Sunday, 23rd April 2017

Cathinones

Mephedrone


Mephedrone (4-methylmethcathinone) is a derivative of Cathinone, which is one of a number of alkaloids which can be extracted from the (fresh) leaves of Catha edulis (khat), a plant widely-used as a traditional stimulant in Somali and Yemeni communities.

Cathinones are structurally similar to amphetamines with a ketone oxygen at the b-carbon atom, other cathinone derivatives include Methedrone (4-methoxymethcathinone), and Methylone (3-4-methylenedioxymethcathinone)[i].  Mephedrone and related methcathinone derivatives were not controlled in the UK until 16th April 2010 from which point they were classified as Class B controlled drugs.

 

The generic definition of cathinones recommended by the ACMD is:

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,


(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.”

 

Mephedrone generally appears in the UK in powder form as the hydrochloride sale, ranging from white to brown in colour.  Prior to the ban internet sites advertised the drug as 95%-99% pure and analyses generally confirmed the powders to be of high purity[ii], although some samples contained adulterants such as benzocaine, lignocaine, paracetamol and caffeine (similar to adulterants found in cocaine powders) or other controlled drugs (amphetamoine, cocaine, ketamine or BZP), 4% of seizures were in tablet form[iii].  Since the ban was introduced users report the quality to have fallen – 90% of Mixmag respondents in 2011[iv] reported pre-ban purities to be excellent (60%) or good (30%) and 10% fair or poor, after the ban only 7% reported excellent and 32% good, with a majority (61%) reporting purities only as ‘fair’ (35%) or ‘poor’ (25%).

 

Prevalence & Patterns of Use

In the UK data from UK-origin Google searches and visits to the Government’s ‘Frank’ website suggest the drug to have become widely available in the autumn of 2009[v], this is confirmed via user interviews[vi]. Several commentators have attributed the dramatic rise in popularity of mephedrone to the lack of, or very poor quality of, street level cocaine[vii].

 

Winstock et al[viii], writing in March 2010, noted “mephedrone is an unknown quantity in terms of harms, risks, and dose related effects; we know nothing of its potential neurotoxicity or the long term consequences of its use.” noting ” On online forums, users report experiencing rashes, cold blue fingers and toes (perhaps related to peripheral vasoconstriction), and, in the days after use, typical stimulant comedown symptoms such as lethargy and low mood.”

 

Newcombe[ix] interviewed 10x regular mephedrone users in Middlesbrough in late 2009, finding users would rapidly increase the dose, sometimes during the first session, from around 50-75mg initially to 125-200mg with some users repeating the dose every 1-2 hours, with one user stating he got through 4 grams in a single night and a couple stating they had used 10g together over the course of a weekend.  He found regular weekend use to be the norm.  Although none of his subjects claimed to use daily, half reported friends who had developed a habit “evidenced by consumption factors like daily use and heavy use; by psychological indicators like craving and tolerance; and by behavioural indicators like taking mephedrone to the exclusion of other activities, continuing regular use despite health problems like skin rashes, and being “off their heads all the time”


In early 2010 the UK dance music Mixmag[x] reported that 41.7% of their online survey respondents reported having tried mephedrone, 33.6% in the previous month making it the fourth most commonly used drug behind cannabis, ecstasy and cocaine.  Based on this sample, Winstock et al[xi] reported “Users were typically younger (P<0.001) and male (P<0.01); 15.1% reported using weekly or more frequently; 49.5% reported using between 0.5 and 1g during a typical session; 69.5% reported that intranasal use was the most common route of use. Intranasal use was associated with increased abuse liability; 54.6% of those who have also used cocaine reported that the quality of the high obtained with mephedrone was better, with those using intranasally being significantly more likely than those who took the drug orally to report that mephedrone was more addictive (P<0.02) and more risky (P<0.02) than cocaine. Route of use was unrelated to any stimulant-related adverse effect apart from palpitations (P<0.005).” The 2011 Mixmag survey[xii] found the lifetime prevalence of mephedrone use to have increased to 61%,  with 51% reporting use in the past year and 25% in the past month, with 75% of those who had ever tried it reported having used it since the ban was introduced on 16-4-10.  Mephedrone was the drug causing users most concern in friends (24%), with 23% of cases where medical help was sought attributed to Mephedrone.

