered in seizures	R1 = Me R2 = Me R3 = Me R4 = H
Ethcathinone Ethylpropion N-ethylcathinone 2-ethylamino-propiophenone Sub Coca II Note: encountered in seizures	R1 = Me R2 = Et R3 = H R4 = H
Diethylpropion (Class C) Diethylcathinone Amfepramone	R1 = Me R2 = Et R3 = Et R4 = H
α-Pyrrolidinopropiophenone α-PPP Note: encountered in Germany	R1 = Me NR2R3 = Pyrrolidinyl R4 = H
Buphedrone 2-methylamino-1-phenylbutan-1-one Note: no seizures reported to EMCDDA but is available via the Internet and user reports are on drug forums.	R1 = Et R2 = Me R3 = H R4 = H
α-Pyrrolidinobutiophenone α-PBP Note: no seizure or user reports but listed on Wikipedia and in a patent	R1 = Et NR2R3 = Pyrrolidinyl R4 = H
α-Pyrrolidinovalerophenone α-PVP α-Pyrrolidinopentiophenone Note: No seizures reported to EMCDDA, but metabolism study by Germany, as a result of 2 seizures, in Germany and Netherlands.	R1 = n-Pr NR2R3 = Pyrrolidinyl R4 = H
Mephedrone 4-Methylmethcathinone 4-MMC Sub Coca I Note: most frequently encountered cathinone derivative	R1 = Me R2 = Me R3 = H R4 = 4-Me
4’-methyl-α-pyrrolidinopropiophenone MPPP Note: seizure report from Germany	R1 = Me NR2R3 = Pyrrolidinyl R4 = 4-Me
4’-methyl-α-pyrrolidinobutiophenone MPBP Note: seizure report from Germany	R1 = Et NR2R3 = Pyrrolidinyl R4 = 4-Me
Pyrovalerone (Class C)	R1 = n-Pr NR2R3 = Pyrrolidinyl R4 = Me
4’-methyl-α-pyrrolidinohexiophenone MPHP Note: seizure report from Germany	R1 = n-Bu NR2R3 = Pyrrolidinyl R4 = Me
Methedrone 4-methoxymethcathinone PMMC bk-PMMA Note: encountered in seizures	R1 = Me R2 = Me R3 = H R4 = 4-MeO
4’-Methoxy-α-pyrrolidinopropiophenone MOPPP Note: seizure report from Germany	R1 = Me NR2R3 = Pyrrolidinyl R4 = 4-MeO
Bupropion (Zyban – medicinal product in UK) Note: To be excluded from control. No reports of abuse)	R1 = Me R2 = t-Bu R3 = H R4 = 3-Cl
Flephedrone 4-Fluoromethcathinone 4FMC Note: encountered in seizures. The 3-fluoro and 2-fluoro isomers have also been found in products from the Internet.	R1 = Me R2 = Me R3 = H R4 = 4-F (also 2-F and 3-F)
Methylone 3,4-Methylenedioxymethcathinone bk-MDMA Note: encountered in seizures	R1 = Me R2 = Me R3 = H R4 = 3,4-methylenedioxy
Ethylone 3,4-methylenedioxyethcathinine bk-MDEA Note: encountered in seizures	R1 = Me R2 = Et R3 = H R4 = 3,4-methylenedioxy
3’,4’-methylenedioxy-α-pyrrolidinopropiophenone MDPPP Note: seizure reports from Germany and Denmark	R1 = Me NR2R3 = Pyrrolidinyl R4 = 3,4-methylenedioxy
Butylone β-keto-N-methyl-3,4-benzodioxyolylbutanamine bk-MDBD Note: seizure reports from 7 countries	R1 = Et R2 = Me R3 = H R4 = 3,4-methylenedioxy
3’,4’-Methylenedioxy-α-pyrrolidinobutiophenone Note: no seizure reports, but mentioned in Wikipedia and in patent	R1 = Et NR2R3 = Pyrrolidinyl R4 = 3,4-methylenedioxy
Pentylone β-Keto-methylbenzodioxolylpentanamine bk-Methyl-K bk-MBDP Note: no seizure reports, but mentioned in Wikipedia and in patent.	R1 = n-Pr R2 = Me R3 = H R4 = 3,4-methylenedioxy
Methylenedioxypyrovalerone MDPV Note: encountered in seizures	R1 = n-Pr NR2R3 = Pyrrolidinyl R4 = 3,4-methylenedioxy

Annex B & C

…Aren’t really worth including here. They contain a list of ACMD members and a list of organisations and individuals who submitted evidence included in the report. Go and read it in the original pdf if you want to. Go on! Go and bloody read it!

Annex D. Letter From The Advisory Council On The Misuse Of Drugs To The Home Secretary

22nd December 2009

Dear Home Secretary,

Re: ACMD consideration of mephedrone (and related cathinones)

The ACMD wrote to you in March to explain that it would be pleased to accede to the Government’s priorities that your predecessor set out in her letter of 13 March 2009. Concerning the issue of ‘legal highs’ the ACMD has provided advice on the synthetic cannabinoid receptor agonists (Spice), 1-benzylpiperazine, GBL and 1,4-BD all of which we note will be controlled in the legislation on the 23rd December. In the ACMD’s letter of 30 September 2009 it was explained that we would next provide you with advice on the cathinones.

Despite the difficulties of the last 2 months the ACMD is committed to providing you with advice on the cathinones. Although attention has focused on mephedrone, five other synthetic psychoactive cathinone derivatives are also widely available. The ACMD explained in a previous letter to you that it has concerns about the apparent prevalence and potential harms of these compounds. Much has been made of these compounds in the media over recent weeks; we find it of concern that this may have had the consequence of bringing such drugs to the attention of a wider demographic sooner than may have been the case.

The ACMD understand that mephedrone, amongst other cathinones, is being marketed as a variety of apparently ‘benign’ products e.g. bath salts or plant food. Whilst the potential harms of these drugs are not yet fully known, it is apparent that the selling of such unregulated preparations in a form that they are clearly unintended for could have serious public health implications.

The ACMD is mindful that, after recent events, our statutory membership requirements need to be fulfilled before providing formal advice, according to the requirements of the Misuse of Drugs Act 1971. However, the ACMD would like to assure you that it will seek to provide you with such advice at the earliest possible opportunity on this important issue.

I would be willing to discuss the issue of the cathinones and, more broadly, new psychoactive substances (‘legal highs’) and the timing of advice with you.

Yours sincerely,

Professor Les Iversen
(on behalf of the ACMD)

***

The original (boringly formatted) report can be found here: ACMD-cathinones-report.pdf

Post from: Synchronium

The ACMD’s Mephedrone Report Part II

You Might Be Interested In:

• The ACMD’s Mephedrone Report Part I
• Mephedrone Banned On Friday 16th April
• A Look At Legal Highs
• Shaun The Sheep
• Should Mephedrone Be Legal?
• Mephedrone: The Facts
• Mephedrone Cat
• Mephedrone Update
• Nutt Sacked Episode III – Revenge Of The Schizoids
• Nutt Sacked Episode II – Attack Of The MPs

Since we’re up to the eyeballs here with a week’s worth of work to catch up on, and this report will have a monstrous impact, I’ll repost it here in full. Kind of. Below is the main body of the report including references. The equally important annexes including recommendations on how to actually ban these substances can be found here: The ACMD’s Mephedrone Report Part II.

I’ve kept page numbers in referring to pages in the original document and included the references, but not included the footnotes. Most of the footnote info has been incorporated in the article somehow though, and if you’re really desperate to read them, you can download the full pdf at the end of part two. Here goes:

Consideration Of The Cathinones

Letter To The Home Secretary From The ACMD

31st March 2010

Dear Home Secretary,

I have pleasure in attaching the Advisory Council on the Misuse of Drugs report on the ‘Consideration of the cathinones’.

The ACMD recommends that the cathinone compounds be brought under control of the Misuse of Drugs Act 1971 in Class B, Schedule I by way of a generic definition. Based on the attached evidence and by analogy with the amphetamines, the ACMD consider that the harms associated with the cathinones most closely equate with other compounds in Class B.

The ACMD also recommend that particular attention is focussed on credible and consistent public health messages that are promulgated both to the public and health professionals – the latter for the purposes of providing advice.

The ACMD is concerned that, particularly in the case of mephedrone, the internet plays a significant part in the marketing, sale and distribution of the drug and social networking sites may also play a role. The ACMD therefore believes that resources should initially be focussed on supply side activities with a concurrent emphasis on educating users of this drug so as to highlight the real dangers of mephedrone and the cathinones.

The ACMD indicated, in its letter to the Home Secretary, of the 22nd December 2009, its concerns about the sale of mephedrone and its plans for review. However, the rapid increase in the use of mephedrone in the UK has been exceptional. This sudden rise in prevalence of what we consider to be a harmful drug has brought to the fore our concerns that we need to consider a range of options for limiting the rapid spread of such substances. The ACMD intend to provide you with further advice on the possible control of ‘legal highs’ concerning recommendations and advice that is broader than the scope of what either this report or that on other individual or classes of compounds will allow.

In addition, I would like to draw your attention to further advice that we will provide on the napthyl analogues of pyrovalerone and other such analogues. The ACMD will meet to discuss other compounds that are not covered by this generic scope in the next few weeks.

