Archive for the 'MDMA' category

DrugFacts 2010 Repost: Yes, it really is the MDMA that killed him

Nov 10 2010 Published by under MDMA, Uncategorized

This is Drug Facts Week, an effort of NIDA to promote understanding of the effects of recreational drugs. Although I'm slightly busy with other matters, I wanted to participate, partially, with a series of re-posts. This post originally appeared July 7, 2009.

I've taken the liberty of providing a title for a new case report on a fatality associated with consumption of Ecstasy which more accurately captures the tone of the article. In this case the authors go to some length to beat home a message that I have been known to blog now and again. The report is in the pre-print stage in the Journal of Emergency Medicine.
Herve Vanden Eede, MD, Leon J. Montenij, MD, Daan J. Touw, and Elizabeth M. Norris, MB, CHB. J Emerg Med. 2009 Jun 3. [Epub ahead of print], doi: 10.1016/j.jemermed.2009.04.057

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Recreational Mephedrone Brief (09/30/10)

Sep 30 2010 Published by under Cathinone, Drug Abuse Science, MDMA

Mephedrone, or 4-methylmethcathinone, is a recreational drug that got very popular in the UK in recent years, no doubt due to it being legal to sell and possess up until April of this year. There is not a tremendous amount known about the pharmacology of this drug at present, however we can deduce quite a bit about where we should start looking from user experiences. I am currently intrigued by the fact that if you look at online user forums you can get Ecstasy fans describing mephedrone as being sortof like Ecstasy...only not as good, or not quite the same. In addition, a recent paper which surveyed a certain subset of users found that many of them report intranasal mephedrone to be as good or better than intranasal cocaine. You will recall, of course, that I have a great deal of blog interest in discussing MDMA-related fatalities.
ResearchBlogging.orgA Case Report that recently appeared in the Lancet helps us to connect up some dots. Sammler and colleagues report on the case of a 15 year old girl who presented to their emergency department one afternoon with "altered mental status, vomiting and nausea". She had been out drinking the night before and had also consumed a "white powdery substance". The clinical workup contained a few interesting clues:

-the cerebrospinal fluid (CSF) opening pressure during lumbar puncture in the lateral decubitus position was raised at 350 mm of water.
-Blood tests showed profound hyponatraemia at 118 mmol/L.
-Serum osmolality was low at 256 mmol/kg, whereas urine osmolality was high at 742 mmol/kg.

Well, well, well. Hyponatraemia is frequently reported in cases of MDMA-related medical emergency and death. This is very likely related to an effect on vasopressin / antidiuretic hormone release that would cause the kidneys to retain water, perhaps in combination with induced polydipsia (urge to drink) or intentional (albeit misguided) prophylactic strategies. This is likely driven by the serotonin transporter inhibition properties of MDMA, this indirect agonist effect perhaps working through the serotonin 3, 2C, 4 and/or 7 receptor subtypes to induce vasopressin release.

I have no good stats but there is a distinct impression from reading MDMA case reports that young women may be particularly liable to hyponatremia following MDMA. This is something I need to take up at some point- is there evidence for increased sensitivity of adolescent women to fluid balance dysregulation?

Returning to the topic at hand, is this just a case of MDMA-induced hyponatraemia?

Fortunately, the doctors ran the tox panels:

We suspected drug intoxication and did gas chromatography-mass spectroscopy of the patient’s urine; this was unequivocally positive for mephedrone metabolites, but was negative for opioids, methadone, barbiturates, cocaine, cannabinoids, alcohol, benzodiazepines, and amphetamines including ecstasy. Analysis of the white powder was consistent with mephedrone.

Interesting. This suggests to me, as it did to the authors, that there is a MDMA-like component to this mephedrone stuff. It may be a dopamine transporter inhibitor and/or dopamine releaser like cocaine, amphetamine, methamphetamine but the hyponatraemia suggests an additional (significant) serotonergic component of the pharmacological response to mephedrone. This would be consistent with those users who report it as being at least somewhat like Ecstasy.

As I discussed before, one prior paper reported on the subjective effects of several cathinone analog compounds using the drug-discrimination assay. The cathinone structure if very similar to amphetamine and supports parallel modifications. The question becomes whether the same modifications of the cathinone and amphetamine core structures convey similar changes in the pharmacology.