 

IDMU conduct large-scale annual surveys of drug users recruited via pop-festivals and the internet.  The 2009 IDMU surveys found no instances of mephedrone use being reported under the write-in ‘other drug’ options, from which decisions on inclusions of named drugs in future surveys were taken, in the 2010 festival survey (n=645) which went to print before mephedrone use had been widely-reported 7/13 of the write-in options were for mephedrone, with an average user rating of 7.67/10.  The 2010 IDMU web-survey (n=1806) included mephedrone in the named drug options, 20% of respondents reported having used the drug (17.8% of females, 24.4% of males), the vast majority reporting experimental or occasional use, with 3% of respondents reporting regular or daily use.  User ratings predicted frequency and likelihood of use, current users gave average ratings of 5.46 whereas those who had never used or who had stopped using gave average ratings of 2.95, with all four daily users giving the drug the maximum rating of 10/10.

 

Table 1 – Mephedrone – Frequency of Use & User Ratings

Frequency

n

% of total

% of ever used

Average Rating

Experimental

142

7.9%

39.2%

4.12

Occasional

74

4.1%

20.4%

6.49

Regular

47

2.6%

13.0%

7.26

Daily

4

0.2%

1.1%

10.0

Stopped Using

95

5.3%

26.2%

3.68

Never Used

593

32.8%

 

2.34

Blank

851

47.1%

 

3.41

Base

1806

100.0%

 

3.38

Total Ever

362

20.0%

100.0%

5.00

Dosages Used

James et al[xiii] reported “The median mephedrone dose reported was 1 g for both telephone enquiries (n=30) and TOXBASE reports (n=8)”  Winstock et al[xiv] reported “49.5% reported using between 0.5 and 1g during a typical session” Newcombe[xv] reported “users would rapidly increase the dose, sometimes during the first session, from around 50-75mg initially to 125-200mg with some users repeating the dose every 1-2 hours, with one user stating he got through 4 grams in a single night and a couple stating they had used 10g together over the course of a weekend”  The Advisory Council on the Misuse of Drugs reported “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.”

 

A users forum reporting side-effects[xvi] collected information on dosage in 71x cases, the percentile data was as follows, with comparable figures from the 2010 IDMU web-survey based on purchase frequencies and quantities:

 

Table 2 – Mephedrone Usage Percentiles

Percentile

Forum Dosages

IDMU Weekly

IDMU Daily

Minimum

0.05g

.092g

.013g

Lower 10%

0.125g

.231g

.033g

Lower 25%

0.30g

.231g

.033g

Median

0.45g

.923g

.131g

Upper 25%

1.0g

2.31g

.328g

Upper 10%

2.0g

10.15g

1.44g

Upper 5%

7.0g

20.77g

2.95g

Maximum

10.0g

50.77g

7.21g

Mean

1.17g

4.41g

0.626g

 

The heaviest levels of use reported were in the region of 10g over a weekend (3-4g per day), some of the top-2-3% of IDMU respondents were clearly buying to sell on to friends or customers.

 

Effects of Mephedrone

Mephedrone is a stimulant drug chemically related to amphetamine and ecstasy-type drugs, the desired effects being increased energy and alertness. In February 2010 IDMU received two enquiries about mephedrone, one from Durham Police the other from a head teacher, at which point only the Gustavson paper[xvii] had been published.

 

User-Reports:

A drug users forum[xviii] had cited 73x user reports of side-effects between Dec 2007 and Sept 2009 (table 3), drug cravings, anxiety, insomnia and paranoia were the most common psychological reactions and the most common physical effects were jaw-clenching and other muscular effects, excessive heart rate/palpitations and pupil dilation and disorders of body temperature, sweating, skin colour and urination.  There were 3x reports of aggression or extreme agitation and two of seizures.

