I found some days ago a german dissertation about the potential neurotoxic effects of beta-carbolines. The investigation was whether or not beta-carbolines are a potential reason for neurodegenerative diseases such as Parkinson's and Alzheimer's disease. They looked at beta-carbolines because they are ubiquitous.
The reason why beta-carbolines are under suspicion to be neurotoxic was that they only differ in a nitrogen-bridge between to benzene rings from the known neurotoxin MPP+ (There is also a sad story about "street heroin" contaminated with MPTP due to esterification at too high temperatures in an attempt to manufacture MPPP an opoid drug. The manufacturer Barry Kidston was suffered from Parkinson's disease due to consumption of his product.)
So if MPTP is a neurotoxin, then some hydrogenated beta-carbolines may also show neurotoxic properties.
Well I'm a physist, so I'm not totally familiar with all the pharmacological terms, but two main things I could extract from this work:
- N2-Methylated Beta-Carbolines seem to be highly neurotoxic. With 1,2,2-Trimethyl-1,2,3,4-tetrahydro-beta-carboline being the most toxic. And if 1,2-Dimethyl-1,2,3,4-tetrahydro-beta-carboline is metabolised to 1,2,2-Trimethyl-1,2,3,4-tetrahydro-beta-carboline same way MPTP is metabolised into MPP+, then 1,2-Dimethyl-1,2,3,4-tetrahydro-beta-carboline, which could form as a by-product if somebody attempts to synthesize DMT from Tryptamine by Methylation via Eschweiler-Clarke due to a Pictet-Spengler-Cyclization. (Again, I'm neither a pharmacist nor a chemist, but I would guess that Pictet-Spengler is favored over Eschweiler-Clarke because intramolecular reactions seem to be more likely. The product would be the neurotoxin with DMT a by-product. So not only the yield would be bad, you would probably end up like Barry Kidston. So, please, stick to the extractions, my fellow Nexians!)
- N9-Methylated Beta-Carbolines which are methylated on the nitrogen-bridge showed neuroprotective properties. (Don't try to synthesize them, even if you have the equipment, because you could also synthesize the N2-Methylated Beta-Carboline. Perhaps I'm too cautious because I'm not an expert in chemistry, but I prefer to stick what's well-known to be safe.)

Sadly, I have no idea what this works says about the neurotoxicity of common beta-carbolines, but if I finished with working myself through all this pharmacological and chemical terminology and mechanisms, I'll post what I have understood. Perhaps there is a german-speaking pharmacologist somewhere in the Nexus.

yes it is a basic problem in synthesis of DMT. Escweiler clarke reaction goes from imine formation with tryptamine and formaline and then the formed imine is reduced by Formic acid. Since formic acid cant give its hydrogen fastly enough the side reaction Pictet-Spengler-Cyclization is also occur. So you see that it is a race between two reaction. IF one is going slow the other reaction goes further.

So in the synthesis of the DMT the thing is that to avoid protonation of the imine that formed. So until a Pictet-Spengler-Cyclization will occur imine will reduced already.
In this purpose for a reducing agent SodiumcyanoBorohydride or SodiumAcetoxyBorohhydride could be use instead formic acid. So the imine product will be reduced just as its forms because of powerfull reducing agents , there will be no time to occur Pictet-Spengler-Cyclization.

Also with powerfull reducing agents reaction can carrying out in neutral ph (Cyclization reaction is much more favorable in acidic media )but takes more time to complete than in acidic media.

Considering all the evidence we have so far regarding the beta carbolines we consume in the dosages we consume, both from actual research as well as anecdotal evidence and traditional use, I`d say they are physically safe. Of course anything is toxic depending on dosage etc.

Here´s two related threads:
https://www.dmt-nexus.me...spx?g=posts&m=226662
https://www.dmt-nexus.me...spx?g=posts&m=169520

By the way, I´ve found what I suspect could be 1,2-dimethyl-THBC in mimosa/jungle spice and possibly some acacias too. But in very very small amounts. There are other beta carbolines there too, namely 1-MTHBC and 2-MTHBC.

Regarding the chemistry part, I`m not well versed enough in chemistry to give feedback on those reactions. But you mentioned the cyclization of DMT would form 1,2-DMTHBC, and someone should correct me if im wrong, but it´s my understanding that the cyclization of DMT forms 2-MTHBC instead (would the cyclization of MET yield 1,2-DMTHBC ? ) .


