Makes Disturbances Melt Away?

July 24, 2010 12:33 AM

In a pilot Phase II study of PTSD sufferers with a median of 19 years since diagnosis, MDMA-assisted therapy resulted in 10 out of 12 patients no longer meeting the diagnostic criteria.

Full paper PDF here.

Mean CAPS scores in the active arm reduced from 79 to 25, and 79 to 59 in the placebo group.
One requirement of the study protocol was hospitalization for 24 hours from the time of dosing. Some may find this an expensive constraint to adoption of MDMA as therapy adjunct.

Check out MAPS for more details on studies involving MDMA.
Previously on the Blue.

posted by daksya (88 comments total)

previously.
posted by empath at 12:37 AM on July 24, 2010

Won't this get discredited to hell and back so the government can keep it on schedule 1?
posted by hamida2242 at 12:38 AM on July 24, 2010 [1 favorite]

This is so transparently obvious that it's a solution to PTSD that it's deeply immoral to keep it illegal. MDMA is a miracle.
posted by empath at 12:40 AM on July 24, 2010 [7 favorites]

Just in terms of how it helped me -- the feeling of going from 0 to pure bliss, with no change to external reality goes to show how much of our perceptions of the world around us are entirely subjective, and that mood can have an amazing ability to transform how we see ourselves and other people. You don't have to earn happiness. You can just choose it.

So much of depression and dealing with trauma are just patterns of thought that are so, so difficult to break, and MDMA just shatters all of them. You can't be afraid on MDMA. You can't stay closed.

It's not something that goes away when it wears off, especially, I would think, if you're working with a therapist that can reinforce those feelings and direct them to real action to change in your life.

I saw so many people transformed in positive ways by it. I also know some people who completely lost their grounding in reality. But I don't know anybody who did it and stayed the same person they were before.

It gave me the push to move out of my parents house, to change jobs, to get my first girlfriend, find an entirely new group of friends, etc, after spending 4-5 years stuck in a rut after graduating from high school, introverted, depressed and lonely. It got me over years of childhood trauma and bullying, more or less overnight. I really don't know where I'd be today without it, but I imagine it wouldn't be a very good place.
posted by empath at 12:48 AM on July 24, 2010 [59 favorites]

Not to mention, it's an insane amount of fun. Which, I guess, is the objection to it. Because it's not about addiction, or brain damage or health problems, because they simply aren't problems with moderate MDMA use. And surely no worse than alcohol.
posted by empath at 12:50 AM on July 24, 2010 [4 favorites]

MAPS is an incredible society doing us a valuable service. When MDMA, LSD, ibogaine, and other psychedelics are finally recognized as medicine, it will be entirely thanks to their work. And they need donations!
posted by mek at 12:55 AM on July 24, 2010

Too bad the PTSD comes back if you listen to Sandstorm
posted by hellojed at 1:01 AM on July 24, 2010 [5 favorites]

Sandstorm rules.
posted by empath at 1:05 AM on July 24, 2010 [6 favorites]

empath, you forgot "helped me choose a mefi user name" in your list of benefits.
posted by telstar at 1:06 AM on July 24, 2010 [4 favorites]

I'm reading the PDF but so far I can't the part where they provide the Vick's Vapor Rub and glow sticks? Help?

Also: 19 of 20 people correctly evaluated whether they had been adminstered the MDMA with 3 of those being unsure. How exactly can you get this one wrong? The effects are not exactly subtle.
posted by Justinian at 1:10 AM on July 24, 2010

Heh, that is actually true. I used to use empathogen.
posted by empath at 1:11 AM on July 24, 2010

Also: 19 of 20 people correctly evaluated whether they had been adminstered the MDMA with 3 of those being unsure. How exactly can you get this one wrong? The effects are not exactly subtle.

It can be, at low doses.

I'm disappointed that everyone is going for the rave jokes, though :(
posted by empath at 1:13 AM on July 24, 2010

It can be, at low doses.

That's true in the same sense that the effects of arsenic can be subtle at low enough doses. (note: I'm not calling MDMA a poison!)

In any case they were given 125mg with a 62.5mg bump at peak if they wanted it. (And they all did, of course! Except for one debbie downer). 125mg in an amphetamine naive individual will have them higher than a kite.
posted by Justinian at 1:16 AM on July 24, 2010

Also: MDMA is strongly associated with rave subculture. The jokes practically tell themselves; it's no different than munchie jokes with pot.
posted by Justinian at 1:17 AM on July 24, 2010

Justinian: 125mg in an amphetamine naive individual will have them higher than a kite.

Except all subjects were experienced with MDMA. Average of 6 times within the active group and 3 times in the placebo group. I suspect this is simply a result of convenience, since Vollenweider caught flak for giving MDMA to MDMA-naive individuals a decade ago. Going forward, we should see trials with MDMA-naive subjects.
posted by daksya at 1:23 AM on July 24, 2010

I didn't even notice that. I'm afraid to say I'm going to take the study

It looks to me like fewer than half were experienced with MDMA. 6 of the MDMA group and 3 of the control. In my opinion that's still too high; all of the subjects should have been MDMA naive and I actually am less likely to trust this study given that almost half the subjects had prior experience with MDMA.
posted by Justinian at 1:32 AM on July 24, 2010

huh that quoted bit was supposed to be Except all subjects were experienced with MDMA. Weird. But like I said it looks to me like 11 of the 20 were MDMA naive.
posted by Justinian at 1:33 AM on July 24, 2010

My bad. 6/12 were MDMA-experienced in the active group; 3/8 were experienced in the placebo group.
posted by daksya at 1:33 AM on July 24, 2010

And surely no worse than alcohol.

Unless there's a study that I am unaware of (which is very likely), my understanding is that we don't really have any conclusive evidence one way or the other on the long term impact of MDMA. Not to say that I think it's something people shouldn't use (for therapeutic reasons), but as far as I know, we honestly don't know if it's truly harmless or not.
posted by spiderskull at 1:38 AM on July 24, 2010

we honestly don't know if it's truly harmless or not

That's not the bar, when comparing with alcohol.
posted by daksya at 1:41 AM on July 24, 2010 [8 favorites]

daksya -- We have a pretty good idea what the long-term effects of alcohol use are. With MDMA, the results on seratonin levels and brain neurochemistry are largely inconclusive for regular, periodic, and rare use. So even with the alcohol baseline, MDMA's effects are an unknown quantity.

