6219 replies to this topic

[medievil]

Dopamine is highly implicated in depression but i need to find the paper, serotonin is not, then again acute depletion of both neurotransmitters does not cause depression, but that excludes downstream effects.

 

There are a plethoria of differened causes for diff mental issues which are each individual, so all proposed causes are most likely true, each for diffferened individuals.

[Solitude]

Has anyone experienced any joint pain on NSI-189?  I find it to be great, except for this issue, and I have read about several similar experiences before I began taking it as well.  

 

All the joints that I use frequently in sports are quite sore - wrists and elbows in particular.  My muscles are also considerably stiffer than usual, even after minimal exertion.  This happened to a minor extent a year ago when I tried NSI-189, but is much more pronounced this time, presumably because I am more active now.

[pheanix997]

Yeah it's weird. I had a sudden flare up of tendonitis on the outside of my foot and was on crutches for days. Obviously there was a preexisting tendon issue but I didn't notice it at all before and NSI probably is the culprit to bringing it out. Never had any issues like this before NSI; it happened the first week in the trial.

Still worth it though IMO.

I wonder the mechanism behind this. Is it coincidence? Negative placebo effect (overly vigilant to perceived side effects)? Or if it's NSI-related, how would its MOA cause this?


Or maybe it's indirectly related for the more mild aches and pains, where NSI promotes greater clarity and thus awareness of preexisting ached and pains. My first time on stimulants for ADD made me aware of all the aches and pains in my body I was either neglecting or simply unaware of prior. At first tho it seemed adderall was causing it

Edited by pheanix997, 29 February 2016 - 02:48 AM.

[Blackkzeus]

 

 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?

 

 

 

 

 

 

   
 

 

 I'd have to disagree. If what you're saying is the case and neurotransmitters are not at all involved in depression then why is a drug like Wellbutrin that increases dopamine effective in treating depression? Personally, I suffer from depression and anhedonia and I find drugs that increase dopamine like wellbutrin, modafinil, or adderall alleviate some if not all my depressive symptoms. My brain fog goes away, anhedonia, and of course I experience a significant boost in energy.  

[jaiho]

The suppression of neurotransmitters is the effect of depression. Early on in a depressive episode, your body is under severe stress, but when you ignore these signs of distress and keep going without changing anything, it can evolve into Anhedonia / numbness.Well, that's the case for me.

I was never actually sad, and never had bad anxiety. I just seemed to get increasingly numb over time. I can only attribute it to work and whacked sleep schedules. Now it feels like im in so deep that it's a big fight to get out of the hole.

 

I've never been suicidal either, which is amazing considering the extreme level of numbness i've reached.

 

My mood is quite intermittent right now. Ive had two horrible days, and noticed i was doing really good when i tried NoFap (controversial, but i'm convinced) NSI-189, im not quite as confident in it as i was in 2014, it was like a magic pill then, the Anhedonia was almost completely gone.

 

 

 

 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]

Ill back up what you said

 

 

 

The Role of Dopamine in the Pathophysiology of Depression

• 
  Boadie Dunlop
• 
  Charles B Nemeroff

 

Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia, United States

Archives of General Psychiatry (Impact Factor: 14.48). 04/2007; 64(3):327-37. DOI: 10.1001/archpsyc.64.3.327

