hERG channel blockade and prolonged QT interval from iboga alkaloids

[i are spectre]

"Ibogaine, the prototypic iboga alkaloid that is utilized clinically to treat addictions, has been associated with QT prolongation, torsades de pointes, and fatalities... In view of the extended half-life of noribogaine, these results may relate to observations of persistent QT prolongation and cardiac arrhythmia at delayed intervals of days following ibogaine ingestion."

https://www.ncbi.nlm.nih.gov/pubmed/25636206

This is kind of the consensus when I browse through many recent articles about ibogaine and iboga alkaloids. Blocking hERG potassium channels in cardiac tissue delays action potentials, prolongs QT, and can ultimately lead to an arrhythmia.

Anyways, what can we do to reduce the risk of cardiac arrhythmia while taking these types of compounds? I have a few ideas...

Maintaining cardiovascular health (exercise, healthy diet, limit smoking/drinking, etc)
Abstain from compounds that prolong QT interval (i'm trying to put a list together of some more common substances here)
Adequate electrolyte intake, mainly potassium (I had litres of coconut water available prior to and during my ibogaine/iboga TA experience)
Maintaining adequate blood pressure via simple hydration (once again, the coconut water, loaded with potassium and other electrolytes)

Any other suggestions?

 

[DotChem]

"Ibogaine, the prototypic iboga alkaloid that is utilized clinically to treat addictions, has been associated with QT prolongation, torsades de pointes, and fatalities... In view of the extended half-life of noribogaine, these results may relate to observations of persistent QT prolongation and cardiac arrhythmia at delayed intervals of days following ibogaine ingestion."

Any other suggestions?

Good question.. But I woudn't say there is a consensus on Ibogaine QT interval prolongation and cardiac K-channels blockade though. Most authoritative paper that looks at Ibogaine and related compounds-induced cardiac arrythmias effect here:


The Anti-Addiction Drug Ibogaine and the Heart: A Delicate Relation https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4382526/ (Free access)

But that study raises more questions than answers.
True for one, Ibogaine dose-dependtly increases QT interval but ONLY in opiates-tolerant patients and NOT in opiates-naive, ppl who've been never been exposed to opiates (there is a study done by deborah mash sometime ago). That paper hypothesis (and the current "consensus") is that Ibogaine-induced arrythmias are due to blockade of cardiac K-channels. The problem is that if that was the case then one would also expect it to show QT prolongation in non-opiates trained individuals too. Keep in mind lots of drugs (recreational, pharmaceuticals, supplements..etc) increases QT intervals but they do so regardless of other drugs used status of the patient. Nicotine, alcohol, cocaine, lots of pharmaceuticals and believe or not sexual orgasm too do that. Ibogaine seems to induce arrythmia ONLY IN OPIATES-TOLERANT individuals which is unfortunate since the drug present use (in the western world at least) is mostly for opiates detox.

The second issue is that in opiates treated subjects, the QT prolongation of Ibogaine is long lasting even after a single large dose (>=500mg/70 kg patient). Sometimes up to a week. long after the drug and its metabolites have been cleared from the body. Blockade of potassium channels as a cause of Ibogaine-induced arrythmias doesnt explain that since it is well known that QT interval prolongation by common K-channels blockers (like nicotine) stops upon removal of cardiomyocetes from exposure to the drug.. The extended half life of its metabolite noribogaine (<24h if I recall) which also causes QT prolongation doesnt explain it either since the QT is seen up to a week as I mention


So the bottom line is that nobody really knows how Ibogaine induces QT interval prolongation in opiates-tolerant BUT NOT in opiates-naive. Most likely it could be by a central mechanism in the brain of OPIATES-tolerant possibly via the drug-induced long term potentiation (?resetting of the opioid-trained brain) which is believed to be the mechanism of its anti-addictive effect in the first place True it does show direct blockade of cardiac K-channels but only in supratherapeutic doses. Unfortunately the drug is illegal in most countries so there's no research to answer that question..

