Ibogaine Synthesis & How It Might Solve the Opioid Crisis / Treat Addiction | Psychedelic Science

[@totalsynthesis]

▶ To try everything Brilliant has to offer-free-for a full 30 days, visit brilliant.org/TotalSynthesis/. The first 200 of you will get 20% off Brilliant’s annual premium subscription. As always, let me know your thoughts on the video - and thank you for watching!

[@ghostwriter1415]

This drug look's like Valium! Obviously not a "di" azepine because of the lone N in the hepta-ring. I think addicts should use good Heroin until they WANT to quit! If you stay on you're quest to discover the "particles of addiction" (you will never get there) you will EXPLOIT a lot of people, and cause suicide. Addiction will cure addiction!

[@ghostwriter1415]

I will credit you with a minimum of honesty in that you used the word, "might" instead of "will", but all of these phases you speak of so casually and convincing, are millions of molecules doing various connected things in all places, to form a system that's completely out of scope for the aspect of a mere "Total Synthesis". When you say, "factor" you must know that factor is a theory, and not a FACT.

[@CannabinatedFantasy]

i thought ibogaine already had a dose of like a gram

[@joalsoal1645]

Tiny note but ethanol is drawn as methanol at 4:50

[@totalsynthesis]

@@joalsoal1645 yea I was zoned tf out it seems when drawing this

[@onespeedbjj3846]

Always impressed with the research, detail, and preparation that goes in to each video. This channel is criminally underrated.

[@totalsynthesis]

Massively appreciated!!! 🥰

[@End0morphin]

I assume the presenter lecturer has at least 20years in the subjects at 400% my ability……dude devours data

[@Saol.Alainn]

Heard a lot about ibogaine a few years back, when I first started trying to kick heroin. Such promising things happening south of the border even then, but of course Suboxone and Methadone were being pushed hard as replacement therapies, where there was still profit to make. Gotta love the US pharmaceutical industry. Glad to hear more about this now, thanks for this one. I'm getting close to 2 years sober now, Sublocade helped for a few months but been off it all since then. To anyone still struggling, don't give up. It's a long road for sure, but you got this. I'm here if someone needs an ear.

[@rdallas81]

Keep up the good work. I know all about it.. Seen many people fall victim to the needle, and many more to pills patches and other means of internalizing narcotics.

[@Saol.Alainn]

@@rdallas81 Thanks :) It's def tough when the best treatment is nearly as or even more difficult to come off of. The public mindset is slowly changing though, and videos like this help immensely. The more real information we have to combat the fear mongering, the better.

[@brianmcnellis5512]

17 days after abstaining from opioids, I did go to right of passage ROP in Las Playas De Rosarito MX🇲🇽 to circumvent the hellish withdrawal symptoms. Not only did I get my life back, I slept like a baby for the first time in 10 years. It came with a change of psyche (afterglow), but it does wear off. I did acquire it directly from Cameroon, Africa. It came to my door by DHL in 4-days, but I had no way to test for a bad molecule in the HCL or the content of the Iboga TA. For those reasons I opted for the clinical environment.

[@christopherleubner6633]

The trip is rough. 😮

[@denisdavid7754]

Keep up with good work!!

[@telotawa]

the hallucination is often a key part of the treatment

[@bigtymer4862]

I had this same exact thought!

[@thomasferris3750]

I don't think that psychs are compatible with the rigidity of western medicine at all and I think alot of this research will lead to another failure to implement it, it only takes 1 shroom therapist to get injured by a patient not having a great time and the baby is out with the bathwater

[@zgintasz2]

Good then because TBG does induce closed-eye visuals in at least some people, I know people who had experience with it.

[@huntcheerio9214]

exactly

[@dianaholmes9221]

That's what I said l o l

[@Couchintheclouds]

This is what gets me. People are not considering that the hallucinations are the key to the effectiveness. It’s the seeing things in a new light. The confronting the cruel reality of addiction that makes things like this effective. You are thinking that hallucinations are a bug and not the feature itself.

[@Battery33]

Exactly

[@kirbfx]

I was treated with ibogaine HCL and TA. I never "hallucinated". In reality, like most patients, it gave me a deeply introspective experience that helped me resolve childhood trauma. It healed me on all 3 levels associated with mental health: neurophysically, psychologicaly, and behaviorally.

[@LiLaLizzy8]

Where did you go for treatment? So happy it helped you.

[@dkozersky586]

I am consistently amazed by the quality of the content you put out. Like others have said, criminally underrated channel

[@totalsynthesis]

Thanks mate!! 💕

[@puddles5501]

"criminally" underrated ;)

[@theWinterWalker]

I dunno if drug scientists are aware, but it's THE hallucination that drive behavior change in psychedelics. Thank you for coming to my Ted talk.

[@ChemicalEuphoria]

Great video! on a side note at 4:48 missing a methylene group on Ethanol and also ketamine has chlorine in 2 position, not 3

[@totalsynthesis]

Yeap, I've been spaced out when writing the structures it seems. Thanks!

[@ChrisSudlik]

Hallucination, in many cases, is a useful effect. I wish the research was more focused on reducing negative effects, anxiety, contraindictions, potential heart problems, etc. instead of focusing on making them less of an experience and more background effects but still toxic. It's like to the researchers, tripping is the worst possible effect and things like heart attack/stroke are minor issues

[@benayers8622]

thats cos tripping removes a lifetime of obedience conditioning and re enables a persons free will.. They found this during mk ultra and then started the war on drugs cos if it was possible to un condition a soldier whos had extreme brainwashing Imagine how effective it would be on normal ppl whov only had school and tv programming them and not a screaming drill sgt preparing them to run towards machineguns :)

[@joseph69678]

Gilgamesh Pharmaceuticals is trying to solve the heart problems with a drug that keeps the trip.

