Data! Well, sort of. MAPS has announced that they are trying to launch a new Phase I clinical trial of MDMA as an adjunct to psychotherapy for Post-Traumatic Stress Disorder. This one will be at a site in Vancouver, BC, Canada. The interesting thing is that they have posted the proposed protocol here. It makes for interesting reading.
To back up a little bit, I have some background on the topic.
A post published Dec 3, 2007 introduced my thoughts on the clinical use of MDMA.
On Jan 25, 2008 I grappled with understanding the clinical doses in a context familiar to the animal research literature (which was authored by quite a few women scientists).
On June 20, 2008 I reviewed the most recent increase (included in the new Canadian protocol) to a 4.5 mg/kg cumulative (2-2.5 hr interval) dose (assuming a 110 lb woman).
I am more than a little happy that the last two posts have been cited on the Wikipedia MDMA entry for several months now.
Okay, so what is interesting in the new protocol? Some actual data? Kewl...
First off, the basics remain familiar in that this Phase I trial will be focused on PTSD and administer MDMA on up to four psychotherapy occasions. Doses are to be 125 mg with a supplemental dose of 67.5 mg to be taken 2-2.5 hrs later. This seems to be the standard approach now. If you have been following along you will recall that they got a series of amendments approved after their initial launch to reach this point of multiple doses per session and multiple sessions. The "optional" (and I believe open-label) fourth session permits an increase to the 150 mg initial, 75 mg supplemental dose that adds up to 4.5 mg/kg cumulative dose in a 110 lb / 50 kg woman. Half this for the other end of the clinical range, i.e., the 220 lb / 100 kg male warfighter with PTSD which is the other target subject population. [In case you are too lazy to go back through my posts, I like to think about the real-world range of body sizes, not just the Pharmacology 101 standard 70kg person.]
New to my awareness (although possibly not new to the cascade of MAPS supported Phase I trials) is the use of a low dose of MDMA as the active placebo comparison. The dose for this will be 25 mg initially with a 12.5 mg supplemental dose for a 37.5 mg cumulative dose (0.38 - 0.75 mg/kg given 50-100 kg subject weight range). There's a handy review table on page 19 of the proposed protocol.
The first bit of interesting data starts at the end of page 40.
The first US phase II trial with MDMA to be completed in September, 2008, was conducted in an outpatient setting with a "crash cart" of emergency equipment on hand and an emergency physician and nurse in the building. ...In this study MDMA was administered on 51 different occasions at a dose of either 125 mg. by mouth or 125 mg. followed in 2 - 2.5 hours by an additional 62.5 mg. Blood pressure, pulse and temperature were closely monitored, but never reached levels that required intervention, nor were there any other medical problems requiring treatment during the MDMA sessions. Subsequently a similar study has been approved in Switzerland and is being conducted in an outpatient psychiatry office approximately 5 minutes from the nearest hospital without a crash cart or emergency personel on site. As of this writing the Swiss investigators have administered 125 mg followed by 62.5 mg MDMA on 20 occasions and administered 150 mg MDMA on two occasions without medical incident.[emphasis added-DM]
Now although it isn't exactly stated, the implication is that none of their safety measures were triggered. Going by the information on heart rate, blood pressure and temperature monitoring provided in this protocol, we might tentatively assume that none of the following were met: body temperature change of 1C above baseline, HR over 110 bpm or blood pressure in excess of 160 systolic or 110 diastolic. Neither were any self-report or clinical/observational signs of distress apparently observed.
There is a good deal of literature review in this thing so it is well worth the read. As readers of my prior posts are well aware, I have serious problems with their interpretation of the implications of much of the literature. In short I think they vastly oversell the apparent safety and dismiss clear evidence of risks that might be informative. This post will not get into that, however. I'm just saying. And as always I would be delighted to be wrong and for no human research subject (experimental or clinical) to ever suffer any adverse effects. Page 69 notes:
To date, MDMA has been administered to approximately 390 research participants, without any occurrences of drug-related serious adverse events.
Okay, finally we get to the tantalizing meat from the Mithoefer study on page 71:
The independent rater conducted a preliminary analysis of CAPS scores at baseline and two months later detected a significant condition effect (p. < 0.05). Average baseline scores for people in both conditions were comparable (79.6 for MDMA condition and 78.4 for placebo), but two months after the second experimental session, the average CAPS score for people in the MDMA condition was 27.6, while the average CAPS for people in placebo was 59.1. Eight of 13 participants no longer met criteria for PTSD two months after the second experimental session while only two of eight placebo participants no longer met criteria for PTSD diagnosis. Furthermore, a comparison of baseline assessment of neurocognitive function and assessment two months after the second experimental session did not find any significant differences in either MDMA or placebo participants (Wagner 2008, personal communication). The data examined in this analysis has not yet been subjected to quality assurance and data from one participant remains to be added, but there were few outliers in the data and it is unlikely that additional data will change results.
I remind you that this is not peer reviewed and is promulgated by those with a confirmed bias to see this study be successful. So keep that in mind. The independence and blindedness and all that stuff is not provided and would, of course, be of critical importance. (The primary PTSD outcome measure, the CAPS is described here.)
I am not an expert inPTSD and so I cannot say what these statistically reliable changes in CAPS mean for clinical significance. Nor whether 2 months of symptom remission is impressive. Nor what the results in this prior-treatment-failure population means for the general PTSD population. Nor whether sexual assault PTSD responds the same as warfighter PTSD (memory suggests they didn't have more than a couple of warfighters in the sample). Nevertheless the result sounds quite positive so far and my ears are remaining tuned to additional developments.