 

Table 3 – Incidence of Mephedrone Side Effects from Drug Users Forum

Symptom

n

Symptom

n

Symptom

n

Drug Cravings

26

Depression

7

Dizziness

3

Jaw Effects (Bruxism)

22

Local Pain/Ulceration

6

Aggression/antisocial

3

Heart racing/chest pain/palpitations

17

Cognitive Impairment/Confusion

6

Headache

3

Insomnia

16

Breathing difficulties

6

Tinnitus

2

Muscle Cramps or spasms

15

Anorexia

5

Memory Problems

2

Paranoia

14

Dry Mouth

5

Seizures

2

Pupil dilation/blurred vision

14

Sex Dysfunction/Genital problems

5

Radical Crash/Withdrawal

2

Excessive/odoured Sweat

12

Fatigue

5

Hallucinations

2

Skin Blotching/Bluing

11

Aphrodisiac

4

Dehydration

1

Body Temperature

11

Numbness

4

Swollen Throat/Choking

1

Anxiety

8

Nausea/Vomit

4

Diarrhoea

1

Urine Problems (excess/inability/odour)

8

Vivid Dreams

4

 

 

 

Although the forum stopped collating data after September 2009, a thread seeking experiences[xix], presumably upon which the database was based, had received 543x posts between 4-12-07 and 4-3-11.  Several subsequently published papers clearly relied on the information from this forum.

 

Mixmag respondents in 2010 reported a range of side-effects, mild effects included reduced appetite, dry mouth, pupil dilation, changes in body temperature & unusual body sensations, moderate effects included insomnia, nausea (27%), trismus & bruxism, skin rashes, nystagmus, pain & swelling/bleeding in nose and throat (when snorted), impaired short-term memory, poor concentration, dizziness, lightheadedness, vertigo (51%), headache.  Severe symptoms included strong cravings for the drug including re-dosing, sweating/chills (67%), increased blood pressure/heart rate/palpitations (43%), serious vasoconstriction in extremities e.g. cold/blue fingers (15%), and hallucinations & psychosis with high doses[xx].

 

Academic Studies:

In a survey of 1006 Scottish school, college and university students, Dargan et al[xxi] found “205 (20.3%) reported previous use of mephedrone; 23.4% reported using only using mephedrone on one occasion previously, although 4.4% reported daily use. A total of 56% of those who had used mephedrone, reported at least one unwanted effect associated with its use. A total of 17.6% of users reported 'addiction or dependence' symptoms associated with their mephedrone use.

 

McElrath & O’Neill[xxii] interviewed 23x mephedrone users in the UK shortly after the ban, of whom 20 had used the drug since the ban, finding “Most respondents reported positive experiences with mephedrone, and for some, the substance emerged as a drug of choice. None of the respondents reported that the once-legal status of mephedrone implied that it was safe to use. Very few respondents reported purchasing mephedrone from street-based or on-line headshops during the pre-ban period, and these decisions were guided in part by respondents' attempts to avoid "drug user" identities. Most respondents purchased or obtained mephedrone from friends or dealers, and mephedrone was widely available during the 10-week period following the ban. Respondents reported a greater reliance on dealers and a change in mephedrone packaging following the criminalisation of mephedrone.”

 

Noting that some ‘ecstasy’ tablets sold in the Netherlands were found to contain between 96mg and 155mg mephedrone, Brunt et al[xxiii] gathered information on the acute subjective effects of mephedrone from 70 regular ecstasy users, finding “Overall, the majority of users considered the effects enjoyable. Mephedrone seemed to evoke effects similar to other amphetamine type psychostimulants, including MDMA. In contrast to MDMA, however, mephedrone induced strong feelings of craving in most users.”  In France, Debruyne et al[xxiv] reported “Users report positive euphoric and entactogenic effects. They also describe negative effects such as increased dependence towards the drug itself and larger craving for tobacco and alcohol. The numerous and various described adverse effects include psychoactive, digestive, cardiovascular... effects. Some fatality cases have been reported in scientific literature or in press and attributed to mephedrone often in association with other substances.” In Greece, Vardakou et al[xxv] concluded “Use of mephedrone is mainly a youth phenomenon. The hazardous side-effects are strong desire to re-dose, uncomfortable changes in body temperature and heart rate, hallucinations and psychosis.”

