12 replies to this topic

[peoplepleaser101]

- JDTic is not appealing due to the cardio effects

 

- Ketamine causes permanent bladder damage, and it's a weak kappa agonist

 

- Salvia Divinorum is quite dysphoric, but perhaps that's the price one has to pay?

 

- CERC-501 might be doable

 

- Erinacine Q is a kappa antagonist in Lions Mane, but it's not prevalent enough in the fungus to make the consumption of the fungus itself worthwile. Perhaps extraction?

 

- Pawhuskin A, naturally occuring, but not easily accesible on the market

 

- Amentoflavone, it's barely bioavailable based on my readings

 

- Noribogaine....just no.

 

- Naltrexone, perhaps, but then it has to be combined with Subutex Buprenorphine

 

- ALKS-5461, not yet on the market unfortunately

 

Anyone? Chime in, help me cure this anhedonia. Thanks

[Mind_Paralysis]

CERC-501 is available, but rare.

 

Buprenorphine/Naltrexone is your best bet when it comes to pure, regulated and available compounds - just get the prescriptions and read up on the dosing.

 

 

Otherwise, the method used in a thread regarding kappa-agonists was to use Menthol, and then take it only during the night, along with an anxiolytic sleeping-aid, to smooth out and simply sleep off the dysphoric acute effects.

 

http://www.longecity...a-opioid/page-2

 

 

Interesting pattern btw... Amentoflavone is a Kappa agonist and Gaba-ANTagonist - this property no doubt increases the dysphoric effects of Amentoflavone - Menthol however, is a Kappa agonist and Gaba-AGonist! Curious how that property is inverted... In theory, this property takes some of the edge off of Menthol, and makes it even more suitable for night-time usage.

 

 

Menthol is available either as high-concentrated peppermint oil or as the PURE perfected chemical. I suggest you try and find a industrial grade vendor of Menthol - it's a fairly well-used substance. The psychoactive effects are also only available at fairly high dosages btw, hence why these aspects where discovered far later than the "cool-feeling" inducing ones. If you want to avoid the icy feelings Menthol causes, then I suggest adding a small dosage of chili to your intake - it's bound to balance it out by affecting the cold/heat receptors in the opposite way.

 

https://en.wikipedia...ical_properties

[peoplepleaser101]

CERC-501 is available, but rare.

 

Buprenorphine/Naltrexone is your best bet when it comes to pure, regulated and available compounds - just get the prescriptions and read up on the dosing.

 

 

Otherwise, the method used in a thread regarding kappa-agonists was to use Menthol, and then take it only during the night, along with an anxiolytic sleeping-aid, to smooth out and simply sleep off the dysphoric acute effects.

 

http://www.longecity...a-opioid/page-2

 

 

Interesting pattern btw... Amentoflavone is a Kappa agonist and Gaba-ANTagonist - this property no doubt increases the dysphoric effects of Amentoflavone - Menthol however, is a Kappa agonist and Gaba-AGonist! Curious how that property is inverted... In theory, this property takes some of the edge off of Menthol, and makes it even more suitable for night-time usage.

 

 

Menthol is available either as high-concentrated peppermint oil or as the PURE perfected chemical. I suggest you try and find a industrial grade vendor of Menthol - it's a fairly well-used substance. The psychoactive effects are also only available at fairly high dosages btw, hence why these aspects where discovered far later than the "cool-feeling" inducing ones. If you want to avoid the icy feelings Menthol causes, then I suggest adding a small dosage of chili to your intake - it's bound to balance it out by affecting the cold/heat receptors in the opposite way.

 

https://en.wikipedia...ical_properties

 

Hey, I saw your reply on the "controlling kappa-opioid" thread, you don't seem to like kappa agonist xD 

I have a panic disorder so I'm probably going to regret taking salvia :/

 

Kappa agonists are f***ing POISON to those of us who have had a constant stress-induction since childhood (read: people with adhd, Sct or autism), so, from my point of view, I honestly don't get why you are f***ing around with AGONISTS??

 

Have all of you MISSED the fact that Atomoxetine - because of its active metabolite - has the highest amount of suicidal idea of ANY drug currently widely used for the treatment of disorders?? Are you that BLIND to the effects?!

 

Seriously, forget agonism... join the Kappa-ANTagonist group buy instead!

[Mind_Paralysis]

 

CERC-501 is available, but rare.

 

Buprenorphine/Naltrexone is your best bet when it comes to pure, regulated and available compounds - just get the prescriptions and read up on the dosing.

 

 

Otherwise, the method used in a thread regarding kappa-agonists was to use Menthol, and then take it only during the night, along with an anxiolytic sleeping-aid, to smooth out and simply sleep off the dysphoric acute effects.