Anyway, I don't care one way or the other in terms of moral stance. But from a scientific point of view, we can't make any claim about it with any reasonable confidence. I'm glad that some people are able to benefit from it, especially with something as psychologically taxing as PTSD. Actually, I think that's what MDMA's original use was (psychiatrists used it on patients). Just don't make the false assumption that it's a totally safe drug, because we don't know yet.
posted by spiderskull at 1:48 AM on July 24, 2010

spiderskull: we can't make any claim about it with any reasonable confidence

That's not true. This was a Phase II study, which means MDMA passed the Phase I safety study. The deficit in our knowledge about MDMA is on the similar order as our deficit in our knowledge of the 30-year effects of a recently FDA-approved medicine. When will we have a definitive picture of MDMA's long term effects? Never, I reckon. Science is still working out all the infinite nuances of fundamental nutrition. But surveying a decent sample of users over a span of a few years should be enough to peg the general toxicity of a drug regimen. And there's over 30 years of anecdotal lore with MDMA, and a series of epidemiological studies covering a duration of couple of years, which found only subtle impairments among regular users. That narrows the window of possibilities. And MDMA is no great demon, cloaked or otherwise.
posted by daksya at 2:06 AM on July 24, 2010 [6 favorites]

Also: 19 of 20 people correctly evaluated whether they had been adminstered the MDMA with 3 of those being unsure. How exactly can you get this one wrong? The effects are not exactly subtle.

The one time I tried MDMA I sobbed my eyes out for like an hour.

I'm willing to believe that it might've just been a fluke though.
posted by Pope Guilty at 2:07 AM on July 24, 2010

Sadly, it's nothing new. Maybe with the new wave of war wrecked minds there will be a slightly greater impetus to continue research. The god damned fantastic results obtained from MDMA used in therapist guided counseling has been known for ages, at least as far back as 1987 when I was researching the university library stacks before deciding which drugs I would attempt. I hope it doesn't get buried again under the OMG not a major pharmaceutical company product carpet.
posted by zengargoyle at 2:46 AM on July 24, 2010

As someone who is currently in treatment and therapy for PTSD - and as someone who has had pure lab grade MDMA a few times a long, long time ago in a safe, non-rave, non-party environment... and as someone who has recently experienced an SSRI...

Please, please hand me about 150mg of pure MDMA and a therapist in a supportive, clinical environment. I've looked for experimental treatment programs. I've joked about it with my therapist wistfully, yet knowing it's not quite yet legal or possible.

Please, I'm begging you. It would save me years of work. It's not cheating. If SSRIs and the wild array of chronically over prescribed antidepressants aren't cheating - neither is MDMA.

To compare the two I would have to use a complicated mixed analogy. Current psych meds feel and seem like a very sharp, cheaply made and dangerous garden trowel - it moves a small amount of dirt, but in each small scoop there is a lot of danger. MDMA feels like an extremely well engineered bulldozer or skip loader. Precise, effective and it moves a whole lot of dirt all at once, without all the labor and struggle. It's not something someone needs to take every day, or even every month or year - or even more than once or twice.

Please, support MAPS and legitimate research on empathogens and psychedelics. There's something there, there. So many people need to process and heal.
posted by loquacious at 2:49 AM on July 24, 2010 [24 favorites]

Too bad the PTSD comes back if you listen to Sandstorm
posted by hellojed

Sandstorm rules.
posted by empath

Why did I click on either of those links?

I guess I'm just thankful that I didn't actually know the name of that fucking song until now.

Unicorn chaser -Heiko Laux
posted by loquacious at 3:07 AM on July 24, 2010 [2 favorites]

we don't really have any conclusive evidence one way or the other on the long term impact of MDMA ... we honestly don't know if it's truly harmless or not.

So basically, it's like all the other the new drugs being pushed to market now?
posted by Avelwood at 6:17 AM on July 24, 2010 [5 favorites]

Does anyone know the case law that prevents some PTSD sufferer like loquacious from suing the federal government over MDMA's classification? I'm sure people tried this with marijuana, yes?

In any case, I'd expect some European countries offer PTSD treatment using MDMA. I've gathered that psychotherapists are kinda whacked out in some European countries, like crazy amounts of Freudian psychoanalysis in Germany, but they've modern approaches like cognitive behavioral therapy too.
posted by jeffburdges at 6:31 AM on July 24, 2010

This is really important stuff. Huge. It's really tempting for me to get all negative about how one trial with 20 subjects is basically ripe for being shat on by big pharma (one dose of a cheap drug vs. a lifetime of SSRIs), government (drugs are bad, give us billions of dollars for law enforcement), corporations (happy people don't respond well to advertising), and religious groups (happy people don't need a cult) everywhere. But I'm not going to do that, because then I'd get really, really furious about millions of miserable lives, geological epochs of wasted human lifetime, and our dystopian society based on the principle of a privileged few elites preying on the tears and broken backs of a proletarian underclass kept permanently in a hypnotically suggestible state of anxiety, fear and self-loathing.

Instead, I chose to believe that despite the best efforts of practically everyone seated at the capstone of the pyramid, there wil come to be before too long myriad underground therapy centres where a few risk-taking therapists and pharmacological professionals will quietly use these drugs to help as many as they can to become what they could truly be if they could only stop being afraid.
posted by seanmpuckett at 6:41 AM on July 24, 2010 [9 favorites]

Given how not "harmless" many of the SSRIs are--and I say this as someone who's generally in favor of psychiatric medication, mind, but the side effects can range from the mildly annoying to the seriously life-disrupting--I am puzzled at the fact that this seems to be the standard things like MDMA (and LSD, and marijuana for that matter) have to meet to be considered acceptable for use in a supervised, prescription capacity.