In my opinion though, even in Opiates-tolerant, the cardiac risk and associated death following ingestion of large doses of Ibogaine is grossly exaggerated: Almost all the patients who died have pre-exsiting cardiovascular risks factors AND/OR are poly-substances users and/or have used just before treatment. The first reported case of a death (a 34-year old male) undergoing Ibogaine treatment has the following drugs in his system: alcohol, heroin, cocaine, methadone, nicotine, diazepam, has hypokalemia and cardiomyopathies at the time of death and weight about 55kg. Ibogaine can hardly be single out as the cause of death. That case was the case that makes the authorities to stop any and all funding of studies of Ibogaine.
Netherless, the single most important advise is to abstein from use of any substance (even the innoucous one like smoking) at least 24 hours and if possible 48 hours ahead of Iboga so there is less chance of any drug-drug interactions. In Brazil where it can be legally precribed, the requirement is at least 48h abstention from opiates, stimilants or alcohol. Yeah, dink lots of electrolytes (40% of people in general lack proper levels of potassium), bananas are excellent K-source, respect the medicines and get proper set and settings .. good luck

 

[i are spectre]

effects on (1) induced pluripotent stem cell-derived cardiomyocetes & (2) mammalian tsA-201 kidney cells, not case studies...

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(1) Anti-addiction Drug Ibogaine Prolongs the Action Potential in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes

Abstract: "Ibogaine is a plant alkaloid used as anti-addiction drug in dozens of alternative medicine clinics worldwide. Recently, alarming reports of life-threatening cardiac arrhythmias and cases of sudden death associated with the ingestion of ibogaine have accumulated. Using whole-cell patch clamp recordings, we assessed the effects of ibogaine and its main metabolite noribogaine on action potentials in human ventricular-like cardiomyocytes derived from induced pluripotent stem cells. Therapeutic concentrations of ibogaine and its long-lived active metabolite noribogaine significantly retarded action potential repolarization in human cardiomyocytes. These findings represent the first experimental proof that ibogaine application entails a cardiac arrhythmia risk for humans. In addition, they explain the clinically observed delayed incidence of cardiac adverse events several days after ibogaine intake. We conclude that therapeutic concentrations of ibogaine retard action potential repolarization in the human heart. This may give rise to a prolongation of the QT interval in the electrocardiogram and cardiac arrhythmias."

Results/Discussion: "By assessing the effects of ibogaine and its main metabolite noribogaine on APs in cardiomyocytes derived from human induced pluripotent stem cells, we provide the first experimental proof that ibogaine application does indeed entail a cardiac risk for humans, and we further unravel the mystery of the surprising longevity of the drug’s potential to cause arrhythmias... 3 μM ibogaine, a concentration at the IC50 value for hERG channel inhibition and well within the free plasma concentration range reached in humans after drug intake (up to 11 μM), significantly prolongs the AP and flattens its repolarization phase in human cardiomyocytes. This effect was fully reversible after washout of the drug (data not shown). Similar to ibogaine, also its long-lived active metabolite noribogaine (plasma half-life, 28–49 h) prolonged the human cardiac AP. This observation goes along with noribogaine’s inhibitory action on hERG potassium channels (IC50 = 3 μM), which very closely resembles hERG inhibition by ibogaine. It further provides an explanation for the delayed incidence of cardiac adverse events, which may occur even several days after ibogaine intake."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5334404/ (full text)

Anti-addiction drug ibogaine inhibits voltage-gated ionic currents: A study to assess the drug's cardiac ion channel profile

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3853361/ (full text, experimental details of the aforementioned text)

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(2) Mechanism of hERG Channel Block by the Psychoactive Indole Alkaloid Ibogaine

Abstract: "...Therefore, we studied in detail the interaction of ibogaine with hERG channels heterologously expressed in mammalian kidney tsA-201 cells. Currents through hERG channels were blocked regardless of whether ibogaine was applied via the extracellular or intracellular solution... Taken together, these findings show that ibogaine blocks hERG channels from the cytosolic side either in its charged form alone or in company with its uncharged form and alters the currents by changing the relative contribution of channel states over time."

Discussion: "The present results elucidated the mechanism of channel block and revealed that ibogaine 1) passes the membrane to bind to the channel from the cytosolic side, 2) blocks the channel either in its charged form alone or in company with the neutral form, 3) is bound to the open and inactivated configuration of the channel, and 4) alters the transition of the channel between the closed, open, and inactivated states..."

http://jpet.aspetjournals.org/content/348/2/346.long (full text)

 

[Limpet_Chicken]

Haven't yet read the papers but a question-how much is this going to tell us, studying hERG channel currents expressed in a non-native system such as tsA-201 (similar to HEK cells, I presume?) when there seems to be a specific interaction between human cardiomyocytes in subjects who are sensitized to opioids, and in isolated systems such as cell lines, if the issue happens to be due to feedback from an intact nervous system in-vivo, as a central issue.

