709 replies to this topic

[addx]

I thought about this one in bed last night, the one about serotonin

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

I'll post the full abstract:

Treatment with a kappa-opioid receptor agonist for 5 days decreases locomotor activity and reduces activity in response to a cocaine challenge 3 days later. In addition, chronic cocaine increases kappa-opioid receptor density, striatal dynorphin, and dynorphin gene expression in the striatum. The upregulation of kappa-opioid receptors after cocaine treatment occurs predominantly in brain regions that are highly innervated by serotonin. To determine if serotonin plays a role in the effects of kappa-opioid receptor agonists on cocaine-stimulated activity, parachloroamphetamine (PCA), which depleted serotonin by 53%-66%, or saline, was given prior to a five-day treatment with U-69593 or vehicle. Three days later each rat received a single injection of cocaine and locomotor activity was measured. Treatment with PCA had no effect on the ability of U-69593 alone to decrease locomotor activity. Thus, the behavioral effects of U-69593 alone were not dependent upon serotonin. In rats pretreated with saline, U-69593 treatment significantly blocked the locomotor-activating effects of cocaine. Following PCA pretreatment, however, there were no significant differences in locomotor activity in rats challenged with an injection of cocaine after treatment with U-69593 or vehicle. Thus, serotonin depletion prevented the long-lasting blockade of the locomotor-activating effects of cocaine subsequent to repeated administration of U-69593 but did not alter the effects of cocaine in rats that were treated with vehicle. Thus, the effects of PCA on U-69593 are not due to non-specific alterations in cocaine-induced locomotor activity. These findings suggest that serotonin plays an important role in mediating the effects of kappa-opioid receptor agonists on the behavioral response to cocaine.


If I'm reading this correctly, KORs require serotonin to perform some of their actions - the one that counteract cocaine(reward). As a number of studies prove KORs upregulate due to excessive dopamine in mesolimbinc structures. They do this to try and reduce the escessive reward dopamine. But they need serotonin to perform this function. If there isn't enough serotonin available they will probably upregulate further as there is still excessive dopamine in mesolimbic structures.

This brings us to SSRIs. SSRIs provide the extra serotonin. In the state of depression the KOR network is already upregulated but working poorly due to low serotonin. Providing serotonin would cause it to work properly and it being upregulated would cause the initial SSRI anxiety and suicidal ideation. After a few weeks of this the KOR network probably manages to downregulate or something else gives. I fear this is how SSRIs work.

[SlimNm]

I'm pretty sure that SSRIs cause some sort of massive cell death in the prefrontal cortex on initiation in some patients. At least, that's what I felt happened to me. I felt literally poisoned, with derealization, anxiety, panic, e.g. for 3-4 days and the symptoms began less than 30 seconds after swallowing the pill on an empty stomach.

Then, I was left with what I wanted: less anxiety, generally blunted emotions.

It took me 9 months to realize that my capacity for romantic love had been obliterated. Then I quit taking it and went through w/d hell for over a year and now it's close to over, but I still suffer from anticipatory anhedonia most of each day.

I wish SSRIs were taken off the market.

[celebes]

I'd definitely be interested. Can you say what kind of price we would be talking about?

The wiki page says that a clinical trial was halted due to adverse events. Which I'm presuming was allodynia, from dynorphin acting directly on NMDA receptors. I wonder if magnesium/zinc would be effective enough antagonists to counteract that or if we would need to add something more potent.

Edited by celebes, 30 August 2013 - 06:00 AM.

[addx]

Allegedly they halted the trials because a heart arythmia showed up in some cases

[Cosma]

You can always use Memantine as an NMDA antagonist which is easily obtainable. i have a stock right here with me, but what i have found is, that when taking it for several days in a row, i seem to become unable to distract myself from scary\annoying thought .
for example, i wached a video online, of a woman who got beheaded when an elevator went up as she was stepping out of it.
for days i couldn't stop thinking about it. i became obsessed to never go on an elevator again in my life, and made plans, just in case i will have to.
i knew it was because of the memantine as this sort of thing happens every time i take it for several days in a row.
it seems strange at first for memantine to do that as it mimics dynorphin's nmda antagonism action, and dynorphin is very important to "forget" scary memories , but dynorphin has another action. it inhibits dopamine release in the nucleus accumbens, and if considering salvia as a dynorphin imitator, it makes you (me actually) feel like you have no sense of self, which makes every "ego" and "self" related problem seem insignificant, so you lose the fear of the effect, that negative emotions like rejection, abandonment, shame and even doom, usualy have on you.