We have all kinds of harmful stuff that we're allowed to do and use all the time. Christ. Tobacco is legal! We know it kills people! You don't even have to have a prescription!

Which, all in all, tends to make it seem like the real problem is that any drug which makes you feel good instead of just making you feel not-awful is considered bad and dangerous.

(Maybe I'd just like them to make them legal so I can finally try them, though. Sigh. Being a law-abiding citizen is rough, sometimes.)
posted by gracedissolved at 7:03 AM on July 24, 2010 [1 favorite]

In any case, I'd expect some European countries offer PTSD treatment using MDMA. I've gathered that psychotherapists are kinda whacked out in some European countries, like crazy amounts of Freudian psychoanalysis in Germany, but they've modern approaches like cognitive behavioral therapy too.

It hasn't quite reached that stage yet, though there have also been studies in Europe (Switzerland and Spain), see the MAPS MDMA page.

Historically, MDMA was used therapeutically in the USA, prior to criminalisation. Apparently it was used, with some success, by psychiatrists as part of couples therapy, to encourage clients to open up to each other (see Nicolas Collin's Altered State).

loquacious: Current psych meds feel and seem like a very sharp, cheaply made and dangerous garden trowel - it moves a small amount of dirt, but in each small scoop there is a lot of danger. MDMA feels like an extremely well engineered bulldozer or skip loader. Precise, effective and it moves a whole lot of dirt all at once, without all the labor and struggle. It's not something someone needs to take every day, or even every month or year - or even more than once or twice.

Of course, taking MDMA every day or even every week is likely to lead to some fairly unpleasant side-effects after a little while. Trust me when I say that, no matter how pure your MDMA is, if you abuse it, then you eventually start to lose the positive effects, and experience more negative ones. (If I took that 150mg with you, I'd probably feel....good. But no more than that. Not that sense of wonder and OMG my life has just been transformed everything is so clear now...). So for someone with more standard depression, MDMA probably isn't going to help so much, compared to SSRIs. But for you, I can only say that I wish you had access to it, in association with therapy.
posted by Infinite Jest at 8:34 AM on July 24, 2010 [1 favorite]

Not much point in taking MDMA every day as it is anti-addictive like LSD.

Having seen heavy usage, there are definite problems with abuse. I can't see what harm a handful of sessions could have.
posted by jcking77 at 9:05 AM on July 24, 2010

Fuck, I can't imagine taking it daily. I had a few weekends about 10 years ago where I did it friday and saturday night, but that stopped being effective really quickly, and I couldn't even do it every week after about 6 months.

All the good I got out of it, I got in the first 2-3 months. Everything after that was just partying.
posted by empath at 9:26 AM on July 24, 2010 [3 favorites]

Not much point in taking MDMA every day as it is anti-addictive like LSD.

I'm not exactly sure what you mean by "anti-addictive" here but assuming you mean non-addictive, that's not true. It's not nearly as addictive as methamphetamine or heroin but it is still an amphetamine and people can and do become addicted to it, especially psychologically.

If you mean it isn't physically addictive like benzodiazepines, well, neither is methamphetamine and we would never call that anti-addictive.
posted by Justinian at 9:41 AM on July 24, 2010

I think he was saying that it stops working with regular use, which is true.

You get less and less euphoria, and you get something more and more like a speed-rush. It's very, very, very rare that people keep going with it once it gets to that point. The folks who have addictive personalities will quickly move on to straight crystal meth or cocaine at this point.

I know a good few dozen people who were regular e users 10 years ago. I can't think of a single one of them who I would say was addicted to MDMA. Some of them went through phases where they over indulged for a length of time (months not years), but at some point they all just started using it less and less, and didn't make a big deal about it and didn't have a hard time quitting.

The ones that became what I would call problem drug users switched to crystal meth pretty quickly and pretty exclusively. And we're legally dosing millions of children with amphetamines daily.

I actually knew more people with ketamine problems than ecstasy problems, to be honest, and that was a pretty small subset of people I knew that used ecstasy. I really can't think of a single person I knew who I would say had an ecstasy problem. The people who became obnoxious, lost jobs, and so on were almost always using other drugs.
posted by empath at 9:57 AM on July 24, 2010

jeffburdges' comment makes me want to know, out of curiosity, have any drugs ever been taken off Schedule I due to the discovery or acceptance of a medical use?
posted by hattifattener at 10:54 AM on July 24, 2010

jeffburdges' comment makes me want to know, out of curiosity, have any drugs ever been taken off Schedule I due to the discovery or acceptance of a medical use?

Yes. I'm sure there are many more. Notably, this was also done for Marinol (synthetic THC) in 1986, in DEA 51 FR 22946-47, and then again (to move it from Schedule II to Schedule III) in 1999. In light of that decision, the history of attempts to move marijuana itself from Schedule I to Schedule II is quite interesting...
posted by vorfeed at 11:21 AM on July 24, 2010

Yeah the list of schedule 1 drugs is absurd.

How are marijuana and MDMA schedule 1, while Crystal Meth, Cocaine and PCP are schedule 2?
posted by empath at 11:26 AM on July 24, 2010

Has anybody ever challenged the scheduling of MDMA in the courts? It seems on the face of it that it would have to be Schedule III at the most.
posted by empath at 11:28 AM on July 24, 2010

Sort of; worth reading about it.
posted by daksya at 11:34 AM on July 24, 2010

Parkinson's Disease is caused by the loss of a brain chemical called dopamine, which is vital for movement. The result in Tim [Lawrence] is the slow freezing up of his body. But, like many people who contract the illness early in life, Tim suffers just as badly from the drug he takes to combat the disease, which gives him wild, flailing movements called dyskinesias. These are the devastating side-effects of L-DOPA, the drug he is prescribed to unlock his frozen limbs.

