A friend of mine is getting $4,000 for trialing "anti-addiction" drug called 18MCHCL: Info????

[MrsGamp]

Friend is not an addict - specifically they wanted non-addicts for this trial. I think the point of the trial is to check for side effects, like inhibited liver function, by experimenting on healthy non-users. It's an in-hospital trial - he's going to be in hospital for 10 days.

I think it sounds rather spooky though. Out of only 50 people in previous trials, two have died, although of course my friend has been assured their deaths were not related to the drug trial. But he's not permitted any visitors except for one 2 hour period, and these visits must be supervised.

As for the drug - 18MCHCL - there is nothing about it on the internet - although when I looked it up there were a lot of references to something called "OBT195", which might just be US name for same drug.

My friend has been told it is a dopamine blocker which prevents practically any drug - opiates, amphetamines, cannabis, alcohol, cigarettes, caffiene - from having the (ordinarily) desired effects. It's even being booted about as a possible treatment for food addiction.

But it doesn't sound like dopamine-inhibition only occurs IF you have a drug. It's a dopamine inhibitor full stop. My friend has been warned he may become depressed and experience "personality changes" during this trial because of reduced dopamine reduction.

I can't imagine how reducing the dopamine levels of addicts even when they are SOBER is going to help them.

And $4,000 "danger money" for being in this trial seems sinister.

Anyone know anything about this

 

[4meSM]

The drug is called 18-Methoxycoronaridine and it's not really a dopamine blocker but a nicotinic antagonist (it's supposed to be a selective antagonist for the Alpha3Beta4 receptor subtype). It can also behave as an opioid agonist apparently. It's structurally similar to ibogaine.

I found this 75 page document (a PDF) where they describe the objectives of the study and some of its pharmacological properties in case someone is interested:
https://www.google.com/url?sa=t&sou...FjAAegQIBBAB&usg=AOvVaw0p2lGFKamPo0Ecyvg315pC

 

[Cotcha Yankinov]

I can't imagine how reducing the dopamine levels of addicts even when they are SOBER is going to help them.

I'm curious if there are some dysphoric effects from Kappa Opioid Receptor agonism. Normally ibogaine doesn't activate the KOR in a way that causes the normal dysphoria like eg dynorphin does as its released during opiate withdrawal. But I wouldn't say that possible undesired effects on mood/personality would have to be from effects on nicotinic acetylcholine receptors, and they are almost certainly not from direct actions at dopamine receptors.

18-MC is essentially an ibogaine analog that will hopefully preserve some of the helpful effects of ibogaine on addiction without ibogaine's dangerous cardiac effects
and potentially harmful effects on purkinje cells in the cerebellum

Those two effects (plus the psychedelic effects) were seemingly the primary blockers to bringing ibogaine to market. In addition to the fact that there would be no virtually profit in doing the clinical trials because you couldn't sell it as a brand name medication to recoup costs from trials to prove a favorable risk to benefit ratio.

The nicotinic acetylcholine receptors that ibogaine is thought to target are expressed in various places in the human brain but in particular in a structure called the habenula, which plays a large role in habit and reward/reinforcement related behavior. The effect that such a drug may have is much more complicated than raising or lowering dopamine levels.

While I have heard rather rare reports of long term mood issues from ibogaine, I would hope that there is a favorable risk to benefit ratio with regards to decreasing the addictive behavior while not affecting mood too much. Addiction is certainly an extremely serious and deadly disease, and many addicts would still take ibogaine if they were told it had a 50% chance of curing them and 50% of killing them outright, or had a serious chance of impacting their mood for the next 6 months.

There are many anecdotal reports of profound relief of psychiatric illness and chronic mood improvement following ibogaine flood doses, and I was under the impression that that is the more common effect rather than a persisting negative effect on mood. I personally I am not concerned about how arduous the acute effects of the drug are, I'm much more concerned about eg sobriety rates at 6 months after a dose compared to controls. The acute effects of addiction are known hell. It would also be nice to know if 18-MC can help relieve some acute withdrawal symptoms like ibogaine can.