Edited by Cosma, 30 August 2013 - 12:44 PM.

[addx]

NMDA networks purpose IMO is to facilitate active short and long term emotion intensity regulation. In other words, it's job is to adapt and normalize emotional signal currents. In short term it adapts via sensitization or desensitization. If sensitized it increases the emotion, if desensitized it decreases the emotion(dissociates). In the long term the dynamic sensitization is slowly "emptied"/"replaced" and returned to baseline by plasticity - brain growth. In these two ways the NMDA network actually represent a memory circuit responsible for remembering how strong emotional currents are apropriate for a given event and also for using this to modulate the currents. The conscious receives emotions after they have been amplified or numbed by NMDA so antagonizing NDMA provides dissociation.
NDMA

The NDMA network is a tool network, a sort of an equilazer/compressor/normalizer service for higher networks

A higher network - the opioids on the other hand are charge for approach/avoid learning/prediction. It assigns approach/avoid values to memories(meaning they also facilitate the essence of fear extinction) and also uses these memories to actively guide the organism. KORs are in charge of avoid part. That means fear. The fear as we can see from experience causes dissociation. KORs activation(via dynorphin) causes dissociation via inhibiting NMDA - the tool network. This causes analgesia of the self of the pain or wherever the activation happened. Salvia causes it system wide obviously

I take memantine intermittently as well and have also noticed that I quite feel half the pill working meaning 5mg. I only take half a pill every few days.

While I'm at it:

Dopamine is the drive/percpetion network. It facilitates the intensity of drive/perception for varios subsystems and organs. It is evolutionary the first I think and it is quite low level(thus all the sideeffects)

Serotonin is the state/satiety network. It facilitates the state/satiety for various subsystems and organs.

Serotonin and dopamine work together. Low serotonin = low satiety -> high dopamine = high drive. High serotonin = high satiety -> low dopamine = low drive. But you must understand, this is very low level. High serotonin in sexual centers = high sexual satiety -> low dopamine in arousal centers = low arousal.

Noradrenaline is fight/flight network.

NMDA networks offers blunt low level emotional signal adaptation. Strong signals cause sensitization, chronic low desensitization etc. Not sure if they do much more, perhaps together with AMPA, not sure.


Opioids hooked into the lower networks and formed a system that governs the lower networks. It provided the approach/avoid learning/prediction and uses the lower network for input and output. it is strategically placed where pain/pleasure is sensed, piggy backed onto the existing lower networks and connected at the output(KOR at mesolimbic dopamine) to control. It is a higher, orchestrated level of control over the lower networks. Since approach/avoid is a not a function of a subsystem/organ but a function of the entire body - this is a higher level system/network.

There's also acetylcholine which is IMO a lower network providing low level muscle control and sensing. Dopamine controles the drive/fluidity/vigor of muscle movement as it controls the vigor of your penis. I believe acetylcholine facilitates storing and retrieveing raw sense memory(images, sounds).

Cannabidoids seem to be in charge of gestation states and trance like states, time perception etc.

there's more but not that important for now... havent researched it that much

Edited by addx, 30 August 2013 - 04:18 PM.

[socialpiranha]

Allegedly they halted the trials because a heart arythmia showed up in some cases

where did you hear that addx? reliable source?

