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MDMA as a Probe and Treatment for Social Behaviors (2016) (cell.com)
91 points by bookofjoe 34 days ago | hide | past | web | favorite | 55 comments

> How have we come to a point where we are arguing that a DEA schedule 1 drug (i.e., no accepted medical use) may be among the most promising lead therapies for psychiatric disease and a powerful probe of important brain functions?

I’ll make the observation that if recreational drugs weren’t doing interesting things to the brain, people wouldn’t use them, but psychedelics in particular do near miraculous seeming things with reproducibility that prescription drug companies would kill for in a candidate for a commercial drug.

What reproducibility are you referring to?

LSD was marketed as a medicine under the name Delysid for over 10 years mid-century but only afterward did it gain a schedule 1 classification after it was declared to have no medical uses.

LSD almost certainly has medical value when administered properly; viz. https://en.m.wikipedia.org/wiki/Spring_Grove_Experiment?wpro.... It was banned in spite of its medical potential, not because of it.

Those studies were pretty terribly done, with no control and other confounding factors. Maybe indicative of more study but nowhere near substantial or reproducible.

Edit: Replying with a 45 year-old study with extremely low scientific merit is silly especially on HN. I was asking specifically for references to the reproducibility op mentioned.

Thank you

If you're interested in the topic of medical history of psychedelics, I would highly recommend "How to Change Your Mind" by Michael Pollan of nutrition fame. He decides to experiment with psychedelics for the first time in his late 50s, and the book describes his journey as well as changes in personal philosophy. He masterfully combines history lessons and personal experiences to paint an informative picture of where this topics might head.

In NYC, for example, it is now perfectly legal to get a heavy dosage of ketamine administered by Columbia University doctors (see https://www.columbiadoctors.org/specialties/psychiatry-psych...)

It's perfectly legal to get ketamine from any doctor! The program you linked costs $650/infusion.

> A typical case would be 8-12 infusions over 4-6 weeks.

That's $7,800 for a month of treatment. That's a lot of money when considering that ketamine is not a cure and the patient will need future treatments.

I'm taking 250mg sublingual every day and paying ~$3000/year. Most of the cost is taxis, planes, and shipping because I'm out of state and have to fly in to see my doctor. If I lived in Maryland the cost would be much lower.

Also, if infusion clinic docs weren't bankrupting patients by picking the most expensive (read: lucrative) ROA the cost would be much cheaper.

That document you linked is fascinating. It's especially relevant to me because I'm currently taking a class through my university's pharmacy department on drug discovery and development in the pharmaceutical industry. Just last week I wrote about PCP's origins as an aesthetic (similar to ketamine). This[1] is a good source on the topic.

Do you happen to know of other documents in a vein similar to the LSD one you linked? Pharmacology is one of many bizarre topics I endeavor to understand in my free time (this weird thing called "programming" also happens to be one).

[1]: https://onlinelibrary.wiley.com/doi/abs/10.1002/dta.1620

Matthew, that document appeared on the first page of a Google search for Delysid, where it was the first result of 187,000 [https://www.google.com/search?newwindow=1&hl=en&source=hp&ei...]. I'd never heard of it until seeing the name in the comment I replied to. It's a one-off as far as my having others like it to send on. FWIW, as a retired neurosurgical anesthesiologist (38 years experience/age 70) on three antidepressants (lithium/Wellbutrin/Paxil) for life after four severe episodes of major depression, I found it (the document) as fascinating as you did. P.S. This: https://mattwie.se/ is very cool.

LSD cured alcoholism with high success rate.

As an anecdote: the founder of AA suggested LSD as a treatment to alcohol addiction. https://www.theguardian.com/science/2012/aug/23/lsd-help-alc...

> MDMA, better known as the recreational drug “ecstasy,”

> clubgoers and college students primarily know MDMA as “ecstasy”

Not exactly. "Ecstasy" is usually the name of pills that have MDMA as a main ingridient, but also often contain MDA, amphetamine, methamphetamine, mephedrone and other similar drugs.

If you consider consuming MDMA, always search the pure crystal MDMA if you can, by the way. It's usually these other ingredients (mixed in to "push through" a user's tolerance level) that are responsible for the worst of adverse effects and neurotoxicity.

I had some pills, supposedly E tabs, which gave me a quick up. Nice, but they weren't pure MDMA though it took me a fair while to realise that.