Here´s DMT


Here´s 2MTHBC


Here´s 1,2-DMTHBC



Here´s 1MTHBC / Tetrahydroharman



and Harman:


Both harman and norharman are found in tobacco smoke and some food, specially well cooked meat:

http://www.ncbi.nlm.nih.gov/pubmed/15764332

@Viperoid: Thank you for your comment. It sounds reasonable to me.

@Endlessness: Thank you for your correction. Indeed, you're right. Of course, it's 2-MTHBC which forms from formaldehyde and tryptamine by attempts of Eschweiler-Clarke-Methylation of tryptamine. But 2-MTHBC with its similarity to MPTP in such high quantities as in the Eschweiler-Clarke-Methylation of tryptamine approach to DMT should also be regarded as a risk not worth taking. Well one can purify the product somehow, but the properties of DMT and 2-MTHBC are quite similar I guess its not too easy for an amateur chemist to be 100% sure, there is no 2-MTHBC left especially without any analytical devices like spectrometers.

Yeah what you say makes sense. I was talking from a theoretical point of view, we generally don`t talk about synthesis that require watched or dangerous chemicals and proceedures, we focus more on extractions or simple safe synthesis (harmaline to thh etc), which already allow for more things to explore than most people will ever need. Not to say you shouldn´t do whatever you want, with awareness

If those Beta-carbolines formed in Eschweiler-Clarke approach to DMT synthesis wouldn't be under suspicion to be such strong neurotoxins, then one could say, that the products of this approach could be seen as a one-pot pharmahuasca synthesis. I like the idea because it shows people who know only a little bit of chemistry and pharmacology some insights about the whole ayahuasca issue from a pharmacological point of view. If only the conditions (in this case pH and choice of hydrogenating agent) are varied then the two types of products are either tryptamines (tryptamine, NMT, DMT) or beta-carbolines (THBC, 2-MTHBC). So if there is such a fine line in the synthetic pathway between the two main active ingredients of ayahuasca then one can easily see how the structure-activity-relationship works with consideration to the affinity of DMT and beta-carbolines to MAOs and perhaps why sometimes DMT is found in trace amounts in plants with beta-carbolines as main alkaloids and the other way around. If this is true one could assume that the biochemical pathway to beta-carbolines leads over DMT, NMT or tryptamine depending on what beta-carboline is found. So this issue can lead to an working hypothesis in one's research about the pharmacology and chemistry of ayahuasca. Well, as it is with every assumption about the world not every working hypothesis that can be extracted from this will be true, but it will be a good start to learn something about the pharmacology and chemistry of ayahuasca. I'm speaking from a didactical point of view. (After all, we are a entheogenic university. So didactics should also be an issue. I'm you amazed how clear my inner picture of this topic gets.)

Off topic : congrats for your promotion Bonanza

I know your post was well-meant, but you don't need to congratulate me because it's not my work.
I don't want to take false credit for someone else's work. I'm only about to finish my bachelor in physics* the next semester.
(* That's also the reason why I am not that well educated in chemistry and especially in pharmacology. But things can always change. )

I think he meant your promotion to full membership in the forum

By the way, do we even know that 2MTHBC has any significant MAOI activity? We`d need to find IC50 values.

pictet-spengler still occurs with NaCNBH3 as H+ (acid is the catalyst) is added dropwise in formalin solution. the quat-ammonium readily cyclizes prior to alkylation. I've characterized the end-product (n-methyl-tryptoline..acetic acid was used) via lc-ms.

I won't go into a synthesis discourse, as it is against Nexus policies, but reductive alkylation typically yields beta-carbolines.

Wow. Nice. I didn't realize that.
Well, then thank you, DansMaTete. And thank you endlessness for drawing my attention to that.

Yes, I only stated it is a start. I'm still learning. For example that not all beta-carbolines inhibit MAOs. The picture gets even more detailed. I like learning things.

I studied the work further and it says, that N2-Methylated beta-carbolines don't inhibit MAOs. But N9-Methylated beta-carbolines do. It is further stated that this is also a factor in their neuroprotective properties. N2-Methylated beta-carbolines showed to inhibit the Complex I of the respiratory chain (cellular respiration) which leads to apoptosis. Some if one could get a hand on N9-Methylated beta-carbolines one could make a "nootropic ayahuasca".