Fingers crossed. Your friend is a necessary part of the scientific process, until we can accept prisoners as volunteers et cetera and give them time off their sentences or what have you this is what we have to work with. The creators can't exactly go full Shulgin and guinea pig themselves to get it FDA approved

CY

 

[MrsGamp]

he's a bastard and I hope his dopamine plummets ....

 

[MrsGamp]

Hello.

Nice and very interesting post and information.


Good point. I can't imagine how reducing the dopamine levels of ANYONE is going to help ANYONE without causing other problems e.g. depression. One would ASSUME they've thought this through very well. But as somebody above mentioned (the way I interpreted it anyway): what if this works and becomes an across the board preventative measure i.e. almost like vaccinating an entire population against addiction possibility before such addiction in a specific individual has even reared its ugly head (and may never have done so ever for said individual).


Well that would raise my dopamine levels for sure. I hope he's given the $4K BEFORE the trial otherwise it's going to mean nothing to him!

Edit:

I have to be honest here:

After having begun posting actively on these forums and reading so many posts on the topic of addiction and from addicts: I'm actually starting to wonder which is worse i.e. addiction and being high as the sky most all of the time or having to deal with the very issues that got you started in the first place. Before and for me: it was always a sort of "black and white" type thing. But now I'm not so sure anymore to be honest. I think that if something like this works: the addict has to be VERY sure and have VERY good reasons for wanting to get, and stay, clean. From the reading that I've done and some personal introspection of late: simply being clean and sober, in many instances, doesn't necessarily mean that life is going to suddenly become "peachy" (and I think that this is an expectation that many seem to have and end up being sorely disappointed once this sinks in for real).

I'm with you, or would be ....cept I am middle aged now and look and feel like absolute shit. When I was younger I chugged away cheerfully in the best of health.

Not the least of my issues is FUCKING INTERNET ADDICTION, too.

 

[Shady's Fox]

It's possible.

 

[MrsGamp]

4:38 PM (1 hour ago) to me

Well for what it's worth I laughed my head off when I saw this post of yours last night (which takes a lot i.e. not too much laughter about here these days).

 

[vecktor]

great, 18MC the drug that keeps on giving, this is the trial you refer to

ClinicalTrials.gov

clinicaltrials.gov

Here we have yet another Phase 1 trial for 18MC only this time rebranded as Mind Medicine and moved to Australia

What new information they hope to obtain that wasn't already available and in the hands of Savant HWP is a mystery. Are they trying to see if it works the same way in the southern hemisphere? (news guys, it was P1 and P2 trialled in Brazil against leishmaniasis- data umpublished )? Or is this a new bunch of grifters looking for a new set of investors (suckers) having run out of options in the USA. The Mind Medicine Australia board is very remiscent of Theranos, a bunch of ex politicians investment bankers and military people. We know what happened the Theranos.

A bit of back story, 18MC this is the drug that Stanley Glick touted as the future of Ibogaine 25 years ago well Stanley we are now 25 years in the future and where hell is your fabled 18MC?
Having nailed the patents a few shady moves along the way, Glick then made a lot of money failing to develop it, wasting time, generating publications, sucking up millions of dollars of NIDA grant money in the US, running P1 trials, creating Savant HWP and then not publishing the data or moving it forward.
Investors and other people that got caught up in this 18MC whirlwind have regretted it because 18MC brings out the worst in people who work with it (Glick previously screwed Lotsof over ibogaine perhaps that is the common theme of these drugs?) . If I had a dollar for every rebranded, repurposed, repeat clinical trial of 18MC I would have quite a few dollars by now, but less than the owners of the 18MC money extracting machine.

but hey take the money and go for it, at least someone ends up with 4k more than they started with and could use that constructively.

 

[Cotcha Yankinov]

great, 18MC the drug that keeps on giving, this is the trial you refer to

ClinicalTrials.gov

clinicaltrials.gov

Here we have yet another Phase 1 trial for 18MC only this time rebranded as Mind Medicine and moved to Australia

What new information they hope to obtain that wasn't already available and in the hands of Savant HWP is a mystery. Are they trying to see if it works the same way in the southern hemisphere? (news guys, it was P1 and P2 trialled in Brazil against leishmaniasis- data umpublished )? Or is this a new bunch of grifters looking for a new set of investors (suckers) having run out of options in the USA. The Mind Medicine Australia board is very remiscent of Theranos, a bunch of ex politicians investment bankers and military people. We know what happened the Theranos.