I suspect, without evidence, that they had methamphetamine mixed in (they started working in as little as 10 minutes). That benefits the dealer as they clearly "work" so no complaints from the buyers, and in a strange way may benefit the user as they won't start popping more because they think they have a dud, and real MDMA takes maybe 25 to 45 minutes to start, and the effects cam be subtle and overlooked particularly if you are new to them.

It's a strange argument, and please note I use the word 'benefit' here in a very odd way - meth is neurotoxic, so it's really not the right word. And mixing random stuff in, also bad.

Also, I once was given an E which was huge, I broke it into quarters and that may have saved me a trip to hospital or the morgue. It was vastly too strong. Also had some other tabs which I suspect were pure meth (I'm guessing but they are the only thing that I could find described that started working so fast, and caused bruxism) which I thankfully broke in half. They were overwhelmingly strong.

So the advice to break up tabs and take the pieces slowly (and don't assume pill A has the same composition or strength as pill B apparently from the same batch) is very well founded. It has definitely saved me hospital trips and wasting NHS money. You have an entire night, don't rush!

There's an excellent word in Russian, кайфожор, (I can't adequately translate to English - it's more or less "glutton of high"), which describes behaviour that stands behind most of drug user's health problems. Basically, it's a desire to get high, on anything, at any cost, which drives people to do the most stupid things with alcohol and drugs. Sadly, that's also the most paying client base, so you see a lot of drug producers catering to this audience specifically, always emphasising the strength of substances as a primary selling point. Among hundreds of shops on the marketplace, 99% talk about how strong their stuff is and how it can beat tolerance and almost none - about health.

Such behaviour is exactly what is causing me to doubt my long-held belief that all drugs should be legalised. I just don't know any more.

Of course they should. People should bear responsibility for their own behavior.

That people Should does not mean they Will. Supposing for the sake of argument that ruining their lives and only their lives is acceptable, then yes, legalise and let people suffer the consequences of their decisions; they are adults.

But there's often an inevitable spillover from that individual to others, say spouses and children, and bystanders (like pedestrians cos someone got pissed and knew they were safe to drive home - and alcohol is a drug, and very legal). Even non-drugs like food is blatantly abused - ever seen a morbidly fat person?

If we legalise drugs then I am coming to the conclusion that we need to take a society-wide approach, which means at the very least banning all advertising and probably banning production by privately owned companies because their job is to make money which precisely leads to their wanting to increase the number of users and their amount used - look at alcohol advertising.

I don't disagree or agree any more, I've simply lost my certainty. HTH.

FYI this is short and incredibly informative: <https://www.spectator.co.uk/2015/05/the-case-for-prescriptio...

I’m a fan of MDMA but be warned you need to know what you’re doing and be well-prepared before and after due to the neurotoxic side effects which may permanently lower your ability to produce serotonin. Also cannot/should not take it more than a few times a year with at least 3-4 months between doses.

Hmm. your handle is strangely similar to mine. Whatever.

Anyway I disagree with your claim of neurotoxicity which you don't justify. If you make a claim, back it up otherwise it's FUD.

Here's some actual data mostly opposing that, and a very interesting story of the US government keeping a pet researcher who'll report whatever they want <https://thedea.org/mdma-risks-science-and-statistics-technic.... It's a good read.

> Also cannot/should not take it more than a few times a year with at least 3-4 months between doses.

Justify this. With facts.

People who take it every weekend will get a kind of permanent tolerance where they'll never feel the magic again no matter how long they wait. And apparently permanently affect their ability to feel happiness.

This is common knowledge in the drugs community and harm reduction sources frequently quote the 3 month thing, although I'm not sure where it originally came from.

This doesn't match my personal experience at all. I'm in my 40s, husband is in 50s, both took massive amounts of mdma in the 90s and 2000s, way above the guidelines you are describing both in terms of single night usage and frequency, and still do today but much less frequently. Large cohort of friends with similar histories. We seem fine. Husband is about the most naturally happy, well adjusted person you could meet and his consumption of mdma at times was sort of over the top.


It absolutely does screw with some people's mood for the worse, but definitely not everyone, or even most people. I do think for people predisposed to depression and anxiety, heavy usage can be a bad triggering or worsening factor.

That is an absolute statement without any references. Please don't quote hearsay.

I don't speak for anyone else but it does not match my experience and FWIW I've been taking it once a week for ~4.5 years.

(Explanation; I consider that dose and rate as a definite abuse of it, not sensible use, but the past few years have been just terrible god knows how I would have coped without it. I'm improving now and started cutting down, and looking forward to going out without any drugs, even alcohol).

IIRC it comes from only of the early researcherson the subject who I think was ballparking in regards to safety.