[celebes]

This was presented by the guy who owns the patent on JDTic at Harvard earlier this year:




Standard preclinical studies did not accurately predict an apparent clinical toxicity of JDTic



Walters BB, Buda JJ, Carroll FI, Gay EA, Gilchrist KH, Gilmour BP, Grego S,
HimelHD,IV, NavarroHA, Kosten TR, Leshin SJ, Pitruzzello AM, RehderKS,
SwearingenD, Wang-Smith L

RTI International; RTI Health Solutions; Center for Organic and Medicinal
Chemistry, RTI International; Pharmacology and Toxicology, RTI International;
Center for Materials and Electronic Technologies, RTI International; Discovery
Sciences, RTI International, Research Triangle Park NC; Dan Duncan Institute
for Clinical and Translational Research, Baylor College of Medicine, Houston TX;
Celerion Inc.,Tempe AZ; INDAPharma LLC, Chapel Hill NC



Healthy, adult, male subjects were to be enrolled as 3 cohorts in a
double-blind, placebocontrolled study to evaluate the safety, tolerability, and
pharmacokinetics (PK) of single, escalating, oral doses of JDTic (1, 3, or 10 mg).
Pre- and post-dose safety assessments included: orthostatic vital signs; 6 lead
continuous telemetry monitoring (approximately 15 hours predose to 24 hours
postdose); 12 lead ECGs; clinical chemistry, hematology, and urinalysis;
psychomotor functioning (using the Wayne Saccadic Fixator [WSF]); and
adverse events. Safety results were unremarkable with the notable exception
that two subjects each experienced a single event of multiple beats of non-
sustained ventricular tachycardia. Both subjects had received 1 mg JDTic, and
their events were temporally similar with respect to dose time (and to a
preclinical NSVT event in a monkey). Both subjects were asymptomatic and
without sequelae. These events triggered a study-stopping rule. No apparent
differences were observed between the 6 placebo and 6 JDTic subjects with
respect to clinical chemistry, hematology, urinalysis, vital signs, WSF, or 12 lead
ECG parameters. Plasma JDTic levels were below the lower level of quantitation
(0.05 ng/mL) in all subjects.

The lowest concentration at which QTc prolongation occurred in
monkeys was 430 ng/mL (920nM). Subsequent, preliminary in vitro
experiments were performed on cultures of beating human cardiomyocytes
derived from induced pluripotent stem cells. In studies using microelectrode
arrays, JDTic reduced beat rate and conduction velocity at 300 nM, the lowest
concentration studied. The usual single site of beat initiation clearly was
disrupted after two hours’ exposure to 1 μM JDTic (the only concentration
evaluated in that paradigm); by 4 hours beat rate variability was significantly
increased. Using impedance measurements, amplitude was reduced at 10
ng/mL, and the concentration at which >20% of the beats were arrhythmic was
estimated to be between 1 and 10 ng/mL.

[celebes]

On one hand I can see why this might rule out an FDA approval for JDTic. On the other, with its long duration of action and the transience and inconsequence of the tachycardia it might not be an issue if we are only taking it, say, fortnightly. The first paragraph reads like they halted out of an abundance of caution. The second seems more threatening at first glance. Can anyone here translate the ratio between the offending concentrations and the clinically effective dose?

I can vouch for the effect kappa antagonism has on my functioning and quality of life. It (almost laughably literally) feels like having a physical blockage holding back feeling and sensation cleared. Drano for the soul. So for the moment, it looks like it's still a worthwhile route for someone like me to go down. For someone whose kappa dysfunction is more ambiguous or not at all, perhaps not? Or is the risk small enough for that to not be a consideration?

[celebes]

Only two of them had this reaction in vivo... I'm thinking maybe magnesium is all we need to counteract this after all.


Wiki:

Problems with blood levels of potassium, magnesium and calcium may also contribute. High dose magnesium is often used as an antidote in cardiac arrest protocols.

As hypomagnesia is a common cause of VT, stat dose magnesium sulphate can be given for torsades or if hypomagnesemia is found/suspected.

[addx]

Allegedly they halted the trials because a heart arythmia showed up in some cases

where did you hear that addx? reliable source?

Pearce

On one hand I can see why this might rule out an FDA approval for JDTic. On the other, with its long duration of action and the transience and inconsequence of the tachycardia it might not be an issue if we are only taking it, say, fortnightly. The first paragraph reads like they halted out of an abundance of caution. The second seems more threatening at first glance. Can anyone here translate the ratio between the offending concentrations and the clinically effective dose?