Yours faithfully,
Professor Les Iversen FRS

1. Background

1.1. In March 2009 the then Home Secretary requested advice from the ACMD on so called ‘legal highs’. The ACMD have looked at a number of substances to date and provided advice on the piperazines and the synthetic cannabinoids (‘Spice). The ACMD wrote to the Home Secretary in December 2009 (Annex D) setting out the ACMD’s concerns regarding the cathinones and mephedrone in particular, which first came to the ACMDs attention in the summer of 2009. On the 2nd February 2010 the ACMD Chair (Professor Les Iversen) met with the Home Secretary to further discuss the issue and to provide an update.

1.2. The ACMD gathered evidence on the cathinones at a special meeting of the Technical Committee (22nd February 2010) and discussed additional evidence and possible recommendations at a further Technical Committee meeting on the 25th March 2010, and at the ACMD Council meeting on the 29th of March 2010.

2. Introduction

2.1. Cathinone is one of a number of alkaloids which can be extracted from the (fresh) leaves of Catha edulis (khat). It is structurally very similar to amphetamine (1-phenylpropan-2-amine) and represents the β-keto analogue of amphetamine.

2.2. Cathinone (Class C), methcathinone (Class B), diethylpropion (Class C) and pyrovalerone (Class C) are controlled under the Misuse of Drugs Act 1971. The three controlled cathinone derivatives are listed in the United Nations Convention on Psychotropic Substances (1971) and have been reveiwed by the WHO Expert Committee on Drug Dependence (WHO, 1995). However, other derivatives and analogues are not presently controlled (including mephedrone). Notwithstanding the potential harms of the cathinones it is apparent that mephedrone and other cathinones are being sold without any apparent effective regulation.

2.3. The ACMD has communicated its intentions to review the cathinones to the Home Secretary, over recent months, through meetings and correspondence (see the ACMD’s letter of the 22nd Dec 2009 – Annex D). The ACMD has been concerned about the rise in prevalence of the cathinones and potential harms initially through reports from drug services, young people’s treatment services, head teachers, drug surveys, the police and media, among others.

2.4. Other countries (including: Sweden Denmark, Norway, Ireland and Israel) have recently controlled specific cathinones. However, we are not aware of any country that has developed generic legislation to control the cathinones as a class.

2.5. The ACMD is aware of the collation of data on mephedrone by Europol and the EMCDDA in the form of a joint report under Article 5.1 of Council Decision 2005/387/JHA. The ACMD wrote to the UK focal point (the Reitox NFP) that would be providing information as requested by Article 5 of the Decision.

2.6. This report is compiled from oral and written evidence considered at the meetings (paragraph 2.3) above. A full citation of the evidence received and considered is provided in Section 10 and submitting individuals and organisations are given in Annex C.

3. Chemistry And Pharmacology

Chemistry

(White, 2010)

3.1. Cathinone (2-amino-1-phenyl propanone) is one of a number of alkaloids which can be extracted from the (fresh) leaves of Catha edulis (khat). However, the ACMD understands that most of the cathinones seized, and those that have been tested, are synthetic in origin.

3.2. Cathinone is structurally very similar to amphetamine (1-phenylpropan-2-amine), differing only in the functionality present at the β-carbon. Cathinone possesses a ketone oxygen at the β-carbon; cathinone can therefore be considered as the ‘β-keto analogue’ of amphetamine (see Figures 1 and 2).

Figure 1: The structural similarity between amphetamine (left) and cathinone (right)

3.3. Structural modifications to the 1-phenylpropan-2-amine (amphetamine) backbone have produced a range of different compounds, many of which are closely related structurally to amphetamine; these are known as the ‘amphetamines’. In a similar manner, the molecular architecture of 2-amino-1-phenyl propanone (cathinone) can be altered to produce a series of different compounds which are closely structurally related to cathinone. Together these are known as the ‘cathinones’ or ‘cathinone derivatives’.

3.4. The N-methyl derivative known as methcathinone or ephedrone is the cathinone analogue of methylamphetamine, while 3,4-methylene-dioxymethcathinone (methylone) is the cathinone analogue of MDMA (ecstasy); 4-methylmethcathinone (mephedrone) has no commonly used amphetamine equivalent.

3.5. The basic cathinone structure (see Figure 2) can be altered in a number of predictable ways, such as the inclusion of additional functionality to the aromatic ring (ring substitution, R4), N-alkylation (or inclusion of the nitrogen atom in a ring structure, R2 and R3), and variation of the (typically alkyl) α-carbon substituent (R1). Multiple modifications may of course be present in a single derivative; cathinones are all usually N-alkylated (or the nitrogen is incorporated into a ring structure, typically pyrrolidine) and many also bear ring substituents.

Figure 2: Generic sites for structural variation of cathinone, detailing α and β positions

(The generic cathinone backbone (see Figure 2) possesses a chiral centre (the α-carbon atom if R1≠H); cathinone and its derivatives can therefore exist as stereoisomers, the potencies of which may be markedly different. Although it is the S-enantiomer of cathinone which is found in the fresh leaves of Catha edulis, the chirality of the cathinones is not determined during routine forensic analysis of seizures. There is, however, no evidence to suggest that the synthetic cathinones currently available are enantiopure; it is instead likely that they are supplied as racemic mixtures. The qualitative or quantitative differences between the enantiomers of the non-controlled cathinones is not known.)

3.6. The genesis of synthetic cathinone chemistry is rooted in the synthesis of cathinone over 120 years ago. Since this time, many synthetic cathinones have been reported, the vast majority of which have not been used in a medicinal setting. However, a handful of cathinones, such as diethylpropion, bupropion and pyrovalerone have been used in pharmaceutical preparations, and the properties of novel cathinones (such as napthylpyrovalerone (Meltzer et al., 2006)) is still an area of active research.

3.7. Bupropion (page 42) is used medically as an antidepressant and an aid to smoking cessation and is a prescribed drug, marketed under the trade name Zyban®. Although it is a ring substituted cathinone no samples of Bupropion have been encountered in forensic analysis of seizures in the UK, and there is no evidence for its misuse.

3.8. The misuse of selected synthetic cathinones is not new; methcathinone (ephedrone), originally used as an antidepressant in the former Soviet Union in the 1930’s, went on to be used recreationally there (especially during the 1970s and 1980s) and in the USA (1990s). The emergence of six synthetic cathinones in Germany was reported between 1997 and 2004. All six substances bear an α-pyrrolidino functionality and are therefore closely related to pyrovalerone (page 41).

3.9. More recently, there have been an increasing number of reports of other synthetic cathinones encountered within the European Union. Although many of these compounds are simply β-keto analogues of well-known amphetamines, the presence of the ketone functionality often circumvents any control measures which may already be in place for the related amphetamine congeners. Since 2006, the following cathinones have been reported in the European Union (see Table 1; for the position of the substituents R1 to R4, see Figure 2). According to data from UK forensic providers, since January 2006 six of these have been encountered in the UK (emboldened in Table 1).

Table 1: Some of the non-controlled cathinones encountered in the European Union since 2006 (excluding reports of pyrovalerone derivatives from 1997-2004). those in bold type have been encountered in the UK.

3.10. Of the total number of cathinone derivatives encountered by UK forensic providers, by far the most commonly encountered is 4-methylmethcathinone (mephedrone) (89% of seizures). However, data from the Forensic Science Service indicate that cathinones accounted for a very small fraction of Police seizures submitted in 2009. Tentative data also indicate a rapid rise in the number of cathinone submissions during 2009, with a concomitant decrease in the number of piperazine submissions.

3.11. Data from UK forensic providers suggest that the cathinones are normally submitted as either white or brown powders (the freebase forms of the cathinones are unstable and readily decompose; the cathinones are normally encountered as the hydrochloride salts.); data from January 2006 to mid-February 2010 indicate that, of all cathinone derivatives submitted, 95% were in powder form, 4% being submitted as tablets or capsules.

3.12. Purity data for the cathinones are not available from UK forensic providers, since it is not usually determined during routine forensic analysis. However, cathinones are normally advertised as being of ‘high purity’, typically >95%. Some adulterants, including benzocaine, lignocaine, caffeine and paracetamol, have been detected in a small proportion of seizures of the cathinones. Some submissions have been adulterated with controlled drugs such as cocaine, ketamine, amphetamine and 1-benzylpiperazine (BZP), although these are rarely encountered.

3.13. There are currently no colorimetric field tests available to identify all of the cathinone derivatives, although some chemical tests, such as the Simon’s test and Chen test may be used to give an indication of the presence of a small number of the cathinones. More specific field tests based on immunoassay technology are not yet available.

3.14. As with the amphetamines, both systematic (IUPAC) and non-standard nomenclature is common in cathinone chemistry. Often, the assimilation of a common structural motif is reflected in non-standard nomenclature. Thus, structural incorporation of the ‘2-methylamino-1-phenyl-1-propanone’ fragment, which is also known as methcathinone or ‘ephedrone’, is often indicated in nomenclature; 4-methylmethcathinone is ‘mephedrone’ and 4-fluoromethcathinone is ‘flephedrone’. The use of acronyms is also widespread; 3,4-methylenedioxypyrovalerone is known as ‘MDPV’, whilst α-pyrrolidinopropiophenone, one of a number of α-pyrrolidino cathinones, is simply known as α-PPP. As a consequence of the β-keto substituent, it is also common practice for widely accepted amphetamine acronyms to be augmented with the prefix ‘bk’. For example, 3,4-methylenedioxymethcathinone (methylone), the cathinone analogue of MDMA, is often referred to as ‘bk-MDMA’. Mephedrone [2-(methylamino)-1-(4-methylphenyl)-1-propanone] is the most commonly used cathinone derivative and forms the focus of this report.