[@decepticonne]

they treat molecules like drugs, it's the only thing they know how to do

[@danwilkinson2797]

I found ibogaine to remove the withdrawal from a 10 year Daly methadone addiction but although rare caused me to experience a hart failure at the 18th hour of treatment this was in 2005 and there has been some protocols put in place by ibogaine providers since that use much less than I took and do extensive cardiac research on the patient before administration. The drug changed everything for me for the good especially seeing it didn’t kill me.

[@totalsynthesis]

Dang, good to hear you came out of it well! Thanks for sharing your experience

[@benayers8622]

i been thinking it could be best to get off my meth for 2 3 weeks and take H/morphine/oxy instead and then do an ibogaine session, my thinking being meth is wayy longer lasting and harder to get over than H morph oxy etc. So i thought it would help to be on the easiest to quit stuff when i do the ibo? Would appreciate if you have any advice please:) do you smoke cigs or bud too? If so was any of that affected after and is there really zero withdrawals?? Thanks for your time :)

[@danwilkinson2797]

There can be a echo of withdrawal right at the end and then that goes completely away if you take a fairly large dose but from the time it kicks in until wares off usually after 18 hours you probably won’t feel withdrawal but you should be in the awakening dream state and you will not feel like moving and it can feel rough on the body though after wards you feel brand new again no withdrawal. You should look at the David Dardashti clinic and watch some of their testament videos. You may also quit smoking and quitting other addictions as well by choice . You may feel more content and not feel like you want to smoke weed for many years after a treatment but many continue just with more control.

[@Experience_Ibogaine_Aeden]

​@@benayers8622your going to want to switch onto a short acting opiate for at least 4-6 weeks if you want ibogaine to be most effective in getting off methadone.

[@margodphd]

​​@@benayers8622for the love of all that's holy don't use opioids to wean off stimulants and don't use ibogaine after abusing cardiotoxic compound. Your plan is just expensive self harm.

[@alexrecort]

I really think that the psychedelic experience is needed for a complete healing, isolating just the main compound, like fresh psilocybe mushrooms vs psilocin in a pill, changes the game completely, is not the same when psilocybin, baeocistin and friends participate in the process and some of them do the hidroxylation inside the body turning into psilocin by our intestine. We have a wrong focus when trying to do new synth small molecule based on other, probably the best point would be to do supermolecules that would be like all these alkaloids together, like nature does itself, like having a tabernetha iboga pill instead a ibogaine pill, and play with the concentrations. Just my opinion

[@joshireinard1106]

love the clearer focus on biochemistry in your recent videos. Imo more interesting!!

[@totalsynthesis]

Good to hear it resonates. More interesting than organic chem you mean? That's next level treason

[@levtrot3041]

Just imagine the number of people who'd be pissed off at that "it'd be better if patients don't hallucinate" statement

[@totalsynthesis]

No imagination needed, check comments in a few weeks haha

[@jtmediaholdings7877]

www.ncbi.nlm.nih.gov/pmc/articles/PMC218001/

[@ultrainstinctgarfield2661]

they are pissed off because it’s a dumb thing to say

[@mythics791]

Keep the good work up. Maybe one day the governments of the world will finally realize a lot of these restricted or banned substances have a very beneficial uses.

[@elenanicole084]

Best psychedelics store

[@elenanicole084]

Mushy_bible

[@elenanicole084]

On Instagram

[@dextermorgan1]

They already know. Why do you think they're banned? Their friends in the pharmaceutical industry would go out if business if natural cures were allowed.

[@BKDenied]

Theyre acutely aware of many of the benefits of things like cannabis, iboga, psylocin, etc. That is exactly why they are banned. Why buy methadone, when I can beat an addiction? They're not in the business of cures. Why buy standard rope, paper, concrete, insulation, many painkillers, anti nausea medicine, sleep aids, or any of the other number of industries upset by legal cannabis? The more industries it upsets, the more people lobby against it, to maintain the status quo, and make more money. You probably knew this but I wanted to get it out there

[@happyninjafighter2]

I understand that hallucinations aren't ideal. But they tend to work best WITH mystical experiences. I happened to be struggling with poly substance abuse, even though I had been through rehab, and was actively in NA, AA had a sponsor, was in half way etc. as an atheist, working the steps was pretty much impossible. Eventually, I had a mystical experience with mushrooms, and finally understood a god. Now, with my god as I understand him, I am able to work the steps, and I'm not longer white knuckling. I'm 4 years sober and my kids are great for it!

[@sh.lslate3517]

I did Ibogaine. The mystical experience is vital to remaining sober. Like you said. You should absolutely do Ibogaine in a medical and therapeutic setting. Let a doctor check your heart with an EKG before you go. It’s God’s gift to people with addiction struggles.

[@elliott614]

When I stop microdosing psilocybin, bad things tend to happen later. It may be that my mindset is going downhill and I don't care anymore or it could be a cause and effect who really knows. The answer is probably a gross Grey blob of nuance and not black and white

[@elliott614]

@@sh.lslate3517 does it really stop wd immediately? I have experienced classical psychedelics speeding up the homeostasis for post acute wd. And put myself through the hell of having acute wd begin in the middle of an intense trip (on the other side I usually tell myself it was beneficial but tbh... it's kinda cruel to yourself and unnecessary) I am mostly a proponent of maintenance. Sublocade/suboxone, not methadone (the former is harder to get ON bc precipitated wd though... latter has insanely restrictive laws and messes with your endocrine system which also affects bones/joints [men need to test their T levels] and is way more likely to cause nodding). It saves lives. Being 100% clean with the benzo fentanyl dope out there is dangerous, deadly should a relapse occur, and those on maintenance are way, way, way more likely to survive a relapse than those who went cold turkey. I've lost too many people to count outta the living world. If you need it subs don't make you high, you actually feel like you're withdrawing for a month or so after you get on/back on them. Depending on how long it's been a thing for you and how strong what you did was. Buprenorphine has higher affinity for the receptors but is only a partial agonist, and even antagonist at one of the receptors. So it kicks whatever off so even if you are sick from wd, it will make them worse when dealing with fentanyl bc fent has an active metabolite that lasts way longer than anything active from diacetylmorphine. And yet the dope these days is capable of overpowering 16 to 24mg of subs somehow (ceiling effect territory). Years ago you couldn't get high within 72hr of even 1mg of sub

