Ibogaine Analog Freebase to Fumarate Conversion

[Shizballs]

What's up guys? I've been a long term user of iboga alkaloids due to mental health issues and I gotta say, they really possess something unique despite their cardiovascular risks. Anyways, I've been following the development of a similar compound, tabernanthalog, which can induce the same neuroplasticity and benefits of ibogaine without the cardiovascular and perceptual complications (I understand this is a bit controversial, I definitely agree that the actual experiences possess a wealth of medical value).

Sorry if this got a bit long, but I managed to acquire a few grams of the stuff and as expected, I am seeing some benefit but I am depleting my stash quickly. I learned yesterday that I possess the freebase form of the substance. Due to scarce supply and understanding bioavailability and first-pass metabolism, I'd ideally like to convert this into either an HCl or Fumarate salt and possibly switch to IM administration. So I was wondering if I could simply use a modified FASA method to achieve this?

Here is a link to the structure of the molecule. It seems similar enough that fumarate can work, albeit probably less stable than DMT fumarate.

TL;DR can I use FASA on other tryptamines? What modifications might I need to make? Can I assume the same mol ratio? (I believe this is 2:1 for DMT?)

 

[downwardsfromzero]

Yes, this should work. It might precipitate as a 1:1 fumarate though so check the literature as thoroughly as possible.

Be sure to report your results.

Finally, please think very carefully before injecting any product. Maybe sublingual administration would be more efficient than oral, and much safer than IM?

A couple of pertinent links:
A non-hallucinogenic psychedelic analogue with therapeutic potential
Engineering Safer Psychedelics for Treating Addiction

 

[Shizballs]

Be sure to report your results.

Finally, please think very carefully before injecting any product. Maybe sublingual administration would be more efficient than oral, and much safer than IM?

I actually got impatient and did a quick tech this morning. I assumed since DMT and TBG appear to be similar enough that it would work fine; albeit, probably with less stability over time.

It looks like from the very uniform color that it still had the 1:2 ratio I was expecting. Is there any way to tell for sure? This is what the precipitate looked like.

Reaction Notes:

I used a modified version of the quick tech quoted here. I used 100 mg TBG and 25 mg of Fumaric acid each (mostly) dissolved in about 6 mL of acetone. I started with 5 mL each but added a little more thinking it would help dissolve the last of the solids. Idk just felt right and figured it would be harmless since any excess would just evaporate if heated.

I mixed these together rather abruptly which produced a very cloudy milky acetone mixture which eventually settled to precipitate at the bottom. Then I used double burner method to evaporate the acetone.

 

[Twilight Person]

I have not too much about neither Ibogaine nor IM stuff, but I think Benzoate salts also are a thing as it seems to produce salts of Alkaloids?

Those are also used in pharmaceutical chemistry. So if you would like to experiment more (on a reasonable base) with that stuff I might just go for salts that are also used for medic drugs. Plus point is also that Benzoic Acid will always form the same salt in a 1:1 ratio - not like fumaric acid where you maybe dont know if you have 2 or 1 molecules of your drug packed together.

 

[Shizballs]

I have not too much about neither Ibogaine nor IM stuff, but I think Benzoate salts also are a thing as it seems to produce salts of Alkaloids?

Those are also used in pharmaceutical chemistry. So if you would like to experiment more (on a reasonable base) with that stuff I might just go for salts that are also used for medic drugs. Plus point is also that Benzoic Acid will always form the same salt in a 1:1 ratio - not like fumaric acid where you maybe dont know if you have 2 or 1 molecules of your drug packed together.

This is a really good idea, unfortunately I am nervous ordering a new reagent due to alarming other people living at my current address.

I'm assuming that the concern here is that the reaction may have been 1:1 and thus some acid may be in the IM solution which would damage muscle tissue. Would it also be a suitable alternative to simply decant the solution since any excess fumaric acid would still be soluble in the acetone?

 

[downwardsfromzero]

I actually got impatient and did a quick tech this morning. I assumed since DMT and TBG appear to be similar enough that it would work fine; albeit, probably with less stability over time.

It looks like from the very uniform color that it still had the 1:2 ratio I was expecting. Is there any way to tell for sure? This is what the precipitate looked like.

