Are we stuck in a semi permanent high opioid state?

[Numbed]

I noticed most of us have anhedonia and we so far have only been trying to target the dopamine side of it, however you cannot feel joy without opioids (especially mu-opioid I believe).
Now after an alcohol binge I temporarily feel normal, could this be due to temporary mu-opioid receptor downregulation?

Also what are people their experience with withdrawal from things such as Kratom (or even while being on kratom), there have been reports of LOW dose of certain strains of kratom (especially green ones) increasing receptivity and emotional response, could it be that the low dose of kratom creates an adaptive response in the opioid system, where as high doses act as full blown analgesics?

[Numbed]

Ive ordered some green kratom strain, going to use a low dose, im pretty sure we are stuck in a high opioid state semi-permanently.
Im pretty sure that the experience that some kratom users have by using kratom as a sex enhancer is that atleast in them, a short activation of a low dose kratom causes a compensatory downregulation of certain opioid receptors.

This is a theory of mine and I will put it to the test, im glad people have tried Ella (if you think about it, it shows how fucked up pssd really is that people are actually trying things like this and hopefully it will bring attention to the world..).

[DoIt]

I agree with this and I think this is why tianeptine doesn't help, why ketamine doesn't help, why we don't get that endorphine rush from training and why we don't enjoy things as before.

Btw. where is Ghost? I miss his research and writings...:/

[Numbed]

I would like to add that I think that we have problems RELEASING OPIOIDS, I think the release of opioids is what causes the rush/euphoria/orgasm, and after the release is done craving for the reward starts setting in (conditioned place preference in drug models).

My theory is by taking alcohol or other opioid releasing type of drugs we can chemically induce opioid release, once the drug leaves our body and opioid receptors adapt and motivational systems kick back in (an attempt to re-aquire the 'opioid high').
Opioids for example are antagonistic to GnrH.

These are a must read:

http://www.tandfonline.com/doi/full/10. ... ccess=true

https://www.macalester.edu/academics/ps ... ation.html

https://www.researchgate.net/publicatio ... asm_in_Man

Also opioid withdrawal (such as in heroin junkies) is associated with spontaneous orgasms

Here methadone as an example:
https://en.wikipedia.org/wiki/Methadone

"Withdrawal symptoms:
Spontaneous orgasm"

On top of that, look at every opioid forum where people are detoxing, the first week of their withdrawal they have masturbating sessions and insatiable libido for about a week or so on average.

Once again I think we have a chronic buildup of opioid peptides in our brain but are unable to release them (its the release that causes euphoria/orgasm/etc?)
This would also explain why naltrexone blocks orgasm (it occupies the receptors and thereby unable to release the opioids?), its the low opioid state that causes craving including the need for sex.
Im not sure what the mechanism behind the actual 'release' of opioids is like, but wouldnt LDN/blocking the receptors with naltrexone only increase the receptors but not the release.

[Numbed]

edit:

"Two candidates for pharmacological challenges are suggested by animal and human studies: the α2 adrenergic antagonist yohimbine, which reinstates alcohol seeking in rats in a manner similar to stress (Le et al, 2005), but was not effective in inducing cravings in human alcohol dependent subjects in the one published previous attempt (Krystal et al, 1994); and meta-chlorophenylpiperazine (mCPP), which did produce a craving response (Krystal et al, 1994; George et al, 1997)."

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3077446/

I have tried yohimbine in the past but I believe I dosed too high, I had problems looking people into the eyes was very anxious, I guess a lower dose would have been better.

Can someone explain the difference between alcohol seeking and craving (way I see it both is chasing a known reward???)

mCPP is a metabolite of trazadone (a 5ht2c agonist known to be capable of producing priapism...)

[Halan]

undertimated topic
I think we should look more into opioids too...
I'm gonna try yohimbine soon, I bought before seeing this topic anyway

[JayR]

Well considering Kappa-opioid activation CAUSES Anhedonia, and is responsible for all negative BEHAVIORAL effects of opiates...I'd say if anything, we have too much Kappa-activation. It could be a real game changer for us when CERC-501; the Kappa antagonist for treatment of Depression and drug addiction - is released.
--> https://clinicaltrials.gov/ct2/show/NCT02218736
--> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5288841/

[Halan]

Well considering Kappa-opioid activation CAUSES Anhedonia, and is responsible for all negative BEHAVIORAL effects of opiates...I'd say if anything, we have too much Kappa-activation. It could be a real game changer for us when CERC-501; the Kappa antagonist for treatment of Depression and drug addiction - is released.
--> https://clinicaltrials.gov/ct2/show/NCT02218736
--> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5288841/

nice
Amentoflavone is an avaiable substance that antagonize kappa-opioid
but I think mu opioid could be also more activated than normal

[JayR]

Well considering Kappa-opioid activation CAUSES Anhedonia, and is responsible for all negative BEHAVIORAL effects of opiates...I'd say if anything, we have too much Kappa-activation. It could be a real game changer for us when CERC-501; the Kappa antagonist for treatment of Depression and drug addiction - is released.
--> https://clinicaltrials.gov/ct2/show/NCT02218736
--> https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5288841/

nice
Amentoflavone is an avaiable substance that antagonize kappa-opioid
but I think mu opioid could be also more activated than normal

Amentoflavone needs to be paired with Milk Thistle and Bioperine (black pepper extract) to efficiently be absorbed.
--> https://area1255.blogspot.com/2016/07/n ... eptor.html