Hacker News Reader

My brother and I, along with our siblings, all have various psychological issues (like PTSD, anxiety, etc) caused by a pretty brutal period in our childhood that resulted in the neighbors calling Child Protective Services and us being placed in foster care.

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 have an older family member who experienced something very similar, having suffered abuse and self-abuse for 50+ years. A single experience unlocked their life in ways that they could have never imagined and allowed proper healing and recovery to begin. This person is now doing better than ever.

Thanks for sharing your experience.

Have some childhood issues too and a hit of acid changed me for about fifteen years. Hadn't done it before or since. It was like my brain was suddenly rewired to see good in the world and desire to be a part of it. Literally I sprung out of my support job and launched a superstar career, changed the world a little through good honest work.

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.

Worth reading:

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

The verdict is still up in the air

> 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)

p-values. They gotta stop relying on p<0.05 which is really a low bar.

Thus why this new approval is such a big deal. We can finally research it and make some scientific conclusions instead of DEA conclusions.

Something to keep in mind is that cumulative toxicity is important. The regimens typically used in non-human primates were 5.0mg/kg doses twice daily for 4 days taken subcutaneously instead of orally. A regimen of 2.5mg/kg given orally (p.o.) to Rhesus Monkeys once every 2 weeks for a total of 8 doses over 4 months produced no detectable effect on 5-HT and 5-HIAA levels.

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.

https://www.maps.org/news-letters/v05n3/05310neu.html

I personally worked on developing the Investigative Brochure for procedure in preparation for the Phase 3 clinical trials at MAPS. The concerns regarding neurotoxicity are mitigated through dosage and low frequency. The ideal treatment plan would only include one session with a therapist in which the patient is given a dosage of MDMA, over a six month period. During that session it's possible for the patient to receive a supplemental dosage dependent on the needs of the patient and the recommendations of the therapist. This can be adjusted and in previous trials some patients have had 2 MDMA-assisted sessions over 6 months but it is not common so far and other options are being considered.

Can you comment at all about how the MDMA therapy session is conducted and/or structured, compared to a normal 50 minute session?

Rick Doblin, founder of MAPS, talks a bit about this in his interview with Duncan Trussel: http://www.duncantrussell.com/episodes/2016/7/18/rick-doblin

(i'd imagine this information is available elsewhere, this is just the instance i happened to come across myself...)

Read: https://rollsafe.org/mdma-therapy/

Anecdotally, I went to a lot of raves in the 90s and did what I would consider to be a stupid amount of ecstasy now, as did most of my friends, and everyone that I've kept in touch with are fully functioning members of society. Most of us are making six figures, have families, etc. The people whose life turned into a mess were people that got sidetracked into methamphetamines or opiates.

ahhhh, those were the days...

It's likely your "ecstasy" in the 90s was laced with something else too like MDA, methamphetamines, etc.

But yes, MDMA anecdotally is much safer than anything else.

Your body metabolizes MDMA into MDA, though. And MDA is actually just the amphetamine analog to MDMA. Just thought that's important to mention, despite it not changing the fact that putting mda into mdma is still "lacing".

This is misleading - a bit like saying "ethanol is metabolized to acetaldehyde". Technically true, but you can't just take acetaldehyde and expect the same effect as alcohol. Alcohol itself is bioactive. You also don't want to injest acetaldehyde directly since you don't want high concentrations of it in your blood (its quite a bit more toxic than alcohol).

MDMA is itself bioactive/psychoactive, and MDA is more neurotoxic.

Fair point and good analogy. While I can't comment on the neurotoxicity, I will definitely say MDA itself has a more LSD like effect than MDMA does and contributes significantly to differing effects.

From my experience in the 90s rave scene the most common adulterants were DXM and speed since they're cheap and press more easily than meth. Acid was the drug of choice when I started going to parties in 94 but then ecstasy overtook it by a long shot and acid pretty much dried up.

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.

