Recreational Mephedrone Brief (8/18/10)

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The recreational drug 4-methylmethcathinone (4-MMC; aka mephedrone, MMCAT) was legal in the UK up until mid April of this year. I had previously covered the only work in a behaving animal model that I could find, a paper using drug-discrimination techniques to evaluate the discriminative stimulus (aka, subjective) properties of several cathinone derivative compounds (but not 4-MMC) in comparison with amphetamine and MDMA. In a subsequent post I mentioned what appears to be the first well characterized death of someone due to 4-MMC, the relative dearth of scientific evidence about this compound and speculated on what I'd like to see happen if I were a Program Officer in NIDA.

I was very interested to see news accounts that investigators at John Moores University in Liverpool were going to start some laboratory studies in human volunteers. It really is unfortunate that we know very little about cathinones at all and essentially zero about 4-MMC, particularly when you compare it to research on the amphetamine class derivative compounds that are in recreational use. By the news account the JMU study was approved by the local IRB and it appeared to be heading into standard territory for looking at the subjective/affective, cognitive and physiological reactions to a drug in human subjects.

The public health department at JMU has won "ethical approval" to begin researching the drug with the help of students determined to get their weekend thrills.
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While getting "high", they will be questioned by university academics throughout the night about their different states of consciousness. Tests will study their thoughts and ability to think coherently, as they are asked to describe how they feel on an "adjective bar", with "sad" or "depressed" at the bottom and "euphoric" or "very happy' at the top. Further tests include matching objects to numbers and being asked to recall logical sequences.

Well, plans have changed. A piece in click Liverpool reports

A study testing the effects of the controversial deadly drug mephedrone has been scrapped by a Liverpool university.

Liverpool John Moores University (JMU) were given the green light to research the one-time legal high after the project initially raised eyebrows in March.

Scientists planned to monitor the effects of the white powder also known as "Mcat" or "Miaow Miaow", which became popular among party-goers.

But now after months of deliberation, the university has cancelled its research following several casualties since the plant food hit shelves across the country.

A spokeswoman said: "This particular research project at the School of Natural Sciences and Psychology was discontinued following the change in the legal status of mephedrone.

Bummer. Far be it from me to question the actions of an IRB but given that the Swedish fatality occurred in late 2008 and the link to 4-MMC was clear by fall of 2009, well, I'm not certain I see where the risk/benefit has changed. Lots more people were taking it by early 2010 so the identification of a few more fatalities that were linked to 4-MMC shouldn't really change the odds. Oh well, perhaps the JMU IRB simply overlooked the Swedish death or something.

There is one minor bit of hope for those of us that want to see some research data become available.
"However, a team at the School of Pharmacy and Bimolecular Sciences is continuing its own area of research into the damaging effects of this drug."

They don't specify but I'm thinking that perhaps this means animal studies are ongoing. So we should see at least something out of this University over the next year, hopefully.

If, and admittedly this is an assumption, the JMU IRB got cold feet over reports of fatalities in the popular press, this turns our attention back to the tox reports. In the case of MDMA (see prior link) we often resort to the Case Report literature for additional clues as to the likely causal role of the recreational drug in medical emergency and fatality. I have on offer one such report for 4-MMC that has just popped up in pre-publication form.

ResearchBlogging.orgA Letter to the Editor published in Forensic Science International by Torrance and Cooper presents an analysis of blood levels of 4-methylmethcathinone in four fatalities. This is not a full Case Report so the details are a bit sketchy. The main point seems to be identifying the presence of 4-MMC and the levels observed (22, 3.3, 5.1 and 1.2 mg/L). The authors do make clear that in only two of the four cases was 4-MMC identifed by the medical examiner as being causal in the death of the decedent. The first two cases involved suspicion of 4-MMC/mephedrone from presentation. It doesn't specify but presumably friends or acquaintances of the victims identified drug taking in the interval immediately prior to the death. In the two other cases 4-MMC was not suspected or causal (one case involved an abdominal stabbing, the other is unspecified) but rather was identified in the victim via tox screening.

So the main result from this paper is the identification of a range of blood levels of 4-MMC that might be associated with fatality (3.3-22 mg/L) and the mention of the presence of other drugs

Case1 had less than 0.1mg/L of diazepam and nordiazepam and 0.34mg/L of amphetamine. In case 2,mephedrone was the only drug detected in blood with low concentrations of benzoylecgonine [cocaine metabolite-DM] and 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid detected in urine only.

We'd prefer more of a full Case Report workup, of course. Including more details about the subjects, their use timeline and the clinical picture prior to death. But as always in science you have to build the case, brick by brick, so every little bit can be informative. We'll just have to stay tuned.
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Torrance H, & Cooper G (2010). The detection of mephedrone (4-methylmethcathinone) in 4 fatalities in Scotland. Forensic science international PMID: 20685050

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