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Hey guys.

First and foremost; I wish I could put this all coherently in an elaborate article like I did with Coluracetam, however my current state does not allow for that, so forgive me if this all seems a bit vague or wishy-washy.
This is a substance I've been wanting to try for months now.

Basically what it is, is an orally active selective long and fast acting (~2 weeks) potent kappa opioid receptor (KOR) antagonist. Say that three times fast.

The KOR is implicated in many things. Salvia Divinorum (more specifically, its active agent Salvinorin A), which I'm sure most of us are acquainted with, is a KOR agonist. So is Ketamine (see here a study with both aforementioned and JDTic).

These both (as well as all KOR agonists) known to induce a state of dissociation, depersonalization, derealization, anxiety, cognitive impairment, as well as hallucinations/visual distortions, and perhaps some others nuisances I'm forgetting.

 

Dynorphin is the endogenous KOR agonist, which appears to increase in levels under circumstances of stress and depression (see wiki), and also blocks glutamate release. Glutamate is also implicated in DP/DR as recently discussed, moreover it's the precursor to GABA, hence hypoglutamatergia is no fun. Furthermore, trying to agonize NMDA receptors for instance, would be kind of like mopping the floor with the faucet running. Though, as a side note, NRX-1074 (GLYX-13 derivative) would be really cool to try.

Ok well.. I don't seem to be good at tying up the loose ends here, but in any case it seems to me to have a high chance of abolishing dissociative symptoms. Oh yes, Naloxone and Naltrexone have been used to treat DP, the former of which completely abolished it in several individuals, however Naloxone is unsustainable.

JDTic seems to be relatively safe.. some concerns about 2/14 individuals having a transient heart arrhythmia or something benign like that, which is why they halted studies (protocol I guess).

I'll try to add more later, but if you've any questions, please ask.

This stuff is not available yet. I know many of you, like myself, are very willing to experiment if it's worth a shot, and this one most certainly is. There's not a group buy yet, but currently there are already 16 people interested in doing one. If you want to be a part of the group buy, and for far more elaborate discussion (and a lot of interesting articles), check out the Longecity thread. Also, for the only user review in the world, check out jdtic.com (bear in mind, this person did not suffer from any dissociative issues).

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This sounds very interesting my friend. 

 

The duration of action sounds insane though, if one has any negative effects at all from this then you could expect them to last for up to 2 weeks, that doesn't sound fun! Although I read that 'It's binding to the KOR is not irreversible and it's long-acting effects are instead caused by altered activity of C-jun-N-terminal kinases, no idea what that is, I've tried reading it but nothing is going in today.

 

Perhaps it would be worth at least giving Naloxone/Naltrexone a try before considering this? 

 

I'd love to find a report or something of someone's dissociative symptoms being cured by a KOR antagonist with HPPD. It would at least confirm that the pathogenesis of our dissociation is no different to other sufferer's dissociative symptoms. I've often thought that in HPPD, the DP/DR was a direct result of the excess excitation / 'cerebral disinhibition' as there appears to be no good reason for the DP/DR in us, yes we do experience anxiety and DP/DR can be a symptom/result of that, but in HPPD it is insane, I'd say AT LEAST half experience chronic dissociative symptoms, which seems a little off to me.

 

I'm surprised this hasn't been looked in to more, as finding a cure for the visuals is nice, but in chronic DP/DR sufferers, most will agree that the DP/DR is their most troubling and disabling symptom.

 

Anyway, nice find, I'd never heard of this before myself, I'll have a keen eye on this one.

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Haha yeah I guess! Or 2 weeks of feeling much better without re-dosing. I'm prepared to flip that coin.
It would, though the doses required for significant KOR antagonism from Naltrexone are very high, hence include much side effects. Or so I've read; same with the new opioid antagonist Nalmefene. Getting a shot of Naloxone.. would probably take you months to get the go-ahead from your doc, if you get it at all. I've read several accounts of Buprenorphine+Naltrexone being ace for DP/DR (one was induced by DXM), however, Buprenorphine is also a Mu agonist I believe, hence "Hello addiction". But all evidence so far (scientific and anecdotal) points towards KOR antagonism a high chance at resolving these issues, moreover what's very interesting is that KOR antagonism is relatively new, and there have only been a handful of people in the world to try it. Hence, who knows what potential it may hold.. Mysterious almost.

As for why this isn't looked in to more.. I don't know.. AFAIK, besides the glutamatergic theory, this is the only one that makes any sense. I guess that most people with DP/DR are afraid of meds. There seems to be a lot less neurotalk over at DPSH for example. To be honest, personally I seem to be running out of ideas, and this is one of my last hopes.

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Yeah, I suppose I took the more pessimistic view there haha!

 

I've read about the KOR and Dynorphins and remember reading that Dynorphins are directly related to one's sense of self, I suppose that holds merit as agonising the receptor causes ones sense of self to disintegrate.

 

The theory does hold good merit though, I myself have read good reports from Naloxone, Naltrexone, Nalmefene and Suboxone (Not sure where, I think the majority were over at DPSH, although I question the authenticity of some of these reports).

 

It would be nice to find a 'wonder drug'. Even 50% improvement in symptoms would be a huge improvement for the majority.