 

[DotChem]

Hello .. the followup study seems pretty convincing but doesnt say much about what's is happening in vivo ..yes the issue is not whether Ibogaine and/or Noribogaine does increase QT interval: they do. The problem is that blockade of cardiac K-channels cannot account for that. The observed QT and TdP are seen only in opiates-tolerants but not in healthy (ie opiates-naive) individuals:

Ascending-dose study of noribogaine in healthy volunteers: pharmacokinetics, pharmacodynamics, safety, and tolerability. https://www.ncbi.nlm.nih.gov/pubmed/25279818 ..

Noribogaine is the active metabolite of the naturally occurring psychoactive substance ibogaine, and may help suppress withdrawal symptoms in opioid-dependent subjects. The objectives of this Phase I study were to assess the safety, tolerability, pharmacokinetic, and pharmacodynamic profiles of noribogaine. In this ascending single-dose, placebo-controlled, randomized, double-blind, parallel-group study in 36 healthy drug-free male volunteers, 4 cohorts (n = 9) received oral doses of 3, 10, 30, or 60 mg or matching placebo, with intensive safety and pharmacokinetic assessments out to 216 hours, along with pharmacodynamic assessments sensitive to the effects of mu-opioid agonists. Noribogaine was rapidly absorbed, with peak concentrations occurring 2-3 hours after oral dosing, and showed dose-linear increases of area under the concentration-time curve (AUC) and Cmax between 3 and 60 mg. The drug was slowly eliminated, with mean half-life estimates of 28-49 hours across dose groups. Apparent volume of distribution was high (mean 1417-3086 L across dose groups). No safety or tolerability issues were identified in any cohort. No mu-opioid agonist pharmacodynamic effects were noted in pupillometry or cold-pressor testing. Single oral doses of noribogaine 3-60 mg were safe and well tolerated in healthy volunteers.

QT issues were not observed in that study
In Opiates-tolerant:

Ascending Single-Dose, Double-Blind, Placebo-Controlled Safety Study of Noribogaine inOpioid-Dependent Patients . https://www.ncbi.nlm.nih.gov/pubmed/27870477

Ibogaine is a psychoactive substance that may reduce opioid withdrawal symptoms. This was the first clinical trial of noribogaine, ibogaine's active metabolite, in patients established on methadone opioid substitution therapy (OST). In this randomized, double-blind, placebo-controlled single ascending-dose study, we evaluated the safety, tolerability, and pharmacokinetics of noribogaine in 27 patients seeking to discontinue methadone OST who had been switched to morphine during the previous week. Noribogaine doses were 60, 120, or 180 mg (n = 6/dose level) or matching placebo (n = 3/dose level). Noribogaine was well tolerated. The most frequent treatment-emergent adverse events were noneuphoric changes in light perception ∼1 hour postdose, headache, and nausea. Noribogaine had dose-linear increases for AUC and C_max and was slowly eliminated (mean t_1/2 range, 24-30 hours). There was a concentration-dependent increase in QTcI (0.17 ms/ng/mL), with the largest observed mean effect of ∼16, 28, and 42 milliseconds in the 60-, 120-, and 180-mg groups, respectively. Noribogaine showed a nonstatistically significant trend toward decreased total score in opioid withdrawal ratings, most notably at the 120-mg dose; however, the study design may have confounded evaluations of time to resumption of OST. Future exposure-controlled multiple-dose noribogaine studies are planned that will address these safety and design issues.

True the highest dose in the first study was 60 mg and 180 in the second.. But still even at 60mg, there was a small but significant QT prolongation in opiates-tolerant. Same thing should've been observed in the first study of opiates-naive subjects if direct blockade of cardiac K-channel was involved.. there are even more convincing rats studies showing that this happens only in opiates-dependent rats but not naive .. good'day to all.

 

[i are spectre]

From the healthy volunteers administration of 60mg noribogaine or less...