However, within 90 minutes of taking an Ecstasy tablet, Tim is able to get off the floor and perform backflips, somersaults and swallow-dives in a gym. The trouble is, of course, that Ecstasy is dangerous and illegal - a Class A drug deemed of no therapeutic value.

more here:
This revelation immediately led to research to see if the effect experienced by [Tim] Lawrence could be used to help other patients with Parkinson’s disease. An extensive study conducted in the UK and published in 2003 indicated that the effect was a real one. However, MDMA itself is not likely to be used as a treatment — having patients taking a drug that significantly alters their mood everyday is impractical. Instead, research is now focussed on working out what it is about MDMA that makes it useful for patients with Parkinson’s and developing drugs that operate in a similar way but without the mind-altering effects.
posted by Bwithh at 11:48 AM on July 24, 2010

I'm not citing studies but merely relating personal experience, but I do believe MDMA has the possibility of becoming dangerously addictive.

For a couple years in high school, with the usage period constrained to about 7 months, I had access to free, very strong and pure MDMA. I tried it the first time for fun and partying, and found the effects so incredibly attractive. As a PTSD sufferer from childhood trauma, as well as someone struggling at the time with severe depression and anxiety, MDMA was an absolute miracle.

The problem was that existence outside of MDMA was a nightmare. A living nightmare. So when I took the pill, I had a good 12 hour break from that nightmare, as I would always, always, ALWAYS re-dose to keep the high going. But eventually I had to stop, and go to class and be around people and situations that didn't allow for the high. Black Monday syndrome is absolutely real. There is a feeling of loss that comes at the end of a high. And if you're default state is one of depression, stress, and anxiety, Black Monday and the associated nightmare of daily life is that much blacker for the relative comparison.

Eventually, you run out of pills. And you've eaten a lot of serotonin up in the brain. And normal events that might cause extreme happiness or feelings of elation don't stack up.

This all ended in rehab and SSRI/SNRI medication. Taking MDMA did not solve a single problem for me. It didn't move the dirt of trauma anywhere, it just took the feeling of being covered in dirt away for a short amount of time. I haven't touched the stuff in 12 years, and probably won't ever touch it again.

The best thing I can say about "legal" medications is that they don't take me waaaay up. They don't elevate me to a level that makes every other level seem distant and unattractive. That works for me. Might not for others, YMMV, etc.
posted by lazaruslong at 11:58 AM on July 24, 2010 [6 favorites]

EMDR did some amazing things for my PTSD. I still ended up taking an SSRI as a compliment and long term maintenance thing to deal with some background anxiety. Three sessions of EMDR and I was having markedly fewer episodes and things that had previously triggered me didn't. When my therapist suggested it, I read up on it and concluded it was new age junk. Still I was pretty desperate to try anything as life had become intolerable. So I did and it worked. I have no idea if MDMA is an effective treatment but I think we should let doctors do more studies. As a patient it is my conclusion is that medical science is still pretty much fumbling around in the dark on PTSD.
posted by humanfont at 12:04 PM on July 24, 2010

Also have to add that marijuana is truly a godsend. There is not a single medication on the planet I have found yet that has the range of beneficial effects marijuana induces in me. I highly, highly recommend sampling various strains for folks with crippling depression and anxiety until you find the right one. It will mostly likely help at least a little, and possibly help a whole heaping shit ton.
posted by lazaruslong at 12:05 PM on July 24, 2010

How are marijuana and MDMA schedule 1, while Crystal Meth, Cocaine and PCP are schedule 2?

I know this is a rhetorical question but Cocaine is schedule II because it is a very useful topical anesthetic. PCP is schedule II mostly because, so far as I am aware, they never got around to rescheduling it as I after far better anesthetics replaced it's short-lived medical use. Crystal is schedule II because you can't dose up little Bobby with a schedule I drug. (And, yes, meth is an approved ADHD treatment.)

Marijuana is schedule I again for historical reasons; there was a huge scare campaign a while back where idiot white folks were convinced the brown people were coming for them all hopped up on goofball wacky tabbacky. MDMA is schedule I because nobody wants to watch adults suck on pacifiers and hug puddle.
posted by Justinian at 12:05 PM on July 24, 2010 [1 favorite]

And just in case someone reads that and decides to try it, please start with the weaker stuff first. Try a nice outdoor sativa way before you go up to the crazy strong 14% indicas. The feelings of paranoia and anxiety those strains can cause is not pleasant for folks like me looking to get rid of those feelings. But a nice 6% sativa is a fucking miracle.
posted by lazaruslong at 12:06 PM on July 24, 2010 [3 favorites]

MDMA is schedule I because nobody wants to watch adults suck on pacifiers and hug puddle.

Man, I could sure use a hug puddle right about now. It's been entirely too long.
posted by ApathyGirl at 12:34 PM on July 24, 2010 [2 favorites]

"Also: 19 of 20 people correctly evaluated whether they had been adminstered the MDMA with 3 of those being unsure. How exactly can you get this one wrong? The effects are not exactly subtle."

Take a group of people who have disassociation--which makes you feel like the world is unreal, disoriented, you can't feel anything, can't think well. And they have other fucked-up brain hiccups like flashbacks, panic attacks, hyperalertness, paranoia. Then they don't know what MDMA feels like. I'm not surprised that some would be confused.
posted by internet fraud detective squad, station number 9 at 12:44 PM on July 24, 2010

In any case, I'd expect some European countries offer PTSD treatment using MDMA.

They may offer it, but not legally.
posted by Obscure Reference at 2:35 PM on July 24, 2010

I've never tried MDMA, so I'm curious as to how it might be used in therapy.

Is it effective in small doses? Does one have to get "fucked up" for it to be effective?

I currently use an SSRI, but the side effects kinda suck and if I miss doses the symptoms of discontinuance are just cruel and evil.

If it really has long term positive effects it sounds like a miracle and psychological life saver.
posted by snsranch at 5:12 PM on July 24, 2010

snsranch: I dont think this thread accurately represents what is known about MDMA's effects on the brain:

FACT: In mammals, MDMA exposure causes a diminished activation of serotonin releasing neurons that is measurable months and years afterward.

FACT: Serotonergic neurons are involved in regulating affect, mood, and emotions.