Pharmacology

3.15. As with the amphetamines, the cathinones act as central nervous system stimulants, although the potencies of the cathinones are generally lower then their amphetamine congeners, probably because the increased polarity conferred on a cathinone by the presence of a β-keto group reduces their ability to cross the blood-brain barrier.

3.16. Several cathinones have been used as active pharmaceutical ingredients (API). Bupropion has been used as an antidepressant, and as an aid to stop smoking cigarettes. Diethylpropion (Amfepramone) and pyrovalerone have both been proposed as appetite suppressants, although they are not currently in clinical use. 4-methylmethcathinone (mephedrone), the most commonly encountered synthetic cathinone derivative in the UK, has never been used as an API or patented as a potential API.

3.17. Little data are available on either the pharmacokinetics or pharmacodynamics of the cathinones. Research on the metabolism of the ring-substituted cathinones bk-MBDB and bk-MDEA has implicated N-dealkylation, demethylenation followed by O-methylation and β-keto reduction as major metabolic pathways (Zaitsu et al., 2009).

3.18 The effects of cathinones bearing ring-substituents in human subjects are reportedly similar to those of cocaine, amphetamine and MDMA (Table 2; CairScotland, 2010). Self reported subjective effects of ring-substituted cathinones include:

• Feelings of empathy (openness, love, closeness, sociability, well-being);
• Stimulation / alertness / rushing;
• Euphoria / mood lift / appreciation of music; and,
• Awareness of senses.

3.19.  Studies of the effects of cathinones on monoamine neurotransmission in rat brain confirm their mechanisms of action to be similar to those of the amphetamines. Both groups of drugs bind to monoamine transporters for dopamine, serotonin and noradrenaline (norepinephrine) in brain and promote release of these monoamines (Cozzi et al., 1999; Nagai et al., 2007). As with the different amphetamines, individual cathinone derivatives vary in their relative potencies as inhibitors of the three monoamine transporters – summarised in Table 2. There are no published data on the effects of mephedrone on monoamine transporters, but it may be expected to be intermediate in its profile between methcathinone and methylone.

Table 2: Actions of selected drugs on monoamine transporters

Data from Cozzi et al., (1999) and Nagai et al., (2007). Values are depicted as relative affinities since the studies did not use the same units. + = low affinity; ++++ = highest affinity

3.20. It is notable that the cathinones examined were potent inhibitors of the noradrenaline (norepinephrine) transporter (NET). This helps to explain the strong sympathomimetic actions of cathinones – due to their ability to promote release of noradrenaline from the sympathetic nerves in various peripheral organs, notably the heart and vascular system.

3.21. Cathinone and methcathinone are amphetamine-like behavioural stimulants. When administered to experimental animals they cause hyperactivity, with methcathinone being approximately 10 times more potent than cathinone (Feyissa and Kelly, 2008; Glennon et al., 1987)

3.22 When administered in vivo to rats trained to recognise and to distinguish the subjective effects of amphetamine, the animals cross-generalised completely to methcathinone (i.e. they were unable to recognise this substances as having different effects from amphetamine). Methylone, however, showed only weak cross generalization to amphetamine, but cross generalized completely to MDMA in rats trained to recognize this as the discriminative stimulus (Dal Cason et al.,1997).

4. Epidemiology Of Cathinone Use And Methods Of Use

Availability and use

4.1. Many of the cathinone compounds, particularly mephedrone, can be purchased from many different sources, and are readily available over the internet. Although the provenance of the substances is often not clear, several suppliers source compounds from China (Ramsey, 2010; UK Border Agency, 2010). Exercises at Heathrow targeting air courier traffic from China for delivery to UK domestic addresses gave rise to seizures of mephedrone. Claims of manufacture in a number of other countries are made on the internet.

4.2. Intelligence from Australia Customs and Border Protection Service has identified China and the UK as being the principal source of mephedrone. However, it is likely that in the case of the UK, this represents transit of the drugs and not necessarily production in the apparent country of origin.

4.3. Mephedrone and other cathinones are predominantly sold over the internet and in ‘head shops’. Websites selling cathinone based compounds – generally mephedrone – normally exhibit a disclaimer that the compounds ‘are not for human consumption’. Instead, they are sold as research chemicals, ‘novelty bath salts’ (3-fluoromethcathinone) or, more commonly, as plant food/plant growth regulators (Sumnall, 2009). However, none of the cathinones has any recognized efficacy as a plant fertilizer nor would they suitably function as bath salts.

4.4. Slang terms for some of the cathinones include Bubble(s), miaow, meow meow, 4-MMC, Mcat, sub-coca, toot and Top Cat.

4.5. Cathinones (generally mephedrone) are usually sold as white or brown powders, sometimes as capsules, or more rarely as pills, and are often advertised as being of ‘high’ purity (> 95%). CairScotland (2010) report that ‘Bubbles’ was originally sold in capsules, but now more often in 1g bags. Reports suggest varying prices: around £10-15/g if purchased from ‘headshops’, clubs or dealers (Druglink, 2010; Linell, 2010).

4.6. Self-reported dosages range from 5 mg or less (for MDPV) to 200 mg or more (for mephedrone), with some mephedrone users reporting ‘re-dosing’ (bingeing) to prolong the euphoric experience, leading to 1-2g being consumed in a session. The cathinones are sometimes used in conjunction with alcohol or controlled substances; co-abused substances include cocaine, cannabis, ketamine and MDMA. Studies of polysubstance use with the cathinones are not available, however, it should be noted that polydrug use is increasingly a feature of UK illegal consumption patterns more generally.

4.7. The reason for the apparent emergence and sudden increase in mephedrone use in the UK in 2009 is unclear. However, interviews with users and community workers (Newcombe, 2010; Measham et al., 2010, NME, 2010) suggest that the unavailability and/or low purity of cocaine and MDMA in 2009 (Hand and Rishiraj, 2009) have contributed to the increase in mephedrone use. In addition, the cathinones are presently a legal alternative to other drugs and are widely available from internet websites.

4.8 Mephedrone powder may be snorted (insufflated) (sometimes by keying – approximately 5-8 keys per gram (Linell, 2010)). The drug may also be swallowed – often after wrapping in tissue paper (bombing or dabbing) or, more rarely, injected (CairScotland, 2010; Linell, 2010; McVean, 2009; Measham et al., 2010).

4.9. Reports from users presenting at hospital A&E units are that mephedrone is taken in staggered doses (Wood pers. comm.).

4.10. Emergent research with mephedrone users suggests that they may appear to develop tolerance quickly and as a consequence tend to consume higher doses more frequently.

4.11. Evidence from the Bailiwick of Guernsey Customs report an increase in the prevalence of mephedrone from seizures and this has superseded the seizures of ‘Toot’ (identified predominantly as Butylone and methylone) (McVean, 2009 and 2010). It is reported that mephedrone and ‘Toot’ are being injected by users and has become popular among users of heroin (McVean, 2009 and 2010).

Prevalence and reported data

4.12. There are little published data on the prevalence of the cathinones; most available data are from self reported surveys of particular demographics.

4.13. Since many of the cathinones are not controlled, they are not included in the ‘stimulant’ group of substances in the British Crime Survey (BCS). However, we understand that the BCS will now include a specific question on mephedrone – interim data should be available to the ACMD after 6 months of the question becoming part of the survey.

4.14. The Mixmag survey (Winstock, 2010) is a cross sectional, self reported, self nominating, survey of over 2,000 UK individuals using the online website “Don’t Stay In” for the dance magazine Mixmag. The most recent survey included a question on mephedrone. Of self reported drug use, mephedrone was the fourth most commonly used drug in the last month (Cannabis (any), ecstasy (any) and cocaine powder ranked higher in terms of % use in the last month). The survey data show that 41.7% of respondents indicated they had ever used mephedrone, 33.6% in the previous month. These data suggest that the use of mephedrone is a new phenomenon since lifetime and past month prevalence is so similar in this survey. The synthetic cathinone methylone had been tried by 7.5% of respondents in the last month and 10.8% in their lifetime. Also other surveys of drug use show no reported mephedrone use amongst similar groups of young adults surveyed in bars and clubs in 2004-8 (Measham and Moore, 2009).

4.15. Data from the National Poisons Information Service (NPIS) show that telephone inquiries and TOXBASE accesses relating to cathinones increased sharply over the latter part of 2009 into 2010 (Thomas, 2010). NPIS enquiries more commonly involved males (2:1 sex ratio) and fitted an age profile similar to those taking MDMA with the greater proportion being in the 10-19 and 20-29 age groups, compared to cocaine which has a greater proportion of enquiries concerning the 20-29 and 30-39 age groups.

4.16. The most up to date information regarding visits to the FRANK website relating to the cathinones page are presented in Table 3. The number of visits has more than doubled in the past six months and has shown a month on month increase since September 2009 when the page was first published. This is mirrored by similar increases in calls to the talk to FRANK helpline.

Table 3: Visits to selected pages of the FRANK website between September 2009 and February 2010*.

*percentages are of total visits to individual drug webpages on FRANK website.

4.17. ‘Google Insights for search’ is a tool that allows search volume patterns, specifically using the Google search engine, to be compared across regions, categories, time frames, and properties. ‘Google Insights for search’ has been used in this instance to determine the proportion of searches, using Google, to search for the word ‘mephedrone’ since January 2009 to March 2010 in the UK (England region only). It can be seen from Figure 1 that there is a rising trend in the searches, although the month of March 2010 includes only partial data at this time. Please note that some months overlap due to the way in which the data is collated (weekly rather monthly).