[@elliott614]

@happyninjafighter2 you know the founder of AA really intended 13 steps and one of the steps was a mystical LSD experience of a higher power Of course he's also incredibly misogynistic and outdated... just look at the "for wives" section of the book

[@happyninjafighter2]

@@elliott614 yup. The 12 steps isn't outdated tho. It's very useful.

[@gracefullyyours6508]

Saved me. Ten years dr prescribed high level opioids and two weeks with three Ibogaine txs healed. Never thought about taking a pain pill again. The only deadly thing is what the dr gave me.

[@jaapmat]

“It would be nice if patients don’t hallucinate” Finally, someone who actually values the clinical efficacy of these compounds over simply them being contrarian to ‘big pharma’. Ibogaine isn’t your friend, and the companies stand to profit from it are the same ones people think are Ibogaine’s medical use would stick it to. Non-psychedelic psychoplastogens will also be MUCH more medically accessible to those in need. Psilocybin will require that a practitioner or psychologist be present for 6+ hours. Imagine how ridiculously expensive that would be for people who can barely afford a 30 minute doctor’s visit.

[@jaapmat]

Also, fantastic video! So glad to have found your channel this year.

[@totalsynthesis]

Thank you man! And good points raised.

[@margodphd]

Not to mention how great we are as doctors at treating patients that, by nature of their illness, already experience hallucinations... I've yet to meet a schizophrenic who wasn't treated worse than an animal by medical professionals. While I understand that psychodelic experience can be valuable to some, many patients that would benefit from the treatment itself, would have strong contraindications.

[@disorganizedorg]

[Psilocybin will require that a practitioner or psychologist be present for 6+ hours] Correction: an overly aggressive regulatory framework is what requires that.

[@jaapmat]

@@disorganizedorg No. This has nothing to do with the regulatory framework and everything to do with medical ethics. A middle-aged treatment-resistant patient is not going to be ok taking a psychotomimetic at home with no guidance, at least not for the first few doses.

[@James_14_4]

There's a lot of potential in psychedelics, I can't wait to try any of them mushroom specifically but it's just so hard to find a reliable source over here, l'll be glad if anyone can be of help

[@Ameliagrace812]

The Trips I've been having have really helped me a lot,I finally feel in control of my emotions and my future

[@James_14_4]

@@Stephanie56739how do I reach out?ig?

[@Stephanie56739]

@@James_14_4yeah he’s got good stuffs

[@yr0]

Grow ur own.

[@Experience_Ibogaine_Aeden]

Grow them yourself.

[@CatboyChemicalSociety]

14:31 to make that cyclic ketone guy do they just react methylamine with bromobutyric acid which can be made by rxn of THF and bromine then oxidation with KMnO4. Then the resulting compound is heated and it cyclyzes forming that product.

[@toolinaround-est2024]

I concur.

[@maciejjakubiak2828]

As always comprehensive, digestable, and objectively presenting the important data. I love the organic chemistry sections! Would you happen to be planning an episode on the dissociative anaesthetic Ketamine? Keep up the good work!

[@totalsynthesis]

Thanks man 💪 I definitely have it on my list, probably will make a few non-psychedelic/drug vids first to keep the balance :)

[@maciejjakubiak2828]

@@totalsynthesis Thanks for answering! Knock urself out, make a couple of non-psychedelic videos to throw off the DEA, but know I'll still watch 'em.

[@totalsynthesis]

🤣@@maciejjakubiak2828

[@llamamusicchannel7688]

"optimally, not make folks trip out" I fail to see how removing the trip from psychedelics could be useful whatsoever.

[@jakobejonesbary4403]

your channel needs to blow up, i appreciate the content

[@totalsynthesis]

Thanks man, fingers crossed haha

[@science_and_anonymous]

Although not mentioned here, oxa-noribogaine (benzofuran heterocycle instead of indole) seems to hold a great deal of promise as a pharmaceutical as well. The product also has a great deal of range synthetically that it can be substituted, just as the indolic class does. In this manner, perhaps there can be a change of reasoning as to how much the atoms themselves within the ring change the pharmacology.

[@totalsynthesis]

Thanks for sharing!

[@Weisior]

The mechanisms of action of NOP and sigma opioid receptors are still not fully understood as of today. But I truly hope we will get to that point, and that beyond it lies the answer for such a tragedy opioid addiction is.

[@DrSpooglemon]

I don't get why there is a problem with hallucinations. I believe it is probable that much of the beneficial effects are a result of the psychedelic effects. Increased activity in the pyramidal neurons is the neurological correlate with psychedelic "hallucinatory" experiences and this may also by part of the healing process - facilitating the creation of new patterns of neurological activity. This is like trying to get the beneficial effects of MDMA without the euphoria.

[@totalsynthesis]

Fair points - cant hurt to try though! We will see how it works if we ever get robust clinical efficacy data on these non hallucinogenic molecules

[@lachousalle31]

Psychedelics are probably horrible for certain people with anxiety and panic attacks. I can't even have a little bit of weed because it makes me feel like I'm dying. Now imagine someone like me taking a powerful Psychedelic... Fuck that. I'll stick to kratom.

[@Experience_Ibogaine_Aeden]

​@@lachousalle31well aside from ibogaine and if you had an addiction, what benefit would you get from psychedelics without the psychedelic experience?

