

Ecstasy for PTSD: Not Ready for Prime Time - tokenadult
http://www.sciencebasedmedicine.org/index.php/ecstasy-for-ptsd-not-ready-for-prime-time/

======
Alex3917
Once again Science Based Medicine shows that it's just a propaganda outlet for
big pharma:

"The study is characterized as blinded; but the blinding didn’t work, since
95% of subjects were able to tell which group they were in."

As the researchers themselves say, the purpose of the study was to test their
methodology before doing larger trials, including whether or not their
blinding protocols were effective. They are going to be using active placebos
for phase III, which are much more effective for blinding. In fact many of the
other studies they've done already use active placebos, either a lower dose of
MDMA or else something like methylphenidate. The authors address this in the
actual study and explain that they now have FDA approval to use a three-arm
protocol in the future, but SBM is pretending that this a methodological
problem they found themselves.

"There is only a pilot study with scanty, preliminary, unconfirmed evidence."

There have been at least a dozen studies looking at MDMA as a treatment for
PTSD, but again the author is pretending that this is the only one.

"Experiments using illegal drugs are always problematic, because researchers
tend to be advocates for legalization and may be biased by their emotional
investment."

Most of the MDMA studies use a triple blind methodology which is far more
rigorous than the methodology that big pharma uses. What this means is that
not only are the patients and the people administering the drug blinded (or
will be going into phase III trials), but also the people analyzing the data
were not the ones administering the drugs so they have no idea who was in each
group.

Also, these are multi-site trials going on in various countries around the
world, including ones where the legal status and cultural baggage surrounding
MDMA is wildly different in both researchers and the general population.

"The patients in the placebo group improved, too; so a large part of the
benefit could be attributed to the psychotherapy."

As one would expect. However, they still had PTSD whereas the people who got
the MDMA didn't. Additionally, studies have shown that the MDMA group
continues to improve in the months and years after therapy much more than the
control group.

"The addition of MDMA to psychotherapy might prove helpful in refractory cases
of PTSD, but the preliminary results of this one small pilot study will need
to be confirmed by larger studies in combat veterans before the treatment can
recommended to patients."

Agreed. Except for that again there have been many studies of MDMA as a
treatment for PTSD, not just this one.

"Unfortunately, the history of medicine is full of equally promising
treatments that didn’t pan out. Probably the most typical course is this: a
strongly positive pilot study is followed by larger studies with weaker
positive results, then by studies with equivocal or negative results, then
reports of serious side effects or other problems, and eventually by rejection
of the treatment. I sincerely hope this one will prove an exception to that
course, for the sake of suffering veterans with few remaining options. But I
am not optimistic."

The reason why this has happened consistently in medicine is because the
studies are being funded by for profit companies and they are using extremely
biased methodology to make their drugs look much better than they actually
are. Whereas MAPS is a non-profit, and their methodology is designed to be as
neutral as possible. The research may well still not pan out as trial sizes
increase and patients are more effectively double blinded, but there is
definitely reason for optimism based on the results so far.

For what it's worth, there are numerous videos online where you can watch the
researchers (and MAPS) talking about these studies:

<http://www.maps.org/videos/source/video3.html> (This video is with Michael
Mithoefer, one of the researchers behind this study.)

<http://vimeo.com/32062578> (Talk given by MAPS about the roadmap for getting
MDMA approved.)

There are several more videos online here about both the mechanisms of action,
the pharmacology, and the results of other trials:

<http://www.maps.org/media/videos/>

~~~
bitwize
Yeah, maaaaaaaaan.

And weed cures all forms of cancer -- that's why it's illegal.

If Big Pharma wanted to push dangerous or ineffective drugs on the public,
there are far easier and cheaper ways to go about it than coming up with
elaborate double-blind, randomized, placebo-controlled testing protocols. See:
Vioxx.

 _Experiments using illegal drugs are always problematic, because researchers
tend to be advocates for legalization and may be biased by their emotional
investment._

But MAPS, a pro-psychedelics organization, is neutral. Shyeah -- about as
neutral as _High Times_.

This person is expressing sincere doubt -- probably because she's seen enough
medical research to know that drugs that seem like miracle cures in pilot
studies often pan out to be not so miraculous when tested in broader studies
with larger cohorts -- and that's true whether the drug in question is
politically controversial (like MDMA, LSD, or marijuana) or not.

I say this as one who supports drug legalization and wants to see further
research conducted with MDMA. Until the results of larger studies come in,
there's still room for doubt here.

