6219 replies to this topic

[pheanix997]

The vision enhancement I notice is no joke, it's very very real and I dread that I'll have to continue to take this to maintain that. Ugh. This isn't supposed to be taken for long.

[medievil]

I take clonazepam which has been shown to inhibit ltp, depress forskolin increased camp in rodents etc.

 

It makes me wonder wheter it could prevent the benefits i may get from this compound, any experiences here of people that combine it with benzodiazepines.

 

I never noticed any color enhancement.

[Zhivili]

Guys, may i ask what is your dosage daily?

From what I've gathered, most people tend not to exceed 50mg per dose, as preliminary research shows no increase of effects at 80mg.

 

NSI-189 may cause anxiety and other (minor) side effects when first starting out, so it is recommended to start at 10-20mg once a day for the first few days to gauge your reaction. 40mg seems to be the typical dose.

 

I do see some people here dosing twice daily, though I'm not sure that's entirely necessary. Depends on how well you can tolerate it, I guess.

[pheanix997]

I was at 20 mg bid (morning and afternoon) sublingual. I get the most potent cognitive effects at this dose. However over time like others I noticed my anxiety increasing a bit, and some head pressure that wasn't there before, and I was sleeping longer hours because I felt more need for it.

So now I've lowered to 15mg bid. I'll see how this goes. Almost done my stash.

[jaiho]

I believe nsi 189 is working again, or starting to. This is exciting. I'm getting immersed in activities, my social intelligence and efficiency at activities is sky-rocketing. Hell yeahh

[MichaelTheAnhedonic]

Gz, and I'm still here sitting and trying to not lose my mind. FFS.

[medievil]

?

[jaiho]

Have you tried a month long trial of nsi, Michael?

[justabody]

I believe nsi 189 is working again, or starting to. This is exciting. I'm getting immersed in activities, my social intelligence and efficiency at activities is sky-rocketing. Hell yeahh

 

lol gfu man. i've been following your anhedonic log for quite some time. the ride never ends.

 

I'm hedging my bets on modafinil for anhedonia at this point. NSI put me in some weird funk when I took it.

Edited by justabody, 26 February 2016 - 05:05 AM.

[MichaelTheAnhedonic]

I have never tried NSI, I don't even have a source of it. 

[jaiho]

Strangelove here sells it. Yeah justabody, the fight never ends. Too much to ask to have normality I guess

[medievil]

 

I believe nsi 189 is working again, or starting to. This is exciting. I'm getting immersed in activities, my social intelligence and efficiency at activities is sky-rocketing. Hell yeahh

 

lol gfu man. i've been following your anhedonic log for quite some time. the ride never ends.

 

I'm hedging my bets on modafinil for anhedonia at this point. NSI put me in some weird funk when I took it.

 

You might be interested, ive been looking into treatments for anhedonia for a long time and on dr bob there are a few anecdotes of modafinil being effective after giving it enough time.

 

I wouldnt expect nsi to work for anhedonia, unless its a direct result of depression.

[jaiho]

im not depressed, my moods are still fine, the whole issue is emotions really. nsi-189 induces hyper emotionality in normal people. nsi-189 is excellent for anhedonia if it works for you

[medievil]

Your saying it would work for ppl suffering from just anhedonia and not depression? i dont see how, anhedonia is mostly dysregulation of the reward system and nsi induces braingrowth and recovery and brainareas associated with depression such as the hipocampus, i dont see how that can help anhedonia unless depression is the cause of the anhedonia

[MichaelTheAnhedonic]

Let's be honest... we really don't know exact mechanism of anhedonia, we know so little about the brain - even the docs... So it is possible. 

NSI is still in research, one of the mechanism is neurogenesis but it can have another mechanism. 

Edited by MichaelTheAnhedonic, 26 February 2016 - 07:15 AM.

[medievil]

Well we can have an idea but i cant deny that you could be right, we cant say anything for certain.