 

Case studies and hospital admissions:

Wood et al[xxvi] reported the case of a 22 year old male who had purchased 4g of the drug over the internet, noting “He initially ingested 200 mg of the mephedrone orally, with no perceived clinical effects, and thereafter injected the remaining 3.8 g intramuscularly into his thighs. Shortly after the injection, he developed palpitations, "blurred tunnel vision," chest pressure, and sweating and felt generally unwell; he presented to hospital with continuing features of sympathomimetic toxicity” Wood et al[xxvii] reported 15x emergency admissions following self-reported mephedrone use, noting “Significant clinical features seen included agitation in 53.3%, tachycardia in 40%, systolic hypertension in 20% and seizures in 20%. Twenty per cent required treatment with benzodiazepines, predominantly for management of agitation. All patients were discharged with no sequelae. Previous user reports have suggested that mephedrone use is associated with cool/blue peripheries; this was not seen in any of the patients in our series.”  In a further study with toxicological confirmation of mephedrone, Wood et al[xxviii] reported “Acute mephedrone-related toxicity was analytically confirmed in seven male patients; the mean ± SD age was 24.6 ± 6.5 years (range 16-36 years). Agitation (four patients) was the most common symptom/sign reported; other common symptoms/signs included: palpitations (two patients); chest pain (two patients); self-limiting pre-hospital seizures (one patient) and headaches (one patient). The mean heart rate was 109.1 ± 21.8 (range 80-140) beats per minute; one patient had a "severe" tachycardia (heart rate of ≥ 140 bpm). The mean systolic blood pressure was 153.0 ± 39.6 (range 110-210) mmHg; three patients had clinically significant hypertension (systolic blood pressure ≥ 160 mmHg)… These analytically confirmed acute mephedrone toxicity presentations had clinical features of toxicity consistent with an acute sympathomimetic toxidrome (e.g. hypertension, tachycardia and agitation). These findings are similar to the pattern of toxicity seen with other sympathomimetic recreational drugs such as 3,4-Methylenedioxymethamphetamine (MDMA) and cocaine.”

 

Dargan & Wood[xxix] reported 25x cases of mephedrone toxicity from a London hospital, finding agitation (52%), palpitations (20%), seizure, vomiting, sweating (12% each), headache (4%) but no reports of skin discolouration or cool peripheries.  40% of patients had tachycardia over 100bpm, 16% over 140bpm with a similar number with hypertension (>160mmHg) or with coma-type symptoms (GCS≤8/15), one case each presented with bruxism (jaw-clenching) and hyperreflexia.  Nicholson et al[xxx] reported a case of acute myocarditis following mephedrone use.

 

James et al[xxxi] of the National Poisons Information Service reported “In 131 telephone enquiries concerning mephedrone, alone or in combination with alcohol, common clinical features reported included agitation or aggression (n=32, 24%, 95% CI 18% to 33%), tachycardia (n=29, 22%, 95% CI 16% to 30%), confusion or psychosis (n=18, 14%, 95% CI 9% to 21%), chest pain (n=17, 13%, 95% CI 8% to 20%), nausea (n=15, 11%, 95% CI 7% to 18%), palpitations (n=14, 11%, 95% CI 6% to 18%), peripheral vasoconstriction (n=10, 8%, 95% CI 4% to 14%) and headache (n=7, 5%, 95% CI 2% to 11%). Convulsions were reported in four cases (3%, 95% CI 1% to 8%). One exposed person died following cardiac arrest (1%, 95% CI 0% to 4%), although subsequent investigation suggested that mephedrone was not responsible.” They found that in 45% of phone enquiries adverse effects persisted beyond 24hours after last use, and in 30% effects persisted for in excess of 48 hours. They commented: “The occurrence of severe features including hallucinations, chest pains and convulsions is of particular concern. The reported episode of apparent myocardial infarction is of interest; it is not possible to demonstrate causality from this single report, but an increased risk of myocardial infarction has been reported in users of khat[xxxii]. Other effects such as confusion, fever or myoclonus may reflect serotoninergic actions of the drug. “