Here is a short summary of the effects of beta carbolines on brain cells, receptors, MAOs and reuptake inhibition:

1,2,3,4-Tetrahydro-beta-caroblines:

Tryptoline (1,2,3,4-Tetrahydro-beta-carobline):


Inhibits Norepinephrine- and Serotonin reuptake [Rommelspacher et al., 1978]

Pinoline (6-MeO-1,2,3,4-Tetrahydro-beta-carobline):


inhibits Serotonin reuptake [Ho et al., 1973; Komulainen et al., 1980]
Antioxidant properties [Pahkla et al., 1998]
stimulates Insulinsecretion through binding at Imidazolin I_3 and Ryanodin-receptor [Squires et al., 2004]

Plectomine (2,3,4,9-Tetrahydro-beta-caroblin-6-ol)



Strongly inhibits Dopamine, Norepinephrine and serotonin reuptake reversibly
[Rommelspacher et al., 1978]

Tetrahydroisoharmol



High affinity to opiate receptor probably linked to addiction and death of neurons in combination with alcohol abuse [Wrona et al., 1997]

Adrenoglomerulotropin (1-Methyl-Pinoline or 6-Methoxy-1-methyl-2,3,4,9-tetrahydro-1H-β-carboline)



strong tranquilizing effects [Zhukov et al., 1983]

Beta-carbolines:

Harmol (1-Methyl-9H-β-carbolin-7-ol)



Antioxidant properties, changes mitochondrial membrane permeability [Park et al., 2003]
inhibits dopamin-uptake [Drucker et al., 1990]

Harmalin (7-Methoxy-1-methyl-4,9-dihydro-3H-β-carbolin)



Antioxidant properties, changes mitochondrial membrane permeability [Park et al., 2003]
inhibits dopamin-uptake [Drucker et al., 1990]


Norharmane (9H-β-Carboline)



inhibits MAO B [Herraiz et al., 2005; Rommelspacher et al., 2002]
stimulates phosphoinositol-phospholipase C
inhibits glucose-regulating protein 78
inhibits triosephosphatisomerase

Harmane (1-Methyl-9H-β-carboline)



inhibtis MAO A [Herraiz et al., 2005; Rommelspacher et al., 2002]
stimulates Insulinsecretion through binding at Imidazolin I_3 and Ryanodin-receptor [Squires et al., 2004]

2-MBC ()

inhibits the Complex I of the respiratory chain [Sayre et al., 1991]
substrate of N2-Methyltransferases [Gearhart et al., 2000]
inhibits acetylcholineesterase [Dekhane et al., 1993]

9-MBC

strongly inhibits MAOs [Ho et al., 1970]

2,9-DMBC

inhibits the Complex I of the respiratory chain [Collins et al., 1992]

3-Carboxymethylester (beta-CCM; methyl 9H-b-carboline-3-carboxylate)



inverse agonist of the benzodiazepine-receptor [Glennon et al., 2000]
improves memory [Dekhane et al., 1993]

By the synthesis of DMT only beta carboline specie that produced is Tryptoline. I dont do general research about it but in time when i researched about DMT synthesis many authors told that its neurotoxic and can cause to parkinson disase.

http://en.wikipedia.org/wiki/Tryptoline

here it referenced in wikipedia

@Viperoid:
Don't you think that N2-methyl-tryptoline might be formed as well?
Do you have any references that Tryptoline is neurotoxic?
And do you have any idea about the mechanism that explains its neurotoxicity?

no since i cant acces to isi for now all refference i can get you is tahat the wikipedia refferences

http://link.springer.com...cle/10.1007%2FBF00508615
http://www.reference.md/files/C009/mC009804.html

I dont know about N2-methyl-tryptoline . Some says it's forming some says its not. I dont have any scientific paper that tells this.

And no i dont researched about its neurotoxicity

apparently, even the thermolytic decarboxylation of tryptophan can give beta-carboline derivatives, with their structures varying with the ketone catalyst used

http://www.ncbi.nlm.nih.gov/pubmed/16569488

For anyone searching for information about the alleged neurotoxicity of 2MeTHBC, there's another thread discussing this.

After a cursory investigation of the commonly referred source of these claims, one specific wikipedia article, I suggested in this post that this rumor might be mostly FUD that was hyped up to get funding for research into Parkinson's disease.