[justabody]

Your saying it would work for ppl suffering from just anhedonia and not depression? i dont see how, anhedonia is mostly dysregulation of the reward system and nsi induces braingrowth and recovery and brainareas associated with depression such as the hipocampus, i dont see how that can help anhedonia unless depression is the cause of the anhedonia

No one except neuralstem knows the exact mechanism of NSI. Analysis of human trials seems to disprove the hippocampus regrowth theory

Gz, and I'm still here sitting and trying to not lose my mind. FFS.

My heart goes out to you, man. Anhedonia's a massive bitch.

Edited by justabody, 26 February 2016 - 04:09 PM.

[medievil]

But it can be treated, lets not forget that, so we can stay optimistic, never give up hope as even anhedonia can usually easily be treated, with what again is individual.

[jaiho]

I'm not entirely convinced that Anhedonia is a unique diagnosis for emotional numbness and inability to feel pleasure. I think it's a deep depression that's isolated from mood disorder. Afterall, Anhedonia is the #1 symptom of depression, and depression suppresses all neurotransmitters, for us it just happens to be the reward centre, or anterior cingulate, which us why i found meditation actually helps Anhedonia a bit, since it increases activity there. Nsi 189 feels like meditation in a pill to me

[medievil]

Explain a deep depression isolated from mood disorder to me.

 

Anhedonia can come in many forms, but mainly its a seperate disorder unrelated to depression, anhedonia in depression is corrolated with differened brainareas

[jaiho]

People experience depression differently. Many depressives describe it as a deep sense of nothingness. Others experience it in the form of guilt, self hate, or extreme sensitivity and emotion. But for most it is a sense of dread and abscense of feeling, emotions, actually you don't feel dread, just nothing. The only way Anhedonia could not be caused by depression is via severe amphetamine abuse or substance abuse for the long term, (mdma, opiates, amphetamine) for Anhedonia to suddenly appear, it's likely a deep depression. Or severe long term anxiety that's evolved into disassociation to protect yourself.
I found that even though I can be in an excellent mood, the Anhedonia is still there, that feeling of detachment and nothingness, and I still think it's depression just by my experience talking with a renowned psychiatrist, he describes Anhedonia as depression without sadness

[pheanix997]

My favourite psychoanlytic writer thinks real depression is actually anhedonia; inability to feel, experience pleasure, express joy / sexuality, etc. Just numbness; a shutting down of emotive contact with the world.

The other kind is a more active depression; struggling with affects or conflicts or anger; working it out. This is actually a healthier state. If the conflicts aren't worked out then they become repressed, leading to numbness. I think therapy tries to get numb patients to start to feel their emotions to bring it to consciousness where it can be worked through. The idea is to bring the distress back to the patients awareness instead of "numbing" it, the same way therapy with an acting out aggressive person who externalizes all their conflicts before they feel them tries to get them to reinternalize their conflicts so they can feel it as coming from within instead of without so they can work it out.

So I think MDD is numbness, which NSI is proposed to help; whereas conscious sadness, anger, guilt, etc. is better either worked through in therapy or managed with anxiolytics, temporarily.

IMO all active, highly emotional depression turns into numbness eventually. You can't stay in a sympathetic state constantly; you burn out. And I don't think the active conflict is termed depression in the official anhedonic sense... I don't know what it might be referred to. Stress reaction? Separation stress from a breakup or loss of narcissistic supply? And if it's guilt they would call it guilt. I know today everyone calls crying and sadness "depression," I'm just adding that I read somewhere that depression is really anhedonia.

However, there are the subset of people who never experienceel the "anxious depressive" state to begin with because their entire psychic structure is based more on emotional control, repression, etc., like OCDP's, avoidants, schizoids, etc. Still, healing for these types is to again make their repressed conflicts conscious.

With that said, I'm a combination of the sad/ shame state and anhedonic state and I haven't found NSI to make me hyperemotional. And personality wise I'm a feeler type.

Edited by pheanix997, 26 February 2016 - 09:22 PM.