In very brief overview of the drug-discrimination procedure, you train rats to tell you if the drug you have just given it is similar to a reference drug such as amphetamine or MDMA. The prior paper found that methylenedioxycathinone (MDC) and methylenedioxymethcathinone (MDMC) fully substituted for MDMA at reasonably similar doses. MDMC also fully substituted for amphetamine whereas MDC did not; in both cases the potency was much lower-higher doses had to be employed for comparable effect to the reference amphetamine.

This is complicated, because if anything MDA is closer in subjective and behavioral effect to amphetamine than is MDMA. And if there are any data on the 4-Methylmeth modification of amphetamine, I am unaware of them. Nevertheless it provides some clue that we are not totally out of line to suspect that the 4-Methylmeth modification to cathinone adds on a serotonergic agonist component, very likely mediated by blockade of the serotonin transporter (with perhaps some releasing effect)...just like one sees with the methylenedioxymeth modification of amphetamine in the case of MDMA.

Final note: The 15 year old girl in this Case Report made a full recovery. That's a very good thing.
Sammler EM, Foley PL, Lauder GD, Wilson SJ, Goudie AR, & O'Riordan JI (2010). A harmless high? Lancet, 376 (9742) PMID: 20801405

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Mephedrone (4-Methylmethcathinone) appearing in "Ecstasy" in the Netherlands

Sep 19 2010 Published by under Cathinone, Drug Abuse Science, MDMA

I have in the past discussed the fact that a substantial amount of recreational drug being sold as "Ecstasy" on the street contains psychoactive constituents other than 3,4-methylenedioxymethamphetamine (MDMA). This is old news and you can play around with one source of data for yourself at*. In addition, I have mentioned the UK explosion in use of 4-methylmethcathinone (4-MMC, aka mephedrone) over the past year (here, here, here, here).
ResearchBlogging.orgBrunt and colleagues have provided an update from the Netherlands Drug Information and Monitoring System which obtains drug samples, described in their prior paper, from recreational users at clubs and somehow turned over to police. For this paper they have included analysis from 12,331 tablets collected from 2008-2009. The first major observation is that the proportion of tablets containing zero MDMA increased sharply in late 2008 which is a big change from the ~90% MDMA-containing samples in prior years. Something on the order of 50-60% of the Ecstasy obtained in the Netherlands in 2009 didn't have any MDMA in it. Bummer, dude.
The other fascinating thing is that even though the usual suspect non-MDMA components were found (23-54% mCPP, methamphetamine/amphetamine, caffeine are common) the substituted cathinone 4-MMC/mephedrone is a new player.

A total of 995 (11.5% of the total ) tablets sourced from the DIMS system in 2009 contained only mephedrone. The authors note that this compound was also found in samples derived from over 100 police seizures. Although it is unclear how the proportions match up, at least the sample biases represented from the voluntary (?) user submissions and the police actions are grossly comparable in the sense that mephedrone tablets are appearing in the Dutch market. The paper goes on to note that 4-MMC is not yet "under the Scheduled Substances Act" so presumably it is a situation much like the UK up until April of 2010.

A final note of interest is the downturn in the proportion of non-MDMA tablets in late 2009- it will be interesting to see if this MDMA-drought was a shortlived blip or if actions such as Cambodia, Vietnam and Thailand finally getting serious about controlling the production of the safrole oil used as a precursor in MDMA manufacture is having a lasting effect on world markets.

One thing that I would personally like a little more clarity on is the degree to which the authors assert that the tablets they are analyzing were "sold as ecstasy". Given the popularity of the drug under its own name in the UK, one wonders if it is merely being marketed as mephedrone/4-MMC instead of deceptively as "Ecstasy" which I think is commonly understood to mean MDMA. There is also the usual problem with samples sourced from users in this paper- there could always be a substantial bias to submit or turn over tablets (which are likely batch-identifiable by stampings/color) of unexpected or suspicious subjective character. Likewise, it is hard to determine marketshare for a particular batch or appearance of tablet. This makes it hard to infer what the constituents are in the population of pills actually being consumed by users with high accuracy. Nevertheless these data are very welcome since across time and geographical region we can get some confidence on relative MDMA content, the appearance of new drugs, etc.