[@margodphd]

​@@Experience_Ibogaine_AedenNeuroplasticity and pharmacokinetical ones. Psychedelic experiences can be harmful and are contraindicated in many mental disorders that often coexist with drug addiction which would limit treatment accessibility.

[@dinadaughtry8993]

​@@lachousalle31totally different type of experience than weed, I would not want to take a high enough dose of THC to cause hallucinations either but shrooms and acid are a nice experience but you should be around people who are not going to mess with you and set and setting are very important to, but wait until you are comfortable with the idea, you don't want to start out nervous and anxious better to be calm and know that you will be ok, that the experience is temporary and start with a lower dose and work your way up until you get the desired therapeutic effect

[@williambouthillier8611]

Great video! I love how you mix in pharmacology and chemistry concepts into these very educational med chem videos. Just a small thing regarding your Fischer indole synthesis, the aminal is likely not eliminated in a concerted E2 fashion as shown but rather an E1 type elimination consisting of the collapse of the tetrahedral aminal to an iminium ion followed by tautomerization. It may seem like an unimportant detail for most people but they becomse important once you try to explain regio-/stereo-/chemo- selectivities of more complex examples. The E2 type elimination has a higher entropic cost of being 2nd order (necessitates proper orbital overlap of 2 separate molecules during a collision) and actually requires the deprotonation of a tertiary carbon which is very hindered, all of which is most likely translated into a higher activation energy barrier, not to mention that it would require the proper stereochemistry for this to work (aka to the H- and the -NH3 groups to be antiperiplanar). On the otherhand, intramolecular reactions such as the collapse of the aminal tetrahedral center to form the iminium generally happen much faster than any kind of intermolecular reactions (in relative terms) simply due to the low entropic cost of being a pseudo 1st order reaction (still depends on the proton concentration but it is likely in excess at low pH, hence the "pseudo" terminology). Proton transfers and tauromerizations are also generally very fast compared to any other ionic transformations so all in all the entropic costs of E2-type elimination makes it very unlikely compared to the E1-type process in the case of aminals and acetals. You can also think of it this way: you can eliminate NH3 from an aminal just fine even with no alpha-protons are available

[@totalsynthesis]

Agree - I didn't want to draw more steps 😂

[@williambouthillier8611]

@@totalsynthesis ahahahah yes I figured as much once I started watching the rest of your videos but I guess it's still good information for other less experienced viewers. Keep up the good work !

[@totalsynthesis]

Yes, thanks for that detailed explanation and the kind words!@@williambouthillier8611

[@rainerlanglotz3134]

Really interesting that a 6-Meo versus 5-Meo causes the molecule to become a 2B antagonist, which is of course very healthy. Wonder if simple Harmaline from syrian rue (6Meo as well) would also be a 2B antagonist.

[@ChemicaLove]

3:25 I think you mean 'free hydroxyl' 5:02 that's methanol

[@totalsynthesis]

Damn

[@Grateful.For.Everything]

Appreciate You putting all this together for us, really nice work!

[@totalsynthesis]

Thank you!!

[@LUCASHOMINID]

Awesome vid, keep up the good work man! I am confused on one aspect of the synthesis section however. At 25:35 of the video when you’re discussing the palladium catalysed heteroannulation, the palladium catalyst shown is palladium acetate which is a Pd(II) species. However, for the oxidative addition to the C-I bond on the SM to occur doesn’t the catalyst have to be Pd(0)? As the Pd(0) would then get oxidised to Pd(II) which could then do a heck type insertion into the triple bond? Is this a mistake or is there something present that reduces the Pd(II) first?

[@totalsynthesis]

Thanks!! Yes, indeed Pd(II)-ligand complexes are pre-catalysts which are first reduced in situ to Pd(0) which then gets the action started. This can be mediated by various additives and species present in the reaction. For example you can check here for some reading: pubs.acs.org/doi/10.1021/jacs.7b01110

[@aSCrouton]

going to have to rewatch a few times, great info!

[@totalsynthesis]

Thank you!

[@brianmcnellis5512]

How does one get a test kit to test the purity of the HCL and ,purity & content of the Iboga TA?

[@DavidConnerCodeaholic]

The experience is a large part of the transformative potential of psychedelics. It forces you to experience altered states where you lose control over your conscious mind. Safety is a relative term, esp. when you consider the predictable trajectory of patients for which psychedelics would be most beneficial.

[@DavidConnerCodeaholic]

Sigma 2 receptors are related to mAmp’s neurotoxicity.

[@ToreMix7400]

Noribogaine is a misnomer for desmethyl-ibogaine, as nor is short for "N-Ohne Radikale".

[@totalsynthesis]

Nah mate it's not. From wikipedia: False etymologyEdit It is suggested that "nor" is an acronym of German "N ohne Radikal" ("nitrogen without radical"). At first, the British pharmacologist John H. Gaddum followed this theory,[8] but in response to a review of A.M. Woolman,[9] Gaddum retracted his support for this etymology.[4] Woolman believed that "N ohne Radikal" was a German mnemonic and likely a backronym, rather than the real meaning of the prefix "nor". This can be argued with the fact "that the prefix nor is used for many compounds which contain no nitrogen at all".[9]

[@klauskarpfen9039]

@@totalsynthesisI also was raised in the belief that "nor" means "N ohne Radikal" (such as in nor-morphine) and simply out of nonchalance and sloppiness chemists then went on to use it on other derivatives, which lacked a methyl group compared to the parent compound. Being a German myself I can easily believe this.