There is no dispute among neuroscientists about these two facts. Unfortunately government propaganda in the 90s in the US and especially in the UK means that now cautionary voices have little credibility. The anecdotal benefits in this thread need to be reconciled with the above two facts before anyone reading this can make their own decision whether to use MDMA. Ordinary personal decisions regarding illicit drugs might involve considering a drugs toxicity or maybe considering how addictive the drug is. Neither of these work in this case. MDMA is not toxic in the sense that we can point to a biological structure that is destroyed or damaged (yet). And it is not physically addictive, but it is a profound experience---you will want to do it again after the first time. Therein lies the peril of MDMA.

The lesson from the literature for people who want to use it:

MDMA should be used infrequently at the lowest effective dose.
posted by dongolier at 5:14 PM on July 24, 2010

Dongolier, consider the following:

FACT: In mammals, H20 exposure causes confusion, muscle weakness, twitching, nausea, vomiting, and in extreme cases death.

That is a true statement, just as yours is. The issue is at what dose this happens, repeated how often. My suspicion is that any permanent damage requires very high doses taken relatively frequently. The current state of knowledge on MDMA appears to be consistent with that view although it is still unclear at exactly what dose you start seeing big enough changes such that users only experience partial recovery.
posted by Justinian at 6:41 PM on July 24, 2010

Citation, dongolier?
posted by empath at 6:43 PM on July 24, 2010

He linked to the Wikipedia article on the subject in his comment. Yeah it is wikipedia, but the wikipedia article itself links to credible journal articles.
posted by Justinian at 6:45 PM on July 24, 2010

snsranch: I would not recommend it as a replacement for anti-depressants or for long term depression. In fact, it would probably make depression worse for a lot of people. You're basically taking a somewhat off balance scale and kicking it. Sure it goes way up, but then it goes way down when it comes back.

I would recommend it for things like social anxiety, etc, that have to deal with fear and closing yourself off from others.

But yes, it's effective at low doses, imo. There's definitely a 'omg, please hug me, let's talk about our feelings' dose, and an 'OMG I am so fucked up I can't even see straight' dose.

At lower doses, you'll definitely see things as more beautiful, have more energy, feel talkative, want to hug strangers, etc.

At higher doses, you get the jaw clenching, urge to dance, restlessness, visual and audio distortions, sweating, etc..

Either way, though, the feelings don't last very long. The first few times you do it, you might feel good for days or even weeks afterward and not really have much of a come down. By the 6th or 7th time you do it, you'll already be building up tolerance and the comedowns will be noticeably worse.

Basically, if you feel like you have an issue you need to work out with how you relate to people or see your relationships with other people, it can be a miraculous eye-opener. If you actually have a chemical imbalance, though, you may have a fun several weeks and months while you ride an emotional rollercoaster, but at the end of it, you'll still have a chemical imbalance.

And, btw, if you're taking anti-depressants -- some of them interact dangerously with MDMA. Some of them just weaken the effects. Either way, you'll have to stop taking them if you want to try it.
posted by empath at 6:52 PM on July 24, 2010 [1 favorite]

The two facts: That's exactly what SSRIs do.

but it is a profound experience---you will want to do it again. Yea, dongolier, thanks for that. I'm definitely not looking for an "experience", I'd just like to be able to perform as I did prior to whatever psychological damage I experienced. Precisely why I'm curious about dosage and effects.

If effective doses are such that one has to have an "experience" I suspect that use in therapy would probably have to be in a controlled environment. As mentioned above, not everyone has a good experience with MDMA.

However, medical marijuana use might set a precedent for safely getting high with great therapeutic benefits.
posted by snsranch at 6:56 PM on July 24, 2010

Justinian, I'm not seeing anything in the Wikipedia article that justifies his 'fact'. I'll just quote from the relevant section at length:

Experiments indicate that both moderate and high dose or rapidly repeated MDMA exposure may lead to long-lasting changes in neurons that make serotonin. Serotonergic changes have been demonstrated experimentally in the brains of all mammalian species studied, with most studies involving rats. In these studies, the brains of animals who are given high or repeated doses of MDMA show long-term decreases in all measures of serotonergic functioning, including concentrations of serotonin, tryptophan hydroxylase, and binding of the serotonin transporter protein. Although measures of serotonin are decreased, there are no decreases in the number of cells in the dorsal raphe, which indicates that the serotonin neurons have not died. Limited studies attempting to stain and photograph serotonergic axons shortly after high-dose MDMA exposure have reported that axons appear swollen and misshapen, as if they might be degenerating. However, few studies have attempted to stain and examine axons and with the measures commonly used in MDMA studies it is difficult or impossible to distinguish axon loss from decreases in production of markers of serotonin.[41][42]
Animal studies show that there is recovery of serotonergic markers. However, if axons are actually regrowing, there is no assurance that they will reform their original connections. While rats show extensive recovery that sometimes appears complete [43][44], some primate studies show evidence of lasting alterations in serotonergic measures. Human studies, discussed below, show recovery, but these studies use indirect measures that may lack sensitivity for detecting subtle changes.

I don't think anybody disputes that MDMA use depletes serotonin. That's obvious to anyone that does it more than a few times. The question is whether it recovers, how long it takes, and how much loss there is.
posted by empath at 6:57 PM on July 24, 2010

Black Monday syndrome is absolutely real. There is a feeling of loss that comes at the end of a high. And if you're default state is one of depression, stress, and anxiety, Black Monday and the associated nightmare of daily life is that much blacker for the relative comparison.

It's especially brutal as a teenager (oh I can still remember some of those Mondays), but even generally true: the serotonin flood caused by MDMA can lead to a serotonin deficit for a day or week or even month after. This side effect is almost entirely dependent on diet, though, and can be totally neutralized with supplements (5-HTP, the pre-cursor to serotonin, is available at most herbal supplement stores. It's also great at extending REM sleep... = crazy dreams!). In my opinion it's pretty irresponsible to offer anyone MDMA without providing 5-HTP as well, because in certain individuals the "black monday" can be utterly devastating. Unfortunately this is very poorly known because, well, it's illegal.
posted by mek at 6:59 PM on July 24, 2010 [1 favorite]

I think this is probably the best depiction of the ecstasy come down I've seen. It was never so much depression as it was unpredictability. I'd go from wanting to dance on street corners to music I could only hear in my head to wanting to punch somebody for coughing at the wrong time and back to being all smiles again a minute later. Or terrible songs on the radio making me cry, just because they were so beautiful sounding or they reminded me of something. That would last for like a day. Then back to 'normal', whatever that was.