Until people come out with some real data I would stick with the cautious approach.

Are you suggesting to drip feed this in the water supply of rats

Until it gets legalized reagent kits and pill reports are the best way to verify active ingredients. https://www.ecstasydata.org/ https://dancesafe.org/shop/

There is a beta app for reverse image searching pills. https://play.google.com/store/apps/details?id=be.harmreducti...

Its still very alpha, but could make it easier for people that don't have access to kits.

It's not chemical validation tho.

By all means use your camera on your phone tied with near-legal certainty to your credit card thus your identity to take pictures of drugs then send them over the interwebs possibly sniffed by various gov't agencies. If it's not actually a honeypot run by them.

If all images (or suitable digests) are uploaded to the phone first then a comparison made strictly on the phone then you get some plausible deniability, but it sounds seriously risky.

Sounds a bit paranoid, but there is definitely some truth in your concerns.

Also that is very depending of your local laws. I know for a fact that this feature is currently being developed by a harm reduction group of the EU.

Surprisingly I would much rather have it owned by the EU.

Matching pills with pictures/dimensions/etc. in pill reports isn't meaningful at all without the results of the reagent kit. If the reagent kit results line up with the pill report results it provides SWIM with an idea of the strength of the active ingredients. It's a sad joke that in 2019 intelligent adults in America can't just walk into any pharmacy and buy a box of 100mg cross scored MDMA tablets with expiration dates.

We live in a world where Michael Pollen, a widely known author, wrote a best selling novel on his experience taking illegal drugs while in the US.

Someone needs to ask Buttigieg what he thinks about MDMA. If he admits using it in the past he'd make a great President and if he says he never tried it he needs to drop out of the race.

honestly i thought of building something like that once. Someone else was talking about making one for mushrooms.

but the poisonous and the safe ones are so hard to tell apart you could be liable for deaths.

And similar could happen with pills.

From what I've researched it's minimum 2-4 weeks between doses (I go for 4 to be on the safe side). Vitamin C or fruits rich with it should be taken before and during consumption for protection from oxidative stress. And of course moderation, mdma has a sweet spot in dosage so taking more won't really increase the positive effects. For the "hangover" in the day/s after 5-htp does wonders. That's my anecdotal safe mdma recipe.

Took 1/10th of a dose during a party (where everybody was doing it).

I did not feel high but was very unanxious (absolutely no adrenalin rush when 2 guys started a fight near me).

Now the problem is that I started to grind my teeth for one year on after that night.

So basically I did not get high but managed to fuck my teeth pretty badly (now 5 years later I'm considering orthodontia since my lower jaw bone has moved left with respect to the upper part of my mouth).

So yeah. MDMA. What a fun substance.

It doesn't give you much of a rush anyway.

> Now the problem is that I started to grind my teeth for one year on after that night.

1/10th dose and a year later you get grindy-jaw, and you're linking those???

<https://en.wikipedia.org/wiki/Bruxism> "Bruxism is a common behavior; reports of prevalence range from 8% to 31% in the general population"

Even I have it and it started 20 years before I took my first E - but I guess evil MDMA can reach back through time just as easily as it reaches forward.

Hint 1: 99.9999% sure they're unrelated. Hint 2: see your dentist who will tell you the same. Hint 3: it may be stress <https://en.wikipedia.org/wiki/Bruxism#Psychosocial_factors>

Hold my bag of Es while I reach for Vice:

> Sometimes, bruxism triggered by MDMA can become chronic, Chandwani adds. He had one patient who grinded her teeth for two years after using MDMA just once.

Source: https://www.vice.com/en_us/article/d3kz9m/mdma-ecstasy-makes...

Edit: to clarify I got awake bruxism while on the influence of the substance (this is normal) and nocturnal bruxism for one year after that. I wasn't able to chew in the morning because of the toothache.

Edit2: Oh and did i mention one of the girl in the group used to be a heavy MDMA user and wear a dental guard at night ?

Shit, I misread you! - "started to grind my teeth for one year on after that night." - for one year after, not after one year.

OK, my stupid. I accept what you say. I genuinely regret it didn't give you the magic I got.

oh dear this explains my experience now so much, i had not connected these two things..

"due to the neurotoxic side effects"

Have you a reference for a study on that toxicity?

There’s a ton of research online...


from the paper

> Animal research suggests that when a neurotoxic dosage of MDMA is given, damage to the axons starts to occur in as little as an hour or two

So when neurotoxic doses are administered, neurotoxicity occurs. Well, call the president, we must do something.