I can vouch for the effect kappa antagonism has on my functioning and quality of life. It (almost laughably literally) feels like having a physical blockage holding back feeling and sensation cleared. Drano for the soul. So for the moment, it looks like it's still a worthwhile route for someone like me to go down. For someone whose kappa dysfunction is more ambiguous or not at all, perhaps not? Or is the risk small enough for that to not be a consideration?

I'm sorry if this might be too personal but would you care to explain in more detail what troubles you in life and exactly what changes with kappa antagonism?

I can't understand the ratios but I don't really care about the heart arrhytmia. It might not apply to me and even if it does I can always stop, it wont kill me to try it, it didn't kill anyone and it is obviously reversible. If I get the effects I wanted I know I'm on the right track, only then will I pay attention to making the treatment long term safe.

Edited by addx, 31 August 2013 - 12:42 PM.

[Cosma]

I am suffering from severe DP\DR and currently try to counteract at least the nmda antagonism effect of dynorphins by taking sarcosine and d-serine.

What exactly are the effects you want to get from JDtic addx?

[addx]

In a nutshell, I want to remove this impervious layer of anxiety that's blocking any ability to enjoy life. I think I'm OCPDish or something.


In long, I have already explained it to you in a private conversation but then again, why not post it here:

relatively recently i have had a very unusual experience that, for the first time in my life, enabled me to see through an almost imperciavable anxiety blockade

story but i will never forget this. i wrote it on another forum so just posting now. this is what i'm hoping to get from kappa antagonists

relatively recently i have had a very unusual experience that, for the first time in my life, enabled me to see through an almost imperciavable anxiety blockade that i've obviously had all my life. let me explain.

first of, let me say that i have had some kind of inner restlessness/drive/tension in me all my life. it has led to me achieve great things, make video games at 13 years old, do amazing stuff that none of my peers could even fanthom, even now. but i've always had some kind of a distance to people, even my parents. some kind of undescribable blockade that disables me from becoming too intimate/relaxed with anyone. i have little friends and even the best friend(and now best man) i have some kind of a distance/awkwardness always in between us. and i'm the cause. it's kind of imperciavable as my friends can't really put their finger on it and they remain my friends but i have a feeling they also feel that there's a distance. there's especially physical awkwardness in like greeting and hugging and maybe even eye contact.
i've always needed a topic to carry a conversation. i can be funny and witty but i need someone else in the crowd to lead in funnines. i can only follow and add on and im good at that but i need someone elses energy etc.
im always thinking i can never stop, im always ahead of my self, im the fastest typer in my company, im very goal oriented and dont notice life, only goals and dont remember anything because im not immersed in life just my goals and this is caused by this drive that i have.
the only thing that has in a way removed at least a part of this was alcohole and thc. thc slows me down and enables me to enjoy simple things like video games or painting the walls in my appartment and such.