 

http://www.longecity...a-opioid/page-2

 

 

Interesting pattern btw... Amentoflavone is a Kappa agonist and Gaba-ANTagonist - this property no doubt increases the dysphoric effects of Amentoflavone - Menthol however, is a Kappa agonist and Gaba-AGonist! Curious how that property is inverted... In theory, this property takes some of the edge off of Menthol, and makes it even more suitable for night-time usage.

 

 

Menthol is available either as high-concentrated peppermint oil or as the PURE perfected chemical. I suggest you try and find a industrial grade vendor of Menthol - it's a fairly well-used substance. The psychoactive effects are also only available at fairly high dosages btw, hence why these aspects where discovered far later than the "cool-feeling" inducing ones. If you want to avoid the icy feelings Menthol causes, then I suggest adding a small dosage of chili to your intake - it's bound to balance it out by affecting the cold/heat receptors in the opposite way.

 

https://en.wikipedia...ical_properties

 

Hey, I saw your reply on the "controlling kappa-opioid" thread, you don't seem to like kappa agonist xD 

I have a panic disorder so I'm probably going to regret taking salvia :/

 

Kappa agonists are f***ing POISON to those of us who have had a constant stress-induction since childhood (read: people with adhd, Sct or autism), so, from my point of view, I honestly don't get why you are f***ing around with AGONISTS??

 

Have all of you MISSED the fact that Atomoxetine - because of its active metabolite - has the highest amount of suicidal idea of ANY drug currently widely used for the treatment of disorders?? Are you that BLIND to the effects?!

 

Seriously, forget agonism... join the Kappa-ANTagonist group buy instead!

 

 

I believe, when I wrote that, I was somewhat irrational - I hadn't REALLY surveyed the evidence regarding Kappa agonism properly.

 

I was also under the influence of both NSI-189 and Atomoxetine -  combined NRI/Kappa Agonist/NMDA-antagonist/SRI (mostly an NRI though) - hence I was angry because of NSI-189, it increases emotional tone radically, yet also kind of depressed because of Atomoxetine - however, it's somewhat debatable if the depression ATX induces is really caused by the Kappa agonism - it does work in multiple ways.

 

It might be that it's just the combination with NRI which causes such effects, and then there's also the fact that I'm a slow metabolizer, so the metabolite with kappa agonism wouldn't have been in any higher level in my blood.

 

 

As such, my opinion on Kappa agonism is not as black and white as it once was - I've been made to see the light, as a proper scientist should, that there is more nuance to it.

[Deaden]

Hey, I'm also very interested in finding a way to downregulate kappa receptors. I'm going to be trying to get Buprenorphine + Naltrexone prescribed but I might have a hard time with that...

 

Is there any other solution?

 

Should I try menthol? Where can I buy this? I understand it's a kappa agonist, but after the dysphoria would it reduce KOR activation and with the effects being sustainable?

[Galaxyshock]

I took plenty on menthol oil back in 2012/2013 winter. I think it upregulated endorphins or something because I experienced some pleasant effects but they were all short-lived. I don't think it's much of a plausible treatment to reguate the (kappa) opioid system to any major extent.

[Deaden]

I took plenty on menthol oil back in 2012/2013 winter. I think it upregulated endorphins or something because I experienced some pleasant effects but they were all short-lived. I don't think it's much of a plausible treatment to reguate the (kappa) opioid system to any major extent.

Crapppp, Stinkorninjor I need your wisdom!

[Mind_Paralysis]

I took plenty on menthol oil back in 2012/2013 winter. I think it upregulated endorphins or something because I experienced some pleasant effects but they were all short-lived. I don't think it's much of a plausible treatment to reguate the (kappa) opioid system to any major extent.

 

Well, not every treatment is going to work for everyone, or if they do, it has to be in combination with something else - diseases of the brain are often complicated, and hence needs complicated solutions.

 

I myself am currently on THREE f***ing ADHD-medications, with very different modes of action, and only now am I *kind of* feeling a half-decent effect.

 

Where you trying to treat some form of anhedonia, loss of pleasure, with kappa-agonism? I believe that is one of your issues, if I recall correctly?

 

 

I suppose you may simply be one of the lucky people whom doesn't have the same kind of overtly powerful homeostasis effect as the majority population - remember, using kappa agonists to down-regulate the Kappa-system is basically hedging your bet on the homeostasis effect that underlines the problem of tolerance to drugs - there ARE a number of people whom really can use both stimulants, gabaergics and hey... even opioid pain-killers for YEARS on end, without any appreciable tolerance - it's entirely possible that you're one of these types of people.