Source: PubMed

ABSTRACT

Multiple sources of evidence support a role for diminished dopaminergic neurotransmission in major depression. The physiological alterations underlying reduced dopamine (DA) signaling could result from either diminished DA release from presynaptic neurons or impaired signal transduction, either due to changes in receptor number or function and/or altered intracellular signal processing. There are data supporting each of these mechanisms, although interpretation of previous research is confounded by issues around study population, medication status, and technological limitations. In some patients with depression, DA-related disturbances improve by treatment with antidepressants, presumably by acting on serotonergic or nor-adrenergic circuits, which then affect DA function. However, most antidepressant treatments do not directly enhance DA neurotransmission, which may contribute to residual symptoms, including impaired motivation, concentration, and pleasure. Animal models of major depression show considerable responsiveness to manipulations of DA neurotransmission. Several studies, including postmortem investigations, particularly of subjects with severe depression, have demonstrated reduced concentrations of DA metabolites both in the cerebrospinal fluid and in brain regions that mediate mood and motivation. Although the neuroimaging findings are not unequivocal, several studies support the hypothesis that major depression is associated with a state of reduced DA transmission, possibly reflected by a compensatory up-regulation of D(2) receptors. These alterations in DA signaling may underlie the findings of increased "liking" or "high" feelings reported by severely depressed subjects treated with d-amphetamine compared with the response of less severely ill and normal control subjects. The efficacy of medications that directly act on DA neurons or receptors, such as monoamine oxidase inhibitors and pramipexole, suggests that subtypes of depression stemming from a primary DA dysfunction exist. Further research on the contribution of DA to the pathophysiology of depression is justified to improve outcomes for patients with treatment-resistant and nonremitting depression.

and much more with this google search

 

https://www.google.c... depression pdf

Thats a reply for the hungry hippo

[medievil]

 

 

The suppression of neurotransmitters is the effect of depression. Early on in a depressive episode, your body is under severe stress

I dont see how depression causes severe stress, an atypical episode made me feel depressed so i slept all day, seems the opposite of stressfull, yes depression can perhaps lower neurotransmitters but you are generalising to everyone, depression has differened causes for differened people there is no unified cause.

[jaiho]

No i mean that depression is triggered from that severe stress, you're feeling that stress early in the depression episode, and it worsens it the longer you let that stress continue.

[medievil]

The depression i had wasnt triggered by stress, again thats something individual but can you go to the thread i made to continue this discussion or we are gonna piss ppl off here, and i find it an interesting discussion

[Solitude]

Yeah it's weird. I had a sudden flare up of tendonitis on the outside of my foot and was on crutches for days. Obviously there was a preexisting tendon issue but I didn't notice it at all before and NSI probably is the culprit to bringing it out. Never had any issues like this before NSI; it happened the first week in the trial.

Still worth it though IMO.

I wonder the mechanism behind this. Is it coincidence? Negative placebo effect (overly vigilant to perceived side effects)? Or if it's NSI-related, how would its MOA cause this?


Or maybe it's indirectly related for the more mild aches and pains, where NSI promotes greater clarity and thus awareness of preexisting ached and pains. My first time on stimulants for ADD made me aware of all the aches and pains in my body I was either neglecting or simply unaware of prior. At first tho it seemed adderall was causing it

I'm fairly certain it's more than just coincidence.  I have been doing the same sports for over a year now, and the day after I started, both my elbows and both my wrists have become fairly sore.  Usually, I train 4 times a week - I have been doing this for a long time, and I don't get sore muscles after training anymore.  Yesterday, I had a very light training session due to joint pain, and today I'm so sore that I had to take the day off.

 

Although it is possible that it makes you more aware of injuries, I seriously doubt it would do so to the extent that you get tendinitis, end up on crutches, or become unable to exercise.

 

Unfortunately, I am seriously considering stopping.  However, since you seem to have responded in a similar way to me, what did you find over the long term?  Did you continue using it?  Do you believe that it had positive effects?

[Londonscouser]

 

The suppression of neurotransmitters is the effect of depression. Early on in a depressive episode, your body is under severe stress, but when you ignore these signs of distress and keep going without changing anything, it can evolve into Anhedonia / numbness.Well, that's the case for me.

I was never actually sad, and never had bad anxiety. I just seemed to get increasingly numb over time. I can only attribute it to work and whacked sleep schedules. Now it feels like im in so deep that it's a big fight to get out of the hole.

 

I've never been suicidal either, which is amazing considering the extreme level of numbness i've reached.

