FDA grants Breakthrough Therapy designation to MDMA for treatment of PTSD
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I believe there's a case that funding MDMA research has very high dollar/impact returns - or at least that it's likely enough that it's worth a thorough exploration.
It sounds like they still need to raise about $12 million, which is shockingly small compared to the ~$1.5bn/yr NIMH budget - and all of it will come from private philanthropists, as governments aren't yet willing to fund the work and for-profit companies don't see much profit yet due to the lack of patentability.
If you're on HN and this is the first you're hearing about this research, some resources:
- A short video excerpt from a documentary on MDMA therapy - https://www.youtube.com/watch?v=W9iKx2MKS70
- NY Times article - https://www.nytimes.com/2016/11/29/us/ptsd-mdma-ecstasy.html
https://store.maps.org/np/clients/maps/donation.jsp?campaign...
Obviously for certain classes of PTSD sufferers the tradeoff would be worthwhile (similar to how the negatives of stimulant therapy for ADD are a trade-off if it enables an otherwise healthy and productive life) - so I'm hoping this will enable further research into the negative side-effects of stimulant therapy for PTSD - as well as better research into supposed damage-mitigation techniques - so far a lot of published research on stimulants has been only performed on rodents whose CNS are considerably different compared to our own.
Anecdotally, I have comorbid ASD and ADD with an anxiety disorder and I found that amphetamine-based drugs prescribed for my ADD (Adderall, Vyvanse, et cetera) have worked wonders for my anxiety issues - which surprised my psychiatrist because typically worsening anxiety is a side-effect of amphetamine.
The therapeutic dose is likely a fraction of a single recreational dose (1/10-1/2). Neurotoxicity is likely most pronounced by crazy recreation drug users taking tens of doses in a single day/weekend. I'd be surprised if therapists found it useful for their PTSD patients to be 'rolling face', but I'm no expert.
EDIT: Seems like I'm wrong - therapists are using roughly 1 full dose for therapy
See http://journals.sagepub.com/doi/full/10.1177/026988111246482...
Is oxidative-stress the only mechanism of neurotoxic action, or are there other effects at work, such as dopamine-downregulation or exhaustion?
The really interesting thing is that these effects somehow persist beyond the acute trip. The experience seems to include learning, i.e. the patient experiences positive emotions while (and possibly because of) connecting with people, and sees that any fears they may have had do not materialise (i.e. judgement). As a consequence they tend to become more open in everyday life, and especially with the therapist they shared this experience with.
I'd love to read some therapists' experiences. For them, it must be quite an exhilarating experience as well–just imagine how you'd feel if you suddenly became 10x as effective as your job.
I wish I could feed my laptop a pill that would make it write better code for me
This is why I am so glad to see this approach tightly coupling carefully controlled monitoring and talk therapy alongside administration of the drug. I myself had a great experience of 'opening up' at a rave once upon a time, but the comedown was horrible and I felt much worse afterward than before. It was like rising out of purgatory, getting a glimpse of heaven and then having to go live in hell, with a strong sense that heaven had only been an illusion.
A later experience was better. Which reminded me that as with anything else that's strongly psychoactive, set and setting are absolutely key.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3053129/
> In a study designed to minimize limitations found in many prior investigations, we failed to demonstrate marked residual cognitive effects in ecstasy users.
> We found little evidence of decreased cognitive performance in ecstasy users, save for poorer strategic-self-regulation, possibly reflecting increased impulsivity. However this finding might have reflected a premorbid attribute of ecstasy users, rather than a residual neurotoxic effect of the drug.
Good news, seems like even in long-term ecstasy users they have good cognition.
Edit, also:
> MDMA researcher Matthew Baggott: “To the best of my understanding, doses around 1.5-1.7 mg/kg MDMA (roughly 100 to 125 mg MDMA) are unlikely to cause long-lasting serotonin changes. Studies by MAPS have looked for changes in mental abilities after people participated in their studies, with some participants receiving 125 mg followed by 62.5 mg, and have not found any changes.” MAPS study protocol involves 3 - 5 week breaks, and a total of 2 or 3 MDMA sessions in total.
https://rollsafe.org/mdma-side-effects/#possible-long-term-s...