[@serbianfemboy]

You should do a video on the pharmacology of DXM, i think that would be cool

[@totalsynthesis]

I had this on my list of potential topics - interesting to see someone bringing it up. Thanks

[@serbianfemboy]

​@@totalsynthesis yep, love your videos btw keep it up

[@disorganizedorg]

In discussing DXM, its use along with Bupropion (as a fixed combination of 45mgDXM and 105mg Bupropion as "Auvelity") should be touched on. I'd been taking both Bupropion and Mirtazapine for some time with poor resulting getting myself "unstuck" from the depressive place I was in and decided to experimentally add DMX (though my ratio was different (30mg/150mg). I did in fact note increased efficacy -- an anecdote probably hopelessly compromised by confirmation bias & placebo effects.

[@TheToemeister]

Great video, though the structure for ketamine at 4:56 is incorrect (in addition to ethanol). The chlorine should be at the 2 position of the phenyl ring, not 3.

[@zhou_sei]

good catch

[@totalsynthesis]

Must have been mentally somewhere else when designing that page 🤣🤣🤣

[@fooraapkotjakker8131]

I am curious to seeing the results of the non halucinating compounds, i am skeptik tough. By eliminating the halucinations may also eliminate the insight gained from them. It’s reducing a spiritual world into a pure materialistic world. It’s the dogma for science today.

[@Weisior]

Well... Humans are biological machines, and so its safe to assume, that every action a biological body takes has its biological source. We also dont know everything about the inner workings of our organisms, so there is still room for a breakthrough discovery.

[@chadkline4268]

Fwiw, a woman i was not attracted to once poisoned me with yohimbine, 1/2oz of some extract where the dose was supposed to be only a few drops. Apparently, she wanted me to turn on to her. I was so ill, i lay on the floor, unable to breathe, extremely nauseous, in extreme pain, near death for an hour, similar to anaphylactic shock.

[@johanvisser2364]

Seperating the medicinal and psychedelic part of ibogaine is missing the point of the natural compound. TBG may be therapeutical but does it harbor the love bonding effect that comes with Ibogaine. Big fan of the Fischer indole synthesis though!

[@PotooBurd]

This is so informative!!! Fantastic reporting; I enjoy this kind of content!🌻🌼🐝

[@totalsynthesis]

Thanks!! 🦉

[@dunar1005]

18:24 well.. if your receptors are already activated/modulated/occupied and so on. I would also consume less. It would be interesting if they do this days or weeks after, not DURING the active metabolites are in the brain

[@totalsynthesis]

Good point, the durability is definitely important - potentially, this would require repeated dosing such as we are seeing in recent MDMA trials

[@Experience_Ibogaine_Aeden]

Most short acting opiates asides from fentanyl are fine to have in the system even, even 8 hours before treatment it is fine to take your last dose of opiates. Long acting opiates and blockers like methadone and Suboxone have to be out of the system for a minimum of 4 weeks, preferably 6.

[@yevlyan4060]

@@Experience_Ibogaine_Aeden do you think with fentanyl it will need more flood doses to work ? one clinic told me they will have to do 2 big doses and micro dosing in between in order to work. i know fent stays in fat sells. do you think its possible to do ibogaine on Fent without switching to morpheein or Oxy, to work properly.

[@felixbums6240]

Nice Video! Imagine if we could one day synthesize a morphine like anastetic without its psychoactive features! That would be worth at least 10 Nobel prizes

[@totalsynthesis]

Thanks!

[@science_and_anonymous]

It has been done many times over, but it seems that a non-addictive opioid means little to no efficacy for pain management (sadly).

[@defenestrated23]

Look into enkephalinase inhibitors. We haven't hit a home run yet, but they are very promising.

[@matthewcrome5835]

@@science_and_anonymous How come? Is it just because the side effects are too much despite the pain relief, so the lack of addictiveness prevents the person from using the opiates again? I would know, opiates make me feel like shit and I would never dream of abusing them due to how shitty they make me feel.

[@Experience_Ibogaine_Aeden]

Or a morphine that wasn't physically addictive. Methadone has little paychoactive effects but is a million times more addictive than heroin.

[@christopherbettridge]

Interested in the challenge

[@ziadelhassan8888]

Thank you for the video, really informative. Love your channel from Morocco 👍👍

[@totalsynthesis]

Thank you!!

[@samlazar1053]

Addiction = mailfunction of the reward system

[@zhou_sei]

why is it NOR-ibogaine when it's not the nitrogen losing the carbon? (not saying this is your fault, i see others have called it this... just wonder is it simply a trope/ mistake, or is there a good reason?)

[@totalsynthesis]

It's not atom specific actually - see e.g., nortestosterone. As a side note, Nor is also unspecific to the group that is removed/not present across 2 molecules (so it can be things other than methyl)

[@zhou_sei]

​@@totalsynthesis oh snap! i had learned that it stood for "N ohne radikal", but apparently that is a misrepresentation. thanks for prompting me to look it up! lol cheers.

[@chemdelic]

Always high quality videos

[@totalsynthesis]

Thanks mate - you have also been killing it

[@AdinathJichkar]

At 24:28 why was NaOCl used after nabh4 reduction?

[@skyethebi]

15:41 I find it interesting also that there was less head twitching on the higher doses. Could that mean that the drug is in fact inhibiting the hallucinogenic effects somehow?

[@totalsynthesis]

So head-twitch response is often bell-shaped - so high twitching at low doses, then decrease at higher doses. Beyond a certain dose, compounds can activate other, potentially non-specific mechanisms beyond serotonin receptors which can override the initial effects ("biphasic dose relationship"). But I'm not an expert so I actually don't know which pathways exactly :)

[@Experience_Ibogaine_Aeden]

Great video! Just wish you were more able to specify which clinics in Mexico were questionable based on evidence.

[@totalsynthesis]

I'm the wrong person to judge this!

[@chrisbell8418]

This video has provided me with tons of insight. Thank you.

[@totalsynthesis]

Thanks!