Figure 1: Relative number of searches on Google for the term ‘mephedrone’.

4.18. Data provided by the Forensic Science Service (FSS) of police seizures show that the cathinone derivatives account for only a small proportion of total drug seizures. Although the cathinones are not illegal they generally present as ‘white powders’ (predominantly mephedrone – 89% of cathinone seizures).

5. Physical Harms (Toxicity, Dependency And Mental Health)

Acute toxicity

5.1. Most data regarding the harms of the cathinones (mephedrone in particular) are self-reported and there are very few clinical data available.

5.2. Wood et al., (2009) report the first case of sympathomimetic toxicity related to mephedrone (4-MMC) confirmed by toxicological screening where no other drugs or alcohol were detected.

5.3. Data from Guys and St Thomas’ hospital toxicology (Dargan and Wood, pers. comm.) over the last year show that from a total of 1600-1800 cases, of which 40% are due to recreational drugs, 25 of which presented with toxicity due to self reported mephedrone use (Table 4). Of these 25 cases cases, 80% were male with a mean age of 28.5y (SD ± 8.0 y). Reported clinical symptoms are shown in Table 5, clinical examination data are shown in Table 6.

Table 4: Cases of toxicity in individuals presenting due to self reported mephedrone use to Guys and St Thomas’ hospital

Table 5: Reported Clinical symptoms for cases of toxicity in individuals presenting due to self reported mephedrone use to Guys and St Thomas’ hospital

Table 6: Clinical examination for cases of toxicity in individuals presenting due to self reported mephedrone use to Guys and St Thomas’ hospital

5.4. The clinical management of those cases at Guys and St Thomas’ was that:

• Four (16%) required benzodiazepines for management of agitation
• Twenty (80%) discharged from ED/observation ward
• Five admitted to hospital
• Four to general medical ward
• One to ICU (for other drug toxicity: GBL)

5.5. Various user reports and clinical observations indicate that mephedrone abuse can cause a number of adverse side effects. Table 7 summarises self reported side effects of mephedrone in terms of increasing severity.

Table 7: Self reported side effects of mephedrone

*Data from Mixmag survey n=>2,000 (Winstock, 2010)

5.6. When taken in large quantities self-reported experiences by ‘psychonaut’ users described vivid hallucinations during 3 day binges of mephedrone (Linell, 2010). However, the quantities reportedly consumed are not likely to mirror those of most users.

5.7. The ACMD has received anecdotal reports from members of the public that when taken in conjunction with other drugs e.g. amphetamines the effects can be quite marked and lead to personality changes, paranoia and sometimes violent episodes.

5.8. Some of the adverse effects reported for methylone (Table 8 ) are similar to those reported for MDMA (ecstasy) (ACMD, 2009)

Table 8: Self reported side effects of methylone

5.9. It is notable that several commonly reported side effects reflect the sympathomimetic actions of the cathinones. The NPIS is another important, independent source of information collected from telephone enquiries made by health professionals managing people presenting after mephedrone exposure and website visits. The most commonly reported clinical effects included tachycardia, palpitations, agitation, anxiety, palpitations and mydriasis. Chest pain, breathlessness, nausea, vomiting, headache, hypertension, confusion, hallucinations, peripheral vasoconstriction and convulsions have also been reported in some cases (Thomas, 2010). It is notable how closely the NPIS data match those provided from other sources.

5.10. Data from clinical examination confirms that tachycardia is a common symptom of mephedrone ingestion. Severe cases of cardiovascular toxicity or conditions such as hypopyrexia due to use of cathinones have not been reported (Dargan and Wood, pers. comm.). The majority of presentations have been recent and during the winter months, it is not known if the number of presentations due to conditions such as hypopyrexia will change during warmer weather.

5.11. Users also report severe vasoconstriction of extremities, leading to bluing of fingers or hands. It is worth noting that hyperpyrexia and vascular collapse are among the most dangerous life-threatening side effects of amphetamine misuse. Some of the acute adverse side effects induced by methylamphetamine include (ACMD, 2005):

• Insomnia
• Increased physical activity
• Decreased appetite
• Increased respiration
• Hyperthermia
• Increased heart rate and blood pressure
• Irregular heart beat
• Cardiovascular collapse and death (in overdose)
• Confusion
• Anxiety
• Tremors

Cases of death where cathinones have been implicated

5.12. There have been at least 18 deaths in England where cathinones have been implicated. Currently, seven of these have provided positive results for the presence of mephedrone at post mortem. To date, in one case the coroner concluded that the death was “natural” and that an inquest was not required. The remaining cases are awaiting inquest.

5.13. There have been at least seven deaths in Scotland where cathinones have been suspected. Of these, one has been confirmed as the result of the “adverse effects of methadone and mephedrone”. Another case is probable, but underlying health issues contributed to the death and it awaits formal confirmation by the relevant Procurator Fiscal. The presence of mephedrone has been confirmed in a third case.

5.14. One case on Guernsey has provided positive post mortem toxicology results for mephedrone and is awaiting inquest.

5.15. One suspected case in Wales and a further case in Northern Ireland are awaiting toxicology and inquest.

5.16. The UK number of cases are subject to several caveats:

• Not all suspected cases may have been identified;
• That mephedrone may have been involved in a death cannot be confirmed until the relevant coroner or Procurator Fiscal has concluded her/his inquest or other formal inquiry; and,
• The presence of mephedrone in post mortem toxicology does not necessarily imply that it caused or contributed to a death.

5.17. Mephedrone has been linked to the death of an 18-year old girl in Sweden (Gustaffsson and Escher, 2009). The report (December 2008) indicates that she had taken mephedrone and smoked cannabis. The woman was observed to first become sick and then unconscious. Forensic autopsy showed severe brain swelling, preceded by respiratory and circulatory arrest. No other sedatives, narcotics or alcohol were detected in the blood.

Chronic toxicity

5.18. There are so far no reports of the potential harmful effects of the long term use of mephedrone and related cathinones because the substances have only been used in recent months in the UK.

Dependence

5.19. Reports from a case study of mephedrone use (Linell, 2010) suggest that users can become regular users rapidly, although they are generally not in a ‘state of dependency’. However, this conclusion contrasts with the same report whereby users knew people who became daily users. Some users have reported developing cravings for mephedrone, methylone and MDPV after use. Arguing again by analogy with amphetamines, it is clear that the chronic use of amphetamines can lead to dependence, and a downward cycle of bingeing and periods of recovery associated with depression (ACMD, 2005), therefore it is likely that mephedrone use carries a similar risk of dependency.

5.20. Dargan and Wood (2010) report a single case of dependency on mephedrone in Glasgow where the individual had been using the drug for 18 months.

5.21. Data are not available on the number of individuals in treatment services related to the cathinones. However, the evidence suggests that the number is likely to be very small at the time of writing.

6. Societal Harms

Prevalence

6.1. The current prevalence of mephedrone and the related cathinones is not accurately known. Reports from drugs agencies, drug researchers, criminal justice, public health (Talk to FRANK) and education professionals suggest that mephedrone use appears to be very widespread and is growing. From emergence to current levels of usage, commentators have suggested that the rise in mephedrone use is unprecedented. Namely within a year it has risen from a very low baseline to become popular amongst adolescents and adults.

Young people

6.2. Media reports from the 8th March indicate that secondary school children were missing classes due to the use of the drug mephedrone causing sickness. The DCSF minister of State for Schools and Learners has written to schools. In the letter it makes clear that they do have the power to confiscate inappropriate items including a substance that they believe to be mephedrone (or any other drug, whatever its legal status); in line with the school’s behaviour policy and that such items do not need to be returned.

6.3. Mephedrone is sold by online retailers for an average price of £10/g. Given that users take approximately one gram over the course of a session, this makes the drug relatively cheap compared with other intoxicants, as well as being more easily available than alcohol and cigarettes for under 18 year olds who have access to the internet or a high street ‘head shop’.

6.4. There is some evidence that use has escalated following media reports. For example, Google Trends (which collates Google searches) shows that UK Google searches have increased from a very low base in the last twelve months (see paragraph 4.17), with peaks which coincide with media coverage of mephedrone use and deaths where mephedrone might be implicated. The most popular Google search term is for the words “buy mephedrone online”, with four of the top five search terms containing the words “buy” and “mephedrone”. Furthermore online mephedrone retailers have reported an increase in sales following media coverage (The Guadian, 2009)

Anti-social behaviour / acquisitive crime

6.5. The ACMD has been presented with two recent cases where mephedrone users have reported that their use was funded by acquisitive crime (robbery and burglary). At present there remains only limited evidence of a relationship between mephedrone and anti-social behaviour; mainly related to the open dealing and consumption of mephedrone. Notwithstanding the legal implications, the dealing in unspecified white powders for the purposes of intoxication can amount to a public nuisance with a detrimental impact on public confidence.

Organised crime

6.6. There are indications that criminal groups are becoming involved in the supply of mephedrone to the public in the UK (SOCA, 2010). At present the mephedrone retail trade operates mainly through internet importation and distribution and ‘head shops’. However, there are reports of some UK drug suppliers selling mephedrone in dance clubs and at street level either as well as, or instead of cocaine and MDMA, due to mephedrone’s relatively low price, high purity and easy availability. Reports from Guernsey, where importation is currently banned (and prices are reported to be considerably higher), suggest that a street trade in mephedrone has developed. Reports from Guernsey customs officials note that supply is through illegal drug suppliers and incidences of violence have emerged associated with the street trade in mephedrone (McVean, 2010).