[pheanix997]

The point I wanted to make was NSI, if it works as an anti-anhedonic, is probably useful for everyone - it just depends on the timing. Obviosuly if you're in a highly anxious state it might be better to wait to take NSI, but unless the anxiety is dealt with in therapy eventually the high anxiety will turn into a numbness by psychological protection - the same way avoidants can appear like schizoids but the latter have an emotive deficit and the former have calloused over their emotions for protection.

Even borderline personalities, the quintessential "highly emotional labile" personality, by definition experience "emptiness and numbness".

[Water Buffalo]

 

Your saying it would work for ppl suffering from just anhedonia and not depression? i dont see how, anhedonia is mostly dysregulation of the reward system and nsi induces braingrowth and recovery and brainareas associated with depression such as the hipocampus, i dont see how that can help anhedonia unless depression is the cause of the anhedonia

No one except neuralstem knows the exact mechanism of NSI. Analysis of human trials seems to disprove the hippocampus regrowth theory

Gz, and I'm still here sitting and trying to not lose my mind. FFS.

My heart goes out to you, man. Anhedonia's a massive bitch.

 

Why would you say that? The 1b trial in MMD showed changes in qEEG particularly, near the hippocampus. Sure, they did not see significant changes in hippocampal volume over the course of the 28 day treatment period, however someone earlier in the thread mentioned the President saying they expect to see changes in the hippocampus in the Phase II trial with a 90 day treatment period.

Edited by Water Buffalo, 27 February 2016 - 01:11 AM.

[medievil]

 

 

The point I wanted to make was NSI, if it works as an anti-anhedonic, is probably useful for everyone

There is so much dysregulation in the brain of shizos, heck the body too, for example test levels, pretty much everything gets dysregulated in shizo as its a disorder that you can compare by letting a domino fall to another one, basicly starting from what someones trigger is with shizo and then those domino blocks reach glutamate, and once that is fucked it dysregulates everything.

 

That said anhedonia in shizo is a defiency of phasic dopamine hypoactivity, i dont see how nsi can help with that.

 

 

That said the reward system in the brain is not made of steel and immume to dysregulation, such as many disorders etc are caused by damage, imbalances in neurotransmitters, in a bad ratio with something opposing or whatever you get the drill.

 

Saying that anhedonia can only be caused by depression is basicly saying that issues in the reward system of the brain cant naturally occur, which is impossible, theres evidence that bpa plastic we ingest in toxic doses can dysregulate the reward system, you can be born with overexpression of certain peptides or whatever, there will be alot of potential causes

 

That said i beleive anhedonia with most drugs of abuse disappears after a few months, i dont get tolerant to the anti anhedonic effect of stims, also dont notice it being worse during the comedown

[pheanix997]

I don't know anything about brain physiology so I'm probably wrong, but dopamine hypoactivty as central cause in schizo seems too simple. And even if it is the main cause, if NSI causes hyperemotionality but whatever mechanism it would undoubtedly be useful for schiz disorders. There are probably dozens of physiologic causes/ contributors to repressed emotion/ anhedonia.

And even if NSI doesnt lift apathy, it's still proposed to repair hippocampal atrophy which is probably seen in all personality / mental disorders.

I wonder if the FDA would approve NSI solely on the basis of a cognitive repair agent that only peripherally treats depression. Because like I said I notice more cognitive than mood benefits. Then again I think my depression is more personality based, reactive to external events and not Major depressive disorder.

[Londonscouser]

obviously we don't know, but i believe there are different forms of anhedonia induced by different mechanisms....

 

 

@jaiho

since you stopped smoking weed, how are you feeling right now !?

[Water Buffalo]

I don't know anything about brain physiology so I'm probably wrong, but dopamine hypoactivty as central cause in schizo seems too simple. And even if it is the main cause, if NSI causes hyperemotionality but whatever mechanism it would undoubtedly be useful for schiz disorders. There are probably dozens of physiologic causes/ contributors to repressed emotion/ anhedonia.

