• Log in with Facebook Log in with Twitter Log In with Google      Sign In    
  • Create Account
  LongeCity
              Advocacy & Research for Unlimited Lifespans

Photo
* * * * * 1 votes

anxiety/depression/anhedonia/addiction/withdrawal

anxiety/depression/anhed opioid kappa dynorphin naltrexone endorphins ldn anhedonia

  • Please log in to reply
74 replies to this topic

#1 addx

  • Guest
  • 711 posts
  • 184
  • Location:croatia
  • NO

Posted 13 August 2013 - 01:15 PM


Since the thread where I posted all this information is probably not getting much views and I seem to be obsessively pointing people to it I decided to make a separate thread explaining how all this works.


Mu and kappa opiod networks facilitate the basic reward/fear system.
Kappa opioid receptors(KOR) when activated shutdown dopamine in mesolimbic structures = this is the main cause of anhedonia
Kappa opioid receptors upregulate when there is too much dopamine in mesolimbic structures. They do this to tame the neurotoxic dopamine levels. You become more fearful/anxious and this counteracts the extra dopamine from whatever you're pushing into your system(cocaine, morphine)
Thus, kappa opioid network is the main network responsible for facilitating drug tolerance and withdrawal.
Once the drug use is stopped the kappa opioid network remains upregulated causing fear/anxiety(and not even having a source origin as in an event since the the cause was chemical). This state leads to drug relapse.
Tha kappa opioid network downregulates slowly, painfully slowly.
Thus, the only know substances to actually reverse tolerance are kappa opioid agonists.
Only known methods are salvia divinorum or ibogaine. Perhaps low dose ketamine could do it, ketamine does agonize kappa and I fear that the known ketamine afterglow glow effect is due to KOR downregulation, just as is Salvias and Ibogaines. Ibogaine has the extra merit of its metabolite noribogaine I think is an antagonist. So after Ibogaine downregulates it, the metabolite disables it for months.
Kappa antagonists on the other hand should not downregulate KORs it but should simply instantly stop the effect of it being upregulated. Kappa antagonists should immediately kill withdrawal.
Having said that, JDTic as a kappa antagonist infact in a way does downregulate KORs. It corrupts them. Thus the long effect. JDTic AFAIK corrupts receptors so its effects last until your brain grows new ones.
As far as mental health is concerned, most mental disorders are fear/anxiety fueled, these are people who have their kappa opioid system upregulated due to trauma, abuse or genetics. Thus, these chemicals are invaluable to treat the entire pallete of mental disorders.
The list starts with anxiety, anhedonia, depression, compulsions and goes on...
Fear causes anxiety. Anxiety is dopamine in the fear system. Fear also kills dopamine in the reward system. After a while the anxious dopamine causes downregulation of the fear-dopamine channels at which point you become less anxious and more lifeless, learned helplessness. So, you become a zombie, your reward dopamine is locked out by fear. And the same fear can't even produce dopamine to provide anxiety, just lethargy and anhedonia.
As you see, dopamine is just the perception-drive neurotransmitter, be it drive to approach or avoid. Thus stimulants cause anxiety more often than reward and prolonged use causes upregulation of KOR system killing dopamine in mesolimbinc structures leaving the stimulants to increase dopamine only for anxiety purposes eventually leading to paranoia.
The only question is, does the mu opioid system upregulate to counter anxiety-dopamine is does the numbing of anxiety only facilitated by dopamine receptor downregulation. If it does then antagonizing KORs in a state of upregulated MOR would lead the person into mania. This interplay might be the mechanism of bipolar as it obviously provides the mechanism for depression/anhedonia.


So, the KOR system facilitates the basis for depression, anxiety, anhedonia and drug tolerance/withdrawal/dependance. It seems like a miracle. But if you look at studies from way past you'll see that the KOR system was ignored by science for anything other than treating regional pain. They found out early that the pushing the KOR for pain management system doesn't cause tolerance unlike pushing mu opioid with moprhin and such. This is logical the KOR system actually facilitates drug tolerance. But they only started experimenting with KOR for other than pain management in the last few years. Almost all of the studies are still in animal testing phase. Only JDTic had a human trial start and it was halted allegedly due to some people having side-effects of heart arrythmia.



Here's some studies about all this, proving various points I made above. Some of the studies are summary studies that also confim this concept. Also, some of the studies link the KOR system to serotonin and GABA to show why meds that push those have some effects for anxiety. SSRIs antianxiety is iffy and benzos is not but they are sedating and cause dependancy and tolerance.



http://www.ncbi.nlm....pubmed/18395712

Depleting serotonin causes kappa opioid agonists failure to inhibit cocaine effects. I would that in that situation suspect kappa opioid receptors upregulate even further in an effort to try and control reward pathways neurotoxic dopamine levels. Providing serotonin enables kappa opioid network to produce its effects and reduces the need for it to upregulate. That's what I read from this, but it is jumping to conclusions.

My point is trying to link up the iffy efficacy of serotonin for depression/anxiety.