[@s0cializedpsych0path]

NO! The "hallucinations" are not hallucinations, they are memories. You revisit your trauma with complete objectivity. Essentially, it replaces a psychotherapist altogether. Sure, it has the side effect of interrupting physical dependence.... but the "trip", actually removes the urge. I know, you would only give Ibogaine to someone, if you really wanted to see them healed. However, this would rob you of years of income from the patient.... but it IS what is better for them. Sadly, people enjoy looking down on addicts, and if they were to all heal, who would they look down upon? They might be forced to actually have to better themselves, to feel superior. Also, Ibogaine is naturally occuring, so you wouldn't make billions from it..... so why allow it? That might get in the way of suboxone and methadone profits.

[@Naturalmedicineprescription]

correct

[@nigelmorgan7502]

I thought the head twitch response indicated binding with 5ht2a receptors, suggesting, but not confirming psychedelic activity.

[@totalsynthesis]

You are right in that it's complex - so saying TBG has low hallucinogenic potential/likelihood is correct. There are compounds which elicit head twitch but they are non hallucinogenic, and also its not fully clear which receptor(s) can be responsible (2A, 2C and even others)

[@some_guy___]

My guess for the four step sequence is reduction of ketone, Hoffmann rearrangement, cleavage of the carbamic acid to the enamine + unmasking to ketone, then acetylation

[@MaxiRoeder]

I love your Videos! But wouldn't the chlorine in Ketamine be ortho instead of meta?

[@elliott614]

Why would you draw a line to a lone "Me" instead of just drawing a line? Like when some methyl groups are just a line but others are CH3 in the same line diagram sometimes. Just curious

[@elliott614]

Oh is it bc the line came from a Nitrogen and not a Carbon? (I don't remember that rule from organic chemistry) Edit: and I see lines coming from N to represent a methyl group in the same diagram where it's a line to Me elsewhere in this video. I'm confused. I'm not a chemistry major tho. EE/CS

[@totalsynthesis]

I only did that in the noribogaine comparison to better show the difference But usually you show everything consistently either as Me, CH3 or plain line (if you saw this anywhere else its because I might was not consistent) No rule!

[@elliott614]

@@totalsynthesis yeah I Googled it and saw a blog explaining that the Me or CH3/H3C is to distinguish from a lone hydrogen bc sometimes chemists draw a line to imply a hydrogen (?)

[@elliott614]

@@totalsynthesis Et-Et == butane 😆

[@eiriksu]

Highly interesting! But a strange ethanol molecule at 4:45...

[@kozu3884]

this was amazing

[@chadkline4268]

I don't agree that 5-MeO-DMT is hallucinogenic. In my view, it is 90% similar to the highest state of meditation, Cessation, at around 15mg, and it ought to be studied because it is related to the mechanism that binds the spirit to body+mind consciousness. Calling it a psychedelic is like calling aspirin a pain killer, which it may be, but its definitely not going to stop anything moderately painful. It's a big exaggeration.

[@chadkline4268]

I can say this: The difference between Cessation, or 9th jhana, and 15mg of 5-MeO-DMT is that Cessation is pure and serene. The chemical method still has some minor anxiety, some concern or steadying is involved, and there is still some mental involvement. But the aspect of disassociation of the spirit from body+mind consciousness is very similar. I tested it about 6mo after attaining the meditative path. And in no way do I imply it was easy. I can only attribute it to decades of practice in concentration and virtue and a big sacrifice of this lifetime. It can only be called a glimpse of death. I say the spirit is awareness+conscience+power of intent, at least. I also think there is more to it because my 'visual' imprint of Cessation, the stages, and actions I took, remain. Some say I should remember anything or it is not the real thing, but it's not a memory that needed memorizing, it's more similar to the memory used in recognition. So I concluded that some aspect of our visual history in life is not biological, and I do not think the brain is capable of performing instant recognition of an acquaintance we haven't seen in 40 years. I do not think chemistry/biology has that kind of processing power or storage capacity. In Cessation, there is only awareness of emptiness, but perfect clarity and serenity. I have a knowing, like conscience, that any intentions connected with mind+body will instantly bind me to mind+body, so I dare not exercise any such intents. I see that I am presence, sentience, being, an observer, zero dimensional and outside of spacetime. I see that I can go no further. When the entire universe has dropped away, even spacetime itself, there is nothing more that can be done. Nothing more that can be released. I don't say this is all that can be known. This is only what I know. And that 5-MeO-DMT is very very similar, and I can see why some call it the spirit molecule, and if someone can understand its mechanism of action, they will be very near to understanding the interface between awareness and body/mind consciousness, very near to understanding the defining mechanism between so-called life and death. And this could lead to other knowledge, perhaps alternative and safer routes to anesthesia where instead of trying to affect consciousness, we can simply disconnect the spirit temporarily. And instead of using pills for all psychiatric problems, we may discover that some people have spiritual problems, problems with conscience, and need other treatments. The 8th jhana, known as the sphere of neither perception nor non perception, is similar to entering the sleep state in full awareness. The world/mind/body disappear, but meditation space remains. Cessation is leaving even meditation space behind. I am old now, so I just want to leave some documentation behind for the future in case it is helpful. I had to maintain awareness of each and every breath, without missing a single one, for 12-16 hours. That's how difficult it was. I failed 2x before because even missing 2 or 3 breaths was not good enough. It requires perfection in concentration. As a child, I thought science and spirituality will meet at the ultimate truth, and maybe that is true 🙂

[@chadkline4268]

One last note: we know matter is comprised of the tau (magnetic field particle), muon (electric field particle), electron, and their anti particles. And the up/down, bottom/top, and strange/charm quarks. Atoms cannot create what they do not already contain. There is no awareness particle for atoms to establish any basis of awareness. And atoms are mechanical. They cannot establish intentions either.