 

I read on Wikipedia that in animal studies, JDTic showed antidepressant and anxiolysis qualities, I wonder how these effects are mediated, unless they are a direct result of antagonising the KOR. Hmm.. 

 

Yeah, I have a certain respect for DPSH but I think that most of the talk over there isn't necessarily for the benefit of the majority, and instead seems to leave me feeling worse about the condition when I leave the site, but that's just me.

 

Anyway, I do hope it works out when you finally get to try it. Like I said before, if anyone is going to find the next wonder drug then it'll most likely be you haha! 

 

Some things I found that I thought were interesting and relevant:

 

these results suggest that kappa opioid receptors play a prominent role in the modulation of human perception. - http://www.uptodate.com/contents/intoxication-from-lsd-and-other-common-hallucinogens/abstract/13

 

The dysphoric component of stress is encoded by activation of the dynorphin kappa-opioid system". - http://www.jneurosci.org/content/28/2/407

 

Also on the same as the above link.. 

 

Prodynorphin gene deletion increased anxiety-like behaviours, impaired the anxiolytic effect of bromazepam and altered GABAA receptor subunits gene expression in the amygdala

 

Activation of the kappa opioid receptor in the dorsal raphe nucleus mediates the aversive effects of stress and reinstates drug seeking

 

The Link between the {kappa}-Opioid Receptor and Dysphoria

 

Asymmetry of the Endogenous Opioid System in the Human Anterior Cingulate: a Putative Molecular Basis for Lateralization of Emotions and Pain (Note EMOTIONS)

 

People with Depersonalization also report a reduced sensation of pain, I know I for one definitely experience this, so the endogenous opiate system probably does play an important role.

 

It's interesting to note that an opiate high is often described as 'dreamy', Depersonalization is 'dreamy' too..

 

http://www.ncbi.nlm.nih.gov/pubmed/20358363 - SalvA and ketamine produced the same pattern of disruptive effects in the 5CSRTT, characterized by increases in signs often associated with reduced motivation (omission errors) and deficits in processing (elevated latencies to respond correctly). Sessions in which rats were fed before testing suggest that reduced motivation produces a subtly different pattern of behavior. Pretreatment with the KOR antagonist JDTic (10 mg/kg) blocked all salvA effects and some ketamine effects. Binding and function studies revealed that ketamine is a full agonist at KORs, although not as potent or selective as salvA. 

 

SalvA and ketamine have previously under-appreciated similarities in their behavioral effects and pharmacological profiles. By implication, KORs might be involved in some of the cognitive abnormalities observed in psychiatric disorders such as schizophrenia.

 

A Kappa Opioid Model of Atypical Altered Consciousness and Psychosis: U50488, DOI, AC90179 Effects on Prepulse Inhibition and Locomotion in Mice - http://www.academia.edu/5059666/A_Kappa_Opioid_Model_of_Atypical_Altered_Consciousness_and_Psychosis_U50488_DOI_AC90179_Effects_on_Prepulse_Inhibition_and_Locomotion_in_Mice

 

I thought this was very interesting, a direct link between benzodiazepines and KOR (Seeing as Benzo's are the one thing that seem to improve symptoms user-wide, minus the drawbacks)

 

The effects of benzodiazepines on human opioid receptor binding and function. - http://www.ncbi.nlm.nih.gov/pubmed/11473860

 

the effect of midazolam was prevented by a selective kappa antagonist (interesting)

all three benzodiazepines are kappa-opioid agonists

 

Naloxone blocks the antianxiety but not the motor effects of benzodiazepines and pentobarbital - http://link.springer.com/article/10.1007%2FBF02246192

 

 

 

This forum post is also very interesting; as it mentions the role of dynorphin and the KOR in adhedonia, depression, anxiety etc.  http://www.longecity.org/forum/topic/63691-jdtic-kappa-antagonist-bulkgroup-buy/

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  • 3 weeks later...

Sorry for never replying to all that Sam. Interesting stuff you posted though!
Anyways; JDTic synthesis seems to be coming along finally. See here.
So anyone who's interested; please post in that thread. Thanks :)

 

edit: Personally I'd prefer to see feedback from his first group buy to confirm legitimacy, trustworthiness, etc. before buying, so perhaps to anyone interested that is also something to keep in mind. You can find it here.

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I would put JDTic and Naltrexone in their own category away from Naloxone. I may have never tried JDTic or Naltrexone but it is to my understanding they work a bit different than Naloxone. I have been on Naloxone when on Suboxone but it made me a total dick so I got on Subutex and still the bup made me a dick but not anywhere near the dickness Naloxone caused me lol. I think Natrexone or JDTic would be awesome and work for a lot of people, I myself want to try Natrexone at a very very low dosage, IDK much about JDTic but I would still start at the minimum dose and give it a few weeks. If either could cause the level of assholeness I was at I would be afraid to touch either.

 

Also I know I have said this before, opiates have helped me out a lot(while I was on them now I feel like crap lol), it really got rid of a lot of my DP/DR, anxiety and depression. Obviously a antagonist and agonist are different but do they work the same way? I mean like same effects besides one gets you high and one doesn't. If I was to take Naltrexone would I get some of the effects I got from hydrocodone in other words?

 

Thank you,

Andrew

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  • 2 months later...

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