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The ACMD's Mephedrone Report Part I

By John Clarke

MephedroneWhile we were away, what’s left of the ACMD fin­ished their report on mephed­rone and struc­tur­ally similar com­pounds — one of the final few hurdles before these research chem­icals get slapped upside the head with Alan “more insightful than science” Johnson’s banning stick.

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 ß-​​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 ß-​​carbon. Cath­inone pos­sesses a ketone oxygen at the ß-​​carbon; cath­inone can there­fore be con­sidered as the ‘ß-​​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) a-​​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 a and ß positions

(The generic cath­inone back­bone (see Figure 2) pos­sesses a chiral centre (the a-​​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 a-​​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 ß-​​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.

NameCommon nameR1R2R3R4
N,N-dimethylcathinone-MeMeMeH
Eth­cath­inone-MeEtHH
4-​​MethylmethcathinoneMephed­roneMeMeH4-​​Me
Bk-​​PMMAMethed­roneMeMeH4-​​MeO
4-​​FluoromethcathinoneFlephed­roneMeMeH4-​​F
3-​​Fluoromethcathinone-MeMeH3-​​F
bk-​​MDMAMethyloneMeMeH3,4-methylenedioxy
bk-​​MDEAEthyloneMeEtH3,4-methylenedioxy
bk-​​MBDBButyloneEtMeH3,4-methylenedioxy
Methyl­e­ne­di­oxypyro­va­leroneMDPV (cor­rected by me)n-​​Prpyrrolid­inyl3,4-methylenedioxy

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 a-​​pyrrolidinopropiophenone, one of a number of a-​​pyrrolidino cath­inones, is simply known as a-​​PPP. As a con­sequence of the ß-​​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 ß-​​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 ß-​​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

DopamineSero­toninNorad­ren­aline
Amphet­amine++++++++
MDMA++++++++
Cath­inone++++++++
Meth­cath­inone+++++++
Methylone+++++++++
Mephed­rone???

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*.

FRANK website visitsCath­inones% of visitsCan­nabis% of visitsCocaine% of visitsEcstasy% of visits
Sept-​​09 (page pub­lished 18÷09÷09)255,7659,3663.7%5818522.7%3692514.4%225418.8%
Oct-​​09376,75133,1678.8%7247019.2%4714012.5%357459.5%
Nov-​​09444,06947,95410.8%8024618.1%4848910.9%331677.5%
Dec-​​09314,23654,29917.3%5314116.9%3857012.3%286919.1%
Jan-​​10358,53766,23618.5%8198622.9%5373615.0%3791010.6%
Feb-​​10378,57680,96921.4%5131913.6%5373614.2%3802810.0%

*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

Number
January – March 20092
April – June 20090
July – September 20098
October – December 20095
January 2010 – 22nd Feb­ruary 201010

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

% present­a­tions (n=25)
Agit­a­tion52
Pal­pit­a­tions20
Seizure12
Vomiting12
Sweating12
Head­ache4
Dis­col­or­a­tion of the skin0
Cool peri­pheries0

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

% present­a­tions (n=25)
Tachy­cardia >100bpm48%
Tachy­cardia >140bpm16%
Hyper­ten­sion (>160mmHg)16%
GCS = 81516%
Bruxism4%
Hyper-​​reflexia4%

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

Modest severityMod­erate severityMost severe
Reduced appetiteInsomniaStrong desire to re-​​dose, craving to recap­ture initial euphoric rush
Dry mouthNausea (27%)*Uncom­fort­able changes in body tem­per­ature (sweating/​chills) (67%)*
Pupil dila­tionTrismus and BruxismIncreased blood pres­sure and heart rate, pal­pit­a­tions (43%)*
Unusual body sensationsSkin rashesserious vaso­con­stric­tion in extremities, cold or blue fingers (15%*)
Change in body tem­per­ature regulationNys­tagmus and dilated pupilshigh doses can cause hal­lu­cin­a­tions and psychosis
Pain and swelling in nose and throat, nose bleeds, sinus­itis (when insufflated)
Impaired short term memory, poor concentration
Dizzi­ness, light head­id­ness, vertigo (51%)*
Head­ache