Safety: "There were no QTcF values >500 milliseconds at any time. One subject dosed with 10 mg noribogaine had a single increase in QTcF of >60 milliseconds at 24 hours post-dosing."

It would have been nice if they reported more than a 500ms QTcF threshold other than the one instance of QTc increase. Anyway, these are very small doses compared to what myself and others have taken for flood dosing / visionary experiences. Either way, 60ms QTc increase is quite significant from 10mg noribogaine (I think), although there could be (and probably are) numerous other factors for it.

Discussion: "Noribogaine has been reported to interact with hERG channels (ED50 = 5 μM; Demerx, data on file). Noribogaine has a molecular weight of 296 Da, so the reported IC50 value corresponds to a concentration of ~1,500 ng/mL, approximately 13-fold higher than the mean C max values at 60 mg."

Once again, very low doses administered compared to what many people ingest (including myself) reading from various forums and other sources online. Either way, a nice article modeling pharmacokinetics of noribogaine in humans.

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From the opioid-dependent adminstration of 60mg noribogaine or more...

Electrocardiographic Effects: "Noribogaine caused a clear, statistically significant dose and concentration dependent effect on the QTc interval, with the largest mean effect (QTcI) of 16 milliseconds at 4 hours in the 60-mg group, 28 milliseconds at 3 hours in the 120-mg group, and 42 milliseconds at 3 hours in the 180-mg group."

All three of those ΔQTc+ values (60mg, 120mg, 180mg) are smaller than one subject from a 10mg dose in the first study "the healthy volunteers".

Using different QT correction methods can vary the absolute interval (or change in the interval) by several milliseconds in practical resting heart rates and absolute QT interval ranges, so that's not an issue.

"In the 180-mg group, 1 subject had a QTcI value exceeding 480 milliseconds at 1 time, and 1 subject had QTcI > 500 milliseconds at 4 points." So one person in this study has QTcI > 500ms at triple the maximum dose from the first study.

-----

If the two studies were more consistent I might be convinced, but they use double and triple noribogaine doses in the second study and seem to lack comprehensive electrocardiograph data from the first study, not to mention a very low dose regime. Methadone has been shown to increase QT interval as well, so that is also something to consider, even if they did abstain for a week.

DotChem: Can you point me to the opiate naive/dependent rat studies you're referring to? You also mentioned blockade of cardiac K+ channels cannot account for QT interval increase. How exactly did you come to this conclusion, anyway?

 

[DotChem]

Hello.. yes good point.. the doses are admittedly small compared to Ibogaine flood doses. I think the reason of using lower doses to measure QTc prolongation in healthy HV is that the reported QTc interval prolongation is dose-dependent. So conceivably you can extrapolate the data to higher doses. So there's no need to administer flood doses to "healthy" human volunteers and unnecessary put them at risk. As for QTc threshold I have seen the 500ms used by several authors but apparently it is a threshold above which risks of Torsades de Pointe increases so anything below that can be considered "safe".

Another reason I think the two studies used different dosing regimen and way lower IBG doses than currently used for opiates detox is that treating withdrawals and craving/long term cessation are 2 different things: Ibogaine seems to be able to do both at the same time apparently by different mechanisms: Conceivably one can uses lower doses to treat WD and higher doses for cessation or vice-versa depending on which biological target and its affinity for IBG is involved. So that there is no point of using larger doses in both cases.

How Ibogaine molecule attenuate withdrawals is pretty much well understood now, and there is strong evidence that is by blockade of alfa3beta4 subtype of nicotinic acetycholine receptor in the brain (cf stanley glick). a3b4n-AChR antagonists (like bupropion, mecamylamine or memantine..etc) have been demonstrated in rodents or people not only of OP WD but alcohol, nicotine, meth, cocaine.. etc. However, I have yet to see any compound that have effect on craving and long term cessation that is unique to Ibogaine.

A third reason for using small doses is that Ibogaine has more than anti-addictive properties for which it is mostly known. At lower doses (50mg), it is a eugeroic non-amphetamine attention enhancing acting by an as yet unknown totally different mechanism from amphetamines or modafinil.etc. The tribal people of central africa from which the knowledge of Iboga tree psychoactivity originate used lower doses to go hunting. Not only it is focus-enhancing but also wake promoting again in a manner totally different from dopaminergic amphetamines. That's why following Ibogaine experience, subjects feel no need for sleep for days or weeks. Not in the sense of amphetamine stimulation but IMHO possibly because.. A study out of new-zealand measuring psychological parameters of 20-50 mg IBG in HV confirm that (I'll post the study later).. So conceivably these studies may have for secondary objectives applications of low doses Ibogaine as eugeroic nootropic.. but who knows?