*Since I mentioned the pill testing outfit at the top, I should note that a search for mephedrone pulls up 5 different tablets, all sourced from Zurich (it is possible that the other source laboratories are not testing for 4-MMC yet). All 5 contain caffeine and two contain MDMA in addition to the 4-MMC.

Brunt TM, Poortman A, Niesink RJ, & van den Brink W (2010). Instability of the ecstasy market and a new kid on the block: mephedrone. Journal of psychopharmacology (Oxford, England) PMID: 20826554

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Repost: The Women of MDMA Research

There is a #womeninscience meme bouncing around the Twitts today. Click the link and you'll see some of the conversation, even if you are not a habitual Twitter user. Please consider joining in with an observation about, well, anything related to the life of women in science. On the Twitts, on your blog, Facebook or in the comments here or elsewhere.

I have an older post that I wrote some time ago to introduce some of the women who have contributed to the science that I talk about on the blog. This post originally appeared 24 Jul 2008.

A comment left by a reader some time ago took exception to one of my posts highlighting another blogger.

wow, that is some excellent PR for a grad student to get for free. perhaps you could spotlight a female grad student as well...?

The ensuing discussion planted the idea for this post. Continue Reading »

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A belated realization on the media coverage of the MDMA/PTSD paper

Jul 24 2010 Published by under Gender, MDMA, Science Communication

The following is a more casual description of a stream of thought I had about these posts I've been writing on the MDMA/PTSD paper.

ok, so there's this paper that has finally come out. I've been bashing away at the project itself on the blog since, oh, forever. I finally had a chance to get around to blogging the paper. no biggie.
takehome message, MDMA is good for treating PTSD if given in the therapy session.
one of the features of such a study is that it is going to get media attention. I was ignoring that all week so that I could blog the paper unmolested.
Trolling around the media coverage I started on a slow burn.
Going through Google hits, there was a great deal of emphasis on PTSD caused by combat stress. Angles on the story which suggested we have a big ol' problem looming (true dat) and won't it be great to have some new hope (true dat) and then doing a less than complete cockup of the facts of the paper.
Problem is that it is a small study as it is, 12 MDMA-treated, 8 placebo controls, but only ONE had combat trauma as the index trauma. ONE. The rest were mostly sexual assault, crime (not further specified) and childhood trauma (sexual assault and physical neglect). Me, I was happily bashing away at the overselling of the single combat PTSD case in my draft.
On the way home it hit me.

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The media coverage of the MDMA Clinical trial result stinks

Jul 24 2010 Published by under MDMA, Public Health, Science Communication

I am disappointed in the mainstream, and not so mainstream, media coverage of the Mithoefer et al, 2010 paper on MDMA-assisted therapy for Post-Traumatic Stress Disorder. I had been holding off reading any of it because I suspected it might distract me from actually discussing the paper.
After writing up my thoughts on the paper, I went strolling around the Google News hits for MDMA to see what had been written about this paper. There was a whole lot of of really bad journalism. Sure, for the most part they got the basic facts right, but I noticed a consistent issue having to do (I assume) with journalism's penchant for selling a story they'd like to tell over the story that exists.
Let us start with the more venerable news organizations.
ABC News Ecstasy may help traumatised veterans
See the title? Pretty common to see something abut veterans or combat PTSD in the title as well as in the article body.

found that the drug seems to improve the effects of therapy in military veterans

No, there was one combat stress case. I noted that this stuck out as odd in my post on the paper. Well, now you can see why the authors might have been so keen to include this single warfighter subject. They enjoyed much wider press and nobody called them out for this scientific distraction
(This part of the ABC report caused me to laugh though:

The researchers, led by Dr Rick Doblin of the Multidisciplinary Association for Psychedelic Studies

Of course this is true, the driving force behind getting these studies rolling is the recreational legalization Trojan outfit MAPS. It looks better though, if you ask me, when they credit the therapist Mithoefer as being the leader of the project and MAPS as only providing support and assistance. )

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MDMA for PTSD: The first peer-reviewed clinical trial report