Stockpiling

6.7. It is reported that some users are planning to buy large quantities of mephedrone to ‘stockpile’ for future use and future sale should regulation be introduced (Measham et al., 2010; ACPO, pers. comm.). This could lead to an illegal supply of mephedrone coming on to the market should it be controlled under the Misuse of Drugs Act 1971.

Consumption patterns

6.8. It is of concern that there are reports that users of mephedrone have a tendency to re-dose (or ‘fiending’) and for some individuals the consumption of mephedrone is alone at home (Newcombe, 2010; Linnell, 2010). Together these two features of mephedrone consumption patterns may expose users to increased risks such as overdose or cardiovascular problems.

7. Current controls

Present UK controls

7.1. Cathinone (Class C), methcathinone (Class B), diethylpropion (Class C) and pyrovalerone (Class C) are controlled under the Misuse of Drugs Act 1971. However, other derivatives and analogues are not presently controlled (including mephedrone).

7.2. Although paragraph 1(c) of Part 1 (Schedule 2) of the Misuse of Drugs Act 1971 offers some scope for the control of substances which are structurally related to the phenethylamine backbone, it is primarily concerned with ring-substituted amphetamine-like compounds. Specifically, no mention is made of the presence of any substituents (other than hydrogen) at the β-carbon of the phenethylamine backbone (recall that the cathinones all possess a β-ketone oxygen; see Figure 1).

7.3. Irrespective of whether controls for the cathinones are implemented under the Misuse of Drugs Act 1971, the rapidity and easy availability of mephedrone and other cathinones (including websites set up so that vendors that can deliver to individual addresses) does raise the question of whether other legislation and regulation should be available.

International Control

7.4. Some of the substituted cathinones could conceivably be considered as being ‘structurally similar’ to cathinone and methcathinone, which are both already listed in Schedule 1 of the United Nations Convention on Psychotropic Substances 1971. It is therefore possible that some cathinones could be controlled through the implementation of analogue control where such control mechanisms exist.

7.5. Denmark controls a number of cathinones, including mephedrone, methylone and MDPV. Mephedrone has been controlled in Sweden since December 2008; the Swedish authorities have indicated that they also intend to classify MDPV and butylone. Mephedrone is controlled (as a medicinal product) in Finland, and it is anticipated that it will shortly be controlled in Germany, since the German Federal Cabinet made a decision to subordinate a number of materials to the Betäubungsmittelgesetz in January 2009. Methylone is also controlled in the Netherlands.

8. Public Health

8.1. The FRANK campaign (see also paragraph 4.16) provides information on the potential risks of taking cathinone compounds and there was also a recent campaign to highlight the dangers of ‘legal highs’ (‘Crazy Chemist’).

8.2. Lifeline have produced an information leaflet that provides harm reduction advice specific to mephedrone and answers frequently asked questions from users or potential users (Lifeline, 2010). The ACMD is also aware that CairScotland have produced and distributed information leaflets warning of the dangers of these substances (CairScotland, 2010).

8.3. Other than the above there is presently a limited amount of public health information regarding mephedrone and the cathinones. Although recent media profile has presented much apparent public health information it is not always credible or consistent.

9. Conclusions And Recommendations

9.1. Although the current prevalence of mephedrone and related cathionones is relatively low in the UK, use appears to have grown rapidly in the past year.

9.2. The ACMD would like to emphasise that mephedrone and the related cathinones are likely to be harmful to users and in tandem with control mechanisms there should be a credible and comprehensive public health campaign. The messages promulgated by FRANK provide a good basis upon which this should be built.
Control and regulation

9.3. The ACMD consider that the harms associated with mephedrone and the cathinones are commensurate with the amphetamines and therefore those substances in Class B; therefore the ACMD recommend that the cathinones be controlled as Class B substances under the Misuse of Drugs Act 1971.

9.4. The ACMD recommend that, excluding the four compounds already controlled (see paragraph 2.2) and the API Bupropion, the cathinones should be controlled by a generic definition under the Misuse of Drugs Act 1971 – see Annex A, p31, and in schedule 1 of the Misuse of Drugs Regulations 2001.

9.5. The naphthyl analogue of pyrovalerone is now advertised on the Internet and is being retailed as “NRG-1”. The ACMD intend to review these substances and provide further advice at a later date.

9.6. The ACMD recommend that the government implement appropriate additional controls and regulation of the cathinones (which would include mephedrone) through, for example:

• Import controls
• Serious Organised Crime Agency (SOCA)

9.7 The ACMD understand that to implement import controls is not administratively burdensome and would stop non-EU imports; where it is understood much of the importated cathinones originate from. The ACMD also believe that SOCA have a role in informing suppliers of the cathinones of the implementation of import controls, trading standards and, if implemented, forthcoming control under the Misuse of Drugs Act 1971.

9.8. The ACMD notes that the cathinones have no efficacy as plant fertiliser products or as bath salts and could be the subject of a prosecution under the Trade Descriptions legislation.

Public Health

9.9. Directors of public health in PCTs should be tasked with cascading information to raise awareness of the cathinones – symptoms of use and information on where to seek advice – among GP’s, A&E departments, medical directors / advisors and others as appropriate.

9.10. The ACMD recommends that all agencies involved in the health, education and rehabilitation of young persons should disseminate information, in appropriate formats, as provided by the Department of Health and Home Office, as to the risks of using mephedrone (and associated compounds). We include in this Drug Action Teams (and equivalents e.g. DAATs in the Devolved Administrations), Childrens’ Trust Boards, Youth Offending Teams and Schools.

9.11. We recommend that the FRANK webpages related to the cathinones are given due prominence and that supplementary educational material is easily available. The information provided should be credible and consistent.

9.12. In relation to 9.9-9.11 it is important that the risks of mixing these drugs with other substances (including alcohol) are highlighted.

9.13. The ACMD are presently identifying information streams to update ministers and provide information on both emerging drugs of misuse and emerging trends concerning established illegal drugs. The ACMD consider that this work will assist it in advising on ‘legal highs’ in the future. Among other measures, the continuing development of datasets from drug amnesty bins will contribute to providing an early warning of such emerging trends.

9.14. Appropriate treatment advice and provision should be available to those who have developed cathinones-related problems of which health professionals and drugs service providers should be aware.

Research

9.15. Present forensic analytical testing of the cathinones is expensive and a process that can take some time. Currently, there is no simple drug field test available for cathinones. There is an urgent need to develop a simple and reliable field test.

9.16. For the purposes of identification of cathinone derivatives by forensic providers and pathology laboratories, and the development of drug field tests, there is an urgent need to develop and make available a library of reference standards.

9.17. There is presently a lack of data concerning the involvement of the cathinones in drug-related deaths (DRDs). Therefore, we recommend that the Ministry of Justice approach Her Majesty’s Coroners to include, in the case of suspected DRDs, tests for the cathinones.

9.18. The ACMD welcome the collation of a joint report initiated by the European Drug Centre for Drugs and Drud Addiction (EMCDDA) in respect of mephedrone. However, we understand that this review will be limited in scope to mephedrone as an individual compound. The purpose of the present report is to review the broad spectrum of cathinone derivatives already encountered in the UK and to provide advice to ministers at the earliest opportunity. The ACMD will keep under consideration all emerging evidence including the EMCDDA’s forthcoming report(s) and will provide further advice to ministers accordingly.

9.19. There is a need for more basic research to examine the similarities and differences between the cathinones and their amphetamine equivalents.

9.20. We welcome the inclusion of a specific question on mephedrone in the British Crime Survey to develop the knowledge base on prevalence. The ACMD also recommends more social research to inform our understanding of drug trends, motivations for drug use, fluctuations in demand, and policy implications regarding deterrence, displacement and desistence.

9.21. The ACMD would welcome the continuing collation of data sets concerning toxicity, clinical case reports and dependence liability collected from hospital admissions and treatment services.

10. References (Including Written And Oral Evidence

Post from: Synchronium

The ACMD’s Mephedrone Report Part I

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• A Look At Legal Highs
• Shaun The Sheep
• Should Mephedrone Be Legal?
• Mephedrone: The Facts
• Mephedrone Cat
• Mephedrone Update
• Nutt Sacked Episode III – Revenge Of The Schizoids
• Nutt Sacked Episode II – Attack Of The MPs

Mephedrone has achieved this unusual status thanks to a number of factors. Firstly, it’s an effective stimulant, which is more than can be said for ecstasy and cocaine these days; the former consisting mainly of disagreeable piperazines (due to their cheapness, and until recently, their legal status) rather than MDMA, and the latter being incredibly inpure. Next up is the lack of a comedown that would normally be experienced with other stimulants, especially for new users. This means people can keep taking it for days on end with little to no perceived negative effects. The other major contributor is the price – at around £10 a gram, it undercuts a great many of its illegal counterparts, while often being more effective, or at least more reliable. Other factors include (potentially inaccurate) purity measures, the ease of buying it from the comfort of your own home  with a credit card, rather than handing over a fistful of crumpled notes to a typical drug dealer, and of course its legal status.  Although the majority of users understand that legal doesn’t mean safe, the fact that you can’t be imprisoned alongside murderers, rapists and other violent criminals for possessing it is certainly a plus. Oh, and it’s psychologically addictive – it won’t kill you if you stop taking it, but you might be able to think of nothing else.