*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

Modest to mod­erate severityMost severe
Increase in heart rate and blood pressureInsomnia
General change in con­scious­ness (as with most psychoactives)Hyper­thermia and sweating
Pupil dila­tion, can lead to blurred visionDizzi­ness, confusion
Dif­fi­culty in focusing, restlessnessDeper­son­al­iz­a­tion, hal­lu­cin­a­tions, para­noia, fear (with high doses)
Change in per­cep­tion of timeUnwanted life-​​changing spir­itual experiences
Slight increase in body temperatureGastrointest­inal dis­com­fort, nausea and vomiting
Muscle tension and achingSkin rashes common
Trismus and bruxismHangover may include exhaus­tion, depres­sion, dis­or­i­ent­a­tion, head­ache, amnesia

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© 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 ß-​​carbon of the phen­ethyl­amine back­bone (recall that the cath­inones all possess a ß-​​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

ACMD, 2009. MDMA (‘ecstasy’): a review of its harms and clas­si­fic­a­tion under the Misuse of Drugs Act 1971. ISBN 978−1−84726−868−6

ACMD, 2005. Methyl­amphet­amine Review.CairScotland, 2010. Report to the ACMD.

Cozzi, N.V., Sievert, M.K., Shulgin, A.T., Jac­o­bill, P. and Ruoho, A.E. (1999) Inhib­i­tion of plasma mem­brane monoamine trans­porters by beta-​​ketoamphetamines. European Journal of Phar­ma­co­logy. 381: 63 – 69.

Dal Cason, T.A., Young, R and Glennon R.A. (1997) Cath­inone: an invest­ig­a­tion of several N-​​alkyl and methyl­e­ne­dioxy sub­sti­tuted analogs. Phar­ma­co­logy Bio­chem­istry and Beha­vior. 58: 1109 – 1120

Druglink March/​April 2009. Mephed­rone: The future of drug dealing?

Druglink. January/​February 2010. Teenage Kicks. Vol 25. Issue 1.

Druglink. January/​February 2010. World Wired Web Vol 25. Issue 1. [Syn­chronium: This article quotes me. Woo!]

Feyissa, A.M. and Kelly, J.P. (2008) A review of the neuro­phar­ma­co­lo­gical prop­er­ties of khat. Pro­gress in Neuro-​​Psychopharmacology and Bio­lo­gical Psy­chi­atry. 32: 1147 – 1166.

Glennon, R.A., Yousif, M., Naiman, N. and Kaliz, P. (1987) Meth­cath­inone: a new and potent amphetamine-​​like agent. Phar­ma­co­logy Bio­chem­istry and Beha­vior. 26: 547 – 551.

The Guardian, (2009), Mephed­rone and the problem with ‘legal highs’, 5th December. Online at: http://​www​.guardian​.co​.uk/​s​o​c​i​e​t​y​/​2​0​0​9​/​d​e​c​/​0​5​/​m​e​p​h​e​d​r​o​n​e​-​p​r​o​b​l​e​m​-​l​e​g​a​l​-​h​i​ghs [accessed 30th March 2010]

Gust­affsson, D. and Escher, C. (2009) Mefedron. Inter­net­drog som tycks ha kommit för att stanna. (Mephed­rone — Internet drug that seems to have come to stay). Läkartid­ningen. 106: 2769 – 2771.

Hand, T., Rishiraj, A. (2009) Seizures of Drugs in England and Wales 200809. Home Office Stat­ist­ical Bul­letin 1609. London: Home Office.

Life­line. 2010. Mephed­rone Fre­quently Asked Ques­tions. www​.life​linepub​lic​a​tions​.org (publications@​lifeline.​org.​uk)

Linell, M. (2010) Case study: use of mephed­rone in a Northern Town. The Life­line project. Oral evid­ence to the ACMD.

McVean, C. (2009) The adverse effects of those “Legal High” powders con­taining cath­inone deriv­at­ives on the com­munity in Guernsey. States of Gurnsey, Customs and Immig­ra­tion Service.

McVean, C. (2010) The impact of cath­inones on a small island com­munity. States of Gurnsey, Customs and Immig­ra­tion Service.

Measham, F. and Moore, K. (2009) Rep­er­toires of Dis­tinc­tion: Exploring pat­terns of weekend poly­drug use within local leisure scenes across the English night time economy; Crim­in­o­logy and Crim­inal Justice, 9: 437 – 464.