~~~
Alex3917
"If Big Pharma wanted to push dangerous or ineffective drugs on the public,
there are far easier and cheaper ways to go about it than coming up with
elaborate double-blind, randomized, placebo-controlled testing protocols."

That's demonstrably false. There are dozens of books on the topic, many of
which I link to here:

<http://news.ycombinator.com/item?id=4807436>

"Until the results of larger studies come in, there's still room for doubt
here."

No question there's room for doubt. My issue isn't with the fact that the
author doubts that MDMA will be effective, which it may well not be, but
rather that she is being intellectually dishonest in her arguments.

~~~
bitwize
_That's demonstrably false._

You haven't demonstrated it false; I can demonstrate it true.

 _she is being intellectually dishonest in her arguments._

Or she is just unaware of the scope of MDMA reesearch conducted thus far. I
doubt this is her specialty.

------
dmix
Warning: people on PTSD are most likely on anti-depressants such as SSRI's and
MAOI's which have interactions with MDMA, potentially causing serotonin
syndrome.

<http://en.wikipedia.org/wiki/Serotonin_syndrome>

It can take weeks to a month of widthdrawl from SSRI to prevent interactions.

~~~
veb
Not necessarily. PTSD is a lot more complex than simple depression.

Doctors will try and fix the depression, but then something else will "arrive"
and wreck havoc. Whether that's anxiety, flashbacks or something else that's
not "always there" when you're simply "just" depressed.

It's nearly impossible to treat PTSD as a whole with conventional medicine.

~~~
dmix
Yep, I'm not saying SSRI's are more effective, but theres a good possibility
that someone with PTSD is already on it and self-medication could be
dangerous.

> The most commonly prescribed class of medications for PTSD (and the one
> approved by the U.S. Food and Drug Administration) are the selective
> serotonin reuptake inhibitor (SSRI) antidepressants.

[http://psychcentral.com/lib/2006/an-overview-of-treatment-
of...](http://psychcentral.com/lib/2006/an-overview-of-treatment-of-ptsd/)

------
tokenadult
Thanks for the several comments that came in while I was busy with a work
project. The author of the submitted commentary article, Harriet Hall, M.D.,
is a retired military physician. It is reasonable to assume that she has a
personal bias toward finding effective treatments for military post-traumatic
stress syndrome (PTSD), and perhaps also a personal bias toward finding
effective treatments for PTSD after rape.

Contrary to several comments posted while I was busy, the edited group blog
Science-Based Medicine is about applying the methods and settled factual
conclusions of science to the existing practice of "evidence-based medicine."
As the group of authors put it, "Science-Based Medicine is dedicated to
evaluating medical treatments and products of interest to the public in a
scientific light, and promoting the highest standards and traditions of
science in health care."

[http://www.sciencebasedmedicine.org/index.php/about-
science-...](http://www.sciencebasedmedicine.org/index.php/about-science-
based-medicine/)

There have been a variety of posts on the site over the years critical of
large pharmaceutical companies, and there have been a variety of posts
critical of various aspects of current medical practice. The tenor of the site
is that everyone involved in treating human patients and guarding their health
needs to be truth-seeking, considering prior probabilities and scientific fact
when evaluating new treatments. The authors are not a propaganda outlet for
any industry, and they have no financial conflicts of interest on the issues
they write about.

Dr. Hall correctly points out that "Prolonged exposure therapy is a widely
recognized therapy for PTSD. The rationale for using MDMA is to suppress
anxiety and allow patients to talk about their traumatic experiences without
feeling excessive fear and hyperarousal." Any effort to find a new treatment
for PTSD, whether a prescribed drug or a new form of talk therapy, will have
to be evaluated against what is already available to treat that tough
disorder.

Any reader of Hacker News who hasn't seen the link below already should
definitely check out LISP hacker (and Google director of research) Peter
Norvig's article "Warning Signs in Experimental Design and Interpretation,"

<http://norvig.com/experiment-design.html>

which is a great checklist of what to look for in a report of a new research
finding. Dr. Hall knows how to evaluate research reports in this framework,
and she urges that people (like her) who hope that more effective treatments
for PTSD are developed proceed carefully so that the new treatments are truly
safe and effective.

------
jpdoctor
> _Exit poll: 95% correctly guessed which group they were assigned to._ [ie,
> knew they had taken XTC or not]

This pins the WTF meter. 1 out of the 20 could not figure it out?

In related info: The controlled studies for viagra were a bit comical.