 

Unless you've taken a VERY powerful, and VERY selective Kappa-Antagonist, I don't think you can write off Kappa-modulation, even for yourself - and let's not forget that we're all different, neurodiversity is probably a very good thing evolutionarily, so different responses to different things is to be expected.

 

 

 

I took plenty on menthol oil back in 2012/2013 winter. I think it upregulated endorphins or something because I experienced some pleasant effects but they were all short-lived. I don't think it's much of a plausible treatment to reguate the (kappa) opioid system to any major extent.

Crapppp, Stinkorninjor I need your wisdom!

 

 

See above... different strokes for different folks.

 

Let's not also forget that different issues can give similar symptoms, even though the underlying mechanisms, and hence the necessary treatment, is different.

 

That's what you're entire anhedonia -thread is all about, yes? You talk about how anhedonia can come from different mechanisms than the classic two or more types of depression and Schizophrenia, yes?

 

 

Just because kappa-antagonism doesn't work on some people doesn't mean that there's a number of people out there who will benefit.

[Deaden]

 

I took plenty on menthol oil back in 2012/2013 winter. I think it upregulated endorphins or something because I experienced some pleasant effects but they were all short-lived. I don't think it's much of a plausible treatment to reguate the (kappa) opioid system to any major extent.

 

Well, not every treatment is going to work for everyone, or if they do, it has to be in combination with something else - diseases of the brain are often complicated, and hence needs complicated solutions.

 

I myself am currently on THREE f***ing ADHD-medications, with very different modes of action, and only now am I *kind of* feeling a half-decent effect.

 

Where you trying to treat some form of anhedonia, loss of pleasure, with kappa-agonism? I believe that is one of your issues, if I recall correctly?

 

 

I suppose you may simply be one of the lucky people whom doesn't have the same kind of overtly powerful homeostasis effect as the majority population - remember, using kappa agonists to down-regulate the Kappa-system is basically hedging your bet on the homeostasis effect that underlines the problem of tolerance to drugs - there ARE a number of people whom really can use both stimulants, gabaergics and hey... even opioid pain-killers for YEARS on end, without any appreciable tolerance - it's entirely possible that you're one of these types of people.

 

Unless you've taken a VERY powerful, and VERY selective Kappa-Antagonist, I don't think you can write off Kappa-modulation, even for yourself - and let's not forget that we're all different, neurodiversity is probably a very good thing evolutionarily, so different responses to different things is to be expected.

 

 

 

I took plenty on menthol oil back in 2012/2013 winter. I think it upregulated endorphins or something because I experienced some pleasant effects but they were all short-lived. I don't think it's much of a plausible treatment to reguate the (kappa) opioid system to any major extent.

Crapppp, Stinkorninjor I need your wisdom!

 

 

See above... different strokes for different folks.

 

Let's not also forget that different issues can give similar symptoms, even though the underlying mechanisms, and hence the necessary treatment, is different.

 

That's what you're entire anhedonia -thread is all about, yes? You talk about how anhedonia can come from different mechanisms than the classic two or more types of depression and Schizophrenia, yes?

 

 

Just because kappa-antagonism doesn't work on some people doesn't mean that there's a number of people out there who will benefit.

 

I mean I agree with what you said, I ordered some menthol will try that on thursday. So is there anything else than menthol that could be promising? I can't do salvia or ibogaine I react badly on anything that is psychoactive. Also, I'm still unsure on what is best, potent kappa antagonism, or kappa agonism for downregulation? Would the brain aim in returning to homeosthasis with a combination like buprenorphine + naltrexone as soon as I go off it? Man, I have a lot of faith in KOR downregulation, but it seems there's not much available that does that. Maybe start a group buy? I'm done with shitty anti depressants.

[Deaden]

Also do you know if menthol has any negative interactions with Parnate?

[Mind_Paralysis]

 

 

 

Well, not every treatment is going to work for everyone, or if they do, it has to be in combination with something else - diseases of the brain are often complicated, and hence needs complicated solutions.

 

I myself am currently on THREE f***ing ADHD-medications, with very different modes of action, and only now am I *kind of* feeling a half-decent effect.

 

Where you trying to treat some form of anhedonia, loss of pleasure, with kappa-agonism? I believe that is one of your issues, if I recall correctly?

 

 

I suppose you may simply be one of the lucky people whom doesn't have the same kind of overtly powerful homeostasis effect as the majority population - remember, using kappa agonists to down-regulate the Kappa-system is basically hedging your bet on the homeostasis effect that underlines the problem of tolerance to drugs - there ARE a number of people whom really can use both stimulants, gabaergics and hey... even opioid pain-killers for YEARS on end, without any appreciable tolerance - it's entirely possible that you're one of these types of people.