And if you want to become an expert and get a summary of all of the safety research, ~1 page of reading here: https://www.mdmawiki.org/wiki/Is_MDMA_Neurotoxic%3F
> Our largely negative findings appear inconsistent with many past studies as well as some more recent investigations (55-57) that report lowered cognitive functions in ecstasy users. Indeed, our findings are inconsistent with several findings in our own pilot study (15)
Its likely that the monkeys that are seeing neurotoxic effects are taking something like 4-8+ doses at once and doing that twice a day for four days straight. That would fry anyone.
(i'd imagine this information is available elsewhere, this is just the instance i happened to come across myself...)
But yes, MDMA anecdotally is much safer than anything else.
MDMA is itself bioactive/psychoactive, and MDA is more neurotoxic.
I think RCs as adulterants like 2cb or similar phenethylamines started to creep into the scene in the early 2000s. Then cat was _huge_ mid 2000s until it and the other RCs started to get prohibited.
This is just what I picked up from people I knew doing these things btw. I was there for the music and girls.
This sort of subject matter is absolutely fascinating to me. The intersection of pharmacology, law, society and culture and the actual evolution and changes they all go through.
I feel like you could tie phases of electronic music to the drugs people were taking at the time.
It would appear that the risk of severe and/or long-term side effects is actually pretty low, otherwise we'd be seeing many, many cases by now.
Note that this isn't evidence that there weren't more subtle long-term effects, but it seems clear that the fear of devastating brain damage was somewhat overblown, especially given that you and many of your peers were consuming drug of dubious purity in uncontrolled settings.
Note that this isn't an endorsement of taking MDMA recreationally, but it seems to me that it's almost certainly safe enough to use in treatment, especially for something as devastating as PTSD (where no treatment or ineffective treatment so often result in death).
Some people still enjoy the effects of such a second dose and freely consume MDMA every weekend, but for many it seems to be more of a 'meh' in comparison, and not worth the health and legal risks.
When I was 19 years old I went to a rave and took a pill which definitely contained MDMA (in addition to whatever else the dealers put in it) and what I will say is this:
It was literally a life-changing experience for me. I felt emotions that I had literally turned off, and walls I didn't know I had were opened up. I remember being shocked days later, when I realized that the drug was no longer in my system, and yet I was smiling and making eye contact with my roommates and classmates, holding real conversations with them. These were things that had been pretty crippled in me before.
MDMA is powerful stuff, and it's a shame that this hasn't been properly researched due to our Federal Government's juvenile, ignorant attitude on drugs.
I'd done some 'e' before that but the positive effects lasted more on the order of several weeks, while I have some fond memories of feeling loved for the first time and meeting people and being social, I'm not sure if or how it contributed to my good years.
So apparently it is common for childhood issues to resurface during middle age. Common as in the therapists retort "Well what else do you expect?" I hope this doesn't happen to you... I am too old and responsible to be taking risks with street drugs. Mainstream pharma seems to affect patients very differently, and I have heard regrets about doing mdma and bad trip stories about LSD.
Thanks for relating your experience, it is very interesting to me because we have some similar background and got such great assistance from taboo chems. I have related the results of my acid trip to various kinds of people across the social spectrum, from beatniks to white shirt C levels and a USN Admiral, and not many people get it.
We won’t really have proper evidence on the neurotoxicity of MDMA unless we can study people whom we know actually ingested MDMA - rather than MDA, speed, 2-CB etc.
Furthermore, neurotoxicity is not inherent to any substance, since it must depend on dosage (I know no substance which is toxic when a single molecule is ingested). Dosage must be a parameter, or the study makes no sense — ingesting 100 grams of table salt will kill you, but we don’t call salt “toxic” because of this.
What will be interesting is if the phase 3 is successful. The DEA won't have any choice but move MDMA from schedule 1 to a lower schedule, as schedule 1 is defined as "no currently accepted medical use in the United States".
The hilarious part is MDMA is given as an example of such schedule 1 drug on their website.[1]
If only it were that simple.