Now let me speculate: the second phase of ibogaine experience, the visionary oneirogenic phase responsible for long term cessation of OP, alcohol, nicotine is more dreamlike that 'pure"hallucinogeninc. How the molecule does that, nobody knows imho.. only speculation. One thing we know is Ibogaine induces REM slow wave sleep State while awake (the EEG pattern in IBG-treated is same as that seen during REM sleep). Except the subject is awake!. That is why subjects feel no need for sleep for days or weeks after single large doses: the brain has gone through REM State (which it normally does every night for 1.5h-2hours) during the duration of the experience which can go anywhere from 24hour to 48hours. So in other words, as far as the brain is concerned, it is like the subject has been sleeping for 10-20 nights STRAIGHT! Considering that all the restorative effect of sleep like hyppocampal LPT memory consolidation takes place during REM sleep, one can speculate that Ibogaine's eugeroic attention-enhancing effect is probably due to its oneirogenic (dream-inducing) REM sleep-inducing effect.. but who knows.. If anybody can come up with an answer as to the mechanism of Ibogaine.. the Military would like to hear from you

 

[i are spectre]

That's pretty interesting stuff, can you link me to the REM things you mentioned?

I am just trying to figure out how to minimize risk from the hERG block / QT increase.

 

[DotChem]

Hello.. The REM effect of Ibogaine is actually called Goutarel hypothesis, the frenchman who propose that. it's backed by solid evidence.. here is an exert on Goutarel's Ibogaine REM hypothesis from here (with some studies reference on this in there):

There is some evidence that may be viewed as consistent with Goutarel’s hypothesis. Goutarel’s belief in a relationship of the ibogaine-treated EEG state to that of REM is supported by studies in animals treated with ibogaine that report
an apparently activated or desynchronized EEG state consistent with arousal, vigilance, or REM sleep (90,191). The observation that ibogaine enhanced an atropine-sensitive theta frequency rhythm (191) suggests the possible involvement of ascending cholinergic input, which is an essential determinant of EEG desynchronization during REM sleep (192). The possible reconsolidation of learned information due to heightened plasticity during both the REM and ibogaine-induced desynchronized EEG states is suggested by the observation that EEG dyssynchrony is associated with an increased facilitation of Hebbian covariance (194), which is believed to be an important determinant of the neural plasticity involved in consolidation of learning and memory. Also, with regard to a possible analogy of the REM and ibogaine induced brain states, some ibogaine treatment guides have anecdotally mentioned that they have observed REM-like eye movements in awake patients during treatments (195,196).

You can google for more studies if you're interested
Again, as the molecule is technically ILLEGAL and banned in most countriesyou will not find lots of study confirming or not Goutarel'hypothesis
But here is a brand new study from Mexico that came out a week ago that claim that actually Ibogaine does the exact opposite of what Goutarel claims, ie it SUPPRESS REM sleep in rats instead of promoting it:

Ibogaine acute administration in rats promotes wakefulness, long-lasting REM sleep suppression and a distinctive motor profile Front. Pharmacol. | doi: 10.3389/fphar.2018.00374

which doesnt make senses to me: because it is known that the effect of REM sleep deprivation is the exact opposite of "no need for sleep" felt by subjects following Ibogaine. should have been the opposite.. but who knows?


Going back to Ibogaine's QTc prolongation, IMHO am afraid you'll have hard time dissociating Ibogaine's QT effect and its anti-withdrawals effect..only way I see it is lowereing doses; the original Iboagaine study funded by US NIH before they stopped funding uses 100-300 mg which was pretty safe and as effective as flood doses (~1.5mg people use). But future larger studies were stopped on counsel from Pharmaceutical industry consultants of NIH so we'll never know for sure.