 

Unless you've taken a VERY powerful, and VERY selective Kappa-Antagonist, I don't think you can write off Kappa-modulation, even for yourself - and let's not forget that we're all different, neurodiversity is probably a very good thing evolutionarily, so different responses to different things is to be expected.

 

 

Crapppp, Stinkorninjor I need your wisdom!

 

 

See above... different strokes for different folks.

 

Let's not also forget that different issues can give similar symptoms, even though the underlying mechanisms, and hence the necessary treatment, is different.

 

That's what you're entire anhedonia -thread is all about, yes? You talk about how anhedonia can come from different mechanisms than the classic two or more types of depression and Schizophrenia, yes?

 

 

Just because kappa-antagonism doesn't work on some people doesn't mean that there's a number of people out there who will benefit.

 

I mean I agree with what you said, I ordered some menthol will try that on thursday. So is there anything else than menthol that could be promising? I can't do salvia or ibogaine I react badly on anything that is psychoactive. Also, I'm still unsure on what is best, potent kappa antagonism, or kappa agonism for downregulation? Would the brain aim in returning to homeosthasis with a combination like buprenorphine + naltrexone as soon as I go off it? Man, I have a lot of faith in KOR downregulation, but it seems there's not much available that does that. Maybe start a group buy? I'm done with shitty anti depressants.

 

 

The brain would probably return to homeostasis after you quit bup + nalt - but it's hard to say if that state would be one wherein you have quite as powerful DP/DR symptoms - I guess it could depend on how long you'd be on it. It's not going to magically rejigger your brain after a week.

 

For what it's worth, no one in the CERC-501 group buy reported their symptoms becoming worse after quitting CERC-501, so at least there doesn't seem to be any appreciable upregulation taking place because of use of that particular kappa antagonist. Naltrexone + Buprenorphine might not be exactly the same, but it's possible that it's a recurring trend in the receptor - some receptors downregulate from antagonism instead of upregulating.

 

 

Btw, at the dosage you would have to take Menthol in order to get Kappa affinity, it WOULD be a psychoactive substance, I mean, that's the whole point... I'm guessing you meant substances which are dissociative or hallucinogenic though, which both Salvia and Ibogaine are. (seriously... Ibogaine is the worst idea ever for a DP/DR-er... stay away!)

 

 

Also do you know if menthol has any negative interactions with Parnate?

 

I don't, sorry.

 

From what little I do know, I don't think it would... at least not directly, since as far as I know, Tranylcypromine (parnate) doesn't affect the breakdown of the neurotransmitters which effect the cold-sensation receptors which Menthol has the biggest affinity for. (it works sort of in reverse of how chili and other hot spices do)

 

I don't know if they would interfere with each others metabolism though, which could be a problem...

 

You have to read up on Menthol - which I certainly recommend for any substance you're going to ingest.

[Galaxyshock]

 

I took plenty on menthol oil back in 2012/2013 winter. I think it upregulated endorphins or something because I experienced some pleasant effects but they were all short-lived. I don't think it's much of a plausible treatment to reguate the (kappa) opioid system to any major extent.

 

Well, not every treatment is going to work for everyone, or if they do, it has to be in combination with something else - diseases of the brain are often complicated, and hence needs complicated solutions.

 

What I meant was menthol / peppermint oil is quite weak for true modulation on kappa-opioid, not that the opiate system is not a good target for various issues. Personally I found some relief from high amounts of chamomile (Apigenin in antagonist of all opiate receptor along with being GABA-A ligand) and Panax Ginseng which seems to be a partial kappa-antagonist. Ginseng is also 5-HT2A agonist which is therapeutic for ahedonia, although it's weaker than psychedelic agonists of the same receptor.

[Mind_Paralysis]

 

 

I took plenty on menthol oil back in 2012/2013 winter. I think it upregulated endorphins or something because I experienced some pleasant effects but they were all short-lived. I don't think it's much of a plausible treatment to reguate the (kappa) opioid system to any major extent.

 

Well, not every treatment is going to work for everyone, or if they do, it has to be in combination with something else - diseases of the brain are often complicated, and hence needs complicated solutions.

 

What I meant was menthol / peppermint oil is quite weak for true modulation on kappa-opioid, not that the opiate system is not a good target for various issues. Personally I found some relief from high amounts of chamomile (Apigenin in antagonist of all opiate receptor along with being GABA-A ligand) and Panax Ginseng which seems to be a partial kappa-antagonist. Ginseng is also 5-HT2A agonist which is therapeutic for ahedonia, although it's weaker than psychedelic agonists of the same receptor.

 

 

Oh, ok, gotcha'. I suppose I kind of agree with that assessment.

Interesting note about your other combos... it might be worth it to have a closer look at that with more selective specific pure chemical ligands - could be an interesting modulation-scheme, so to speak.