A bit of back story, 18MC this is the drug that Stanley Glick touted as the future of Ibogaine 25 years ago well Stanley we are now 25 years in the future and where hell is your fabled 18MC?
Having nailed the patents a few shady moves along the way, Glick then made a lot of money failing to develop it, wasting time, generating publications, sucking up millions of dollars of NIDA grant money in the US, running P1 trials, creating Savant HWP and then not publishing the data or moving it forward.
Investors and other people that got caught up in this 18MC whirlwind have regretted it because 18MC brings out the worst in people who work with it (Glick previously screwed Lotsof over ibogaine perhaps that is the common theme of these drugs?) . If I had a dollar for every rebranded, repurposed, repeat clinical trial of 18MC I would have quite a few dollars by now, but less than the owners of the 18MC money extracting machine.

but hey take the money and go for it, at least someone ends up with 4k more than they started with and could use that constructively.

I think theory had it that the KOR agonism would be of the hallucinogenic variety rather than the dysphoric variety - do you think the Brazil phase II for leishmaniasis was just a smokescreen to collect more data about tolerability/side effects? Kind of like "Oh yeah we just want to study the effects of DMT on basic parameters like HR/BP, but oh hey, we can take some notes on subjective effects while we're at it"

How did Glick screw Howard Lotsof over? Do you mean the research momentum should've stayed with ibogaine and not been diverted onto 18-MC?

 

[paracelsius]

Very likely a cover to test cardiac issues with unsuspecting people. Biggest issue the FDA objected with Ibogaine and Mash's Noribogaine approval is cardiac hERG liabilities. 18MC is in fact as cardiotoxic if not more than (Nor)Ibogaine. There were a bullshit study showed same hERG long QTc prolongation induced by 18MC as Ibogaine or Noribogaine. But the authors claimed unlike with the latter 2 compounds, 18MC hERG blocakde doesn't lead to dangerous Torsades de Pointe, arrythmia and... sudden death in rats (or mice?). Bullshit!.. My guess those f..ers are testing this specific issue in people!

The only way it will ever be approved by FDA is data showing it is less cardiotoxic than (Nor)Ibogaine. I suspect that is what those Studies are all about.. I'll damn make sure I have my heart thoroughly checked before ingesting that substance ... for a healthy volunteer not looking to treat addiction or anything, I am not sure if $4000 is worth the risk!

 

[Cotcha Yankinov]

Very likely a cover to test cardiac issues with unsuspecting people. Biggest issue the FDA objected with Ibogaine and Mash's Noribogaine approval is cardiac hERG liabilities. 18MC is in fact as cardiotoxic if not more than (Nor)Ibogaine. There were a bullshit study showed same hERG long QTc prolongation induced by 18MC as Ibogaine or Noribogaine. But the authors claimed unlike with the latter 2 compounds, 18MC hERG blocakde doesn't lead to dangerous Torsades de Pointe, arrythmia and... sudden death in rats (or mice?). Bullshit!.. My guess those f..ers are testing this specific issue in people!

I'm actually really sad to hear that. If the FDA approved drug-combos as a discrete entity from the constituents (even if none of the individual constituents were approved to treat a disorder by themselves) then I'd like to think you could assemble ibogaine's effects with selective ligands for each desirable effect, eg the above mentioned selective a3b4 ligand (although there has been some debate about other closely related subunit combinations also being a target), then a selective KOR ligand that doesn't cause dysphoria, then 5-HT2A/NMDAr ligands for the spiritual component.

It would probably be much, much easier to piecemeal the effects of ibogaine together with selective ligands than to try to design a new ibogaine without the undesirable effects.

 

[paracelsius]

..It would probably be much, much easier to piecemeal the effects of ibogaine together with selective ligands than to try to design a new ibogaine without the undesirable effects....