The fact that I knew what it was coming from made it pretty easy to tolerate. If I was like that all the time, for no apparent reason, it would have been unbearable.
posted by empath at 7:10 PM on July 24, 2010

So how difficult is this stuff to make at home?
posted by Jacqueline at 7:52 PM on July 24, 2010

Easy, if you can get your hands on some safrole. Also, you can make root beer while you're at it.
posted by mek at 8:00 PM on July 24, 2010

Pikhal tells you how.

Unfortunately all the precursors are rather strictly controlled.

Also, safrole production harms endangered species :(
posted by empath at 8:07 PM on July 24, 2010

MDMA is schedule I because nobody wants to watch adults suck on pacifiers and hug puddle.

Spoken like someone who's never been in a really good hug puddle.
posted by mosessis at 9:51 PM on July 24, 2010 [1 favorite]

Just a further note of caution on attempting to self-medicate with MDMA: your chances of actually getting pure MDMA may not be very high. Given that it's illegal, there's no quality control in the pills that you might buy. There's also a major crackdown on the precursor chemicals, especially sassafras/safrole oil (mostly harvested in Cambodia/Vietnam/Thailand) which has led to a shortage of genuine MDMA.
posted by Infinite Jest at 2:14 AM on July 25, 2010

I don't think anybody disputes that MDMA use depletes serotonin. That's obvious to anyone that does it more than a few times. The question is whether it recovers, how long it takes, and how much loss there is.

I agree, which is why that's basically what I said myself to dongolier.

My personal belief is that the physical effects on the brain are probably not quite as innocuous as you seem to believe but that it's definitely a lot less harmful than dongolier's comment implies. You aren't going to fry your brain because you take a pill or two a couple weekends a year. Or even a month, probably. Some of the people taking it 3 times a week for months are not doing themselves any favors though. Note that this is also true of getting hammered on alcohol 3 times a week for months.

And, btw, if you're taking anti-depressants -- some of them interact dangerously with MDMA..

Hah, MAOI inhibitors. But MAOI inhibitors kill you if you breathe funny. Have you ever seen the list of things that kill you while you're taking an MAOI? It's crazy.
posted by Justinian at 3:33 AM on July 25, 2010

Oh, I guess there are some anecdotal claims that taking a shitload of MDMA along with SSRIs might occasionally lead to serotonin syndrome but I think the evidence for that being any sort of serious risk are scanty at best.
posted by Justinian at 3:34 AM on July 25, 2010

MDMA Neurotoxicity Research in Humans [PDF] from the FPP has alot of interesting info for anyone trying to determine for themselves what a "safe level of exposure" might be.

p14 has a graph that shows spinal fluid concentrations of an MDMA metabolite decrease by half over the range of zero to 50 MDMA lifetime doses.

p19-30 broad catalogue of clinically significant neurocognitive deficits in users/non-users, with several mentions of a dose-dependent relationship. if so, it is reasonable to imagine that small doses cause small cognitive deficits, larges doses... large deficits.

p44 frequent use of MDMA is a risk factor for lasting neurocognitive changes (I would interpret this might prevent its future use as a substitute for SSRI psychiatric treatment).

The diminishing quality of subsequent MDMA experiences reported by users (like empath) cannot be interpreted optomistically: very simply whatever/wherever/however MDMA acts upon the relevant functional systems in the brain, its diminished ability to do so, represent a loss of function in those systems. In a benign setting---eg. getting drunk---a tolerance effect goes away weeks or months after the repeated stimulus is ended---there is no measurable evidence that you my have gotten drunk once a few week ago. MDMA is different: we can see long term changes; and we can see a sequential dose-response of a diminishing level or lower quality of experience: this is not tolerance it is lasting impairment.
posted by dongolier at 6:47 AM on July 25, 2010

[Im not against using MDMA, It just seems like MDMA users are as biased and unreliable a source of info as the government propanda]
posted by dongolier at 6:49 AM on July 25, 2010

dongolier, from the first page of that review,

"the reported differences between matched groups of ecstasy users and nonusers are clinically subtle and can, so far, only be detected with sensitive neurofunctional and neurocognitive measures."
posted by daksya at 7:34 AM on July 25, 2010

I'm going to have to partially agree with dongolier. Only partially, because it could be that PTSD and situational depression are special cases where MDMA is an appropriate treatment for brief periods and minimal effective doses.

empath, I would not say that "you cannot be afraid on MDMA." The second time I used it, I had a horrible episode of paranoia, thought I was dying, mildly hallucinated, etc. I then had panic attacks off and on and depression for 9 months afterwards. Now, I will be the first to admit that I am an outlier. Most people do not react that way. It is also possible that the MDMA was laced with something else.

Take home message: It is possible to be very afraid on MDMA. If you have any immediate family or personal history of bipolar disorder/severe clinical depression /schitzophrenia, MDMA should be avoided.
posted by janakf at 7:48 AM on July 25, 2010 [2 favorites]

There's no way I'd take any drug from anyone that wasn't sealed and certified for purity and dosage. Especially with psychedelics, if the drug is cut, laced, impure, or poorly metered there's no telling what the trip will be like, what the side effects will be or how long they will last.

So, basically, I consider reporting of negative short term or long term effects of any drug obtained on the street to be worthless except as guidance to not take street drugs. Positive effects are similarly suspect but can be used as a guide to which drugs might have a positive effect under controlled dosing and purity conditions.

It's just too scary for me. I won't take a nutrition supplement without carefully checking its lab analysis. There's no way in hell I'm going to sample a random pill or tab from someone at a party. May as well borrow a gun from someone while assured that it isn't loaded and immediately point it at my temple and pull the trigger. Fucking crazy, man.

