709 replies to this topic

[lammas2]

Selective κ Opioid Antagonists nor-BNI, GNTI and JDTic Have Low Affinities for Non-Opioid Receptors and Transporters

http://www.plosone.o...2B4E2C96C218FD9

Fatalities after GNTI
After 30 mg kg^-1 GNTI dihydrochloride, all three mice unexpectedly became ataxic, followed by convulsions and death within 11 minutes of injection. To confirm that this was not due to an impurity, the experiment was repeated with an equimolar dose of a different salt from a different supplier (bis-trifluoroacetate, 39 mg kg^-1). Again, all three mice died within 18 minutes. At 10 mg kg^-1, GNTI caused no fatalities in 15 mice monitored for at least 30 minutes. This difference was of extremely high statistical significance (p < 0.0001 by Fisher’s Exact test, two tailed). Even at 100 mg kg^-1, no fatalities occurred after nor-BNI (3 mice, p = 0.01 vs. GNTI) or JDTic (6 mice, p = 0.002). Only mild behavioral effects, such as hiccup-like spasms and shivering, were observed. The lower toxicity of these two drugs, despite their comparable potency as κ antagonists, suggests that GNTI's toxicity may involve some form of efficacy or a different target.

http://www.biomedcen.../1471-2210/12/5

Is there any evidence that nor-BNI is orally active?

[formergenius]

There is evidence that it's not (sort of): http://link.springer...kinside/000.png (from http://link.springer...0213-010-1846-3)
Only JDTic and RTI-194 are known to be orally active KOR antagonists according to that article.
edit: Still seems JDTic is superior according to that article as well.

Edited by formergenius, 15 January 2014 - 07:34 PM.

[totflare]

I'm not sure I'm willing to pay $100 for only 2.5 mg. David Pearce used 2 mg a day and the human trial had doses varying in between 1 mg, 3 mg and 10 mg. We have no idea how much is needed for a long lasting effect and 2.5 mg might not be enough. And then there's the question if it's better to take one small dose a day or one bigger dose once in a while. As I understand it's supposed to activate an enzyme that disrupts the KOR transmission for a long time even after the drug is out of the system.

[meatsauce]

The guy from JDTic.com (I don't know if that is David Pearce) says that the effective dose is approximately 100mcg per day and also every other day on another part of the website.

[formergenius]

David Pearce used 100mcg every other day as meatsauce said. The only other known anecdote of JDTic experience indeed used 2mg, however it's of questionable legitimacy.
Though, like you, I'd prefer to have more, but for now I'll take whatever I can get, especially considering the many months I've been waiting for this.

I found this study on JDTic:

Together, these results provide no evidence of a link between the dynorphin/KOR system and deficits in sensory gating processes. Additional studies, however, examining whether dysregulation of this opioid system contributes to cognitive deficits and other behavioral abnormalities associated with psychiatric disorders are warranted.

Which is unfortunate, seeing as I was hoping to enhance my sensory gating. Though the study uses CRF-induced PPI disruption as a model, thus disruption by endogenous dynorphin is not considered (despite CRF effects considered to be mediated by the dynorphic system), hence the study was inadequate and non-conclusive. Also, I believe it was acute treatment, hence long-term may have better results.

But that may not be as interesting for everyone else. This study does explore the dopaminergic interplay with KORs, which I guess may be of more interest.

socialpiranha, if you do not succeed in getting 20 participants, would you still order? If, for example, you have 5 orders placed, you could still go ahead with ordering 10mg. The only downside would be that people get 2mg and not 2.5mg. Just something to consider.

[socialpiranha]

Yes we will just play it by ear and get as much as possible. I can't place an order until i know how much money we're working with though. That's why i set up the payitsquare page. What happens with the money in the payitsquare account will be subject to democratic debate between those who contribute.

[lammas2]

I can only take part in this group-buy if someone from the European Union reships it to me. Otherwise, the customs will confiscate the package.

[totflare]

I would have the same problem as lammas.

[formergenius]

Wish I could facilitate those needs; however currently it appears I'm agoraphobic, so that's not going to happen alas. Anyone else?