That is a pretty tall order. You’d have to combine no less that a dozen drugs to mimic the effect of a flood dose of Ibogaine: NMDAr antagonist, DAT/SERT inhibitor, kappa agonist, sigma agonist, nicotinic a3b4 antagonist, neurotrophic promoter, 5HT2a agonist, 5HT3 channels blocker..etc. To make matter worse, the major metabolite Noribogaine has its very own pharmacology targeting these receptors/transporters..etc with different affinities. Plus of course, your drugs would have to be devoid of hERG liabilities as well as drug-drug interactions. So you could imagine the hassle required to achieve Ibogaine effect.

On the other hand, my guess is there are 2 Ibogaine targets most relevant to addiction; NMDAr and a3b4nAChR ion channels. The first is probably responsible for the physical opioid-withdrawal alleviation of Ibogaine. This is easy to do: any NMDAr dissociative would do (Memantine is pretty good at that or high doses DXM).

The second, a3b4-nAChR ion channels blockade, is probably responsible for the “visions” and elimination by Ibogaine of long term craving of opiates. This is more important imo, especially the “visions” aka “hallucinations” aka “introspection”..etc of an Ibogaine trip. Which is why I think 18MC, claimed not to have Ibogaine “hallucinogenic side-effects" is bullshit! The “hallucinations” ARE the cure!! anybody who’ve benefited from Ibogaine treatment would tell you the “visions” the introspection phase is what helps them stay sober. So a ‘non-hallucinogenic” Iboga analog would be useless snake oil, no different from placebo sugar pill!

Why do I thing a3b4nAChR are responsible for Ibogaine “visions” and “cure”? Well for one a3b4 are expressed in very specific brain areas, besides peripheral, ganglionic sites: the Interpendencular Nuclei IN and the Pineal gland. Now the IN connects the limbic system to the hippocampus. So it is probably mediating storage of dopaminergic info (ie dopaminergic drug stimulus) from limbic system and reinforcement. Injecting an a3b4 antagonist directly to the IN prevents development of morphine dependence and tolerance in rats (ref). And some people having genetic mutation on a3 subunit of a3b4nAChR do not develop dependence nor tolerance to morphine (lucky them ! IIRC the a3-KO and the b4-KO mice weree not viable and didn't strive. Would've confirm even more the role of a3b4 in the process of dependence/tolerance formation.

The pineal gland on the other hand, the second site where most a3b4 are expressed is a very mysterious organ. It is what the Hindus called the “third eye” that lets you “see” Shiva, God, the “Ancestors”..etc. Renee Descartes called it the site of the “soul”. Research that if interested. Now, I don’t know about that, but people on Ibogaine sometimes describe encounters with what looks like “Ancestors”. Like the guy who describe scenes from 18 century England complete with horse carriage and his long dead "family"!!! Could a3b4 blockade on the pineal gland mediating that phenomenon? I don’t know. Would be interesting to see the psychoactive effect of selective a3b4 antagonist. A company in california iirc is developing selective a3b4-nAChR anatagonists. And from their studies it seems to work blocking the formation of dependence/tolerance to opioids, nicotine and alcohol in rats iirc. Then again, you can’t ask rats if they were tripping and meeting the Rat-Shiva God and that is what actually help them!

 

[JessFR]

Fingers crossed. Your friend is a necessary part of the scientific process, until we can accept prisoners as volunteers et cetera and give them time off their sentences or what have you this is what we have to work with.

Not to thread jack, but that sounds is horrendously unethical.

Prisoners aren't slaves.

 

[Cotcha Yankinov]

Prisoners as volunteers? I also consider the wages that workers work for the world over unethical, and I am willing to pay more for goods to help increase their wages, but I wouldn't necessarily stop them from voluntarily working those jobs

Just as there are many slave wage workers that would rather earn that wage than nothing, there are many in the penal system who would voluntarily take an experimental drug for xyz incentives, many of them are already forced to take medications at very high doses with awful side effects anyways (antipsychotics). Sorry if what I wrote seemed coarse