And even if NSI doesnt lift apathy, it's still proposed to repair hippocampal atrophy which is probably seen in all personality / mental disorders.

I wonder if the FDA would approve NSI solely on the basis of a cognitive repair agent that only peripherally treats depression. Because like I said I notice more cognitive than mood benefits. Then again I think my depression is more personality based, reactive to external events and not Major depressive disorder.

Given that the onset of symptoms in Schizophrenia are correlated with the hypermetabolism of the hippocampus by an excess of glutamate, I believe NSI can be of use in anhedonia, at least, through one pathway.

There was an interesting study on the pathophysiological framework of hippocampal dysfunction that proposed that the affective symptoms associated with schizophrenia and depression were driven by hippocampal hypermetabolism. They saw a possible "gain" in affective symptoms when hypermetabolism was increased.

 

@medievil

I'm not sure if you've seen this or not, but there was a recently completed study on the schizophrenia.com main page where they proved the effectiveness of Sarcosine to reverse the damage to the glutamate system. There is a possible risk of cancer progression, but if you are overly concerned you may want to consider D-serine. There has been no cancer risk associated with it, and it reduces the cognitive and negative symptoms to the same extent as Sarcosine when used in doses of 60mg/kg and 120mg/kg. It was not used in the latest study, however.

[Hungry Hippo]

 and depression suppresses all neurotransmitters

 

Do you mean suppression of all neurotransmitters is the effect of depression (or the other way around)?

 

Anyway, I really think depression has not much to do with neurotransmitters. That there's some (slightly) moderate effect when you influence neurotransmitters does not mean that the same mechanism is the cause. Influencing neurotransmitters do also not reverse depression at all, give you even symptoms of depression (anhedonia, not getting reward out of social interaction, suicidal tendencies, sexual dysfunction, unable to feel vividly).

 

Second, the brain is immens dynamic in chemics. When there's a lack of e.g. serotonine in the brain for a while than the number of receptors grow. You even see with SSRI's that the overload of serotonine closes the tiny pathways on receptors. This may be some mechanic of balancing the system. Some say that this closing is the reason why people who took a SSRI are more sensitive to depression than who recovered without it: the structure does not change as easy as the number of chemicals. (Personally, I think that pharmaceutical companies knew this right from the start and that it's the main reason why they choose to develope it. You get a life long prescription.)

 

I still try to understand depression, biological and existential. Stress and inflammation are definitely playing a hugh roll. The hippocampus, on which NSI-198 works, also regulates stress.

 

And there's this: I did an experiment with SR 9009 for 4 weeks and I was a good responder. It grows new mitchondria, you can see it as an alternative to steroids. It had a clear AD effect. Within three weeks a had a close to normal life again (sporting, socializing, studying, cooking). But because it's only tested on mice, four weeks was the max. No neurotransmitter was involved, it was all about muscles and the way the body burns fat. There are more muscle grow related products that tested quite well for anxiety and depression. What to make of that?

 

 

 

 

 

 

   
 

[medievil]

 

 

 but dopamine hypoactivty as central cause in schizo seems too simple. A

Yes offcourse thats not what i said, i ment that hypoative phasic dopamine is the biggest cause for only one symption in shizo, anhedonia. In shizo there is dysregulation by everything caused by the core issue which is glutamate dysregulation which controlls like everything in the brain.

 

Sarcosine and other glycine like things far from normalise the glutamate system but help a bit, theres dysregulation in everything like hormones as testosterone and so on.

 

Theres both glutamate hypoactivity and excess in shizo, heck ampa antagonists like topiramate work for symptions while ampakines are another strategy, glutamate connects to everything in the brain, hypoactivity is the core issue, but it can dysregulate something that causes excess activity somewhere else, its the most complex mental disorder ive ever came across, its pretty much a combination of all mental issues with psychosis.

 

Cancer has the same riskgenes as shizo but they go into the opposite direction, so has bipolar but there the car goes left instead of right instead of turning the opposite way as with cancer.