Ok, lets do some more

http://www.ncbi.nlm....pubmed/20939060

Acute activation of κ-opioid receptors (KOR) decreases dopamine (DA) extracellular levels in both the medial prefrontal cortex (mPFC) and the nucleus accumbens (NAc). Also, the acute activation of KOR prevents alterations in behavior and neurochemistry occurring after repeated use of psychostimulants. Opposing to the acute effects, repeated administration of the KOR agonist, U-6593, potentiates both high-potassium and amphetamine induced DA release in the NAc, suggesting that repeated activation of KOR sensitizes mesolimbic dopaminergic neurotransmission. This study investigated the effect of repeated treatment with U-69593 on basal and stimulated DA and serotonin (5HT) extracellular levels in the rat mPFC. Rats were injected once daily with U-69593 (0.16-0.32 mg/kg) or vehicle for 4 days. One day after the last injection, microdialysis experiments assessing DA and 5HT extracellular levels in mPFC were conduced. The repeated treatment with U-69593 significantly augmented potassium-stimulated DA extracellular levels, without affecting potassium-stimulated 5HT extracellular levels, suggesting an increase in DA releasability.

IMO this basicly says: kappa opioid agonists fix anhedonia(dopamine levels in mesolimbic structures) through periodical dosing. (remember what I wrote: salvia divinorum weekly/biweekly)


Not very interesting but still another study that proves the mechanism: http://www.ncbi.nlm....pubmed/19859697


But here we go in longecity style:

Knockdown of prodynorphin gene prevents cognitive decline, reduces anxiety, and rescues loss of group 1 metabotropic glutamate receptor function in aging. http://www.ncbi.nlm....pubmed/23904614

Prodynorphin is the precursor to dynorphin - the endogenous kappa opioid ligand


More,

Collectively, available data suggest that KOR disruption produces anti-stress effects and under some conditions can prevent the development of stress-induced adaptations. As such, KOR antagonists may have unique potential as therapeutic agents for the treatment and even prevention of stress-related psychiatric illness, a therapeutic niche that is currently unfilled

http://www.ncbi.nlm....pubmed/23836029


More

Together these data demonstrate that CeA dynorphin/KOR systems are dysregulated following excessive cocaine exposure and suggest KOR antagonism as a viable therapeutic strategy for cocaine addiction.
http://www.ncbi.nlm....pubmed/23751206


And more rats

Rats with a history of ethanol dependence showed a significant decrease in open-arm exploration after exposure to restraint, indicating an anxiety-like state, compared to similarly treated controls, an effect that was blocked by nor-BNI
http://www.ncbi.nlm....pubmed/23731692

nor-BNI is kappa opioid antagonist




Kappa opioid receptor signaling in the basolateral amygdala regulates conditioned fear and anxiety in rats.
http://www.ncbi.nlm....pubmed/21531393


Blockade of kappa opioid receptors attenuates the development of depressive-like behaviors induced by cocaine withdrawal in rats
http://www.ncbi.nlm....pubmed/21736885


This one just to connect to the standard benzo anxiety treatment:

Presynaptic inhibition of gamma-aminobutyric acid release in the bed nucleus of the stria terminalis by kappa opioid receptor signaling
http://www.ncbi.nlm....pubmed/22225848

GABA is just an infrastructure network. KOR inhibits GABA. So taking GABAergics is fixing the issue downstream of the source. As are dopaminergics and serotonergics.


One for the topic at hand:

The kappa opioid receptor antagonist JDTic attenuates alcohol seeking and withdrawal anxiety.
http://www.ncbi.nlm....pubmed/22515275


One summary study saying exactly what I'm saying:

Addictions to cocaine or heroin/prescription opioids [short-acting μ-opioid receptor (MOPr) agonists] involve relapsing cycles, with experimentation/escalating use, withdrawal/abstinence, and relapse/re-escalation. κ-Opioid receptors (KOPr; encoded by OPRK1), and their endogenous agonists, the dynorphins (encoded by PDYN), have counter-modulatory effects on reward caused by cocaine or MOPr agonist exposure, and exhibit plasticity in addictive-like states. KOPr/dynorphin activation is implicated in depression/anxiety, often comorbid with addictions. In this opinion article we propose that particular stages of the addiction cycle are differentially affected by KOPr/dynorphin systems. Vulnerability and resilience can be due to pre-existing (e.g., genetic) factors, or epigenetic modifications of the OPRK1 or PDYN genes during the addiction cycle. Pharmacotherapeutic approaches limiting changes in KOPr/dynorphin tone, especially with KOPr partial agonists, may hold potential for the treatment of specific drug addictions and psychiatric comorbidity.
http://www.ncbi.nlm....pubmed/22709632



Another withdrawal, this time nicotine

Chronic nicotine enhanced the affective, anxiogenic, and neurochemical effects produced by KOR activation in adult rats. Our data suggest that chronic nicotine elicits an increase in KOR function, and this may contribute to nicotine withdrawal since KOR activation facilitated and KOR blockade prevented withdrawal signs upon removal of nicotine.
http://www.ncbi.nlm....pubmed/22659976


One general, proving that dynorphin regulates fear acquiring and extinction:

Dynorphins regulate fear memory: from mice to men.
http://www.ncbi.nlm....pubmed/22764240


Antidepressant-like effects of kappa-opioid receptor antagonists in Wistar Kyoto rats.
http://www.ncbi.nlm....pubmed/19924112


Another summary study:

Stress is most often associated with aversive states. It rapidly induces the release of hormones and neuropeptides including dynorphin, which activates kappa opioid receptors (KORs) in the central and peripheral nervous systems. In animal models, many aversive effects of stress are mimicked or exacerbated by stimulation of KORs in limbic brain regions. Although KOR signaling during acute stress may increase physical ability (by producing analgesia) and motivation to escape a threat (by producing aversion), prolonged KOR signaling in response to chronic or uncontrollable stress can lead to persistent expression of behavioral signs that are characteristic of human depressive disorders (i.e., "prodepressive-like" signs). Accumulating evidence suggests that KORs contribute to the progressive amplification (sensitization) of stress-induced behaviors that occurs with repeated exposure to stress. Many of the aversive effects of stress are blocked by KOR antagonists, suggesting that these agents may have potential as therapeutics for stress-related conditions such as depression and anxiety disorders. This review summarizes current data on how KOR systems contribute to the acute (rapid), delayed, and cumulative molecular and behavioral effects of stress. We focus on behavioral paradigms that provide insight on interactions between stress and KOR function within each of these temporal categories. Using a simplified model, we consider the time course and mechanism of KOR-mediated effects in stress and suggest future directions that may be useful in determining whether KOR antagonists exert their therapeutic effects by preventing the development of stress-induced behaviors, the expression of stress-induced behaviors, or both.
http://www.ncbi.nlm....pubmed/19782055



AAAAnd I didnt read this study before writing all this but here it is, like someone read my threads from various forums:

The dynorphin-like peptides have profound effects on the state of the brain reward system and human and animal behavior. The dynorphin-like peptides affect locomotor activity, food intake, sexual behavior, anxiety-like behavior, and drug intake. Stimulation of kappa-opioid receptors, the endogenous receptor for the dynorphin-like peptides, inhibits dopamine release in the striatum (nucleus accumbens and caudate putamen) and induces a negative mood state in humans and animals. The administration of drugs of abuse increases the release of dopamine in the striatum and mediates the concomitant release of dynorphin-like peptides in this brain region. The reviewed studies suggest that chronic drug intake leads to an upregulation of the brain dynorphin system in the striatum and in particular in the dorsal part of the striatum/caudate putamen. This might inhibit drug-induced dopamine release and provide protection against the neurotoxic effects of high dopamine levels. After the discontinuation of chronic drug intake these neuroadaptations remain unopposed which has been suggested to contribute to the negative emotional state associated with drug withdrawal and increased drug intake.
http://www.ncbi.nlm....pubmed/19804796



And for all ADHD treated kids:

Kappa-opioid system regulates the long-lasting behavioral adaptations induced by early-life exposure to methylphenidate.
http://www.ncbi.nlm....pubmed/18923399


So there, we have it all covered, all addictions, depression, anhedonia and anxiety. And the underlying mechanism. And even some relations to why current medication semi-works.


So, I can't really find anything that doesn't support this concept. I would value someone actually trying to follow me on this and see how correct this really is because I'm either insane or brilliant and I have been both in the past so...


Comments welcome
  • like x 11
  • WellResearched x 3
  • Informative x 1

#2 addx

  • Topic Starter
  • Guest
  • 711 posts
  • 184
  • Location:croatia
  • NO

Posted 13 August 2013 - 05:20 PM

I have crazy ideas but stop me if you can :)

I've always felt anxiety from visceral heat. Similar to suffocation anxiety. I thought about it and remembered that KORs are placed do provide visceral analgesia.

Here's a study to prove that I remember this correctly http://www.ncbi.nlm....pubmed/12603260

Each receptor presents a distinct pattern of activities, with mu receptors influencing responses to mechanical, chemical and thermal nociception at a supraspinal level, kappa receptors involved in spinally mediated thermal nociception and chemical visceral pain, and delta receptors modulating mechanical nociception and inflammatory pain.

Having a hot laptop on my stomach eventually causes me "gasp for air" anxiety or something akin to that.

If heating up the stomach activates KOR receptors for analgesia, the CNS system is probably informed of this via the KOR network itself or through other infrastructure networks(probably NDMA, I don't have time to actually find that this is the case, it would be a very hard find). Activation of KOR receptors for analgesia I postulate would cause paralell activation of KORs in the CNS - elliciting the anxiety. Thus analgesia is delivered where it is needed and the message to stop heating up your stomach is delivered to the CNS/consciousness.

Now this all nice and dandy. But let's jump to conclusions a bit. MORs are in charge of extremities and such, non-organ parts. If you ellicit pain on your arm causing MOR activation for analgesia of the wound, the connected MORs in the CNS would actually provide reward as that's what MORs do. This is analog to the above. Is this what people get out of cutting themselves?

Edited by addx, 13 August 2013 - 05:26 PM.