anyway, i'll cut this short for now, lemme tell you about the eye opening accidental experience. there i was, working 300 hours a month, deadline aproaching, working on a sunday. i had this urinary tract infection for 3-4 days, pissing blood cloths but had no time for doctors so i was at work like that. i thought if i grow a fever ill go to the ER as i dont want my kindeys shot, if not it'll prolly go away by itself. so on the 4th day i'm working, developing some application and i start getting these impatient urges. very hard to describe. it was like an impatience to move from the place where i'm at, physical impatience. it started with legs, similar to when you need to pee except without the bladder pressure but it spread and pretty soon my entire body was impatiently trying to "leave". i was still programming at the time. there was no weirdness in my thought or emotions other than that, i could clearly think. i also felt like these urges originated from the prostate somehow. there was a slight "prostaty wavy energy" feeling that i sometimes get when coming down from cocaine that seems to kinda emanate from the prostate and there is kinda of a sexual energy in it as well. hard to describe. anyway, after a while the urge/impatience forced me to stand up so i was now standing and programming typing. really had to finish something other 10 people were waiting to use and develop further on top of it. so i now looked like something invisible was dragging me away from the computer. i felt like i had to litteraly hold on to the computer not to be dragged away. eventually i had to climb the chair and was standing on it bent over so i can still type on the keyboard. coworkers were looking at me needless to say... i finished what i needed and decided to go home and have my wife take me to the ER(it was sunday). i went to my car and drove home. while going to my car and driving home the urges kept quiet as the moving - even driving in the car kept them quiet - i was moving. it wasnt necessary to move my body parts physical to keep the urge away - it was necessary simple to go - in a car, on foot, whatever. as i got home i had to pace the apartment while explaining the situation to my wife. i took a temperature reading and it was 38.5. i didnt feel the fever at all(i might have been hypomanic at the time). i went to take a shower before we go. i kept pacing inside the shower impatiently. as i got out i put on clothes and took a whif from a joint that was left over from last night. we went to the car and as i sat in the car the most wonderful thing happened. the impatient urge suddenly completely dissipated and was replaced by something i never felt in my life before but immediately recognized - calmness - content. the life long "pressure" and "drive" were gone. it was like nirvana. i was suddenly able to live in the moment and notice(mentally) everything around. a smile came over my face as i glazed around and for the first time in my life got an emotional feedback from the images that i'm seeing with my eyes. it was like someone removed that drive for me and my brain was suddenly able to live and experience the now instead of daydreaming about something tomorrow or whatever it usually does. it wasnt sedating.

as i got to the ER i talked to the reception lady and i was so charming. witty words came out of me with no anxious preprocessing and censorship. as i was talking to the lady i looked at her free from any anxiety. i was able to look at her and get some kind of feedback with the image my eyes were seeing, something i never feld before. it was like an emotional feedback - mentalization and it enabled me to talk with the person sincerely, not like she was just an object that i had to perform a specific conversation and move on. there was no delay in the conversation. the feedback was used by my brain instantly in forming things to say and they were said without anxious censorship/overanalyzing/freezing. it was just such a fluid and outright normal relaxed conversation. anyway i got sent to the urologist, a woman. now i would normally be pretty anxious about what was going to happen but i wasnt. i thought about it but hardly anxious. there were two nurses there and i had to drop my pants and all, she stick her finger in my ass etc.. normally i wouldnt be comfortable. but i was, i was charming them as the procedure went on and it was all prefectly normal and ok. it not like i was drugged, i felt a slight discomfort about it but that it.

anyway, the magic dissipated within an hour or so i was back to normal. i was never able to repeat this. i have to point out i am an experienced drug user. i was not stoned, the feeling was so different than stoned or anything i've ever felt. in my life i drank alcohol, smoked weed, snorted cocaine, amphetamines and ketamine. none of those come close. it was serene, blissful, joyful, in the moment down to earth with no sedating or drunkedness or euphoria. no problems in functioning whatsoever, just a film of anxiety that's been there all my life removed. this film of anxiety disables me from getting emotional feedback from the image that i see. it like a constant loop of anxiety blocking it - blocking mentalization. it's like i can force myself to look at someone, even though i have a tendency to look away. i look at someone and dont look away but it's like my focus looks away even though my eyes are looking straight at someone. my focus avoids people compulsively and constantly my entire life. it's like the brain needs to do some preconscious processing of an image to identify objects and also bring up an emotional readout of live objects. this emotional readout and even object identifying preprocessing seems to get sqeeuezed out by, im guessing some kind of tonic anxiety.
the stability and imperceivability of this "anxiety" blockade film makes me think this can hardly be caused by some childhood trauma but is simply inborn. i never had any outbursts, emotional, weirdness. i can do everything everyone else can and often more. everything except handle people. i cant give orders, i cant depend on people, i'm alone even when im not.

[Cosma]

Yes i remember that very interesting story, just wondered what is you're real diagnose...
Have you ever thought about trying nmda agonist? it's only my second day on it and i think it makes me a little bit more "connected" and a little less obsessive to rationalize every emotion (if you know what that endless conversation is like).