The DEA has demonstrated pretty clearly that it doesn't give a rat's ass what the medical community thinks about a substance if the DEA has decided it doesn't want to remove it from Schedule 1 classification
"Schedule I but Schedule III when in an FDA-approved drug product"
So it's "no currently accepted medical use in the United Sates", apart from when it is in a FDA approved medical use. wut? :D
21 U.S.C § 812[0] doesn't say anything at all except to give the list of findings:
> (A) The drug or other substance has a high potential for abuse.
> (B) The drug or other substance has no currently accepted medical use in treatment in the United States.
> (C) There is a lack of accepted safety for use of the drug or other substance under medical supervision.
This is a little surprising because the "trailing AND/OR" is fairly common in other areas of the law. Makes me wonder if it's ever been clarified in court.
There is some precedent for having a single active ingredient listed in multiple schedules though, the one that immediately comes to mind is hydrocodone.
Until very recently, we listed hydrocodone in both CII and CIII, depending on which other active ingredients it was combined with.
If it was in a pill loaded with acetaminophen, which would supposedly deter addicts from eating 20 of them at a time, it could be in CIII, otherwise it was strictly CII. Because naturally, anyone getting ready to swallow 20 Vicodin at a time is going to know that acetaminophen can cause acute liver failure and make the rational choice to avoid it.
That was one of the primary reasons Vicodin has been handed out like skittles for every little injury, it's every bit as powerful as the others in CII, but it could be prescribed with less oversight.
In that light it's not too surprising to have GHB listed in more than one schedule, but it's still absurd that one of them is CI, given that as far as I'm aware, there is nothing particularly abuse-resistant about Xyrem.
That is Schedule II.
21 U.S.C § 812.b states:
(2) Schedule II.—
(A) The drug or other substance has a high potential for abuse.
(B) The drug or other substance has a currently accepted medical use in treatment in the United States or a currently accepted medical use with severe restrictions.
(C) Abuse of the drug or other substances may lead to severe psychological or physical dependence.
https://www.law.cornell.edu/uscode/text/21/812
Additional reading at wikipedia: https://en.wikipedia.org/wiki/Controlled_Substances_Act#Sche...
Let's remember that the DEA head (John C. Lawn) in the 80's forced a Schedule I classification, ignoring the recommendation of two separate hearings, and a successful federal lawsuit to do so. This was at a time when MDMA was already in burgeoning, but successful, clinical use.
Paradise Lost took place in that era. If you haven't seen the movies, they're disturbing but good.
https://en.wikipedia.org/wiki/West_Memphis_Three
You millennials think you have it bad, the boomers were absolutely batshit crazy to GenXers (we were also considered lazy BTW).
https://harpers.org/archive/2016/04/legalize-it-all/
"The Nixon campaign in 1968, and the Nixon White House after that, had two enemies: the antiwar left and black people. You understand what I’m saying? We knew we couldn’t make it illegal to be either against the war or black, but by getting the public to associate the hippies with marijuana and blacks with heroin, and then criminalizing both heavily, we could disrupt those communities. We could arrest their leaders, raid their homes, break up their meetings, and vilify them night after night on the evening news. Did we know we were lying about the drugs? Of course we did."
I wonder, is that credible? If so, it's kind of amazing how little has actually changed since those laws were put in place.
(Edit: okay, there are some reasons to doubt that quote) https://www.quora.com/Is-John-Ehrlichman-a-credible-source-w...
Given there's a lot of bureaucratic inertia and jobs at stake here, and:
"It is difficult to get a man to understand something, when his salary depends upon his not understanding it!"
...is it really so surprising?
This aspect of human nature is not isolated to the Drug War. Jaime Escalante was possibly the best teacher in America, and demoted because his success threatened the jobs of others-1
What about the never ending wars for profit? Wolf Blitzer at CNN tells us it's a moral problem for the US to stop funding war because a lot of jobs will be lost-2
The problem is that if we are to truly care about human dignity and equality, we need to fundamentally change the way in which we approve of jobs without critically looking at what they actually produce. This isn't just isolated within the economy of the War on Drugs.