 

My mood is quite intermittent right now. Ive had two horrible days, and noticed i was doing really good when i tried NoFap (controversial, but i'm convinced) NSI-189, im not quite as confident in it as i was in 2014, it was like a magic pill then, the Anhedonia was almost completely gone.

 

 

 

 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?

 

 

 

 

 

 

   
 

 

 

I agree Jaiho ! My brain was under quite a bit of stress for some period of time, and i knew it as well, but i didn't bother reacting to the situation...and now im stuck with anhedonia/depression symptoms.

 

Also, i think people with anhedonia and apathy have a decreased likelihood in committing suicide...my opinion

 

Also, first time in weeks/months i have abstained from masturbation for 4 days, and i find myself nearly laughing at stuff over the internet (although i have had sexual intercourse with 2 different women in these last 2 days)....i dunno if coincidence or not

[medievil]

Ugh i quickly looked and stress induces alot of changes in the brain, like literally not just hipocampal damage which most think, ill put what i can find togheter to help ya, not just that i love to learn about subjects like this and learning improves the brain making it easier to learn more, so doing all this research help me.

 

The brain can store more then 4 billion books, and i allways wanted to learn as much as possible about all sort of subjects, its not just ocd its because i really enjoy learning about all this, thats my hobby haha.

 

anyway i cant get people to post in my depression topic to keep this label ontopic while id make a perfect moderator. jk offcourse

 

I want to discuss nsi again, after i did some research i have some questions ive been pondering about the drug

 

I never masturbate anymore except maybe rarely, mostly because my sexual reward is fucked, benzo withdrawal reverses it tough, my girlfriend didnt understand why i wanted to watch porn when feeling horrible because of withdrawal lol, but some effects are only temporary such as anhedonia relief with phenibut during withdrawal.

 

that said i wonna try to get off benzos but cant untill i can get dex prescribed as rc stims cause too much anxiety.

Edited by medievil, 29 February 2016 - 07:52 AM.

[pheanix997]

Yeah it's weird. I had a sudden flare up of tendonitis on the outside of my foot and was on crutches for days. Obviously there was a preexisting tendon issue but I didn't notice it at all before and NSI probably is the culprit to bringing it out. Never had any issues like this before NSI; it happened the first week in the trial.

Still worth it though IMO.

I wonder the mechanism behind this. Is it coincidence? Negative placebo effect (overly vigilant to perceived side effects)? Or if it's NSI-related, how would its MOA cause this?


Or maybe it's indirectly related for the more mild aches and pains, where NSI promotes greater clarity and thus awareness of preexisting ached and pains. My first time on stimulants for ADD made me aware of all the aches and pains in my body I was either neglecting or simply unaware of prior. At first tho it seemed adderall was causing it

I'm fairly certain it's more than just coincidence. I have been doing the same sports for over a year now, and the day after I started, both my elbows and both my wrists have become fairly sore. Usually, I train 4 times a week - I have been doing this for a long time, and I don't get sore muscles after training anymore. Yesterday, I had a very light training session due to joint pain, and today I'm so sore that I had to take the day off.

Although it is possible that it makes you more aware of injuries, I seriously doubt it would do so to the extent that you get tendinitis, end up on crutches, or become unable to exercise.

Unfortunately, I am seriously considering stopping. However, since you seem to have responded in a similar way to me, what did you find over the long term? Did you continue using it? Do you believe that it had positive effects?

Coincidence for small aches. Is it worth it, yeah I think so. But my pain was acute and is gone now; I don't have any increase in chronic pain, which would be intolerable.

In terms of benefits, remarkably improved vision, some brain fog relief, and mild inprovement in mood. I think I'm more aggressive and less likely to put up with people's stuff than before. But I'm still depressed. Hard to say. It's subtle.

[Junk Master]

Has anyone else here tried NSI in conjunction with Tianeptine?  I seem to recall one post about the two not playing well together, but Tianeptine sure removes those little aches and pains referenced above.