[socialpiranha]

addx i know that feeling... it's mentioned in all religions....i'm not religious but i discovered this for the first time when i was in bed one night...I was just noticing how i didnt have to try to breathe and suddenly my sensory experience totally changed, it was like something powered down...i actually experienced it powering down like the sound of a huge machine being turned off....then there was just silence....heartbeat....ambient noise...kind of like having ear plugs in but so much more intense and not inhibiting at all...something was missing that had always been there and i was so relieved!!! i eventually got up and went out to the living room, my brother was sitting there watching a hockey game and for the first time i could actually sit there with him, just watching the game(i usually can't watch sports) anyway i have been chasing that feeling ever since with varying results....mdma and other amphetamines (even cocaine a couple times) are the closest ive gotten with drugs, really long meditation sessions have worked several times...but by far the whole lying in bed and noticing that breathing is just happening on its own is the most effective method so far.

I am convinced that a part of the brain actually does shut down during these experiences and i don't think it has anything to do with the sleep mechanism...i believe it is a survival mechanism which is triggered by the perception of threat....unfortunately in some people the body sees everything as a threat or is for some reason unable to shut this mechanism off...i have a feeling it is more of a system involving many pars of he brain rather than jus one area but it seems to be a large amount of elecrical signalling which stops very suddenly allowing other systems to work much better with less effort.

I do believe the kappa opioid receptor plays a huge role in this but i'm sure there are plenty of other chemicals and sensors etc involved. When i took ibogaine it was like that system was directly targetted, i even heard the sound/feeling again except this time it was ramping up like a big machine was being turned on...as it did my body whrithed in pain/discomfort and that feeling of unrest grew stronger. I actually grappled with the idea that i might be a machine designed by a highly advanced race for months after because of how mechanical it felt along with the fact that i vividly(more vivid than real life) with eyes open, saw an alien manipulating controls and completely governing my experience. I am a very skeptical person which is why i am still sane lol...i do think though that the kappa system is sort of the volume control for this spectrum of.....intensity.....it would be optimal to be able to control the volume because it can be very beneficial creatively etc of course it is much more complex than just turning it on or off but the kappa system is definitely the heart of the mental illness problem.

On one hand I can see why this might rule out an FDA approval for JDTic. On the other, with its long duration of action and the transience and inconsequence of the tachycardia it might not be an issue if we are only taking it, say, fortnightly. The first paragraph reads like they halted out of an abundance of caution. The second seems more threatening at first glance. Can anyone here translate the ratio between the offending concentrations and the clinically effective dose?

I can vouch for the effect kappa antagonism has on my functioning and quality of life. It (almost laughably literally) feels like having a physical blockage holding back feeling and sensation cleared. Drano for the soul. So for the moment, it looks like it's still a worthwhile route for someone like me to go down. For someone whose kappa dysfunction is more ambiguous or not at all, perhaps not? Or is the risk small enough for that to not be a consideration?

which kappa antagonist did you try?

[LetMusicRule]

Id be interested in participating and trying it out. PM me for more details on price, etc..

[socialpiranha]

Id be interested in participating and trying it out. PM me for more details on price, etc..

still working on a source....awesome username...i'll pm you when we find a reliable source

[celebes]

which kappa antagonist did you try?

Buprenorphine with naltrexone to block the mu-agonism.

[socialpiranha]

yeah i was on suboxone myself, did you take additional naltrexone or just whats in the suboxone? i would like to try samidorphan plus buprenorphine (alks 5461) seems like it would isolate the kappa antagonism more effectively.... i know the low amount of naltrexone that is in suboxone is not enough to effect the mu agonism much which is why it still produces addiction and withdrawal...it seems this alks 5461 does not and is proving to be a very potent antidepressant.

[celebes]

Suboxone has naloxone not naltrexone. Taking between 10 and 3 times as much naltrexone completely blocks the mu agonism. So essentially ALKS 5461. Can't wait for that one myself.

Interestingly, bupe on its own doesn't give me the beneficial effect at all. Not even in the background. I'm thinking it has a higher affinity for the mu receptors, all other things being equal.