1-reason.com/reasontv/2017/08/22/stossel-government-run-schools-crush-in
2-https://theintercept.com/2016/09/09/wolf-blitzer-is-worried-...
We live in a society that puts people on an economic treadmill for their entire life. The government gives incentives for getting into debt - guarantees on student loans, mortgage interest tax break. We have property taxes in most states, so you always have a bill to pay even if you never borrow.
Then people come along an propose things like basic income which can't work (I'll do the math for you one of these days since nobody else has). What they really want is to offset the costs of basic existence. I believe those costs could be lowered if the government would focus on that instead of profits and GDP.
Please do.
Is it merely attitude, or does neuroplasticity come into it? I'm not even old yet (at least I don't think so) but I remember my mind being very resistant to adopting git over SVN and TFS because it was so different to what I was using and "if it ain't broken..." but now I love it. That experience has taught me to persevere: to not criticise something until I understand it, but what if I'm unable to understand something in future? Can I maintain a healthy mental state in that situation?
Likewise an 80 year old that sees themselves as having less than 20 years left might require a higher bar for the payoff for dedicating themselves to learning something new than a 20 year old that sees themselves as having 80+ years left.
Any such 20-year-old is delusional; becoming a centenarian (let alone having good enough health to appreciate it) is not much more common than winning the lottery, at best.
To be fair though Heavy Metal has been playing on the Satanist/Gore imagery for years, and not just in graphics, but lyrics too. Not because they are satanists, but it because it sold well.
That said, the notion that metal bands are fine-tuning lyrical content to minimax paydays is pretty funny. I think income-maximizers generally gravitate towards different careers. But I like picturing a bunch of corpse-paint MBAs sitting on a conference call: "Nice, Sean, I like it, I like it a lot. What about the next line - I think 'Demons dining on your shame' will sell better than 'Demons know this ain't no game'. How does that grab you?"
Slayer certainly has been successful, and have built a nice consistent career. You can do well with niches. But by one statistic, album sales... well, they've never created an album that's gone platinum. (Stryper actually has once!)
The "money" to "maximize" in music, if anything, is in pop. A large portion of pop these days is written by teams of people these days. I'm not sure how it goes down personally, but I can easily see conference calls coming up with the best love metaphors for a teen idol to croon. :)
Just because D&D is no longer one of the things people with a religious agenda hired to advise law enforcement are pushing as dangerous doesn't mean things are more sane, just the targets have shifted.
> You millennials think you have it bad, the boomers were absolutely batshit crazy to GenXers (we were also considered lazy BTW).
To be fair to the Boomers, a whole lot of the crazy we in GenX put up with was from the “Greatest Generation”, not the Boomers. (And to be even more fair to the Boomers, they were treated even worse in their youth for their conflicts with the orthodoxy of their elders.)
It's not all roses.
While the marginal tax rate on the top bracket was very high, it applied to almost nobody, and the effective taxation yield rate of revenue to GDP was actually lower than it is today.
> decades of middle class income growth that was the envy of the world
Largely accomplished because the European post-war economy was damaged enough that the US could take over as the de facto imperial force of the world. It's not like it was due to anything that generation did; it was the global geopolitical landscape of the time, and not one we'd like to repeat.
First, it doesn't matter if it's one person, as it was in 1935, or 1000. The idea that a handful of people get to be hoarders makes the system untrustworthy.
Second, very high marginal tax rates incentivize spending money on deductible expenses rather than ones that aren't deductible. When it's a use it or lose it tax rate, and you don't think the government has the best ideas how to spend it, you can avoid the tax by taking your own risks with your own money. But the point is, again, you can't be a hoarder.
> To be fair to the Boomers, a whole lot of the crazy we in GenX put up with was from the “Greatest Generation”, not the Boomers.
While they are sometimes combined under the “Greatest Generation” label, this actually was intended to refer to the Silent Generation (the one mostly too young to fight in WWII, but born before its end.)
2017 is just as full of crazy people in government and everywhere. They're much easier to spot a few decades later...