Reports of children doing it, entire friendship groups crumbling as a result of compulsive use and the media frenzy have got people understandably worried and calling for this “evil” drug to be banned.

I Disagree.

Why We Shouldn’t Ban Mephedrone

If you haven’t read Top 10 Reasons Why Legal Highs Should Stay Legal, have a quick look now. Here are a few more mephedrone-specific points:

• Changing the law won’t change demand – we’ve already seen this with the reclassification of cannabis and the massive popularity of the synthetic cannabinoids that just got banned. Also, the decriminalisation of drugs in Portugal has resulted in not only a decline in drug use, but also a decline in drug-related illness and death (HIV from sharing needles, for example), as well as a increase in the number of people seeking treatment for addiction.
• The current classification system doesn’t work – Our current ABC system is a shambles, as any scientist, or indeed anyone that values evidence, will testify. Currently, one of the safest drugs, MDMA, sits alongside one of the (if not the) most dangerous, heroin. Cannabis, and soon the synthetic cannabinoids, which haven’t killed anyone, are positioned alongside amphetamine, a drug with far more potential dangers and addiction, meanwhile alcohol, which hospitalises over 1200 people a day and costs the NHS several billion pounds a year, remains legal along with tobacco. I would estimate the harms of mephedrone to be similar to amphetamine, if not a little worse, but placing it in class B would give the message that it is as dangerous as cannabis. Placing it in class A wouldn’t be right, as it certainly doesn’t appear to be as dangerous as heroin, but it’s probably worse than MDMA. Placing it in class C would be ridiculous, as it suggests cannabis is more dangerous. It would be impossible to have a sensible think on how to classify it properly without getting a headache.
• If mephedrone’s popularity persists, more people will die – in the event of an overdose or an idiosyncratic response, people taking illegal drugs are far more likely not to either tell the doctors what they’ve taken or even go to hospital in the first place. That’s not to say that mephedrone will kill a tonne of people, but if no one ever died whilst on mephedrone, that would be pretty weird…

What Should We Do Instead?

Just because I don’t think it should be illegal doesn’t mean I think the current situation is perfect. Instead, I think the best thing the government could do to reduce harm is keep it legal, restrict its sale to people over the age of 21 and slap on a tax of something like £15 per gram. This would make it much harder to buy large quantities at a time, especially for kids with little expendable income, and so curb mephedrone’s addictive nature. Obviously, this wouldn’t be the perfect solution, as some teenagers would still be able to get hold of it just like they do with alcohol, but at least less people will be taking it and a lot more money would be available to better fund the NHS, harm reduction methods, education about the drug and scientific research.

Why Mephedrone Won’t Be Classified Immediately

Heh. The government have certainly shot themselves in the foot here. Thanks to the sacking of Dave Nutt and the resignation of three others on the ACMD, the government now lacks the skills to ban it. Dr Les King, one of the resignees, was responsible for a large part of the ban last month, so without people like him, the government can’t do anything for a while. Looks like it’ll be legal for a good year or so yet.

How YOU Can Help

Well, you can’t really do anything about the mephedrone situation, but you can help me out by posting Mephedrone Cat everywhere!

You might save millions of lives by directing them to some of my harm reduction articles.

Post from: Synchronium

Should Mephedrone Be Legal?

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• Mephedrone Cat
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• The ACMD’s Mephedrone Report Part II
• The ACMD’s Mephedrone Report Part I
• Legal Highs & Terrorism
• Top 10 Reasons Why Legal Highs Should Stay Legal

#1 – Don’t associate with dodgy people

Selling legal highs can be done by a legitimate business. Since these businesses aren’t breaking the law, engaging in any other kind of illegal behaviour (guns, violence, money laundering, etc) is a massive risk. People that deal illegal drugs are already breaking the law – if they get caught, they’re going to prison for a long time. Breaking the law a second time is no longer such a big deal, especially if the price is right. Not only do you get the safety of dealing with an organisation that doesn’t want to break the law, but you’re also not seen with any dodgy characters, whether that’s meeting up on a street corner, visiting their house or them turning up at your place at a suspicious frequency.

#2 – Comparison Shopping

We all live in hope that one day we could type in RateMyWeedDealer.com, find the best prices in town and arrange for a delivery. Fortunately, as customers of legitimate products, legal highs fans can shop around to their heart’s content. Selling something for more than you should be? Then no one will buy it! It’s as simple as that, so, not only can customers get a better deal by shopping around, this behaviour also encourages healthy competition between legal highs vendors. Another plus for the customer!

#3 – Buyer Protection

Perhaps RateMyWeedDealer.com is a long way off, but what about just ringing your dealer to complain about something? Inadequate packaging? Does the product weigh half as much as you were promised? Unfortunately, I doubt your dealer gives a shit. Luckily, for legal highs consumers, most sites out there have some form of customer service, and if they can’t resolve things, facilities for refunds or chargebacks exist to protect the customer.

#4 – A Strength For Everyone

The sheer number of similar products available mean there is usually a strength for every occasion. Want a bit of an energy boost for work? Caffeine! Want to go to a rave all night? Synthetics! Want to go to a rave but it’s not going to be a “big one” because you’ve got work in the morning, and, let’s face it, your joints and muscles aren’t what they used to be? Something herbal!

I think asking an illegal drug dealer for something cheaper and less effective would be a world first.

#5 – Diversity

Not only is there a range in price and strength, there’s also an incredible range of effects available. Clear headed stimulation, total euphoria, intense rushes, powerful relaxants, shit that makes you laugh – whatever you want, there’s probably something available somewhere that will do the trick. In the world of illegal drugs, that kind of product diversity could only be maintained via a database of epic proportions containing your millions of “hookups” and your own data entry guy.

#6 – Passing A Drug Test

Some people might thing it’s unfair that their co-workers can party all night on a litre of vodka, sleep for a few hours in a bathtub alongside their own sick and eventually drive to work still pissed, while they get fired for smoking a bit of weed after work. Sure, people should get fired if they let their abuse of any substance interfere with their work, but some people may feel that what they get up to in their own time is their own business. These people may feel drug tests are massive breach of their privacy, so it’s a good job that they have a legal alternative to turn to, since they shouldn’t show up on drug tests.

#7 – Friends More Likely To Do The Right Thing

People that overdose on illegal drugs will sometimes go without the treatment they need to avoid any legal trouble for themselves or their friends. Perhaps a friend might not tell the doctor what someone else has taken for fear of getting their mate into trouble. With legal highs, there’s no risk of prosecution so a) people can fully disclose what they’ve taken and could even present the doc with the original packaging and b) the quantity of chemicals in pills or powders will be consistent between batches…

#8 – Batch Consistency

Not only can doctors share notes on specific products, but users can too. It’s no good trying to compare ecstasy pills from different ends of the country, since the contents are likely to vary wildly, even if they share the same stamp. With legal highs, that’s a different story. Consistency between brands and batches facilitates a great deal of discussion not only on how good they are, but also harm reduction. Occasionally manufacturers do change their ingredients, but it only takes a short while for the changes to reach the entire country.

#9 – The Government Could Learn A Thing Or Two

Straight away, the fact that the legal highs industry even exists tells us that people want to get high and that people think the current drug laws are stupid. There’s one massive lesson that could be learned from it though – why not use it as a model for eventually legalising cannabis and the rest? Instead of trying to ban every new substance before anyone has died, why not look at regulating their sales with similar legislation to alcohol and tobacco? If we as a country could get this right with legal highs, we could see if it works or not and them maybe think of abolishing our current bullshit excuse for a drugs law.

#10 – Taxes

Here’s a list of taxes that illegal drug dealers don’t pay:

• Personal Income Tax
• National Insurance
• Corporation Tax
• VAT

If legal highs remained legal and were taxed like alcohol and tobacco, the government would even more money on top of the taxes above that they already receive. These products are relatively harmless compared with alcohol, for example, which hospitalises 1200 people a day and costs the NHS at least £2 billion to deal with, so a tax on them wouldn’t be paying for the damage they’d cause to society – they’d be making the government a massive profit to spend on more doctors, nurses, medical research and fucking moats!

Nice one, G’ Brown!

Post from: Synchronium

Top 10 Reasons Why Legal Highs Should Stay Legal

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• Some More Excellent Editing By The BBC
• Mephedrone Cat

I just listened to the worst thing I’ve heard so far about the Nutt Sack scandal – BBC Radio 4′s “The Report“, that aired on Thursday. Not only is this as balanced as a lone fat guy on a see-saw, but their arguments compel you to shout at the computer as you listen along. This program was more damaging to my mental health than any kind of “skunk” might be. My favourite bits are when the reporter asks if he can get high by smelling some cannabis and when this woman’s son has a “schizoid episode” because he robbed his mum’s jewellery. Unbe-fucking-lievable! A BBC Radio producer actually got in touch, and encouraged me to pass the link around (excellent marketing there by the BBC, and for once I’m not being sarcastic) so here goes: you can listen to it here.

So, let’s have some fun! I’ll be giving away a 5g bag of Mellow Yellow to the best comment on this post deconstructing this program. You can pick your favourite bits or you can pick apart the entire thing bit by excruciatingly painful bit. Points will be awarded for thoroughness, any references to relevant facts and the cut of one’s jib. I’ll pick the best one by Dec 14th.