Fatalities:

Gustavsson & Escher[xxxiii] first reported problems with Mephedrone in October 2009 including suspected death of an 18 year old girl in Sweden The woman was observed to first become sick and then unconscious. Forensic autopsy showed severe brain swelling, preceded by respiratory and circulatory arrest.  Dickson et al[xxxiv] reported a suspected mephedrone-related fatality: “A 22-year-old Caucasian male was found unresponsive in his living quarters and was transported to the hospital where he died… Mephedrone was confirmed in the decedent's blood and urine at 0.50 and 198 mg/L, respectively... because of its structural similarities with methcathinone and the high concentration in the decedent's blood, the overall contribution of mephedrone to the death could not be minimized.”  Torrance et al[xxxv] reported detection of Mephedrone in 4x fatalities in Scotland.  In the Netherlands, Lusthof et al[xxxvi] reported the case of “A 36-year old man, having injured himself severely by smashing windows in a rage of fury, was arrested by the police. He died despite resuscitation attempts. The forensic autopsy showed many superficial skin lacerations, bruises and minor brain swelling, but there was no definitive cause of death. Toxicological analysis showed a high concentration of mephedrone in femoral blood (5.1mg/L) and traces of cocaine, MDMA and oxazepam. The remaining dose of mephedrone in the stomach contents was estimated at 113mg. Tablets that were found in the house of the deceased also contained mephedrone. We attribute this man's death to a fatal oral intake of mephedrone, which probably led to a state of excited delirium.”


Reviews:

Schifano et al[xxxvii] reported mephedrone “elicits stimulant and empathogenic effects similar to amphetamine, methylamphetamine, cocaine and MDMA. Due to its sympathomimetic actions, mephedrone may be associated with a number of both physical and psychopathological side effects. Recent preliminary analysis of recent UK data carried out in 48 related cases have provided positive results for the presence of mephedrone at postmortem.”  Following a review of mephedrone-related hospital admissions in Aberdeen, Regan et al[xxxviii] concluded “A profile of largely psychoactive and cardiovascular toxicity is described with drug naivety perhaps explaining the high rates of bingeing and addiction reported

 

Thomas[xxxix] reported “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

 

Mephedrone Summary

Usage:

Users of Mephedrone vary from around one line per month to around 3-4 grams per day of high-purity powder, most commonly snorted or ‘bombed’ (taken orally wrapped in e.g. cigarette paper).  Typical usage by a regular user would be 500mg-1 gram over a session.  A high proportion of users report cravings and tolerance to the effects appears to develop rapidly leading to rapid increases in the amount used and a tendency to repeat the dose at regular intervals.  Lower purity powders now appear more common either sold as Mephedrone or potentially as cocaine (if cut with benzocaine/lignocaine which mimic the numbing effect of cocaine on the oral/nasal mucosae).  The drug appeared suddenly and use of it rapidly became widespread in the UK in late 2009-2010, coinciding with a doubling of wholesale cocaine prices and a dramatic fall in cocaine purities.  As a new drug, users were in the dark as to what was an appropriate dosage and a number of cases of overdose have been reported.

 

Effects:

The effects of mephedrone are similar to those of other stimulants, including euphoria, self-confidence and mental stimulation as desired effects, and with cardiovascular stimulation (raised heart-rate and blood-pressure) the most significant health risks, with reports of seizures and deaths attributed to the drug.  Other common physical effects include bruxism (jaw-clenching), muscle cramps and circulatory problems leading to skin discolouration.

Psychological effects of the drug commonly reported include anxiety, paranoia, insomnia and depression, the most commonly reported effect being drug cravings.  There are also reports of confusion and memory problems as well as psychotic behaviour, aggression and hallucinations.  The pattern of mental effects is broadly consistent with those of other stimulants (e.g. amphetamine or cocaine) where excessive (relative to a user’s tolerance level) or prolonged use is associated with psychosis and unprovoked violent outbursts or assaults.