I'm not suggesting lacing mdma with dxm would be out of the question, and maybe it was more common in the 90s, but it's my understanding that the biggest adulterant of mdma (besides meth) in 2000-2013 was methylone, which could be ordered online until recently, and is known for having a relatively similar profile to mdma, with relatively few side effects and a low risk profile (to the best of our current knowledge)

In the early 2000s I don't think it would have been methylone. MDEA was a big one that was similar (although not legal, was less scheduled and / or was semi legal at some point so there were big stockpiles of it. This was for the UK

Less anecdotally, millions of other people did much the same as you.

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).

The death of every drug study thread is anecdotal stories. They are doing these studies so we can stop referring to that time we got shit faced with our friends.

The data is really difficult to make sense of, and that does indeed make many people weary of overdoing it. But from the anecdata I have, it seems the 6-month intervals are often motivated by the desire to reset one's tolerance. One surprisingly effective safety feature of MDMA (unlike other amphetamines) is how self-limiting it is. A second dose within even a month never creates the same, life-changing experience as the first, not even if the dosage is increased.

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.

As with any substance, it can get toxic with larger doses (you can die from to much water for example). From what I remember when I read toxicity studies about MDMA about 150mg in around 3 month time is "ok", leaving no damage. Now, that is medical grade MDMA. Buying stuff on the street is a lottery every time and you will NEVER get pure stuff. One of the reasons why substances should be legal and regulated in a different way. Regarding supplements for MDMA, yeah things like 5HTP could help mitigate the damage and speed up the recovery if you take too much.

The first study you cite involves an examination of “ecstasy” users, which makes it fairly useless since pill producers can put anything they want in what is sold as “ecstasy pills”, including known neurotoxins (e.g. methamphetamine).

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.

It's pretty well known that stimulants have a calming effect on patients with ADHD. Anxiety can often be a symptom of understimulation.

best source I could find for the 'understimulation' claim was this: https://academic.oup.com/ije/article/39/2/370/684049/Bored-t.... although they attribute boredom as a proxy and not a direct cause of poor health.

Your ADD meds can be as neurotoxic as MDMA, especially with seratonin syndrome. The real discussion here isn't quite safety though. It's more just having the ability to legally study them in the first place. As schedule 1 drugs, its nearly impossible for researchers to even obtain/synthesize the drugs to study in the first place leaving existing research limited to small sample sizes, old data, or subjective stories. This is a huge deal for a lot of reasons.

Citation for first point? Do you mean taking amps with an MAOI?

I would guess that MDMA neurotoxicity is highly correlated with dose.

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...

125mg. Should be "rolling face".

Neurotoxicity is probably also related to people overheating and overexerting themselves while on the drug - I've seen people sweating profusely and not noticing while rolling a few too many times.. which generally results in me giving them water, salty crackers, and nudging them to consider taking a quick break.

Indeed - the more visible research papers about amphetamine-related neurotoxicity in rodents reported most effects when the temperature in the brain exceeded 40 degrees - contributing towards massive oxidative stress.

Is oxidative-stress the only mechanism of neurotoxic action, or are there other effects at work, such as dopamine-downregulation or exhaustion?

The "high" people experience at recreational doses can take any number of forms depending on the circumstances. Enjoyment of repetitive music is certainly among them, and so is intense enjoyment of borderline-sexual behaviour. But even in a club setting, many people tend to get intensely open about their feelings. I'm no expert on PTSD, but I believe therapy is almost always limited by our reluctance to open up, especially about personal issues that we consider embarrassing, shameful, or that could be considered vulnerabilities.

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.

>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

> The really interesting thing is that these effects somehow persist beyond the acute trip

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.

Thanks for writing this. I think that you're second paragraph helps to explain the life-altering, and permanent, behavioral changes I experienced after taking MDMA at a rave when I was 19.

I think a very significant risk of MDMA use has more to do with the difficulty of getting pure, uncut MDMA. Methamphetamine or some of the designer drug alternatives is frequently cut into MDMA to save money because drug dealers are drug dealers.