MDMA synthesis in 3 steps & how it could help PTSD therapy (educational) | Chemistry & Science

🧠 Did you know that MDMA-assisted therapy was recently proven to be highly effective for people with severe PTSD? In this video, we will break down MDMA's history and discovery, synthetic approaches from the literature - including a kilo-scale process route - and clinical data from a Phase 3 study investigating MDMA's therapeutic benefit.

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* Note, some slides spell safrole as saffrole

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00:00 MDMA might have valuable therapeutic potential
00:37 Uncontrolled drug use is dangerous!!!
00:53 History and discovery of MDMA
02:26 Organic synthesis and chemical reactions: Safrole, piperonal, GMP synthesis
05:43 PTSD burden of disease and unmet need
07:08 Clinical trial design and results
09:48 Short-term MDMA safety seems acceptable - still, long-term or regular use is discouraged!
10:53 Outlook on potential FDA approval

Disclaimer - This channel does not provide medical advice!
No information on this channel is intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of your physician or other qualified health care provider with any questions you may have regarding a medical condition or treatment and before undertaking a new health care regimen, and never disregard professional medical advice or delay in seeking it because of information on Youtube.

Key references:
- Fully Validated, Multi-Kilogram cGMP Synthesis of MDMA (ACS Omega 2022, 7, 900−907)
- MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study (Nature Medicine 2021, 27, 1025)
- The origin of MDMA (‘Ecstasy’) – separating the facts from the myth (Die Pharmazie 2006, 61, 966)

Some recommended books on organic synthesis:
- Clayden, Greeves, Warren; Organic Chemistry (basic organic chemistry knowledge)
- Wyatt, Warren; Organic Synthesis: The Disconnection Approach (excellent introduction to retrosynthesis)
- Kurti, Czako; Strategic Applications of Named Reactions in Organic Synthesis (extensive toolkit of functional group reactions and applications thereof with common conditions)
- Nicolaou; Classics in Total Synthesis 1-3 (the ultimate total synthesis trilogy)
- Nicolaou; Molecules That Changed the World (the world's most important molecules and their impact on everyday life)
- Carreira, Kvaerno; Classics in Stereoselective Synthesis (compilation of the groundbreaking methods of stereoselective synthesis and application to synthesis of stereochemically complex structures)

[totalsynthesis]

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[Callummullans]

I took MDMA when I was around 18, I suffered childhood trauma and at the time I would say I felt more stunted than anything and MDMA taught me love in a whole other way like I was loved unconditionally and I knew it in every fibre of myself. Big release into life and a massive step towards my authentic self in a way I could never have imagined. One of the best decisions I could have made as it ended up being an integral stage of development for me that I would have just missed out on entirely without this freeing experience.

[EddieTheH]

I was a victim of paroxetine, thanks for mentioning it.
We should never let that be forgotten.

[keelo-byte]

First synthesis can avoid bromine in first step by reacting catechol with diiodomethane in dmso over a brass powder catalyst... allegedly.

[kategoss]

I really appreciate you stressing the importance of the clinical therapeutic setting. I have had experiences with people on MDMA in a few different social situations and I can say for sure that the wrong setting can be devastating for vulnerable or traumatised people, and the right people in the right place can be extremely valuable. Thanks for this fun & informative video!

[stevengill]

I remember bck in the late 70s when a paper company started offering 1, 3-benzodioxole as a potential feedstock (catechol being a byproduct at that time of paper production). Those of us with dirty minds foresaw a couple synthetic routes utilizing it. However, in those days piperonal, safrole, and even MDP-2-P were readily available, so why bother?
It wouldn't surprise me if the route from 1, 3-benzodioxole was already in use by cartel chemists somewhere...

[ironfeatherstudio]

The very sad thing is... X is super helpful for drug addicts, 'who are typically suffering from abuse' but, yet is illegal. Sad😢

[zizu]

Great video! Was especially interesting as I did a research project investigating psilocybin's viability for treating depression. It's nice to see psychedelics clinical potential getting more attention!

[Thundralight]

I think it could also be helpful for treating disorders such as psychopathy and narcissism as MDMA is also sometimes referred to as the empathy drug. I would like to hear your thoughts on this. Has there been any research on using it for these conditions?
It is unfortunate that when the government bans a drug and places it on a list of scheduled drugs it makes it difficult for researchers to obtain approval and funding to conduct studies which could benefit people.

[lukassorowka]

My FBI Agent watching over me rn: 👁️👄👁️

[gregjackson]

My friend Catherine was one of the publishers of the paper you sited in this synthesis. She is one of the most intelligent people I have ever met.

[tx.hardhead]

I remember in about 1986 when I lived in San Antonio we used to go to teen clubs and they sold it in test tubes for like 3 dollars a tube. It had a dye or something in it that made it look sick under the black-light lighting of the club. They also sold nitrous oxide in balloons, but that's not really relevant. MDMA was legal then and was making lots of news treating marital problems. It was really touted as the next big thing in couples counseling, then overnight it until went poof and turned into a schedule whatever drug..

[dondobbs]

From what I've read; if that Saffrole is coming from Sassafras oil, it could be the equivalent of a "blood diamond." Ancient canopy trees being cut down in places like Cambodia and the oil steamed out of the roots on site and smuggled out + a few potential fire fights along the way. Sounds really "cuddly and huggy" doesn't it?

[Therealogtroub]

Very Interesting, I wish I had people with similar interests to explore.

[sea-ferring]

Great video. Hopefully the law enforcement lobby will not derail this kind of research. There are so many groups that exist because of the war on drugs and they will do absolutely anything to continue their funding.

[knivesnico]

wonderful! may the psychology field get new tools

[andrewgiv]

Look up uncle fester, hate to say it, but meth manufacturing. That book has a few chapters that cover mda and MDMA. I found them very interesting. Science is very cool. Organic chemistry is even more interesting

[teiskovich]

Shulgin published it in PIHKAL, not TIHKAL as you mentioned

[cvspvr]

man, i just want there to be more research done on reducing mdma tolerance and the ~loss of magic~. mdma was the first drug i ever tried and my first time was still the most beautiful drug experience i've ever had. unfortunately, i've never even come close to replicating that, even after waiting a year between doses

[carlpanzram]

Damn.
If I'd be more intelligent and adventurous I'd attempt making it.
I wish there would be a reliable source for clean MDMA, because honestly I don't see why it's illegal at all.