Reaction Notes:

I used a modified version of the quick tech quoted here. I used 100 mg TBG and 25 mg of Fumaric acid each (mostly) dissolved in about 6 mL of acetone. I started with 5 mL each but added a little more thinking it would help dissolve the last of the solids. Idk just felt right and figured it would be harmless since any excess would just evaporate if heated.

I mixed these together rather abruptly which produced a very cloudy milky acetone mixture which eventually settled to precipitate at the bottom. Then I used double burner method to evaporate the acetone.

The stability shouldn't be much of an issue.

So, just to be clear, did you evaporate off all the acetone? Without draining of the excess liquid?
If so, there will be excess TBG in your product (see below). And sorry, none of us can analyse it by looking at a picture of it :lol:

Crystals take time to grow and they require a nucleation point. This means it's better to drip the FASA slowly into the solution of alkaloidal freebase. And, regarding stoichiometry, did you calculate how much fumaric acid might combine with a given amount of tabernanthalog?
Just match twice the MW of TBG as the figure in milligrams of TBG with one equivalent of the MW of fumaric acid - C4H4O4 = 4×(12+1+16) = 4×29 = 116
So, 116mg of fumaric acid should react with 2×(MW TBG)mg of TBG.
And what is the MW of TBG? A quick look at the structure shows that it's the cyclic methylene homologue of 6-methoxy-DMT, so we can use the MW of 5-MeO-DMT and add a carbon atom to it. So, 218.300+12.011 = 230.311 g·mol−¹ ×2 = 460.622
This - ~461:116 - is very close to a 4:1 ratio, so it looks like your 100mg TBG to 25mg fumaric was about right. If anything, you could use a tiny bit more fumaric acid to ensure full precipitation.

It would be wise to weigh the solid that remains after washing the initial precipitate. (Vacuum filtration would optimise the washing process.) If there's 125mg of it, you have the normal fumarate, but if there's only 75mg there's a fair chance that you have the bifumarate (i.e. the 1:1 salt).

Either way, if you really evaporated of all the acetone, you ought to wash your product with some fresh anhydrous acetone. After filtering and drying, weigh your solid again. You may have removed a tiny bit of excess TBG freebase.

Just to be sure, try adding a drop or two of FASA to the now filtered acetone. If no precipitate is observed you have collected all the TBG as the 2:1 fumarate.

PS In the original paper, the TBG was tested as the normal fumarate so I wouldn't worry too much about benzoates. Strassman's original DMT studies used the fumarate as well. Fumarate is a normal component of human metabolism and entirely compatible with medical use.

 

[downwardsfromzero]

PS - considering this is technically a RC you ought to post some safety information to go with it. Them's the rules.

 

[RhythmSpring]

I wonder what a Bwiti shaman would think about this experiment.

 

[Shizballs]

So, just to be clear, did you evaporate off all the acetone? Without draining of the excess liquid?
If so, there will be excess TBG in your product (see below). And sorry, none of us can analyse it by looking at a picture of it :lol:

I am pretty sure. This is my first successful at home salt rxn but the product was extremely dry. I did not drain the excess liquid or decant in any way. I do plan on doing this differently on the next attempt.

Crystals take time to grow and they require a nucleation point. This means it's better to drip the FASA slowly into the solution of alkaloidal freebase. And, regarding stoichiometry, did you calculate how much fumaric acid might combine with a given amount of tabernanthalog?
Just match twice the MW of TBG as the figure in milligrams of TBG with one equivalent of the MW of fumaric acid - C4H4O4 = 4×(12+1+16) = 4×29 = 116
So, 116mg of fumaric acid should react with 2×(MW TBG)mg of TBG.
And what is the MW of TBG? A quick look at the structure shows that it's the cyclic methylene homologue of 6-methoxy-DMT, so we can use the MW of 5-MeO-DMT and add a carbon atom to it. So, 218.300+12.011 = 230.311 g·mol−¹ ×2 = 460.622
This - ~461:116 - is very close to a 4:1 ratio, so it looks like your 100mg TBG to 25mg fumaric was about right. If anything, you could use a tiny bit more fumaric acid to ensure full precipitation.