[i] Advisory Council on the Misuse of Drugs [2010]. Consideration of the cathinones. 31 Mar 2010. http://drugs.homeoffice.gov.uk/publication-search/acmd/ACMD-cathinones-report.html

[ii] Gibbons S, Zloh M. [2010] An analysis of the 'legal high' mephedrone. Bioorg Med Chem Lett. 20(14):4135-9

[iii] Advisory Council on the Misuse of Drugs [2010]. Consideration of the cathinones. 31 Mar 2010. http://drugs.homeoffice.gov.uk/publication-search/acmd/ACMD-cathinones-report.html

[iv] Winstock AR, Mitcheson L [2011] The annual Mixmag drugs survey 2011. Mixmag March 2011

[v] Advisory Council on the Misuse of Drugs [2010]. Consideration of the cathinones. 31 Mar 2010. http://drugs.homeoffice.gov.uk/publication-search/acmd/ACMD-cathinones-report.html

[vi] Newcombe R. [2009] Mephedrone: use of mephedrone (M-cat, Meow) in Middlesbrough. Lifeline Publications.

[vii] 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.

[viii] Winstock A, Marsden J, Mitcheson L [2010] What should be done about mephedrone? BMJ 340:c1605

[ix] Newcombe R. [2009] Mephedrone: use of mephedrone (M-cat, Meow) in Middlesbrough. Lifeline Publications.

[x] Winstock AR, Mitcheson L [2010] The annual Mixmag drugs survey 2010. www.menincarter.net/mixmag/. Mixmag February 2010

[xi] Winstock AR, Mitcheson LR, Deluca P, Davey Z, Corazza O, Schifano F. [2011] Mephedrone, new kid for the chop? Addiction. 2011 Jan;106(1):154-61 Epub 2010 Aug 23

[xii] Winstock AR, Mitcheson L [2011] The annual Mixmag drugs survey 2011. Mixmag March 2011

[xiii] James D, Adams RD, Spears R, Cooper G, Lupton DJ, Thompson JP, Thomas SH; on behalf of the National Poisons Information Service. [2010]  Clinical characteristics of mephedrone toxicity reported to the UK National Poisons Information Service. Emerg Med J. 2010 Aug 25. [Epub ahead of print]

[xiv] Winstock AR, Mitcheson LR, Deluca P, Davey Z, Corazza O, Schifano F. [2011] Mephedrone, new kid for the chop? Addiction. 2011 Jan;106(1):154-61 Epub 2010 Aug 23

[xv] Newcombe R. [2009] Mephedrone: use of mephedrone (M-cat, Meow) in Middlesbrough. Lifeline Publications.

[xvi] Mephedrone Side-Effects Database - http://www.drugs-forum.com/forum/showthread.php?t=97246

[xvii] Gustavsson D, Escher C. [2009] [Mephedrone--Internet drug which seems to have come and stay. Fatal cases in Sweden have drawn attention to previously unknown substance].[Article in Swedish] Lakartidningen. 106(43):2769-71.

[xviii] Mephedrone Side-Effects Database - http://www.drugs-forum.com/forum/showthread.php?t=97246

[xix] Mephedrone (4-methylmethcathinone, 4-MMC) Experiences - http://www.drugs-forum.com/forum/showthread.php?t=43273

[xx] Advisory Council on the Misuse of Drugs [2010]. Consideration of the cathinones. 31 Mar 2010. http://drugs.homeoffice.gov.uk/publication-search/acmd/ACMD-cathinones-report.html

[xxi] Dargan PI, Albert S, Wood DM. [2010] Mephedrone use and associated adverse effects in school and college/university students before the UK legislation change. QJM. 103(11):875-9

[xxii] McElrath K, O'Neill C. [2011] Experiences with mephedrone pre- and post-legislative controls: Perceptions of safety and sources of supply. Int J Drug Policy. 2011 Jan 15. [Epub ahead of print]

[xxiii] Brunt TM, Poortman A, Niesink RJ, van den Brink W. [2010] Instability of the ecstasy market and a new kid on the block: mephedrone. J Psychopharmacol. 2010 Sep 8. [Epub ahead of print]