  • Informative x 1
  • like x 1

sponsored ad

  • Advert
Advertisements help to support the work of this non-profit organisation. To go ad-free join as a Member.

#3 lammas2

  • Guest
  • 137 posts
  • 33
  • Location:Finland

Posted 13 August 2013 - 05:38 PM

Excellent research. The sad thing is, I have no access to salvia, ibogaine nor ketamine. And you are saying, these are the only known methods? :sad:

#4 addx

  • Topic Starter
  • Guest
  • 711 posts
  • 184
  • Location:croatia
  • NO

Posted 13 August 2013 - 05:52 PM

I have no access either... What can I say. We're trying the group buy of JDTic, there's a thread, but also having lots of difficulties as JDTic is research only chemical and they sell it to labs. :/ I am also contacting some other people but they are on vacation now..

I came across salvia and ibogaine by trying to find available chemicals that work on kappa opioid as I saw so much value in them from the research. And when I found them I saw they are used for the above stated purposes and work and totaly confirm the research. Imagine that, doing the research and then having it confirmed just like that. I'm obsessed through the roof....

ibogaine and salvia is legal in Slovenia which is a bordering country to mine(croatia in which they're not legal and even though we just joined the EU, the border is still there...).

since you're all within EU, I'm not sure how this works, there's no borders so what's stopping you from getting it from slovenia? even by mail?

Ibogaine can be done as a one time flood trip so there's clinics available in mexico, canada and slovenia afaik. I'm not sure, but I think there's a clinic somewhere up there near you or a neigbourghing country. The treatment is usually expensive at least a 1000 euros plus flight or so (ibogaine is expensive this explaines a lot of the price, but there's also risk for the sitter which explains the other part of the price)... and you need like at least a few days for it, better a week...

ketamine is available everywhere but not for human use :) vets have it, it is still used for animals. if you can get a vet to try weekly subpsychedelic doses... it's a risk for anyone doing this.. im the least sure about ketamine. it does provide robust antidepression, this is for sure, but i'm not sure if does everything the others do.

i have tried ketamine once and I know I have no issues with it...

Edited by addx, 13 August 2013 - 05:59 PM.

  • like x 1
  • Good Point x 1

#5 focus83

  • Guest
  • 216 posts
  • 21

Posted 13 August 2013 - 06:40 PM

Excellent contribution! So the goal would be to downregulate the KOR system in individuals who suffer from depression, anhedonia and or anxiety?

Did I understand it right that both agonists and antagonists at the KOR have therapeutic potential? While the agonists feel unpleasant (ibogaine, ketamine, saliva) they downregulate the KORs just like agonists would do that target other neurotransmitter systems? Antagonists at the KORs though have the paradox effect of also downregulating KORs, right?

So since kappa agonism feels unpleasent, the ideal drug would be an antagonist like jtdic?

Sorry if my response is a little superficial, but I didn't have the time to thouroughly read all of your posting.

Big thumbs up for this great post!
  • like x 3

#6 addx

  • Topic Starter
  • Guest
  • 711 posts
  • 184
  • Location:croatia
  • NO

Posted 13 August 2013 - 07:17 PM

Yes, you got the gist. Both can work. They're now trying to create antagonists that have normal duration of effects rather than extra long effect like JDTic, lasting weeks or even a month.

The recent one I saw is Zyklophin, it has short action and passes the blood brain barrier. http://www.ncbi.nlm....pubmed/19841255
And don't worry, again the same effect, from the study: "Systemically administered zyklophin (3 mg/kg s.c.) also prevented stress-induced reinstatement of cocaine-seeking behavior in a conditioned place preference assay"
This one lasts only 12 hours but I'm not sure it has ever been administered to humans or tested for toxicity. JDTic has in the halted human trial. Regardless of that, they like to develop short acting antagonists for testing and playing, but if they're really what I think they are, I think I'd be better of dosing JDTic once a month than stuffing Zyklophin in me every 12 hours. Although in the trial they dosed JDTic daily which I can't understand


Agonist do not neccesarily feel unpleasant as flood doses usually cause so much dissociation that the unpleasentness isnt felt, but the drugs still do their work.
Check erowid.
You can read up on Salvia reports, only some of them report feelings of terror. Alas most reports are by adolescents and I think they a bit of a different healthier state of mind stiill, usually.
Ibogaine trips often have a phase of fear and terror, sounds scary but users report not that scary for the most part. There were a few bad trips and what I could see from that is that people didn't get a high enough dose. Very troubled people used it, it caused the surfacing of their most burried fears but they "wouldn't let go" and fought it the entire trip and ended up worse. The "shaman"/sitter usually instructs people if they get into this state to let go, "let the plant teach you". After you let go you get the ability to review and extinct your fears without being scared. Often I think it is a question of requiring a higher dosage disable willfully holding onto fears to let them overwhelm you, to give up. This thing literally breaks you apart and then reintegrates you as a whole. If you read anything on object relations by m, klein and the development of infant/child mindstates from paranoid-schizoid to depressive to 'normal' you can imagine what happens. I believe NPD, BPD and some other disorders never make it past the paranoid-schizoid phase, they never let go of their fear causing them to live life projecting a fear-calculated-solution -> the false self. i feel that ibogaine could be the first and probably only chemical to be able to adress NPD/BPD and very much PTSD.