[socialpiranha]

thats right i get those two mixed up sorry, did/do you notice any withdrawal or addiction potential with this combo? what dosage of naltrexone vs bupe? i was thinking about trying something similar myself i just dont want to get addicted again i just got off subs less than a year ago. There was something different about buprenorphine vs any other mu agonist which was antidepressive/mood stabilizing/anxiolytic like nothing else and i've tried everything under the sun ...gotta be the effects on the kappa system. Very interesting that you didnt notice the effects until the mu receptors were antagonized makes me wonder if the mu agonism actually supresses the effects of kappa antagonism in some way. I always had the feeling while i was on it that the real effect that was making me feel better was being overshadowed by the mu agonism and the drawbacks that come with it.

[celebes]

I figured out what's going on: Buprenorphine saturates mu receptors at 2-4mg. If you were taking it for addiction you would have been taking 8mg+ so you were getting at least 4mg of BPN just to your kappa receptors. In my case, it's the naltrexone occupying the MORs, directing the BPN towards the KORs. Any mu-agonism you allow probably does sneak some kappa agonism into play no matter what else is going on at the KOR.

Here's the study for mu-antagonism doses:

http://www.ncbi.nlm....pubmed/23240906

So 10:1 is fully mu-antagonistic. 3:1 is mu-neutral. I'm currently at 9:1 and I've got no intention of ever going below 4:1.

As for tolerance, I've been on the standard 4.5mg of naltrexone for a while now. After taking 250-500ug BPN alongside it for about 2 weeks I took one on its own... and proceeded to get violently nauseous and groggy. I managed to keep down the NTX I took and within 10 min of it being absorbed, I was back to the same positive feeling I had been getting up to then.

I was worried that I might have been latently developing a tolerance before then, but that experience really set my mind at ease. I don't believe there's any chance of dependence provided you only dose BPN within those ratios and once the NTX has kicked in.

Edited by celebes, 02 September 2013 - 03:23 PM.

[socialpiranha]

so what were you taking naltrexone for to begin with? what was the difference between naltrexone alone and naltrexone plus buprenorphine? i'm very curious about your experience, never spoken to anyone who has tried this combination.

[addx]

http://www.jdtic.com/

this is pearce I think

[socialpiranha]

yeah i thought it was too but on second glance its signed mdk...or is that an abbreviation im not familiar with?

[addx]

Not sure but he owns a hosting company and probably helpers with the "cause". All those minisites that look like opioids.com have sprouted from hedweb.com and are owned by the same company

http://www.who.is/we...ion/opioids.com

http://www.who.is/we...tion/hedweb.com

So IMO, it's either him or someone in his "possee"

[formergenius]

I'm interested in this, though the adverse events are a tad concerning.
What about Nor-binaltorphimine, 5'-Guanidinonaltrindole, or TENA?

[socialpiranha]

hey, these and others were developed before jdtic, jdtic is the first orally active kappa antagonist. There are one or two others one was developed by lily and one by astra zeneca i believe these three are the only ones which showed enough potential to be tested in humans...unfortunately they are even less available than jdtic in terms of information and sourcing the actual compound. jdtic is definitely not a first line option, i think a lot of ppl landing here are sort of at the end of the line in their search. in my own research all roads lead to the kappa receptor being the next best target for mental health.

[formergenius]

Haha, indeed I'm more or less at the end of the line. I'm going to do rTMS soon.. enough said.
Thanks for clearing that up though. What are your thoughts on JDtic's potential dangers?
I've just created a thread (inquiring) about alternative ways to antagonize KOR's, so perhaps you might want to follow it

Edited by formergenius, 22 September 2013 - 10:16 PM.

[celebes]

Haha, indeed I'm more or less at the end of the line. I'm going to do rTMS soon.. enough said.
Thanks for clearing that up though. What are your thoughts on JDtic's potential dangers?
I've just created a thread (inquiring) about alternative ways to antagonize KOR's, so perhaps you might want to follow it

JDtic's main adverse effect is a mild reversible arrhythmia which, in my opinion, was probably dependent on magnesium deficiency.

We concluded it was not a significant risk, without even considering how disabling DP is itself.

Edited by celebes, 23 September 2013 - 12:30 AM.