[xxiv] Debruyne D, Courné MA, Le Boisselier R, Djezzar S, Gérardin M, Boucher A, Karila L, Coquerel A, Mallaret M. [2010] [Mephedrone: a Designer Drug of Recent Use in France.] [Article in French] Therapie. 65(6):519-524

[xxv] Vardakou I, Pistos C, Spiliopoulou Ch. [2011] Drugs for youth via Internet and the example of mephedrone. Toxicol Lett. 201(3):191-5

[xxvi] Wood DM, Davies S, Puchnarewicz M, Button J, Archer R, Ovaska H, Ramsey J, Lee T, Holt DW, Dargan PI. [2010] Recreational use of mephedrone (4-methylmethcathinone, 4-MMC) with associated sympathomimetic toxicity. J Med Toxicol. 6(3):327-30

[xxvii] Wood DM, Greene SL, Dargan PI. [2010] Clinical pattern of toxicity associated with the novel synthetic cathinone mephedrone. Emerg Med J. 2010 Jun 26. [Epub ahead of print]

[xxviii] Wood DM, Davies S, Greene SL, Button J, Holt DW, Ramsey J, Dargan PI. [2010] Case series of individuals with analytically confirmed acute mephedrone toxicity. Clin Toxicol (Phila). 48(9):924-7.

[xxix] Dargan PI, Wood DM [2010] Personal communication in evidence to ACMD, cited in: Advisory Council on the Misuse of Drugs [2010]. Consideration of the cathinones. 31 Mar 2010

[xxx] Nicholson PJ, Quinn MJ, Dodd JD. [2010] Headshop heartache: acute mephedrone 'meow' myocarditis. Heart. 96(24):2051-2

[xxxi] James D, Adams RD, Spears R, Cooper G, Lupton DJ, Thompson JP, Thomas SH; on behalf of the National Poisons Information Service. [2010]  Clinical characteristics of mephedrone toxicity reported to the UK National Poisons Information Service. Emerg Med J. 2010 Aug 25. [Epub ahead of print]

[xxxii] Al-Motarreb A, Briancon S, Al-Jaber N, et al. [2005] Khat checwing is a risk factor for acute myocardial infarction: a case-control study. Br J Clin Pharmacol 59:574–81

[xxxiii] Gustavsson D, Escher C. [2009] [Mephedrone--Internet drug which seems to have come and stay. Fatal cases in Sweden have drawn attention to previously unknown substance].[Article in Swedish] Lakartidningen. 106(43):2769-71.

[xxxiv] Dickson AJ, Vorce SP, Levine B, Past MR. [2010] Multiple-drug toxicity caused by the coadministration of 4-methylmethcathinone (mephedrone) and heroin. J Anal Toxicol. 2010;34(3):162-8.

[xxxv] Torrance H, Cooper G. [2010] The detection of mephedrone (4-methylmethcathinone) in 4 fatalities in Scotland. Forensic Sci Int. 202(1-3):e62-3.

[xxxvi] Lusthof KJ, Oosting R, Maes A, Verschraagen M, Dijkhuizen A, Sprong AG. [2011] A case of extreme agitation and death after the use of mephedrone in The Netherlands. Forensic Sci Int. 2011 Jan 10. [Epub ahead of print]

[xxxvii] Schifano F, Albanese A, Fergus S, Stair JL, Deluca P, Corazza O, Davey Z, Corkery J, Siemann H, Scherbaum N, Farre' M, Torrens M, Demetrovics Z, Ghodse AH; Psychonaut Web Mapping; ReDNet Research Groups. [2010] Psychopharmacology (Berl). 2010 Nov 12. [Epub ahead of print]

[xxxviii] Regan L, Mitchelson M, Macdonald C. [2010] Mephedrone toxicity in a Scottish emergency department. Emerg Med J. 2010 Dec 23. [Epub ahead of print]

[xxxix] Thomas, S. (2010) Enquiries relating to the cathinones. National Poisons Information Service, Health Protection Agency. Oral evidence to the ACMD, cited in: Advisory Council on the Misuse of Drugs [2010]. Consideration of the Cathinones. 31 Mar 2010