Double blind lab testing for the win!

Feb 03 2012 Published by under MDMA, Methamphetamine

It's been awhile since I last talked about MDMA, aka 3,4-methylenedioxymethamphetamine, the canonical ingredient in Ecstasy. I phrase it this way because street drug sold as Ecstasy is notoriously promiscuous in terms of psychoactive drug content. Stroll on over to www.ecstasydata.org if you are new to this topic.

Not that there haven't been more emergencies and deaths, including ones that didn't involve MDMA but something else, like PMMA. And yes, the MAPS folks are marching on with great dispatch, dosing more and more people with MDMA in the context of trying to prove it an effective adjunct to psychotherapy for PTSD. So, you know, I keep up with my interests as expressed in earlier days on the blog, I just don't necessarily bore you with it.

There's a human laboratory paper I've been looking at that makes a point semi-related to some of the above issues. It's from the laboratory of Carl Hart (who I profiled a few years ago as part of D.N. Lee's Diversity in Science Blog Carnival.)

Kirkpatrick MG, Gunderson EW, Perez AY, Haney M, Foltin RW, Hart CL. A direct comparison of the behavioral and physiological effects of methamphetamine and 3,4-methylenedioxymethamphetamine (MDMA) in humans. Psychopharmacology (Berl). 2012 Jan;219(1):109-22. Epub 2011 Jun 30. [PubMed]

The essence of the design is that it was a human laboratory study with a repeated measures design. They orally dosed the subjects with inactive placebo, 100 mg of MDMA and both 20 and 40 mg of methamphetamine with these treatment conditions separated by 3 days. A series of cognitive, physiological and self-report assessments were conducted- I'm not going to overview the findings here, you can go read the paper for yourself.

The interesting part about this paper for today's discussion is that the subjects were really bad at identifying the drug that they'd been given. Keep in mind that the subjects had to have prior experience with both methamphetamine and MDMA. I imagine there are few people in the audience that are not aware that at least the mean, reported subjective effects of MDMA and methamphetamine differ considerably. Although it does have a prototypical psychomotor stimulant character to it, MDMA's subjective properties have people reaching for new terms like "entactogen". Likening it to a hybrid of a classical hallucinogen and a stimulant. Insisting vociferously that it is different.

This ties into the question of the pharmacological diversity of the recreational "Ecstasy" market, people's ability to know what they have just taken, etc. Which may influence their decision to take more drug later on, to take more tablets in the original dose, etc. It also plays into the blinding that might otherwise be assumed to be impossible in the clinical trials and their occasional selection of something else like methylphenidate as their control drug.

Kirkpatrick and colleagues report:

On the questionnaire probing what drug the participants thought they had received, 72.7% of participants (i.e., eight out of 11) correctly identified placebo (18.2% reported MDMA and 9.1% reported sedative; confidence rating= 72.7±9.5), 45.5% correctly identified 20 mg methamphetamine (45.5% reported MDMA and 9.1% reported placebo; confidence rating=76.7±13.3), 72.7% correctly identified 40 mg methamphetamine (27.3% reported MDMA; confidence rating=80.1±5.6), and 45.5% correctly identified 100 mg MDMA (27.3% reported methamphetamine and 27.3% reported sedative; confidence rating=87.6±5.2).

Now, just for reference, the 100 mg MDMA and 40 mg methamphetamine conditions resulted in approximately the same effects on heart rate, blood pressure and self-report measures of "good drug effect" and "feeling stimulated". So no need to go looking there for reasons. This isn't some sort of meta assessment of physiological responses or a good/bad drug binary decision. These compounds must produce subjective effects that are pretty indistinguishable. They did differ in group terms on several of the outcome measures so this really does focus on the subject's awareness and not on the actual effects, so to speak. \

And do recall this was a controlled laboratory study in which the environment was relatively invariant compared with potential differences in environments in which Ecstasy is consumed in the natural setting. There is every reason to expect that situational variables and expectations would hugely influence the subjective response.

My consideration for the blog topics is this. When someone starts going on confidently about knowing the purity and/or nature of other non-MDMA constituents of street Ecstasy they have consumed, this is unlikely to be a credible assertion. In either direction. I.e., it is as dubious if they claim to have the pure stuff as if they claim it "must" have been contaminated with methamphetamine.

Unfortunately the study did not manipulate MDMA dose so we're unable to extend our interpretation in another obvious direction which would be whether or not individuals were very good at identifying how much MDMA they had consumed. I'm betting not very good at this either but we'll have to wait on another study for that evidence.

19 responses so far

  • Neuro-conservative says:

    Do you know whether they have ruled out any such exposure with those teenaged girls experiencing sudden-onset tic disorders? I have wondered whether it is some unfortunate MPTP-like scenario. It is amazing that people will ingest stuff given to them by some dude.

  • My recollection from back in the 1980s when we got certified pure MDMA was that 200-300 mg was the right dose for PARTY TYME.

  • DrugMonkey says:

    That seems like a pretty hefty dose PP. not that you might not be right about what people were doing, but 4-6 mg/kg for a woman ain't chump change. 2-4 for a man is a little more reasonable but still....

  • DrugMonkey says:

    I haven't really followed the sudden tic thing, N-c. Is this some sort of geographically localized issue?

  • If I'm also remembering correctly, one tolerizes to MDMA pretty rapidly: even after only a few doses the required dose starts increasing.

  • drugmonkey says:

    That's what I hear, yes. An interesting question related to this paper would be whether people become differentially tolerant to the different effects.

  • My recollection is that one tolerizes a lot more to the euphoria than to the stimulant effects. If I recall correctly, that's why I quit using it after a couple months: speed was never my thing.

  • drugmonkey says:

    Hmm- hmm. Exactly. And that might then complicate the discrimination between MDMA and methamphetamine, might it not?

  • Wut? You talking about your post about some fucken article? tl;dr.

    Has anyone done a study on long-term effects of MDMA on attention span? HAHAHAHAH!

  • Neuro-conservative says:

    About a dozen teenage girls at one high school near Rochester all came down with a sudden-onset tic disorder a couple of weeks ago. Somehow, this became national news.

    Erin Brockovich is on the case, and blames a toxic spill that occurred in the 1970's. Susan Swedo has offered free evals for PANDAS at NIH. Initial diagnosis by local docs was conversion disorder. There have been some toxicology studies on some of the girls, which were reported to be negative, but I'm not sure what was tested.

  • DrugMonkey says:

    "conversion" disorder? Is that the term for what used to be called hysteria?

  • Neuro-conservative says:

    Yep.

  • DrugMonkey says:

    Yes, PP, I believe Morgan reported attentional deficits some time ago.

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