Measham, F., Moore, K., New­combe, R. and Welch, Z. (2010) Tweaking, bombing, dabbing and stock­piling: the emer­gence of mephed­rone and the per­versity of pro­hib­i­tion. Drugs and Alcohol Today. 10: 14 – 21.

Meltzer, P.C., Butler, D., Deschamps, J.R. and Madras, B.K. (2006) (4-Methylphenyl)-2-pyrrolidin-1-yl-pentan-1-one (Pyro­va­lerone) ana­logues: a prom­ising class of monoamine uptake inhib­itors. Journal of Medi­cinal Chem­istry. 49: 1420 – 1432.

Nagai, F., Nonaka, R. and Kamimura, K.S.H. (2007) The effects of non-​​medically used drugs on monoamine neur­o­trans­mis­sion in rat brain. European Journal of Phar­ma­co­logy. 559: 132 – 137.

New­combe, R. (2010) Mephed­rone: the use of mephed­rone (m-​​cat, Meow) in Middles­brough. Manchester: Life­line Pub­lic­a­tions & Research.

New Musical Express (2010), Mephed­rone – How dan­gerous is the UK’s favourite new drug, 8th Feb­ruary. Online at: http://​www​.nme​.com/​b​l​o​g​/​i​n​d​e​x​.​p​h​p​?​b​l​o​g​=​1​0​&​a​m​p​;​p​=​7​9​5​6​&​a​m​p​;​m​o​r​e=1 [accessed 30th March 2010]

Ramsey, J. (2010) Ana­lysis of white powders seized by UK border agency at London Heathrow airport. Written evid­ence to the ACMD.

Serious Organ­ised Crime Agency (SOCA). (2010) Drugs report – Mephedrone.

Sumnall, H. and Wooding, O. (2009) Mephed­rone – an update on current know­ledge. North West Public Health Obser­vatory, Centre for Public Health, Liv­er­pool John Moores University.

Thomas, S. (2010) Enquiries relating to the cath­inones. National Poisons Inform­a­tion Service, Health Pro­tec­tion Agency. Oral evid­ence to the ACMD.

UK Border Agency (2010) UKBA – Treat­ment of cath­inones at the fron­tier. Written evid­ence to the ACMD.

White, M. (2010) Cath­inone Deriv­at­ives: Chem­istry, Pre­val­ence and Legal status. Forensic Science Service. Oral evid­ence to the ACMD.

Win­stock, A. (2010) Results of the 200910 Mixmag drug survey. Oral evid­ence to the ACMD.

World Health Organ­isa­tion (1995) WHO Expert Com­mittee on Drug Depend­ence. Twenty-​​ninth report. WHO Tech­nical Report Series. No.856.

Wood, D.M., Davies, S., Puchnarewicz, M., Button, J., Archer, R., Ramsey, J., Lee, T., Holt, DW. and Dargan, P.I. (2009) Recre­ational Use of 4-​​methylmethcathinone (4-​​MMC) presenting with sym­path­o­mi­metic tox­icity and con­firmed by tox­ic­o­lo­gical screening. Clin­ical Tox­ic­o­logy. 47: 733.

Zaitsu, K., Katagi, M., Kamata, H., Kamata, T., Shima, N., Miki, A., Tsuchi­hashi, H. and Mori, Y. (2009) Determ­in­a­tion of the meta­bol­ites of the new designer drugs bk-​​MBDB and bk-​​MDEA in human urine. Forensic Science Inter­na­tional. 188: 131 – 139.

7 Responses to The ACMD's Mephedrone Report Part I

  1. Jack says:

    I’m just going to start snorting rat poison and cut out the middle man…

  2. Sharon says:

    Another bril­liant post! You two are shit-​​hot at what you do x

  3. Sharon says:

    I love the way that this site allows you to think, for five mins or so, about what one has just written and enables editing. This is the classiest site in my inbox. I love it. When are you getting married?

  4. Sharon says:

    can I have a go of your rat poison Jack?

  5. MauiGreenDragon says:

    Thanks for a really well written and presented break­down con­cerning Mephed­rone and Cath­inone Deriv­at­ives. I think that it is important for these recom­mend­a­tions to control com­pounds be made public. The health of indi­viduals in any society is a very real and important.

    I find it ironic that natural plant sources that have already been sched­uled under “misuse of drugs” (DEA in USA) have lead to a barage of so called “legal highs” being created and sought after where demand is so high in direct rela­tion­ship to pro­hib­iting the natural compounds.