Which is why these drugs need to be legalized, researched and regulated right fucking now.
posted by seanmpuckett at 8:07 AM on July 25, 2010

daksya:"the reported differences between matched groups of ecstasy users and nonusers are clinically subtle and can, so far, only be detected with sensitive neurofunctional and neurocognitive measures."

is your view that the differences between MDMA users and non-users is not significant because its difficult to detect?

MDMA acts on the parts of the brain that are currently impossible to measure externally: mood, affect and emotion. Deficits in these areas are not likely to be detectable to the actual patient, much less by any other investigation. Our moods, our emotions our feelings, are so close to our own notion of ourselves that they cannot be separately tested or measured: when they change, we have changed.

My personal view is that human experience involves ups and downs, elation and sadness, joy and sorrow; forming a fascinating narrative that trails out behind us as we live out our lives---what happened and how it felt. In some people these peaks and valleys are too high and too low---these are the bipolars and its their serotonergic neurons painting their experience in bolder tones than the rest of us. But in many ways for better or often for worse, people with bipolar simply feel more.

Repeated MDMA exposure potentially has the capacity to make people feel less, to eliminate the emotional response to external events that would otherwise occur as a result of serotonergic neuron activation. But only time will tell if this is the actual nature of MDMA lesions....
posted by dongolier at 2:30 PM on July 25, 2010

But only time will tell if this is the actual nature of MDMA lesions....

I'm unaware of any studies which have confirmed the existence of MDMA-induced serotonin neuron lesions in humans - could you spare a link? Or, for that matter, do I know of any studies which have conclusively determined neural impairment. There are plenty of studies which have demonstrated differences in brain chemistry (as noted above), but that much is obvious since one group is taking drugs and the other is not.

The important thing here, dongolier, is that your criticism of MDMA is using a standard which no scientist should give a good goddamn about. MDMA must affect the brain: this much is obvious in that it causes neurological changes; it can be used to treat PTSD; and it can be used recreationally to get really, really high. The question is, does it cause significant harm in the long-term which outweighs its benefits? It (and other currently-prohibited drugs with medical applications, such as marijuana, LSD, psylocybin, etc) must be compared not to placebo, but to other commonly used drugs, such as SSRIs, painkillers, caffeine, alcohol, etcetera. Total harmlessness is not a standard we measure drugs by - if it were, the pharmacy would be out of business. So far, we have studies confirming its benefits and none confirming long-term negative consequences. Even if the latter is a possibility, it may still have benefits and valid clinical applications.

It should genuinely horrify the public that we have spent more time worrying about the long-term effects of MDMA and pot than we have for every SSRI and atypical antipsychotic patented in the last decade, combined. We certainly have some drug-related fallout in our future, but it's not the ravers that need to be worried most.
posted by mek at 5:07 PM on July 25, 2010 [1 favorite]

I wish I had a dollar for every Phase II study that shows a "very effective" therapy. I'd be wealthy. If I had a dollar for every one of these that panned out in Phase III studies, I'd have enough for a good meal.
posted by Mental Wimp at 6:13 PM on July 25, 2010

dongolier: is your view that the differences between MDMA users and non-users is not significant because its difficult to detect?

In a nutshell, yes. If your clearest encounter of these deficits is in a lab test, then these deficits are diffuse enough that they can't be differentiated from the natural up & downs among humans.

Deficits in these areas are not likely to be detectable to the actual patient, much less by any other investigation.

So you're asserting that MDMA chiefly produces deficits unlikely to be detected by either the subject or others. That's convenient.

Repeated MDMA exposure potentially has the capacity to make people feel less, to eliminate the emotional response to external events that would otherwise occur as a result of serotonergic neuron activation.

Wow. You're claiming elimination of affect towards external events. Let's lower the bar. Please cite any studies that point towards MDMA use leading to blunt affect or anhedonia. Like I said, a few epidemiological studies on MDMA have already concluded. The deficits thay have found are not of the nature you describe nor of significant magnitude (among non-heavy users).
posted by daksya at 9:55 PM on July 25, 2010

daksya: So you're asserting that MDMA chiefly produces deficits unlikely to be detected by either the subject or others. That's convenient..... Please cite studies....

its my own idea: repeated MDMA exposure potentially has the capacity to make people feel less.

there isnt any direct evidence for it, and their wont be until we can actually watch people have "feelings", maybe while in an fMRI machine: our emotions are too close to who we are for us to realize normal versus impaired "feelings". yet the indirect evidence for my hypothesis exists already: MDMA causes diminished activity of serotonin neurons, and, serotonin neurons create mood, emotion and feelings.
posted by dongolier at 9:38 AM on July 26, 2010

we can actually watch people have "feelings", maybe while in an fMRI machine

Leaving aside any conceptual issues, fMRIs don't have the resolution to pinpoint neuro-correlates in realtime.

serotonin neurons create mood, emotion and feelings.

Serotonin is attributed with modulating affect; I'm not aware of any literature claiming the role of creation. Cite, please.
posted by daksya at 10:02 AM on July 26, 2010

its my own idea: repeated MDMA exposure potentially has the capacity to make people feel less.

So, despite the fact that millions of people have taken hundreds of millions of doses over the past 20 years and not a single study has shown that this happen, you have an idea that it does, and we're supposed to just go with that.