Post from: Synchronium

Nutt Sacked Episode III – Revenge Of The Schizoids

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Further to our recent email correspondence about the sacking of Prof. David Nutt, below is a copy of the letter I have sent to Alan Johnson today.  I will send you a copy of the reply I receive.

Next week I am co-sponsoring a cross-party event with Evan Harris (Lib Dem) and Peter Bottomley (Con) at which Prof. Nutt will be speaking to MPs.

Regards, Lynne Jones

And here is that letter:

Dear Alan

Professor David Nutt

As I was unable to be in the House to hear your Statement on Monday regarding the removal of Professor Nutt as Chair of the Advisory Council on the Misuse of Drugs (ACMD), I wanted to write to you to express my concerns.

I have seen a copy of your letter sacking Professor Nutt on the BBC website and I have read the Hansard of Monday’s debate.

During the debate on your Statement you infer that Prof. Nutt was removed for not being clear when speaking personally at a lecture to Kings College (London) that he was not speaking for the ACMD and for publishing documents relating to the Government framework without giving the Home Office first sight of them. You also say it was unacceptable for him to criticise Government Ministers and Government policy.

On the issue of speaking personally or on behalf of the ACMD, I note from a report in the 3 November edition of the Financial Times that Richard Garside, director of the Centre for Crime and Justice Studies at King’s College, who invited Prof. Nutt to give his lecture, stressed that:

“at no point did he make reference to his role as chair of the ACMD, nor did he give the impression that he was speaking on behalf of the ACMD”

Given this, on what basis are you arguing that it wasn’t ‘clear’ that he was speaking personally?  Surely it would be a matter for the members of the ACMD to complain if they felt this was the case (when in fact members of that Committee have resigned in protest at your action against Prof. Nutt).

On the question of publishing documents, unless you want to stop advisers expressing their views publicly, what are the reasons for the Government insisting on first sight of material published on the subject areas advisers give advice on?  Can you clarify what the documents were that Prof. Nutt published without first showing them to the Home Office and what action your Department would have taken had you had first sight of the documents?  Specifically would the Home Office have taken any action to change the content of the documents in question?

In the House on 2 November you said that whilst Prof. Nutt had the right to ‘express his views’ he did not have the right to criticise the Government and its drugs policy framework.  Isn’t this putting restrictions on his right to express himself independently in his role as an academic with expertise in this area?  It seems to me that this is different from campaigning against Government policy as you have accused him of doing.  If the Government wants independent evidence-based scientific advice doesn’t it have to face the consequences if it ignores the advice given?  Why didn’t you just defend your policy if you have confidence in it?

I should also be grateful for your response to the widespread criticism that your decision has received from the scientific community and the concern that you have jeopardised the relationship between independent scientific advisers and Government.  In particular, I noted the letter in the 2 November edition of the Times from Ian Stolerman, Emeritus Professor of Behavioural Pharmacology from the Institute of Psychiatry, King’s College London:

“All scientists who work without pay to advise the Government must surely be considering their positions.”

And no doubt you will have heard Professor Colin Blakemore, former head of the Medical Research Council, on the Today programme and his comment that:

“This is not just an issue about drugs: the Government depends very widely on advice from experts who give their time freely.”

Critics of your decision are backed up by the recent Government response to the Innovation, Science and Skills Committee’s Eighth Report of Session 2008–09, published only a matter of days before the sacking of Prof Nutt, which states:

“The Government agrees that the independence of science advisers is critical. It was precisely for this reason that the GCSA wrote to then-Home Secretary Jacqui Smith to express concern over her criticism, in Parliament, of Professor Nutt (Chairman of ACMD) with regard to an article he published in a peer-reviewed journal“

I note that despite this official Government declaration of concern over criticism by your predecessor of the ACMD Chair, on Monday, you referred to Jacqui’s criticism of Prof. Nutt as if this somehow justified your own action against him.  Do you accept that your dismissal of Prof. Nutt contradicts the Government’s position as outlined in this recent Response to the ISS Committee Report?

Turning to the issue of the classification of cannabis itself, in 2007, before the announcement in 2008 that cannabis was to be reclassified back to class B, I tabled an Early Day Motion about the dangers of cannabis use that I would like to bring to your attention (text printed on the back of this letter).  From this you will see that, whilst I accept that there are hazards associated with cannabis use, as does Prof. Nutt, this would not of itself justify the reclassification to class B, as classification is about relative hazard – the very point of Prof. Nutt’s comments.

Furthermore, in the EDM, I also pointed out that the downgrading of cannabis to class C from class B in 2004 was actually associated with reduced cannabis use by young people, as evidenced by the following table produced by your own Department with information from British Crime Survey respondents:

As you of course know, cannabis was reclassified from B to C with effect from January 2004 and reclassified back to B in December 2008 with effect from January 2009.  As you will note from the above statistics for this period, the proportion of 16-24 year-old respondents declaring cannabis use in the previous year fell from 25.3% in 2003/04 to 18% in 2007/08.  I was therefore very disappointed by your response to the question put to you during the debate on your 2 November Statement by George Howarth:

Mr. George Howarth (Knowsley, North and Sefton, East) (Lab): If my right hon. Friend had taken Professor Nutt’s advice and lowered the categorisation of cannabis, and if as a result more young people had started to use it, would not that have been irresponsible?

Alan Johnson: Yes, I think it would have been. That is why my predecessor decided not to take that advice and why that decision has been endorsed by this Parliament.

I would be interested to know why you did not base your answer on the statistical evidence on cannabis usage rates amongst young people during the period when categorisation was lowered.  Were you unaware of the above data or were you aware but misleading the House in your reply by your suggestion that it was because more young people started using cannabis when it was classified downwards to class C that Jacqui reclassified the drug upwards?

Either way, your failure to refer to your own published data on this particular question serves to reinforce the point that Government is ignoring evidence on issues relating to drug classification.

LYNNE JONES MP

Brilliant! When I first got in touch, I had no idea she’d even respond, let alone write a letter to Alan Johnson! She’ll copy me in on his reply too, should he ever write back. Somehow I don’t think he will…

If you haven’t written to your MP yet, please do so. Details on how to get in touch with them can be found here.

Post from: Synchronium

Nutt Sacked Episode II – Attack Of The MPs

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• Should Mephedrone Be Legal?
• Democracy In Action
• Mephedrone Banned On Friday 16th April
• Shaun The Sheep
• The ACMD’s Mephedrone Report Part II
• The ACMD’s Mephedrone Report Part I
• Music On Drugs
• How To Make Hash – The Ultimate Guide!

Malcolm Tucker: The angriest man on telly

Firstly, as everyone will know Prof. David Nutt was sacked as head of the Advisory Council for the Misuse of Drugs (ACMD). Ever since this news broke, I’ve not been able to shake the image of Prof. Nutt getting a bollocking from Malcolm out of The Thick Of It. On its own, this isn’t big news; people get sacked all the time. But the reason why he got sacked is gobsmacking.

The Situation

It all started in 2008 when the government decided cannabis was far more deadly than ever before, what with all these new “skunk” strains appearing, and reclassified it back up to Class B. Of course, because the cannabis was “much stronger” than in previous years (for more on why that’s total horse shit, read Bad Science), everyone who smokes it will get schizophrenia, or so Gordon “Golden” Brown would have us beleive. Actually, he just pulled that straight out of his arse. Prof. Nutt, et al., wise to this bullshittery, recommended against the reclassification and was ignored. More recently, Dave (I’m sure I can call him Dave) published a paper comparing the dangers of ecstasy with the dangers of horse riding, finding that horse riding was actually more dangerous – “Equasy – An overlooked addiction with implications for the current debate on drug harms” [pdf; 65 kb]. This wasn’t a piece of propaganda published by some idgit with an agenda; it was a paper in a peer-reveiwed journal, alongside other factually accurate and interesting publications – all Dave did was let the evidence speak for itself. Dave’s final piss-take of current policy came when he delivered a lecture on entitled “Estimating drug harms: a risky business?” [pdf; 366 kb], basically saying the same thing that this episode of Horizon says – heroin, cocaine, barbiturates and methadone are the only drugs more harmful than alcohol, while LSD, ecstasy and cannabis are all less harmful that both alcohol and tobacco. As a result, Alan Johnson, our beloved home secretary and ex-postman, has lost confidence in the advice given by Dave, with over 40 years of relevant scientific background in the subject. Here are my top quotes (and interpretations) from Alan “I’m a fucking moron” Johnson:

This was not about Prof Nutt’s views, which I respect though I don’t agree with them.

This means “I don’t understand the importance of evidence” or “I disagree with the evidence because it doesn’t support my conclusion”

You cannot have a chief adviser… campaigning against government

This means “We’re not willing to accept advice that goes against the political message we’re trying to send”

There are not many kids in my constituency in danger of falling off a horse – there are thousands at risk of being sucked into a world of hopeless despair through drug addiction.

This means “What goes on in my constituency is applicable to the entire country.”

More Dangerous Than Ecstasy

This last (and most recent quote) is my favourite. Not only does it show an unbelievable arrogance, it also shows a deep misunderstanding of either the research or his constituency. Horse riding kills more people than ecstasy – that’s a fact. Is he arguing that thousands of people are at risk from a hitherto-unheard-of ecstasy addiction? Bollocks!  Or is he perhaps saying that all drugs are a problem? In that case, the comparison to horse riding isn’t fair, since that only applies to ecstasy, not all drugs. Who’d have thought that one single sentence could make someone look so stupid? Oh, and one final point – what about cheap, legal alcohol? I wonder how many people in his constituency have been sucked into hopeless despair though alcohol addiction?