The reason I said you'll have hard time separating Ibogaine cardiac and brain effect is that hERG K channels and Ibogaine's target in the brain nicotinic acetycholine receptor (nAChR) are BOTH K+ channels! (check their wiki entries).. So the drug would have hard time differentiang the 2 although unlike hERG, some nAChRs also mediates Ca2+efflux in addition to K+..so there is still some difference.. But I a have a pretty good idea how to modify Ibogaine molecule to get new compounds that DOES NOT block cardiac K+ channels but still retain ALL Iboagine CNS properties.. how?.. that I won't tell on BL until I secure patent rights on these..

EDIT: but the study from Mexico does confirm the nootropic wakefulness promoting effect of Ibogaine which as I mentioned is what the tribal people of central africa uses low doses of Ibogaine for

 

[i are spectre]

Ya but just because two channels (hERG and nAChR) are associated with a particular ion flux (ie K+) doesnt mean a compound will have an affect or some sort of affinity with both of those two particular channels. It (ibogaine et al) may kick off another neurotransmitter, find an allosteric binding site, literally impregnate the ion channel, a combination thereof, or some additional mechanism.

Noribogaine and 18-MC have been patented and we'll see studies in the next several years, if you're referring to those or similar compounds. Dr K Alpers had a brief section in one of his articles postulating the hERG effect based on different functional groups of the ibogamine skeleton. Pretty interesting.

I'm gunna check out the REM stuff here shortly. It totally explains the visionary experience though, and the refreshing feeling after a flood dose (massive REM / defrag). Very interesting. I looked into several rat studies but they had no electrocardio data.

 

[DotChem]

Ya but just because two channels (hERG and nAChR) are associated with a particular ion flux (ie K+) doesnt mean a compound will have an affect or some sort of affinity with both of those two particular channels. It (ibogaine et al) may kick off another neurotransmitter, find an allosteric binding site, literally impregnate the ion channel, a combination thereof, or some additional mechanism.

Aha! excellent point.. but in this case, the binding sites of drugs like ibogaine to hERG potassium channels and to nAChR share lots in common.. they both came from the same ancestral gene (you can search for any homology studies that may have been done.. when i have the time.. i'll find out).
The crystal structure of hERG channels has been solved and a "tentative" hERG blockers binding site has been proposed(see here:Towards a Structural View of Drug Binding to hERG K⁺ Channels. ) I said tentative because AFAIK the structure of hERG in complex with a drug channel blocker like Ibogaine has not been solved to get clear answer. Ibogaine fits nicely there (too much to elaborate here..

Similarly, the crystal structure of human alfa3beta4 nAChR (the consensus target of Ibogaine for its anti- nicotine, opioid, alcohol, meth....withdrawal effect) has been solved. A tentative model of Ibogaine (and Bupropion) has been proposed. Once again it is tentative until we see structure of drug bound to a3b4nAChR..(probably some big$ companies already get it but keeping secret until they come up with new drug targeting a3b4 before publishing it.. bu who knows?)

The two sites are very similar which is why I strongly believe you will have hard time coming up with Ibogaine analogs(with same CNS effect as IBG) that selectively binds to a3b4 but not hERG. Besides, hERG is very promiscuous: It binds pretty much "anything". Keep in mind: 15% of ALL pharmaceuticals on the market are hERG blockers. 12-15 marketed drugs ( I don't remember exact number) were pulled out the market because QTc problems.. So the original question you asked on Ibogaine QTc problem is a very interesting issue but very difficult to deal with. Which is why I said earlier Ibogaine is having a bad rap by scientific establishment and big money pharma.

On the other hand, now that you mentioned ibogamine, I think it may actually be safer and more potent alternative to Ibogaine. pretty much the same experience as Ibogaine but since it is most potent than IBG (at brain targets) so lower doses would have same effect as ibogaine and less cardiac issues.
Now one of the problem with Ibogaine, ibogamine and related alkaloids is that you can't patent them. It is like trying to patent THC in cannabis (good luck getting people paying you royalties so they can use THC). 18MC and Noribogaine were just trying go around this matter. They are no superior benefits relative to Ibogaine or Ibogamine or Voacangine..