Here is the math that I used:
DMT: 1 g * (1 mol / 188.27 g/mol) = 5.312x10^-3 mol
Fumarate: 0.309g (1 mol / 116.07 g/mol) = 2.662x10^-3 mol
Checks out, roughly 1:2 mol ratio.

TBG: 1 g * (1 mol / 230.31 g/mol) = 4.342x10^-3 mol
Solving for req fumarate: (4.342x10^-3 mol / 2) * (116.07 g / 1 mol) = 0.2519 g fumaric acid
I used the MW value from chemical websites.

It would be wise to weigh the solid that remains after washing the initial precipitate. (Vacuum filtration would optimise the washing process.) If there's 125mg of it, you have the normal fumarate, but if there's only 75mg there's a fair chance that you have the bifumarate (i.e. the 1:1 salt).

Either way, if you really evaporated of all the acetone, you ought to wash your product with some fresh anhydrous acetone. After filtering and drying, weigh your solid again. You may have removed a tiny bit of excess TBG freebase.

Just to be sure, try adding a drop or two of FASA to the now filtered acetone. If no precipitate is observed you have collected all the TBG as the 2:1 fumarate.

PS In the original paper, the TBG was tested as the normal fumarate so I wouldn't worry too much about benzoates. Strassman's original DMT studies used the fumarate as well. Fumarate is a normal component of human metabolism and entirely compatible with medical use.

For sure. Will report back on this. Thanks for the help!

 

[Shizballs]

PS - considering this is technically a RC you ought to post some safety information to go with it. Them's the rules.

Of course. The pharmacological screening results are attached.

The effects of TBG (10 μM) on a wide range of targets was assessed by Eurofins Discovery. Assays were conducted in duplicate and the results were averaged. Targets with ≥50% inhibition are highlighted in blue. Exact n values for each experimental condition are reported in Supplementary Table 1. Specific statistical tests, information on reproducibility and exact P values are reported in Methods and in Supplementary Table 1.

Something that initially concerned me was inhibition of both the serotonin transporter and MAO-A. It is common knowledge on here that MAOI + SSRI is a potentially lethal combination, so I was extremely careful to start with very low doses below 5 mg and work my way up. I'm guessing that the actual MAO inhibition is much lower in vivo because I haven't experienced even minimal serotonin syndrome symptoms.

 

[downwardsfromzero]

I wonder what a Bwiti shaman would think about this experiment.

One would hope that they might appreciate the clever approach to molecular design that has gone into the development of TBG. Eliminating the cardiotoxicity while keeping the psychoplastogenic effect was a stroke of pharmacological genius.

They might not appreciate the bit about torturing stressing the mice and getting the creatures addicted to heroin, I don't know.

 

[RhythmSpring]

Have you noticed that the studies point to the cardioxicity of ibogaine, not the whole plant material of Iboga? Once we start extracting a single molecule from a plant with a myriad of chemical constituents that balance each other out, we run into danger.

The one case report I see of someone dying on the plant Iboga, they also had methadone in their system, and were taking 50mg of Diazepam. Ostensibly, they thought they could quit that cold turkey during their iboga session, and Iboga does NOT treat that kind of addiction.

Humans are clever, but sometimes they do things that are not necessary.

 

[Shizballs]

I wonder what a Bwiti shaman would think about this experiment.

One would hope that they might appreciate the clever approach to molecular design that has gone into the development of TBG. Eliminating the cardiotoxicity while keeping the psychoplastogenic effect was a stroke of pharmacological genius.

They might not appreciate the bit about torturing stressing the mice and getting the creatures addicted to heroin, I don't know.

Yeah, I've been following this one for a while. Personally, I am extremely interested in trying ibogainalog (the actually psychedelic counterpart to TBG) but it doesn't seem like that might happen any time soon.

I'd also be interested in what a Bwiti shaman thinks about the >200 people per day who die of opioid overdoses. I'd be interested in hearing what the scientists who say ibogaine is too dangerous think about that as well. Seems like sticking a needle in your arm might also be on the risky side of things.

 

[Shizballs]

Have you noticed that the studies point to the cardioxicity of ibogaine, not the whole plant material of Iboga? Once we start extracting a single molecule from a plant with a myriad of chemical constituents that balance each other out, we run into danger.