Jul 23 2010 Published by under MDMA, Neuropharmacology

ecstasypills.jpgMy readers will recall that I have blogged now and again about ongoing efforts to get 3,4-methylenedioxymethamphetamine (MDMA), the psychoactive compound preferentially sought as Ecstasy in recreational users, approved as a medication to be used in psychotherapy. The initial attempts have focused on the treatment of Post-Traumatic Stress Disorder. PTSD is a seriously debilitating condition and we may not have sufficient resources and knowledge to deal with, e.g., an anticipated uptick due to the current wars that the US is prosecuting.
I introduced the MDMA/PTSD Phase I clinical trials here, noting

The short version of the theory is that the subjective properties of MDMA (empathic, inhibition lowering, etc) are consistent with helping people in difficult psychotherapeutic situations (such as for post-traumatic stress disorder (PTSD) and, supposedly, end stage cancer anxiety) make therapeutic breakthroughs during a limited number of treatment sessions of talk therapy. This is not proposed as a chronic medication like a selective serotonin reuptake inhibitor (SSRI). The funny thing is, I approve of the concept of moving forward with clinical trials based on the available evidence.
Why not? I mean PTSD can be a very devastating psychological issue and if there are treatment-resistant cases that can benefit from a limited number of MDMA exposures, great.

I concluded that particular post with this observation.

As is general practice in medicine, sometimes there are going to be risks associated with therapy. Sometimes quite substantial risks can be acceptable if the alternative is bad. However we get ourselves into a world of trouble, sometimes even losing a perfectly helpful medication, if we are not as honest as possible, up front, over the actual risks.

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Another festival, more medical emergencies, another MDMA-associated death

Jul 01 2010 Published by under Drug Fatality, MDMA

From the LA Times we learn that the Los Angeles edition of the Electric Daisy Carnival held this past weekend resulted in about 120 emergency room visits. An estimated 185,000 persons attended the event.
As one might predict, at least one person died from taking Ecstasy. LA Times:

At 15, Sasha Rodriguez did not meet the minimum age requirement of 16 to enter the event without a legal guardian. Family and friends said that she attended the party with a 16-year-old friend and that doctors told them she had the hallucinogenic drug Ecstasy in her system when she was taken by ambulance to the emergency room.
Rodriguez ... died at California Hospital Medical Center downtown before 5:30 p.m. Tuesday after her family decided to remove the comatose teen from life support.

Yes it is the MDMA.
Are teenage girls at particular risk? I don't know the answer to this.

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Tracking MDMA-related medical events in the aftermath of a rave event

Jun 16 2010 Published by under Drug Abuse Science, MDMA

The CDC has an interesting report out in their Morbidity and Mortality Weekly Report (MMWR).

Ecstasy Overdoses at a New Year's Eve Rave --- Los Angeles, California, 2010

This bit overviews a report from the Los Angeles County Department of Public Health which sought information on Emergency Department visits and other fatalities involving people who attended a New Year's event Dec 31, 2009-Jan 1, 2010. The investigation determined that

18 patients visited EDs in LAC for MDMA-related illness within 12 hours of the rave. All were aged 16--34 years, and nine were female. In addition to using MDMA, 10 of the 18 had used alcohol, and five had used other drugs. Three patients were admitted to the hospital, including one to intensive care. A tablet obtained from one of the patients contained MDMA and caffeine, without known toxic contaminants.

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Impaired or improved driving in abstinent Ecstasy users?

Apr 14 2010 Published by under Cannabis, Cognition, MDMA

ResearchBlogging.orgA recent paper set out to examine automobile driving skills in people who had previously used Ecstasy (presumptively 3,4-methylenedioxymethamphetamine; MDMA) but were currently not using. Dastrup and colleagues (2010) used a driving simulator task in which the job was to maintain a set distance behind a lead vehicle (LV) displayed on the computer screen. The job was to stay abut two car lengths (given as 18 meters) behind the LV while accelerating to 55mph. My Google U conversion calculation makes 55 mph out to be about 25 meters / sec. I would therefore estimate the closing time between the cars as about 0.4-0.5 seconds, depending on car length and how much space you assume between these lengths. Thereafter the LV changed speed as depicted in the Figure 2 from the paper.
Dastrup10-fig2.pngThe horizontal line sits at the 55 mph point and you can see that the speed of the LV varies up to about 59 mph and down to about 51 mph with the maximum change taking place over about 18-20 seconds. .

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