~~~
pchivers
From what I understand this 95% figure is not that far off from what is
obtained in anti-depressant trials, but somehow the poor blinding of anti-
depressant trials is almost never mentioned as a serious methodological
problem.

This is discussed in more detail in Irving Kirsch's _The Emperor's New Drugs_.

~~~
Nursie
The issue here has to be that it's hard to mask MDMA - people are going to
know they're on something even at therapeutic (rather than recreational)
doses, are they not? Is that really poor blinding?

Antidepressants tend to be long lasting and slow acting (AFAICT) which MDMA is
not.

~~~
pchivers
True, antidepressants are much slower acting than MDMA, but you're still
looking at 80-90% of people in antidepressant trials who can correctly guess
which group they're in (due to side effects such as dry mouth, sleep problems,
sexual dysfunction, etc.).

Regarding the issue of whether or not it is poor blinding, I guess it is a bit
like the tree falling in the forest but nobody is around to hear it: if you
conduct a placebo-controlled study, but all the participants can correctly
guess which group they're in, is it really a placebo-controlled study?

~~~
Nursie
Likely a rhetorical question on your part there, but it is an interesting
conundrum. Because the drug works directly on the brain and folks emotions,
and because those effects are directly bound up with the therapeutic area
under study, I can't help thinking a placebo would be really hard to do well
here. Any other phenethylamine that subjectively mimics MDMA is going to be
messing with the same systems.

I guess (as may have been suggested elsewhere) you could use a non-
seratonergic stimulant of some sort to give people the feeling that they are
on _something_ , and rely on them not being able to tell what it is. You'd
need to screen for anyone that had any recreational experience though.

~~~
disgruntledphd2
Yeah, placebo controlled studies of mind-altering chemicals are _hard_. I've
done quite a lot of research on placebo, and would never expect to be able to
blind effectively without using an active drug (low dose). Something like
methylphenidrate might work, as noted by the top comment, but even then you
don't really have a control, as you really are just estimating the effects of
one chemical against another (which tends to require far larger studies to
demonstrate an affect).

Speed would probably work. One thing that interests me though is whether or
not the patients were treated seperately. Having been surrounded by people on
MDMA while not partaking myself, at least in my anecdotal experience it can
affect your state of mind, which could be one reason for the rather large
placebo effects (given that the treatment is so obvious, one would expect
placebo effects to be artificially lowered.

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Nursie
I wonder why the focus is on MDMA? IMHO it's entirely possible that the same
or better effects could be found from a related substance like MBDB, and some
(again like MBDB) seem to be less toxic than MDMA.

The page also mentions that the reputation of MDMA preceded it and may have
had an impact on the study. Using a less well known substance may have tackled
this.

~~~
loceng
MDMA is what's popular in the recreation scene and so will draw attention over
others; Even Madonna not-so-subtly promotes it through her "MDNA" album and
tour name - though most are none-the-wiser.

~~~
bitwize
Oh snap, I thought she was punning on a different chemical (to wit:
deoxyribonucleic acid)...

------
bitteralmond
I'm always skeptical of using this stuff for PTSD since the comedown is so
harsh. I would suspect that the period of serotonin depletion could actually
be just as bad for PTSD as the MDMA "high" could be good. Though I guess it's
also important to note that taking MDMA with your therapist in a quiet room is
nothing like taking it in a loud, dark room with your friends.

~~~
Nursie
Is the come-down bad though, if the doses given are sub-recreational and are
followed by proper amounts of sleep?

Not to mention if you can ensure you're getting the right thing and not some
dodgy multiply-substituted cathinone or piperazine!

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teebot
"Placebo controlled: 12 patients got the active drug, 8 got an inactive
placebo Exit poll: 95% correctly guessed which group they were assigned to."

No kidding

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loceng
Who structured this study? They're doing it wrong ...

~~~
wahnfrieden
They're doing it right, this is just piss-poor journalism. See Alex3917's
reply.

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001sky
With a name like "Science-Based Medicine" it just has to be true </sarcasm>