    It has just become so absurd to the point where the average person makes choices to use “com­pounds” that are not clin­ic­ally proven. It is almost like playing “Russian Roul­ette” with your life.

    Whereas, in a direct opposite cor­rel­a­tion, long standing tra­di­tional natural sources have been used by many cul­tures in very real everyday tra­di­tion mostly to the benefit of the group. The right to “freedom of reli­gious sac­ra­ments and expres­sion” and also the uses in a homeo­pathic way can be shown over and over in a wide cul­tural range dating back many millenia.

    So, is “pro­hib­i­tion” driving our society even faster at an alarming rate to “rat poison” altern­at­ives , where people are left wide open to pos­sible irre­vers­ible prob­lems and also death?

    I propose that this apparent race to create “out of control” altern­at­ives to natural botan­icals and herbals should be examined in depth before we find that all we have chosen to unwisely subject ourselves by choice to being “literal walking lab rats”! Be careful what you wish for as is often said.

    I per­son­ally was “pre­scribed” a legal RX from my Internal Medi­cine doctor. Which one? Buproprion. After about 4 months I sud­denly found the taste of “com­mer­cial” chem­ic­ally altered cigar­ettes (tabacum) to be the vilest thing I could pos­sibly inhale. That was 7 years ago and I haven’t pur­chased or smoked them ever since. So there is some value when sub­stances are pre­scribed and used prop­erly as dir­ected by a pro­fes­sional medical doctor.

    It is unfor­tu­nate that not everyone will take a mature and serious approach as to why they are needing to get “high” in the first place.

    I have come to the con­clu­sion that “social” drug use is some­thing “we” need to take respons­ib­ility for and work toward com­mu­nic­ating to ACMD or DEA or whatever agency to correct the wrongs that have been com­mitted from both sides. Any­thing is pos­sible when approached for the good of the whole society we live in and must protect.

  6. Emily says:

    Thanks for a really well written and presented break­down con­cerning Mephed­rone and Cath­inone Deriv­at­ives. I think that it is important for these recom­mend­a­tions to control com­pounds be made public. The health of indi­viduals in any society is a very real and important.

    I find it ironic that natural plant sources that have already been sched­uled under “misuse of drugs” (DEA in USA) have lead to a barage of so called “legal highs” being created and sought after where demand is so high in direct rela­tion­ship to pro­hib­iting the natural compounds.

    It has just become so absurd to the point where the average person makes choices to use “com­pounds” that are not clin­ic­ally proven. It is almost like playing “Russian Roul­ette” with your life.

    Whereas, in a direct opposite cor­rel­a­tion, long standing tra­di­tional natural sources have been used by many cul­tures in very real everyday tra­di­tion mostly to the benefit of the group. The right to “freedom of reli­gious sac­ra­ments and expres­sion” and also the uses in a homeo­pathic way can be shown over and over in a wide cul­tural range dating back many millenia.

    So, is “pro­hib­i­tion” driving our society even faster at an alarming rate to “rat poison” altern­at­ives , where people are left wide open to pos­sible irre­vers­ible prob­lems and also death?

    I propose that this apparent race to create “out of control” altern­at­ives to natural botan­icals and herbals should be examined in depth before we find that all we have chosen to unwisely subject ourselves by choice to being “literal walking lab rats”! Be careful what you wish for as is often said.

    I per­son­ally was “pre­scribed” a legal RX from my Internal Medi­cine doctor. Which one? Buproprion. After about 4 months I sud­denly found the taste of “com­mer­cial” chem­ic­ally altered cigar­ettes (tabacum) to be the vilest thing I could pos­sibly inhale. That was 7 years ago and I haven’t pur­chased or smoked them ever since. So there is some value when sub­stances are pre­scribed and used prop­erly as dir­ected by a pro­fes­sional medical doctor.

    It is unfor­tu­nate that not everyone will take a mature and serious approach as to why they are needing to get “high” in the first place.

    I have come to the con­clu­sion that “social” drug use is some­thing “we” need to take respons­ib­ility for and work toward com­mu­nic­ating to ACMD or DEA or whatever agency to correct the wrongs that have been com­mitted from both sides. Any­thing is pos­sible when approached for the good of the whole society we live in and must protect.

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