[socialpiranha]

I wouldn't think customs would be a problem, it's completely legal, besides i don't even think they look at envelopes.

[lammas2]

Depends on the country I guess. I specifically asked local customs and the local 'FDA' about importing JDTic. They see it as active substance for a prescription drug, therefore it is illegal to import without a special premission (unless imported by a scientific company). Sending it in an envelope might be a good idea, but I wouldn't want to risk sending it with a standard envelope. And if sent by 'tracked mail', I think it also goes trough customs.

Also, this: http://www.apexbt.com/jdtic-2hcl.html !!!
I see no reason why they wouldn't send to individuals. If I were living in the states, I would order it right away.

Edited by lammas2, 16 January 2014 - 07:39 PM.

[formergenius]

Nice one lammas2. Perhaps it's worth checking out. It would definitely save $$$ if they do accept, and despite their higher pricing, it would essentially double the quantity per dollar.

side note: They've also got EVP-6124.

[socialpiranha]

Good find! looks like we might just be able to order it straight from them. might need to fill out a w9 or something i dunno.

[penisbreath]

even if it is illegal to import, you can't really be held liable *unless* you sign for the package .. so an envelope or something is probably best, though might require creative disguising

[fanta2y]

even if it is illegal to import, you can't really be held liable *unless* you sign for the package .. so an envelope or something is probably best, though might require creative disguising

In my country it doesn't work like that, even if you didn't sign for the package you will get in trouble.
I can only participate if someone reships it to me from EU as I've had bad experience with customs in the past and don't want to go through it again...

[therein]

I downloaded the full papers for the group-buy using my subscription. Let me know if you want other papers.

Pharmacological properties of JDTic: a novel n-opioid receptor antagonist
http://www.sendspace.com/file/xmw46k

Differential effects of the novel kappa opioid receptor antagonist, JDTic, on reinstatement of cocaine-seeking induced by footshock stressors vs cocaine primes and its antidepressant-like effects in rats
http://www.sendspace.com/file/9rmm2k

[KieranA001]

I would just like to ask, seen as we're buying directly from the vender. Does that mean we can permanently get this stuff and, does it also mean that we will get this stuff sent to us straight away ? If not, how long do we have to wait until we get it, when does the deadline for payment end ? As I would like to be kept informed or told on the last day, or near to it. (Just so I can sell something to get the money!)

Thanks :-)

[formergenius]

Hey socialpiranha, mind answering Kieran's questions? I'd like to know what the status is too. Thanks.

Edited by formergenius, 20 January 2014 - 03:21 AM.

[socialpiranha]

we wouldn't be buying directly from the vender, it would be via a proxy, apex has the same regulatory measures as the rest unfortunately.. But yes we would be able to order again. As far as time goes at this point i can't verify anything.

[formergenius]

Ahh pity.
When is the cut-off date? Is it safe to presume that the order will be placed directly after it? IIRC it was around the end of this month, so with order placed around that time, we can all expect to have it February?

[socialpiranha]

If we don't find a better supplier before then,then we would have to make a decision to order or not at that point based on how much money is in the pool and how much product we could get. I don't have some grand plan,l'm just one of you guys i'm just sort of taking the lead because no one else has. I'd appreciate questions framed more as suggestions rather than expectations. not directed at anyone in particular just clarifying my role in this.

[penisbreath]

Just wanted to get a second opinion on what people think re: Jdtic's structure ((3R)-7-Hydroxy-N-[(2S)-1-[(3R,4R)-4-(3-hydroxyphenyl)-3,4-dimethylpiperidin-1-yl]-3-methylbutan-2-yl]-1,2,3,4-tetrahydroisoquinoline-3-carboxamide)

and this list of prohibited drugs/precusors in Australia: http://www.health.go...p-precursor.htm

otherwise if whoever's sending could let me know whether they can provide adequate 'stealth' .. I've purchased on the overseas blackmarket before, so getting stuff through clearly isn't impossible.

Have pretty limited funds, so would like to know before I part with the $100.