Please read the link I posted above, here again <https://thedea.org/mdma-risks-science-and-statistics-technic... which largely debunks this work, although it does offer situations where it does occur, so you can avoid them.

If you want to talk actual neurotoxic, methamphetamine is to be, and I've seen the effects on a guy I know. But stop putting about FUD about MDMA.

Edit: I re-read the link properly and it's not as bad as I first thought. It mentions that research by Ricaurte was debunked. My link goes into a lot more detail of what happened, read especially the last couple of pages where Ricaurte's research is entertainingly debunked in a letter to Science magazine.

Edit2: from my link, regarding MDMA neurotoxicity: "More than a year later, after scathing criticism from TheDEA.org, the house of cards collapsed when Ricaurte sheepishly admitted that the experiment never really happened: The monkeys had actually been given massive doses of methampetamine, not MDMA! He also admitted that no matter what they had tried, they had been unable to damage monkey’s dopamine systems with real MDMA"

Thats incredibly scary reading.

The good news is that MDMA(along with plenty of other interesting phenylethylamines) isn't neurotoxic . All the hysteria was the result of bad science and there's actually evidence that MDMA use might improve sleep efficiency. http://www.maps.org/news-letters/v06n1/06108neu.html

I thought it was definitely neurotoxic IF used at high frequency and/or dosage.

Be careful with dismissing the warnings as hysteria.

Enjoy MDMA responsibly: right dosage and long periods between. This also happens to make the experience much, much better :)

Are you really citing a paper from 1995?

I mean I’m a user of illegal drugs and would rather be safe than sorry. If you look at the mechanics of MDMA, it’s basically forcing your brain to release serotonin from the floodgates in a way that can damage neurons.

Drug tolerance is real. Personally I’d rather be safe than sorry.

In some fields the best papers are the oldest ones and all subsequent work adds basically nothing except someone got a phd out of it. Give old and original research a chance, it is often very high quality.

Look into Alexander Shulgin and other intelligent old people who've openly used MDMA for decades and you won't see a lot of obvious brain damage.

The money shot in the conclusion is:

Although common recreational doses of MDMA don’t seem to be neurotoxic, it’s important to practice moderation.

I wouldn't call that "incredibly scary", more like "concerning".

I don't do pills. When I did do things, long long ago in another galaxy, behind the statute of limitations veil, I don't recall people being very good about not doing things to excess. Also, I am told a constant issue with pills is dosage is deeply uncertain, hence the MDMA deaths issue at Australian festivals, and the pressure for pill testing.

"Also, I am told a constant issue with pills is dosage is deeply uncertain, hence the MDMA deaths issue at Australian festivals"

I'll admit I haven't kept up with the research since I stopped going to house (now known as 'EDM' apparently) parties 20 years ago, but back then it was well known that 'mdma deaths' were actually people dying of dehydration or because of hearth issues due to combining mdma with other drugs. What's the status today? Do people actually die from mdma itself, or just in circumstances where mdma is involved?

I don't know. It's not my scene. It's probably contamination.

That's why they have been doing these clinical trial studies on real patients in helping them to treat their PTSD. Last I read the results have been very positive and it is now currently at Phase 3.

The negative stories we often heard from the news most likely resulted from the unknown substances that often got mixed into the drug. This was possible precisely because of the fact that MDMA is still illegal and unregulated. When you leave such a profitable business open in the wild like that, greedy criminals are free to commit any types of harmful actions with disregard to other people's health, just to achieve their next target profit level. Under such environment and conditions, of course it's normal that all we would hear about are just bad stories. Over time this has established a somewhat false negative feedback loop that makes it difficult for the public to break away from or be rightly informed.

At least the idea of just being open and willing to try will pave the way for more of future researches. There is no denying MDMA DOES provide many benefits in some ways. If our brain reacts to the drug by producing happy chemicals and positive feelings then naturally it must benefit us human to some degree. In my opinion this is simply the law of nature and how our universe works. Similar to as when you consuming something bad or not good for your health, your body will attempt to signal by making you either sick, vomiting out, or just feeling overall terrible.

Of course just like everything in life, MDMA does carry some negative properties as well. Perhaps further researches will allow new discoveries and enable combinations of different drugs in order to help lessen its negative side effects. However, that would only be possible if more people are willing to open their mind first. This is a great start and an inflection point.

FYI, here is the link to an article I came across a few months ago. The author will take you through a great short journey in which he himself experienced and show you how much it has helped his life. It's quite an interesting read: https://medium.com/@tuckermax/what-mdma-therapy-did-for-me-4...

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