Also, like all tales from a culture you haven't lived in, people won't understand that actions that seem crazy today made perfect sense without technology X, Y & Z.
A reason I don't respect people's faith (superstition) because legitimized magical thinking still has an outsized effect on elections, laws, and policy, with many examples during our lifetimes.
I remember seeing it on TV (Dateline or 20/20 or similar) they were talking with practitioners using it for couples therapy. It seemed really remarkable. That was well before it turned into a street drug (tainted with other stuff).
Is that the only community acceptable path to changing long standing beliefs about these terrible terrible drugs?
How about taking a general position that the war on drugs has failed and has created far bigger problems than were ever presented by individual people making decisions that impact their own health.
People of the U.S.A. - it's not necessary for every formerly demonized recreational drug to go through a "hey it's medically valid" process. Unless of course yuour goal is to prop up the system of handing out "legal to use marijuana" certificates that the medical profession now depends on.
But you're right of course. Blanket regulation where none is needed is the wrong way to go about it.
While it should not be necessary tactic for ending the war on drugs, don't brandish the label "phony" when it comes to the medical benefits for marijuana and MDMA.
Marijuana has been extensively studied, more so than almost any other prescription drug available today, and its medical benefits are clearly established.
MDMA is not quite as over-exhaustively studied, but it's similarly been shown in a multitude of studies to have real medical benefit. Moreover, that medical benefit is for a disorder which is currently not possible to treat effectively with any other drug available, which makes it all the more important.
Sure, Prohibition is long over, but I suspect the Puritanical "if it feels good, stop" memes and ideas that led to it still remain in the minds of many.
For a governing body, its logical to automatically be suspicious of any recreational drug. Being recrestional means it'll be used more often than a non-recreational or non-addictive drug. The effects of use will be much more widespread.
Even if you have liberal/libertarian beliefs about personal choice and responsibility, the fact is that its not possible to know if a drug is poisonous without careful testing. Putting things in yoyr body by any means is rarely healthy. I'm not saying its a bad idea, just that the odds for any given chemical are objectively long. Its not unreasonable for the government to outlaw a new substance that would be very popular.
Thats how all pharmaceuticals are done; to sell medicine you have to prove not just that it works and is safe but that it works better than the competition. They certainly scoff at the experiences of joe public, and they clearly should. Joe public may know what makes him sick, but he has no idea what may give him liver damage, cancer, etc. Etc.
Once youre on the FDAs bad list, it takes real concerted effort to get off for any drug. The bar should not be lowered for generic remedies. The only problem is that there is no incentive to prove that drugs like this are safe. High profile illegal drugs are not the only examples of this either- melatonin is one of the best sleep aids period, but nobody had any incentive to push it through the FDA until recently, so doctors legally couldn't prescribe an excellent medication.
People making decisions about their own health is a separate issue- there is no data on these drugs (from the governments pov). I'll also note that people having full control over their health is a terrible idea. Sure, it works okay for testosterone, probably. But what about antibiotics? Antibiotic resistance would be a global crisis.
The root of the problem you mean is that theres no process to go from a therapeutic drug like weed to a legal vice like alcohol. The government doednt even have a category for that. Call it moralizing, but still, how would tgat even work? IMO its nontrivial to draw a line there. Weed is definitely on one side, but is testosterone supplementation, or HGH? You can serioudly fuck up your brain taking SSRIs wrong, and you can do much worse with steroids or HGH, and thats without considering extremely dangerous AND addictive drugs like opioids.
I would argue the government has some interest in preventing the abuse of certain drugs. Specifically when a person is addicted and endangering themselves, they are no longer acting like a rational person and its reasonable to assume that they are not in control of themselves. Personally I think the line should be with effect, not cause. If you are an alcoholic I think the government should be able to cut you off. If you want to get high, they should let you. If you want to modify your body, it should be legal until your life is endangered.
Glad to see this is slowly being taken seriously.
https://medium.com/@AliceGut/mdma-for-ptsd-saves-lives-66f78...
I'd say sign up for the maps.org newsletter, they'll likely announce study sites.
Also better for anyone who supports this to donate to MAPS or another psychedelic research institute of your choosing!