Got it.
posted by empath at 10:14 AM on July 26, 2010

empath you apparently are more interested in jusitfiying your own positive experience with MDMA than you are in listening to the science.... i guess im posting for people who want to make their own decisions based on the actual science behind MDMA....
--------------------------------------------------------------------

mek: MDMA...must be compared to other commonly used drugs....harmlessness is not a standard we measure drugs by...

yes, good point.

psychoactive substances (with the exception of MDMA,cocaine and meth) act as agonists or antagonists of endogenous neurotransmitters at the synapse. these molecules are released into synaptic cleft---which is the space between the end of one neuron's axon and the adjacent neuron's dentrite---and bind reversibly to specific receptors (like a lock and key) and in the case of external drugs: they mimic ("agonist") or block ("antagonist") the endogenous neurotransmitter's effect on the downstream neuron. in this way you can group and classify drugs according to endogenous neurotransmitter and receptor target:

LSD and psilocybin: serotonin agonist (specifically 5-HT2a receptor)
alcohol: GABA agonist
caffeine: adenosine antagonist
ketamine and phencyclidine: glutamate antagonist (specifically NMDA receptor)
THC: anandamide agonist (specifically CB1 receptor)
heroin: β-endorphin and enkephalin agonist
nitrous oxide: many receptors, also not well understood

meth and coke (and SSRI's) operate inside the presynaptic neuron: they interfere with reuptake of the endogenous neurotransmitter:

cocaine: dopamine agonist (re-uptake inhibitor)
methamphetamine: dopamine and serotonin agonist (re-uptake inhibitor)

MDMA is a serotonin agonist: it operates on a Serotonin Transport protein (SERT) within the neuron. it binds and causes an immediate flood of serotonin at the synapse as well as prevents the re-uptake of sertonin, and, it also redistributes SERT from the synapse where it is useful to the cell body where it cant influence serotonin levels at the synapse (it does other things as well, but not thought to contribute to MDMA's long term effects). this is a novel mechanism for drug action and suggests that MDMA has longer term consequences than any of the other recreational drugs. this abstract seems agree: "Ex-ecstasy users' verbal memory showed no sign of improvement even after over 2.5 years of abstinence and thus may represent persistent functional consequences of MDMA neurotoxicity." another abstract: "Abstinent regular users show reduced 5-HT transporters,...memory problems, higher cognitive deficits, various psychiatric disorders... Functional deficits may remain long after drug use has ceased and are consistent with serotonergic axonal loss in higher brain regions."

Finally, Association of a Functional Polymorphism in the Serotonin
Transporter Gene With Abnormal Emotional Processing in
Ecstasy Users[PDF], is a fascinating paper that outlines a genetic predisposition to cognitive disturbance from MDMA use. two of the tests that outline differences between users and non-users are the Beck Depression Inventory and Affective Go/No-Go test---a test that measures response times to happy and sad words flashed on a screen. MDMA users in the genetic group with a lower expression of SERT performed worse on this test (ie. their results were similar to those with monoamine (eg. serotonin) depletions). i guess optomistically this study suggests that some people carry genetic protection from ecstasys harm---ie. they have extra SERT protein to burn at raves.
posted by dongolier at 10:19 AM on July 26, 2010 [1 favorite]

Thank you for the FPP.

All I came in here to say is that having had access to this substance in the past has sometimes very, very badly made me want to "play a doctor at the holiday inn".

Having said that, science dammit, it's the neurotoxicity debate again. Anecdotally, I am pretty sure it effects longterm change in individuals. But how much? I couldn't help to note a lack of figures in the cites tacked on to the cut-and-paste "neurotransmitter 101" above. Even with the tiny sample sizes I think we would need to know: On a percent scale or otherwise, how much impairment in real-life terms will which amount cause? Mild users = Under 5%? Moderate = Under 10%? Then we could maybe compare to the posted study and see an impairment/benefit ratio. IMHO we would see the ratio pale in comparison to other things desperate people have tried. Conclusion, someone needs to find more loopholes in the pharma mafia and do studies like this, but bigger. In the meantime, here's some more selectively quoted studies.

On a (neurotoxicity-related) tangent, but not to prove anything, ikkiyu2 posted this interesting answer once in an AskMe.
posted by yoHighness at 11:39 AM on July 26, 2010

yoHighness:this one dude lost over half his SERT protein.... (yeah, sample size: one dead tweaker.)
posted by dongolier at 12:32 PM on July 26, 2010

high dose, polydrug user.
posted by empath at 12:58 PM on July 26, 2010

yoHighness: this PDF has a chart on p2 showing dosage vs. some metrics of impaired serotonin system function (decreased spinal MDMA metabolite, responses to 3 different 5-HT agonists).

there is one paper (McCann, L-Tryptophan) that appears to show MDMA use actually raises response to that 5-HT agonist. but if you look closer the average abstinence period of 18weeks with a standard deviation of 27weeks which means a substantially number in the study had used MDMA recently.
posted by dongolier at 3:17 PM on July 26, 2010

<soapbox>

I won't go on about the science, risks, benefits, and all that. You can read it for yourself and you'll need to draw your own conclusions. But if you believe the drug war is immoral, please give. Give to MAPS if you want to further scientific research. Give to Erowid if you want to make sure people have access to information. Give to NORML if you... I dunno, like getting high.

Just give. We end this war on science and reason though votes, cash, and actions.

</soapbox>
posted by chairface at 7:09 PM on July 26, 2010

Also, vote YES on California prop 19 in November! Even if you don't live here! Hell, vote multiple times!
posted by Justinian at 2:38 PM on July 27, 2010

The media coverage of the MDMA Clinical trial result stinks

A belated realization on the media coverage of the MDMA/PTSD paper
posted by homunculus at 8:17 PM on July 30, 2010

from the above link: "Of course this is true, the driving force behind getting these studies rolling is the recreational legalization Trojan outfit MAPS."

I guess there's something to be said about wearing your bias on your sleeve, but it isn't really conducive to good science reporting to automatically assume that they are not doing good science.
posted by mek at 2:27 PM on August 1, 2010

speaking of good science, this September's Nature has a free article (free account req'd): "The neurobiology of psychedelic drugs: implications for the treatment of mood disorders" (F Vollenweider, M Kometer) outlining how LSD and ketamine might treat OCD, anxiety disorders, cluster headaches and depression.

im still digesting the article, but so far I HIGHLY recommend getting the pdf if not just for the second graphic: a polar graph showing three of Dittrich's "Five-Dimensional Altered States of Consciousness" (5DASC) rating scale for different reference doses of ketamin and psilocybin. the five primary altered states are:

1. Oceanic Boundlessness
2. Anxious Ego-Disintegration
3. Visionary Restructuralization
4. Acoustic Alterations
5. Altered Vigilance
posted by dongolier at 4:00 PM on August 21, 2010