But there seems to be much benefit in microdosing ibogaine, there's a guy who merged his 2 dissociative identities(multiple personalties) with 2 weeks microdosing ibogaine. I shouldn't link to other forums I think but it's easily googleable. He reported progress day by day.

Cool thing about kappa opioid antagonists is that they're not abusable. They don't push the reward circuitry, they just disinhibit it. You can not get high off them, no matter how much you take. But the real human fear/reward baseline when these systems are optimal and not upregulated is I think sublime to what most of us endure. Think monkeys in trees. How happy they are.

Edited by addx, 13 August 2013 - 07:32 PM.

  • like x 3

#7 addx

  • Topic Starter
  • Guest
  • 711 posts
  • 184
  • Location:croatia
  • NO

Posted 13 August 2013 - 07:24 PM

Btw. I can find at least 20-30 more pubmed studies confirming all this directly and many more indirectly. There's just too much to post. Type kappa opioid anxiety or depression or withdrawal or fear into pubmed and see it yourself. I read them all during the last months, didn't really take notes, so I when doing this post I just picked them out within 30 minutes or so.... there's more and it all fits :/

The only other worthwhile stuff I have found is CRF antagonists but they seems to have failed proving efficacy in human testing i think. corticotropin releasing factor is one of the first steps in the stress response. but alas, it would be better if your brain didn't decide that its under stress at all. thus i feel KOR is upstream of this and more usefull to treat.
  • Good Point x 1
  • like x 1
  • Agree x 1

#8 focus83

  • Guest
  • 216 posts
  • 21

Posted 13 August 2013 - 07:30 PM

Thanks for clarifying!

Agonist do not neccesarily feel unpleasant as flood doses usually cause so much dissociation that the unpleasentness isnt felt, but the drugs still do their work.
Check erowid.
You can read up on Salvia reports, only some of them report feelings of terror. Alas most reports are by adolescents and I think they a bit of a different healthier state of mind stiill, usually.
Ibogaine trips often have a phase of fear and terror, sounds scary but users report not that scary for the most part...



Flood doses...Dissociation...Trips...Fear...Terror etc. That doesn't sound like something that can be incoorporated into everyday life. So agonists are something to be used intermittently in huge one time flood doses (e.g. every couple of weeks, months, years?) to fully reverse maladaptations in the kappa opioid system? Or could a once in a lifetime administration theoretically be enough like often done with ibogaine?

#9 addx

  • Topic Starter
  • Guest
  • 711 posts
  • 184
  • Location:croatia
  • NO

Posted 13 August 2013 - 07:41 PM

Thanks for clarifying!

Agonist do not neccesarily feel unpleasant as flood doses usually cause so much dissociation that the unpleasentness isnt felt, but the drugs still do their work.
Check erowid.
You can read up on Salvia reports, only some of them report feelings of terror. Alas most reports are by adolescents and I think they a bit of a different healthier state of mind stiill, usually.
Ibogaine trips often have a phase of fear and terror, sounds scary but users report not that scary for the most part...



Flood doses...Dissociation...Trips...Fear...Terror etc. That doesn't sound like something that can be incoorporated into everyday life. So agonists are something to be used intermittently in huge one time flood doses (e.g. every couple of weeks, months, years?) to fully reverse maladaptations in the kappa opioid system? Or could a once in a lifetime administration theoretically be enough like often done with ibogaine?


most people reported that they wouldnt consider taking an ibogaine trip for years after they did a flood dose. and they dont. neither salvia or ibogaine causes addiction (ketamine is a different story, its kappa opioid effect is weak, and other effects are strong so it is addictive slightly).
most ibogaine users conclude one flood trip is enough to integrate their ego fragments and extinct fears and all that, kill depression and anhedonia and restore connectedness to the world(yes it also kills depersonalization). but yes, i'm having the issue that a flood dose trip would require at least 5 days off work and i can't get that at least then next 7-8 months...
its a bit tougher for heroin addicts, they sometimes require an extra trip or two to be fully healed as i understand it. ibogaine clinics report 50-80% efficacy in treating heroin addicts - meaning they dont relapse for some while(dunno how long). treating also meaning 1-3 ibogaine trips. methadone has a 10% success ratio and only after years of weaning and struggling.

buprenorphin + naloxone is a combination akin to kappa opioid antagonism. kinda. it should produce it but i fear you can't just add and substract stuff like that, receptor affinities are different and they can't really add an agonist and antagonist and call it a draw. but it's the closest thing available legaly and is used for drug abusers treatment.

low dose naloxone is also a known effective treatment. im not sure anyone understand how that works, but naloxone is a full panel opioid antagonist including kappa...



now as for salvia. the salvia trip lasts only shortly, like 15 minutes. you can take a low dose or a break through dose, either way it's out of your system fast. so you can use it daily and incorporate it easily. although biweekly might be smarter, but im just guessing here by reports i've seen. there are many reports of periodical salvia use for well being, there's even a summary of internet case reports on pubmed, i remember. lots of people do this apparently... so this is perfectly doable. the transient fear terror effect will most probably wear off with the first few trips as i have seen. and not all people feel that anyway.