Edited by lucky.pierre, 22 January 2014 - 01:30 PM.

[formergenius]

I got quoted $3000 for a gram (>95%). I'm stilling waiting for other inquiries to be answered, but I think this is about as good as it's gonna get.
This means $150 for 50mg if we have 20 participants. $125 for ~40mg if we have 24 participants. If we manage 30 participants, we can get it for $100/33mg.
Question is, do people think 95% pure is sufficient? I spoke with a analytical lab about another substance for which they'd need 1 gram for NMR. I'm not sure what the required quantity is for HPLC, however if it's near that then it's going to be tough to get it tested at all.

Edited by formergenius, 22 January 2014 - 05:35 PM.

[addx]

Sent in a pm but mighj as well post here

I've been using low dose cocaine on and off for a while now. I have grown a tolerance to cocaine without an addiction. A line of cocaine now puts me to sleep - which is pure KOR action - sedation. I also get pretty "confused" in way, unable or better yet even scared(or so it feels slightly) to think "deep" completely opposite of what should happen on cocaine. I also do not lose apetite any more from cocaine and I also do not gain nearly so much acute impotence from cocaine either.

KOR is now upregulated in my brain to the level I can't get nothing from cocaine. I don't really even have real urges for cocaine since now it generally makes me feel like crap and my brain has learnt that it doesn't do anything any more. It's quite a strange position to be in. Not sure if the "dynamics" of use(low dose, waiting for full withdrawal and again low dose - one line) is what caused it or pairing with marihuana, but it is so.

I actually feel releif as the cocain starts wearing off and if I take a line now it will not be for the high which is not nice for me now, but for the withdrawal.

I need to destroy these extra KORs grown from cocaine and JDTic seems the best way.

I have seen a new drug made based on JDTic with shorter duration, 1-2 days or so. It didn't have a name, only numbers... but it'll take a while before this supstance gets tested at properly least for toxicity...

Anyway, I'm still here for the group buy, just thought I'd pay a visit to the thread.

Edited by addx, 22 January 2014 - 06:17 PM.

[formergenius]

I suggest this article. It covers several opioidergic flavanoids, several of which show significant KOR antagonistic properties. Apparently, apigenin is one of them.

[Missjess]

Hey guys I am interested in getting my hands on some jdtic what do I have to do to go about this? You guys are doing a group buy?

[Puppeteer]

Pending info on whether 95% purity has any chance of killing us, that sounds like a pretty sweet deal, former. Are they willing to ship to a non-lab address?

[Missjess]

Wouldn't it be dangerous to try a research drug that is not pure? Why isn't this stuff made legal yet anyway? I am trying to find a drug that will help relieve dissociative symptoms. I have had depersonalization disorder for years and about 6 months ago I did iboga a full flood dose, yes it helped a lot for DR but it actually made my dp worse and it caused me to have a blank mind and I feel less aware of my body etc I believe I have over active kappa receptor.

[formergenius]

So far I haven't had any indication that they wouldn't, Puppeteer. And yes that is the question. Though I was thinking; even if you were to use 5mg, you'd still only ingest 250 micrograms of impurity per 2 weeks. Nonetheless a higher purity is always preferable of course; I will see what I can do about that.

Missjess, just check in here regularly for updates and it should become apparent when the buy comes close to finalizing. All group buys done here (thus also the product bought) come with a risk factor which all participants should keep in mind. We can only do our best to minimize this risk. Other than that, one should always do their own research and reading.

It's not illegal (unless your country of residence covers it under their Analog Act, which you may want to look in to), but I presume your question meant "Why is it not yet available?", in which case I refer you to the human study which is posted in this thread, in which certain (IMO benign) complications were recorded which provoked a study-stopping rule. After that human research seems to have been dropped.
I suggest you read this post.

[Missjess]

Ok I will, what is the risk factor? You mean because it's only a research chemical or the fact that the purity is only 95%? I would like to read up a bit more on jdtic actually. I wonder if there are any legal kappa antagonist drugs that are currently used for counteracting dissociation from drugs etc?

Thanks