Why Dave Is In The Right

Firstly, the Code o’ Practice for Scientific Advisory Committees states:

Rules of conduct need not affect a member’s freedom to represent his or her field of expertise in a personal capacity. The committee’s rules however should generally oblige members to make clear when they are not speaking in their capacity as committee members.

Guess what – the lecture was given as the Professor of Neuropsychopharmacology at Imperial College, London, not as chairman of the ACMD. This was made perfectly clear. BAM! Next, the Misuse of Drugs act includes the following within the ACMD’s remit:

educating the public (and in particular the young) in the dangers of misusing such drugs and for giving publicity to those dangers

BOOM! If that includes setting the current drugs policy straight in order to better communicate the relative harms of illegal drugs, then well done Dave for doing the job you were hired to do!

The Resignations

So far, other than Dave, Dr Les King and Marrion Walker have resigned. Les is part-time advisor to the Department of Health, and was a senior chemist on the ACMD, who’s responsible for drafting the legislation I’ll talk about shortly. Marrion is the clinical director of Berkshire Healthcare NHS Foundation Trust’s substance misuse service and was the Royal Pharmaceutical Society’s representative on the ACMD. As you can imagine, the resignation of these key figures has been a massive blow to the ACMD’s future credibility.

With any luck, the rest of them will resign next Monday, and no other respectable scientist will take their place.

What YOU Can Do About It

Facebook has been the primary theatre of action in this conflict between reason and the idiot brigade in power. If you use Facebook, you might like to join the “Support and Reinstate Professor David Nutt: We want an evidence based drugs policy.” group, which has been set up by the Students for Sensible Drug Policy UK. There are tonnes of comments, discussion, links ‘n’ all that, and it’s currently just over 8600 members strong. Alan Johnson’s Facebook page was public until very recently. Last time I went on there, it was covered in comments informing him of his own stupidity.

There are also a couple of worthwhile petitions UK residents can sign:

• Reinstate Prof. David Nutt
• Evidence-based Drugs Policy

And finally, I’d suggest writing to your local MP. Obviously, an actual letter would carry more weight than an email, but if you’ve got 10 mins to spare, you can use the website WriteToThem to find your local MP and fire off an email. I sent one off yesterday and got an encouraging reply this morning. I copied one someone else wrote from that Facebook group above and edited a few bits here ‘n’ there, and if you do the same, please edit my letter before you send it – that website won’t send identical messages. Here’s what I wrote:

Dear Lynne Jones,

I am writing to express my disappointment at the recent sacking of Professor David Nutt, Chair of the Advisory Council on the Misuse of Drugs by the current Home Secretary, Alan Johnson.

It is the role and duty of a scientist to objectively determine truth and fact about the way in which the world works, and to present the evidence demonstrating those facts. Whether such facts are convenient, inconvenient, comfortable or uncomfortable or happen to contradict government policy is irrelevant. A scientist influenced by political expediency is not a scientist.

I fully understand that advisers advise and that ministers are responsible for decisions on policy, but the terms of reference of the Advisory Council on the Misuse of Drugs, as laid down in the Misuse of Drugs Act, 1971 include the following:

“educating the public (and in particular the young) in the dangers of misusing such drugs and for giving publicity to those dangers; ”

Professor Nutt has made public remarks about the relative risks of the use of substances currently illegal in the UK, comparing them to other legal substances and other common leisure pursuits. This fulfils the remit, quoted above, of ‘educating the public’, especially since the current drugs classification system does nothing to highlight the relative harms of illegal drugs.

In this case, the facts, as determined by the scientific method, may well cause many members of the public to question current Government policy. This is only right and proper in a democracy.

By asking Professor Nutt to stand down, the Home Secretary has sent a message that he finds it acceptable to disrupt the education of the public and that he is willing to suppress those who have a clear remit to present the public with facts in order to do this.

It is also worth noting that the document: “Putting Science and Engineering at the Heart of Government Policy: Government Response to the Innovation, Universities, Science and Skills Committee’s Eighth Report of Session 2008-09 – Science and Technology Committee ” states the following in Appendix One:

“SAC members should not be criticised for publishing scientific papers or making statements as professionals, independent of their role as Government advisers. (Paragraph 64)

“The Government agrees that the independence of science advisers is critical. It was precisely for this reason that the GCSA wrote to then-Home Secretary Jacqui Smith to express concern over her criticism, in Parliament, of Professor Nutt (Chairman of ACMD) with regard to an article he published in a peer-reviewed journal. ”

To my mind, the actions of the Home Secretary are undemocratic, dishonest, an attempted suppression of freedom of speech and a middle finger to anyone who understands and appreciates the scientific method.

Should not the Home Secretary now be considering his position?

I would be grateful for your thoughts.

Yours sincerely,
John Clarke

Here’s her reply:

I agree with you. When the issue if reclassifying cannabis back to class B in 2007, I tabled the following parliamentary motion:

EDM 209

RESPONDING TO THE DANGERS OF CANNABIS USE

That this House supports the mental health charity Rethink in its call for a public education campaign to convey the dangers of cannabis use; offers this support in light of the recent review of research published in the Lancet, which concludes that frequency of cannabis use increases the risk of psychotic illness such as schizophrenia by up to 40 per cent.; calls for clarity on the cannabis debate, particularly regarding the strength of skunk varieties of the drug; believes that reclassifying cannabis will not in itself lead to a decrease in the number of people who use it; notes that the proportion of young people using cannabis has actually fallen since it was reclassified in January 2004 from 25.3 per cent. of 16 to 24 year olds in 2003-04 to 20.9 per cent. in 2006-07; and urges the Government to commit to the development of a long-term awareness and information campaign with health promotion rather than a change in the law as the main lever to reduce use, in addition to funding research into the link between cannabis use and mental ill health.

If search under cannabis on my website, link below, you will find further information on my views and a report of a meeting of the All-Party Group on Mental Health on cannabis and schizophrenia.

I will pass on your comments to the Home Secretary to get his response.

Personally, as a former scientist myself, I despair at the selective use of science by colleagues from all parties and this latest example will no doubt give me further opportunities to raise my concerns. [My emphasis]

Regards

LYNNE JONES MP

House of Commons
London
SW1A 0AA

http://www.lynnejones.org.uk

That’s certainly much better than I’d have hoped!

Legal Highs ban

Next up is the BZP/GBL/Spice ban – here’s the proposal [pdf; 46 kb]. It looks like it goes into effect on December 23rd. I can’t give much more detail yet, since I’m not really a chemist, but it looks like all the decent smoking mixes will be gone by then. Better stock up before Christmas.

Post from: Synchronium

Nutt Sacked

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• Should Mephedrone Be Legal?
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• Nutt Sacked Episode III – Revenge Of The Schizoids
• Comments From Matt Bowden
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• Shock Horror! Clubs Protect Own Interests!
• Democracy In Action
• Can I Get High Legally?
• Educators Don’t Want To Listen
• Cannabis Reclassification

Nothing makes you want to drink more than already being pissed. “Yeah, sure *burp*, I’ll have one more. Actually *hic*, better make it four…” (Of course, by “you”, I actually mean the majority of the drinking population who don’t drink responsibly. If you eat beforehand, alternate between alcohol & soft drinks and stick to a predefined limit each night, then well done you, but read on anyway.) Unfortunately, legal highs don’t have that effect. Users tend to have a much better time without drinking. Either that, or the drink does nothing but give you a hangover, in the case of many legal stimulants.  This would seem to be the real reason behind this latest move against legal highs. Which, I suppose, is fine in principal (you wouldn’t expect to bring your £6 bottle of Tesco Value vodka into a club, would you?), but at least have the balls to admit it. Not coming clean makes them look far worse, because as we all know, alcohol is far more likely to kill you than most other drugs. Actually, I bet more people have died from seizures in clubs because of the loud music and lights than have died from legal highs.

Another reason in the same vein is that some clubs want to protect their illegal drugs trade too. It sounds a bit conspiracy theorist, I know, but some clubs definitely do have their own supply of illegal drugs. You’d think a bunch of geezers covered with bling that hang out by the fucking bar would get kicked out at the first sign of dealing, but every time I’ve been to this particular club, the same guys have been there, looking as shifty as they are reflective. In another club we go to quite a bit, I’ve actually seen first hand a drug dealer go up and ask a bouncer if he’s got any more pills, who then went to ask the guy behind the bar.

And now for a final twist in the story… These days, “pills” rarely contain any illegal drugs at all! That’s right. Thanks to the increasing popularity and availability of piperazines (such as the infamous BZP), acquiring a pill that contains any actual MDMA is nearly impossible. A popular favourite among dealers at the moment is a compound called mCPP (m-ChloroPhenylPiperazine), whose side effects include massive headaches and nausea. It’s about 5 times cheaper for a chemist to make mCPP than MDMA, as none of the precursors are restricted, so now about 50% of all the pills across Europe contain it. It seems this chemical alone is responsible for the tidal wave of sick that now flows from the toilets of decent clubs across the country.

Like I said, this move is acceptable in principle, but I wish they wouldn’t act like they’re doing everyone a favour. Next, they’ll take away our legal right to tap water in order to prevent that dreaded hyper-hydration.

Fortunately though, there’s always evangelical Christianity to turn to, as seen in this week’s episode of Christian Drum ‘n’ Bass:

Post from: Synchronium

Shock Horror! Clubs Protect Own Interests!

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• Nutt Sacked
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