Edited by addx, 13 August 2013 - 07:47 PM.


#10 focus83

  • Guest
  • 216 posts
  • 21

Posted 14 August 2013 - 12:21 PM

You said KOR downregulate painfully slow. Can you give an approx. time frame? Are we talking about months or years?

Also how long lasts the effect of a single JDTic dose, i.e. how long does it take for the body to replace the "destroyed" KORs?
  • like x 1

#11 addx

  • Topic Starter
  • Guest
  • 711 posts
  • 184
  • Location:croatia
  • NO

Posted 14 August 2013 - 05:18 PM

You said KOR downregulate painfully slow. Can you give an approx. time frame? Are we talking about months or years?


I only conclude that from the struggles of recovering addicts. It takes a long time, they don't really ever become normal I think...

Also how long lasts the effect of a single JDTic dose, i.e. how long does it take for the body to replace the "destroyed" KORs?


I read somewhere it lasts weeks to a month. But the confusing thing is they used daily dosing in human trials IIRC and Dave Pearce also dosed it daily... I have seen a study of exactly JDTic corrupting receptors. And JDTic, norBNI and that third one with the long name all three have their effects last from week up to a month depending on species, dose, whatever.

Zyklophin is the first selective kappa opioid antagonist they discovered that is a short acting one, with cca 12 hours of antagonism.

#12 jakord

  • Guest
  • 57 posts
  • 4
  • Location:here

Posted 15 August 2013 - 04:04 PM

What's about Methoxetamine? It's said to be an agonist of opioid mu and k receptors. It's dirt cheap and still legal in many places.

#13 lammas2

  • Guest
  • 137 posts
  • 33
  • Location:Finland

Posted 16 August 2013 - 10:24 AM

I dont recommend taking Shi shang bai, but if you think its important to take it, your choice. Shi Shang will lower your energy levels, but it is the only natural opioid antagonist.

http://www.longecity.org/forum/topic/61101-please-help-with-post-ibogaine-treatment-recovery/#entry558543

A natural opioid antagonist? Anyone has more information about this?

#14 nowayout

  • Guest
  • 2,946 posts
  • 439
  • Location:Earth

Posted 17 August 2013 - 06:25 AM

Be careful with ibogaine. There happens to be another thread on here just now by someone who is having disturbing and lasting deleterious effects from it.

There is quite a number of less scary substances that can make withdrawal easier, and there have been threads on it here before. I would recommend searching it. Lots of people successfully come off substances, so the picture is not as dark as you paint it.

#15 addx

  • Topic Starter
  • Guest
  • 711 posts
  • 184
  • Location:croatia
  • NO

Posted 18 August 2013 - 10:35 AM

Searched it, found it. And I think his dose was too low. I've seen a similar account, "on the treshold of death", meaning deepest fears were surfaced but the person did not let go, did not let itself "die" but fought against the entire trip. I've read at least 30-40 trip accounts and this is the key moment where you let iboga "kill you", disintegrate you and then reintegrate you. So instead of extincting fear of death it only strengthened it making the person worse.

Too low dose. Ibogaine is tricky and people might do better just microdosing the stuff..

He took 800mg which is IIRC is bare minimum for a break through trip. It wasn't enough for him

I've read a similar report by a woman... also months of bad feelings, she felt she'll never be the same again.

Unfortunately, these people will probably never accept this, but I think they can be fixed by a true flood dose. But I would definitely wait a few months before another attempt.

Other than that, kappa opioid antagonist would probably stop the deleterious effects immediately, but alas, they're experimental. Low dose naloxone would prolly help.

#16 SlimNm

  • Guest
  • 45 posts
  • 31
  • Location:USA
  • NO

Posted 23 August 2013 - 02:33 PM

How safe is Ibogaine? And why does LSD and other hallucinogens seem to have the potential to cause long-lasting negative psychological symptoms in a few people but leave others unscathed (or even healed)?

Where are some user reports of Ibogaine permanently curing anhedonia?

#17 addx

  • Topic Starter
  • Guest
  • 711 posts
  • 184
  • Location:croatia
  • NO

Posted 23 August 2013 - 02:58 PM

There have been deaths on ibogaine floods. There is a youtube movie explaining all the deaths that have medical data.

Here are some user reports that I find compelling

http://www.erowid.or...xp.php?ID=58716

http://www.erowid.or...xp.php?ID=76892






Most user reports are for opiate detox, it's difficult to find people who took it for something else. But there you have it. You can find more on youtube or erowid.

#18 wanderviolet

  • Guest
  • 18 posts
  • 15
  • Location:Australia

Posted 26 August 2013 - 05:49 PM

this is the system I'm suspecting is working against the husband at the moment. He's officially diagnosed with chronic and complex dissociative PTSD. He's stuck numb and dissociated, so the PTSD bit has been missed for oh, ever? Anyway - add in a history of drug abuse. Clean now for quite some years, but essentially went for drugs that I suspect have helped him detach - cannabis, heroin, night-time cold & flu (dextromethorphan), benzo's, alcohol but not enough to be drunk, just a low level but in addictive ways. Looking into the research about using naltrexone treatment for this particular situation actually. Drug-free for the majority of 14 years, alcohol free for 2 years.