[@Experience_Ibogaine_Aeden]

Hallucinogenic is just a derogatory term to discredit the extension of reality that psychedelics offer. Though 5meo is more physical than visual like DMT, they both crack open the same door that meditation gives.

[@ormarion552]

Very cool video it was rly super interesting to listen to, just a little note at 4:44 , the chlorine on the ketamine should be on 2nd position not third :p

[@totalsynthesis]

Thanks! And yes you are right! Seems I was trippin myself when drawing

[@NerdWord]

Please do one on gaboxadol a muscimol derivative. Also on the note of non-hallucinogenic psychedelics maybe look into 4C-DOM

[@christopherbettridge]

I was particularly interested in this subject not only because I'm learning chemistry (though much of this is still beyond my skill level!) but I've had a, quite severe, opiate/opioid dependence for around 25 years. So I've been interested in ibogaine since I saw a documentary on it some years ago, and since I live in Canada and therefore, at last check anywayz, it was still legal here I had thought about trying it. But I don't know where to look; but perhaps some day (soon!) there will be something like these syntheses available. Of course, I would never try to synthesize a psychedelic compound myself. 😇

[@Naturalmedicineprescription]

iboga world chris

[@sh.lslate3517]

DemeRx is bringing this to regulatory approval!!

[@glebanful]

Great video as always! I would have made some breakthrough ibogaine analogues, but B12 seemed more attractive at that time...

[@totalsynthesis]

😂😂

[@tristanlaurent5785]

4:46 Ethanol ? Good Vid :)

[@totalsynthesis]

The simplest things can be the easiest pitfalls! Thanks 🥰

[@wallyslow]

just an idea : Ibogaine and mc-18 work on regulating systemswhich oversees the disribution of receptor-clusters in humans ..namely the 'Orexin A and B' neuropeptides.

[@sambarajmandala123]

Still I didn't get mechanism for step of NaOCl after ketone reduction 😮 at 24:18 minute 😮

[@radeksuchy123]

weerman reaction

[@totalsynthesis]

Let me create a community/IG quiz and solution for this one I have time

[@dianaholmes9221]

I think using the medicine other than naturally is abnormal and unintended. The "trip" is a big part of the soul journey..

[@fasteagle9959]

Please transition to natural morphine prior to ibogaine treatment. 🙏

[@Naturalmedicineprescription]

good advice

[@luphoria]

> Sorry to some of you, but it would be nice if patients do not hallucinate. My understanding is that most benefits of psychedelic drugs is the major effects? At least in both LSD and MDMA, everything I've read about psychotherapeutic use is related to very large uses causing very large effects. Is addiction separate?

[@luphoria]

Wait, so the anti-addictive properties are attributed to the nicotinic acetylcholine receptor activity and nothing to do with serotonin inhibitors / KOR? That's very interesting and this video has me excited for harm red future. :)

[@성이름-d4o4o]

Reduction of ketone, epoxide formation by ocl-, decarboxylative rearrangement to ketone, acetylation?

[@totalsynthesis]

Basically yep, good job mate - however, some clarifications below

[@Kencohtman]

Can you explain the decarboxylative rearrangement please? Is there a name for the reaction?

[@성이름-d4o4o]

@@Kencohtman I don't know the name of the reaction, but epoxide can undergo rearrangement into carbonyl compound and in acidic condition, amide can be hydrolysed into carboxylic acid or just intermidacy tetrahedral structure can collapse leaving nucleophillic carbanion on epoxide ring, basically acting as electrofuge, so decarboxylative epoxide rearrangement. +I found the name of epoxide rearrangement in acidic condition, it's Meinwald rearrangement.

[@totalsynthesis]

@@Kencohtman It starts with oxidative Hofmann rearrangement to give "C-N-CO2Me" (reaction done in methanolic KOH); followed by a hydrolysis/ cleavage of the "urethane" adduct (the carbon alpha to the nitrogen is linked to the N and the O). This comes from the hydroxy group (from the reduced ketone) bridging to the other side in a 5-membered ring (I assumed this is what the first gentleman meant with epoxide, even though it's not 3-membered). Upon heating with strong acid, the adduct is fully hydrolysed - which means C-O and C-N bonds get ultimately cleaved and result in a ketone

[@totalsynthesis]

@@성이름-d4o4o Thanks for responding - also check my other answer. I might have misunderstood and didn't realize you were thinking true formation of epoxide and that thing rearranging. Actually they saw some participation of the free hydroxyl group coming from the ketone, forming a urethane. That adduct can be cleaved in forcing conditions via hydrolysis. Here's the link to the paper where they describe the isolated intermediates: pubs.acs.org/doi/abs/10.1021/ja01087a057

[@pauljones9150]

Soooo how do we get tbg

[@elijahimeh4500]

Johnnycology store. After looking for so long, that's where I finally stumbled on and successfully ordered from

[@elijahimeh4500]

The page is on Instagram

[@DingDongDaddyFromDumas]

The reason psychedelics help is because of how they alter the mind and cause hallucinations. They will never be able to design something with the same benefits that doesn’t have the psychological “side effects.” Edit: Though they definitely should attempt to resolve issues like herg activity, neurotoxicity, 5HT2B agonism, etc

[@robertbrook439]

Your approach is chemically well informed byt therapeutically completely backwards. Why does psilocybin help end of life patients overcome fear of death? Its not because of correcting some chemical imbalance. The experience of ego dissolution and reconnection with other layers of the psyche, the shutting down of the default mode network, is an experience that changes people. People change after ibogaine because they see the harm they cause others from the perspective of the other. Its not a "hallucination" as in seeing something that you believe is real but its not really there. Hallucination is completely the wrong word. It is silly to think you can retain the "effect" but take away the whole phenomenology of the experience. In fact your thinking is more magical than a shaman if you think you can remove the entire experience but magically retain the benefit because "chemicals"

[@Experience_Ibogaine_Aeden]

Spot on.