The one case report I see of someone dying on the plant Iboga, they also had methadone in their system, and were taking 50mg of Diazepam. Ostensibly, they thought they could quit that cold turkey during their iboga session, and Iboga does NOT treat that kind of addiction.

Humans are clever, but sometimes they do things that are not necessary.

It is practically all of the alkaloids that are cardiotoxic. The referenced paper here identified that it is the oblong looking isoquinuclidine ring that causes affinity for hERG and cardiotoxicity. I'm not aware of all but tabernanthine, catharanthine, ibogamine, ibogaline all possess an isoquinuclidine ring.

Ibogaine has taken FAR too much heat and hasn't gotten the credit it deserves. I do think ibogaine can help with diazepam addiction but GABAergic withdrawal and ibogaine is a known lethal combination. Withdrawal and treatment need to be done separately or bad things will happen.

 

[RhythmSpring]

I don't care what chemistry-related justification you have for Iboga being cardiotoxic. As long as there are no case reports of the unadulterated plant material causing cardiac problems, I rest my case.

As they say, "The proof is in the pudding."

 

[endlessness]

I don't care what chemistry-related justification you have for Iboga being cardiotoxic. As long as there are no case reports of the unadulterated plant material causing cardiac problems, I rest my case.

As they say, "The proof is in the pudding."

This paper names 2 examples of rootbark-related deaths and 2 more of total alkaloids-related death and another that could be total alkaloid or rootbark (plus a bunch of pure ibogaine-related deaths). This is from 2012, there might be more cases since then if you search a bit.

 

[Shizballs]

I don't care what chemistry-related justification you have for Iboga being cardiotoxic. As long as there are no case reports of the unadulterated plant material causing cardiac problems, I rest my case.

As they say, "The proof is in the pudding."

This paper names 2 examples of rootbark-related deaths and 2 more of total alkaloids-related death and another that could be total alkaloid or rootbark. This is from 2012, there might be more cases since then if you search a bit.

Luckily, there's been significant adaptations to the ibogaine addiction treatment industry in the past decade. I don't think there are any official addiction treatment centers open that don't have mandatory EKG + liver screens before any ibogaine administration and I believe nearly all have a cardiologist/MD present for the duration of the treatment.

I would be surprised if the deaths haven't tapered off. Fortunately, Ibogaine treatment isn't the "vast, uncontrolled experiment" that it once was.

 

[downwardsfromzero]

Personally, I am extremely interested in trying ibogainalog (the actually psychedelic counterpart to TBG) but it doesn't seem like that might happen any time soon.

The good news, perhaps, is that IBG would be incredibly easy for a skilled chemist to make. Not that I can really add anything to that in this thread, but there you go.

One can dream...

I don't care what chemistry-related justification you have for Iboga being cardiotoxic. As long as there are no case reports of the unadulterated plant material causing cardiac problems, I rest my case.

As they say, "The proof is in the pudding."

Wow - I don't know what kind of pudding you've been eating lately, but chemistry and neuroscience are precisely the right tools for understanding what Shizballs was saying here, for example:

I do think ibogaine can help with diazepam addiction but GABAergic withdrawal and ibogaine is a known lethal combination. Withdrawal and treatment need to be done separately or bad things will happen.

Of course, most if not all GABAergic addiction is a chemistry-related problem. Chemistry gets a deservedly bad rap with its association with a vast number of the world's most pressing problems but in this case I feel you've thrown not only the baby but also the mother out with the bathwater.

 

[RhythmSpring]

I am not saying chemistry is evil. I'm saying there's not enough evidence to give *Tabernanthe iboga* a bad rap (as cardiotoxic) because of stories associated with a single molecule isolated from the plant, or some biochemical rule.

There is no solid evidence that iboga rootbark is cardiotoxic. I stand by my claim.

 

[downwardsfromzero]

In the area of native usage the occasional death from iboga root powder doses is not unheard of. I'm pretty sure this is on the ethnopharmacological record. It would be nice to have a thread specifically discussing this aspect of the matter since this thread is targetted on the pure tabernanthalog compound.

I would personally get an EKG done before embarking on any deeper exploration of iboga in whatever form. Mind you, I am getting on a bit. Maybe a wrinkle and a grey hair or two.