Looking into a dopamine-deficiency as well but the two can co-exist and feed each other, I think? Getting scatty. Zero concept of risk/reward process, motivational issues, sleeps beautifully, can't kick into gear on waking, can sleep whenever regardless of sleep had.

Drugs so far haven't helped - SSRI = more dissociated just happier about it, suspect serotonin levels are fine. Antipsychotics (atypical x2) = same symptoms but worse and angrier. Wasn't even worth bothering to be polite or 'fake' in his dissociated state, the existence of another reality just irritated the hell out of him.

For those already comprehending - any ideas how the interplay might suggest moving forward? Currently on Epilim/sodium valproate (they thought he must have had some kind of bipolar, long story, haven't withdrawn this one yet).

It's almost 4am and I am mostly posting to subscribe - I'll be back tomorrow when I can comprehend a little better though.

#19 SlimNm

  • Guest
  • 45 posts
  • 31
  • Location:USA
  • NO

Posted 26 August 2013 - 06:13 PM

this is the system I'm suspecting is working against the husband at the moment. He's officially diagnosed with chronic and complex dissociative PTSD. He's stuck numb and dissociated, so the PTSD bit has been missed for oh, ever? Anyway - add in a history of drug abuse. Clean now for quite some years, but essentially went for drugs that I suspect have helped him detach - cannabis, heroin, night-time cold & flu (dextromethorphan), benzo's, alcohol but not enough to be drunk, just a low level but in addictive ways. Looking into the research about using naltrexone treatment for this particular situation actually. Drug-free for the majority of 14 years, alcohol free for 2 years.

Looking into a dopamine-deficiency as well but the two can co-exist and feed each other, I think? Getting scatty. Zero concept of risk/reward process, motivational issues, sleeps beautifully, can't kick into gear on waking, can sleep whenever regardless of sleep had.

Drugs so far haven't helped - SSRI = more dissociated just happier about it, suspect serotonin levels are fine. Antipsychotics (atypical x2) = same symptoms but worse and angrier. Wasn't even worth bothering to be polite or 'fake' in his dissociated state, the existence of another reality just irritated the hell out of him.

For those already comprehending - any ideas how the interplay might suggest moving forward? Currently on Epilim/sodium valproate (they thought he must have had some kind of bipolar, long story, haven't withdrawn this one yet).

It's almost 4am and I am mostly posting to subscribe - I'll be back tomorrow when I can comprehend a little better though.


I don't have much to offer besides suggesting that the both of you stay far away from SSRIs/SNRIs in the future. These are poisons that should NEVER be used on people.

Retreating to my underground bunker...
  • like x 1
  • Agree x 1

#20 wanderviolet

  • Guest
  • 18 posts
  • 15
  • Location:Australia

Posted 27 August 2013 - 07:48 AM

That part, I have worked out!
  • like x 1

#21 Galaxyshock

  • Guest
  • 1,211 posts
  • 165
  • Location:Finland

Posted 27 August 2013 - 10:50 AM

Menthol is a kappa-agonist: http://www.ncbi.nlm....pubmed/11897159

Peppermint oil is a strong source for it, definitely something I can feel when taken on empty stomach.
May even be enough for therapeutic effects I'd say, in continous use.

Edited by Galaxyshock, 27 August 2013 - 11:26 AM.


#22 addx

  • Topic Starter
  • Guest
  • 711 posts
  • 184
  • Location:croatia
  • NO

Posted 27 August 2013 - 12:50 PM

this is the system I'm suspecting is working against the husband at the moment. He's officially diagnosed with chronic and complex dissociative PTSD. He's stuck numb and dissociated, so the PTSD bit has been missed for oh, ever? Anyway - add in a history of drug abuse. Clean now for quite some years, but essentially went for drugs that I suspect have helped him detach - cannabis, heroin, night-time cold & flu (dextromethorphan), benzo's, alcohol but not enough to be drunk, just a low level but in addictive ways. Looking into the research about using naltrexone treatment for this particular situation actually. Drug-free for the majority of 14 years, alcohol free for 2 years.


Yep, try the low dose naltrexone therapy.

#23 celebes

  • Guest
  • 226 posts
  • 71
  • Location:TATL
  • NO

Posted 31 August 2013 - 07:36 AM

this is the system I'm suspecting is working against the husband at the moment. He's officially diagnosed with chronic and complex dissociative PTSD. He's stuck numb and dissociated. Looking into the research about using naltrexone treatment for this particular situation actually.


Yep, try the low dose naltrexone therapy.



Your husband and I were in the same boat, minus what he used to cope. I can second what addx is saying about naltrexone and everything else. You will get even better results if you combine it with buprenorphine. Taking between 1/3 and 1/10 of naltrexone's dose in bupe gives you bupe's kappa antagonism effectively without any mu-activation (at one stroke avoiding the dependence issues that come with that). A patentable version of this combo is in phase II trials right now and giving fantastic results.