[@totalsynthesis]

Nice points (serious)

[@robertbrook439]

@@totalsynthesis thank you for the information about chemistry, we can only grow our understanding of psychedelics if we share expertise from all our different fields. I can imagine use cases for a non trip inducing version of a drug for specific people who may not be able to handle a trip due to existing mental health problems/ history of psychosis or whatever and it's worth researching of course but I am still skeptical if the benefit can really be separated from the experience.

[@pucky8231]

That's some woo woo stuff right there man, try reading some journals sometime.

[@robertbrook439]

@@pucky8231 I did hence the discussion of shutting down the default mode network. Do you have any references to journals that disproves that as a useful framework?

[@terralife6467]

i love your channel

[@totalsynthesis]

Thanks so much! Appreciate it :)

[@kemster9495]

Semisynthetics is so behind other medicine like synthetics. Compared to synthetics there are so much more research in it. What about other Kappa agonists.

[@KylesBodyandBraintips]

Wow amazing!! (:

[@kjellkriminell372]

at 2:23 "Methamphetamines (i.e. Adderall)" smh

[@enderpr6659]

I want a video about the study of LSD in ADHD pleaseeeee ❤

[@totalsynthesis]

If you are interested in chemistry, check out my recent lsd video (my very first one is super low production quality). But I might make another one in future about this topic

[@enderpr6659]

@@totalsynthesis I think i saw it but i will do it again :)

[@enderpr6659]

I have ADHD and im interested in psichedelic therapy, because i saw that many of the brain structural and chemical changes that produces on the brain could be benefical for how adhd neurology manifests. @@totalsynthesis

[@enderpr6659]

Hopefully one day i could be normal without taking amphetamines every day @@totalsynthesis

[@kawalier1]

PhenylEthylAmine is also have some potential.

[@ultrainstinctgarfield2661]

that shit made me hallucinate in a very not friendly way, not the traditional psychedelic experience but rather incredibly vivid closed eye fantasy/imagery of terrifying entities and non existent people unlike that of any classical psychedelic 1/10 would not recommend

[@robertbendik1364]

Ibogaine and mytraginine are littlebit similar.

[@margodphd]

Fantastic video. Glad it got recommended to me. Dropping a useless comment for the algorithm.

[@totalsynthesis]

Thanks!!

[@KKILLIAN]

we all know this, but the drug scheduling is so ridiculous. at this point, weve proven that the chart is almost backwards

[@totalsynthesis]

Crazy right

[@ComfyWombat]

Hunter S Was ahead of his time! :D I wonder how many politicians are on this?

[@sitindogmas]

it would be safer if some patients did not hallucinate.

[@BigolCockenhammer-pp9sj]

Litterly order it ...

[@isaacthehuman243]

4:45 that's methanol :/

[@totalsynthesis]

The easiest things can trip you up

[@pucky8231]

Man, you attracted all the woo woos with this one.

[@ethans6539]

The difference is they can patent and profit off a synthesized copy smh

[@ehdyna]

Obligatory comment for the algorithm : )

[@totalsynthesis]

🙏🔥🔥

[@dreamingone615]

I'm looking for a religion without the mystical god stuff...😂

[@RhythmJunkie]

There’s only one true Religion …. Love!✨😉 But when you merge into it it is an infinite mystery✨♾️💖

[@ToreMix7400]

we're living on a Goddess, that's a simple truth..

[@s0cializedpsych0path]

The reason life risking events happen with it, is that people have to fork over 10,000 for one treatment, so they need to be given an enormous flood dose. If it were legal, we could use it in lower doses, over time. This is not an excuse to make a new synthetic version and make it prohibitively expensive. Allow people to grow it, and charge for the facilities needed to treat. Enough of this profiteering. Get rid of the "trip", get rid of the benefit.

[@Experience_Ibogaine_Aeden]

Not exactly. Ibogaine is cheap and exceeding 15/mg per kg is venturing into dangerous territory and will not make the outcome any more successful. It's the cost of doctors, nurses, psychologists, labs, medicine, medical equipment, facilities, buisness license, taxes, marketing to reach addicts, ECT. It's actually much cheaper than your average one month stay in a traditional US rehab, the difference is insurance won't cover it. The most dangerous part about ibogaine is for someone to take it with pre existing health issues or having dangerous contraindication substances in their bodies during the procedure. It takes 7 years for the plant to mature and harvest. Microdosing can be effective but not so much for acute detox.

[@Naturalmedicineprescription]

no the real reason is failure to prep correctly, if patient cut down far enough in advance ... less than a flood works ... but of course profiteering its the pinacle of a-hole evolution

[@MD-qh6ld]

Do i hear a swiss accent?

[@totalsynthesis]

👀

[@stuart6478]

man... you don't do drugs do you?

[@ck2503]

Hate to play devils advocate but the trip is a integral part of the experience. Without it it's just another dubious medicine that may or may not work.

[@totalsynthesis]

Fair point - particularly relevant given the purposefulness is so critical (also why the therapy/support is key). Will be interesting to see if they may indeed work nevertheless!

[@WarlordEnthusiast]

I really don't think ibogaine is worth it, if you want a spiritual experience, shrooms and DMT are extremely safe. There's just too many negative trip reports with horrible side effects for me to want to ever try it.

[@totalsynthesis]

@@WarlordEnthusiast Definitely agree to not risk things and also don't try it in a un-supervised, recreational type of way if you are just looking for an experience

[@Experience_Ibogaine_Aeden]

​​@@WarlordEnthusiastI've oversaw several thousand people undergo ibogaine therapy, and it's pretty far from a lot of the reports you read online. And most Ibogaine clinics also incorporate 5meo into their programs.

[@Naturalmedicineprescription]

@@WarlordEnthusiast not for the faint hearted but if your down so deep , big problems take radical solutions