Ah! now that I remember Voancagine (it is an alkaloid extracted from Voacanga Africanas.. It has exact same molecular structure as Ibogaine but with an extra COOCH3 ester attached at position 16 of IBG). Actually they are some methods reported on how to convert Voacangine to Ibogaine by decarboxylation just like Cannabis CBD conversion to THC). Voacangine experience is exactly same as ibogaine expect you are more in control during the visionary experience( "you direct the show.. so to speak) unlike Ibogaine which throws everything at you.. Now the question is what are the "YOU"?..I mean the part of the mind who is watching the Iboga show.. I think they are a group of neurons expressing mostly kappa opioids receptors located deep inside the pineal gland which incidentally is the target of Salvia Divinorum Salvinorin A..and the "Site of the Soul" according to French Rene Descartes.. but who knows??

edit: ibogaine and voacangine

ibogaine

ibogamine and

Voacangine

 

[i are spectre]

"Voacangine experience is exactly same as ibogaine expect you are more in control during the visionary experience( "you direct the show.. so to speak) unlike Ibogaine which throws everything at you.. "

Oh ya? I've heard the contrary (unpleasant side effects anyway), but it may have been voacanga itself. Either way though, many people are using voacanga instead of iboga to make ibogaine. It tends to have better purity with fewer sustainability/legal issues. Here's the how-to by Dr. Jenks...

https://www.ibogainealliance.org/news/voacanga-ibogaine-production-guide/

 

[DotChem]

Thanks for the reference.. I came across Dr Jenks paper for extraction of Voacangine and then converting it into Ibogaine. very interesting but I would use household microwave oven (1-2 min at high power) for the decarboxylation step (conversion of Voacangine to Ibogaine) if I was Dr Jenks.. that way avoid harsh acids treatment.. but no chemistry discussion allowed on BL .. anyhow interesting

As for side-effects, I was talking about purified Voacangine..not Voacanga total alkaloid extracts.. Unlike Ibogaine which is available (where it is legal!) in purified form (HCl), you can hardly find purified Voacanga HCl anywhere as far as i know. people use Voacanga total alkaloid extracts instead which contains lots of other bioactive alkaloids like voacristine, vobtusine, voacamine, voacafrine, voacrine, coronaridine, tabersonine, ibogamine, ibogaine ..etc. Some of them are pretty nasty! (consulvants!!). So using Voacanga TA like Ibogaine TA extracts is probably not good idea because Iboga root barks contains less alkaloids and high content of Ibogaine Ibogamine and coronaridine mostly.

So far only use of Voacanga I seen is to convert it to Ibogaine as the process of Dr Jenks you refer shows. .some other guys in India used more refined soxhlet extraction process to produce Voacagine and then convert it to Ibogaine (If I recall that's the only supplier of 99.5% Ibogaine HCl).. Pretty good job by Dr Jenks, though: Increased demand for Ibogaine is killing the forest as Tabernathe Iboga tree is rare and it doesn't grow as easily as Voacanga Africana (5-8 years for Iboga to mature and give useful yields of alkaloids). + the alkaloids in Tabernathe Iboga are mostly in the root, so the tree has to be killed and forest cleared.. so it is harder and harder to get. But Voacanga alkaloids are mostly in the bark and seeds so no need to kill the tree+ it is very widespread all over Africa an some part of India..

As for Voacangine experience, as I said it is not as "brutal" as Ibogaine.. The visonary experience of Ibogaine you really don't have control .. the molecule is running the show .. but with Voacangine "you" can decide what the experience is I don't know how to explain it but it has same effects as Ibogaine . It is hard to describe but think of it as dreams where you can interact and ask questions to the characters in the dreams or decide where you want the molecule to take you or go back .. pretty magical actually (the pygmees of cantral africa uses it for 'divinations" like when they have any issue they'll go ask the molecule .. really amazing. It probably has more benefit than ibogaine for other mental issues in the West like depression, PSTD, anxiety and such

My guess is Ibogaine probably also inhibit PFC neurotransmission in addition to its other effects which is why during Ibogaine visionary experience there is no cognitive executives function (like decision, judgement ..etc) only during the introspectve phase that those cognitive executive function return. That's why I said "ibogaine run the show" unlike Voacangine.. With Voacangine though cognitive functions are intact so the experience would be more like that of ibogaine visionary AND introspective phase combined at the same time..

here is an interesting ( a little old) paper on Voancanga Africana alkaloids :Voacanga africana: Chemistry, Quality and Pharmacological Activity (sorry paying article as I dont have $ubscription$ acce$$ to full paper ..)