In fact, the most major respite I had before this combination was from Salvia, which of course downregulates kappa. It really is a master switch for all our centres of feeling (positive and negative) and motivation and reward. The pharmacology is so simple at heart that it's shocking it isn't mainstream already. It is without a doubt the future.

Apart from that my advice is to get him on 500mg tylenol and 10-20mg buspirone 2 or 3 times daily. Give those a few months. There are supplements that helped too, if you want to do everything you can. Today I can say that I'm virtually cured, after spending the best part of a decade as a zombie.
  • like x 1

#24 addx

  • Topic Starter
  • Guest
  • 711 posts
  • 184
  • Location:croatia
  • NO

Posted 31 August 2013 - 02:32 PM

Interestingly, the guy who caused Ibogaine to be classed as a highest schedule drug with no value for research is the same guy who invented buprenorphine.
  • Enjoying the show x 1

#25 wanderviolet

  • Guest
  • 18 posts
  • 15
  • Location:Australia

Posted 01 September 2013 - 10:17 AM

Thanks for your advice - definitely food for thought there!

#26 penisbreath

  • Validating/Suspended
  • 530 posts
  • 29
  • Location:in the mousetrap

Posted 01 September 2013 - 10:32 AM

this is the system I'm suspecting is working against the husband at the moment. He's officially diagnosed with chronic and complex dissociative PTSD. He's stuck numb and dissociated. Looking into the research about using naltrexone treatment for this particular situation actually.


Yep, try the low dose naltrexone therapy.



Your husband and I were in the same boat, minus what he used to cope. I can second what addx is saying about naltrexone and everything else. You will get even better results if you combine it with buprenorphine. Taking between 1/3 and 1/10 of naltrexone's dose in bupe gives you bupe's kappa antagonism effectively without any mu-activation (at one stroke avoiding the dependence issues that come with that). A patentable version of this combo is in phase II trials right now and giving fantastic results.

In fact, the most major respite I had before this combination was from Salvia, which of course downregulates kappa. It really is a master switch for all our centres of feeling (positive and negative) and motivation and reward. The pharmacology is so simple at heart that it's shocking it isn't mainstream already. It is without a doubt the future.

Apart from that my advice is to get him on 500mg tylenol and 10-20mg buspirone 2 or 3 times daily. Give those a few months. There are supplements that helped too, if you want to do everything you can. Today I can say that I'm virtually cured, after spending the best part of a decade as a zombie.


This is interesting, since some of my symptoms overlap with what's being described here. I'm also in Australia and buprenorphine will probably be impossible to obtain with an opiate addiction, but did LDN by itself alleviate any of your symptoms?

#27 celebes

  • Guest
  • 226 posts
  • 71
  • Location:TATL
  • NO

Posted 01 September 2013 - 11:01 PM

This is interesting, since some of my symptoms overlap with what's being described here. I'm also in Australia and buprenorphine will probably be impossible to obtain with an opiate addiction, but did LDN by itself alleviate any of your symptoms?


Yeah, it gradually opened up my senses and thinking. Adding buprenorphine supercharged that. Interestingly, when I've tried bupe on its own I don't get a similar effect. Not even in the background. It might have some preference for binding mu-receptors over kappa where they're both available.

#28 wanderviolet

  • Guest
  • 18 posts
  • 15
  • Location:Australia

Posted 02 September 2013 - 03:42 AM

Definitely a question I have too about obtaining! We do have the opiate addiction, but its in history and not at all current. Finding someone who is thinking outside the square would be good.

#29 penisbreath

  • Validating/Suspended
  • 530 posts
  • 29
  • Location:in the mousetrap

Posted 02 September 2013 - 04:11 AM

sorry, I meant bup would be difficult to obtain withOUT an opiate addiction ..

alldaychemist stocks naltrexone and it seems easy enough to dissolve it in liquid and create LDN. i'll probably give it a shot if things don't pan out with Riluzole (which it doesn't look like they will at this stage)

there seems to be a lot on LDN helping depression/fatigue, but I can't find much on its efficacy in pure anxiety?

sponsored ad

  • Advert
Advertisements help to support the work of this non-profit organisation. To go ad-free join as a Member.

#30 celebes

  • Guest
  • 226 posts
  • 71
  • Location:TATL
  • NO

Posted 02 September 2013 - 06:15 AM

You can get a compounding pharmacy to work it up for you: http://www.ldnaware....s-australia.asp. Finding a sympathetic doctor might be easier if you went to them for both the naltrexone and buprenorphine. Failing that you could always look at extra-legal options.

I had crippling anxiety forever too. Prazosin and buspirone really helped me with that, to the point that I can't really say what effect LDN has on it.





Also tagged with one or more of these keywords: anxiety/depression/anhed, opioid, kappa, dynorphin, naltrexone, endorphins, ldn, anhedonia

0 user(s) are reading this topic

0 members, 0 guests, 0 anonymous users