 

I've tried the two together on a number of occasions and thought the combo was quite synergistic.  That said, I just find it too easy to take too much Tianeptine and the resultant constipation and stomach bloat just isn't worth it.

 

I'm about to start another cycle of NSI but this time I won't be adding Tianeptine, so I'll report on the aches and pains issue-- which as a longtime weight lifter and football player for the age of 10-23, I have PLENTY of.

[StevesPetRat]

Has anyone experienced any joint pain on NSI-189?  I find it to be great, except for this issue, and I have read about several similar experiences before I began taking it as well.  
 
All the joints that I use frequently in sports are quite sore - wrists and elbows in particular.  My muscles are also considerably stiffer than usual, even after minimal exertion.  This happened to a minor extent a year ago when I tried NSI-189, but is much more pronounced this time, presumably because I am more active now.

Yeah it's weird. I had a sudden flare up of tendonitis on the outside of my foot and was on crutches for days. Obviously there was a preexisting tendon issue but I didn't notice it at all before and NSI probably is the culprit to bringing it out. Never had any issues like this before NSI; it happened the first week in the trial.

Still worth it though IMO.

I wonder the mechanism behind this. Is it coincidence? Negative placebo effect (overly vigilant to perceived side effects)? Or if it's NSI-related, how would its MOA cause this?

Or maybe it's indirectly related for the more mild aches and pains, where NSI promotes greater clarity and thus awareness of preexisting ached and pains. My first time on stimulants for ADD made me aware of all the aches and pains in my body I was either neglecting or simply unaware of prior. At first tho it seemed adderall was causing it

  

I'm fairly certain it's more than just coincidence.  I have been doing the same sports for over a year now, and the day after I started, both my elbows and both my wrists have become fairly sore.  Usually, I train 4 times a week - I have been doing this for a long time, and I don't get sore muscles after training anymore.  Yesterday, I had a very light training session due to joint pain, and today I'm so sore that I had to take the day off.
 
Although it is possible that it makes you more aware of injuries, I seriously doubt it would do so to the extent that you get tendinitis, end up on crutches, or become unable to exercise.
 
Unfortunately, I am seriously considering stopping.  However, since you seem to have responded in a similar way to me, what did you find over the long term?  Did you continue using it?  Do you believe that it had positive effects?

Cortisol suppression. This is a documented effect in humans, unlike hippocampal volume increase, which is speculative (I mean, it's probable, sure, since it does so in the animal model, but still).

I had the opposite effect -- much improved athletic endurance, less soreness, etc. -- but I believe my cortisol was way too high to begin with (I don't know this for a fact, because the doctor laughed in my face when I suggested that testing it might be informative).

[pheanix997]

Anyone experience subtle and tiny sparks/ flares in vision? I honestly wouldn't have even noticed this if I hadn't read about it in a reddit thread. But it's happened about 4-5 times.

Question: Does anyone think it's from the welding NSI is doing on my hippocampus? :P

Edited by pheanix997, 01 March 2016 - 03:14 AM.

[Blackkzeus]

Does NSI-189 make any of you tired? I've been taking it for the past few days. The first day I took about 25- 30 mg and felt mildly uncomfortable and anxious. 

I think it may have enhanced my vision slightly too. Besides those effects I felt nothing. Then on the second day I took about 20 mg

and felt nothing. Third, fourth, and fifth day I took it I  became tired and I believe took a nap on two out of the three days. 

So far I'm a bit disappointed that i'm not experiencing those positive acute effects people seem to have with the drug. 

 

[Blackkzeus]

Also, anybody else have weak erections and struggle to orgasm during sex from depression? 

[neuralis]

Does NSI-189 make any of you tired? I've been taking it for the past few days. The first day I took about 25- 30 mg and felt mildly uncomfortable and anxious. 

I think it may have enhanced my vision slightly too. Besides those effects I felt nothing. Then on the second day I took about 20 mg

and felt nothing. Third, fourth, and fifth day I took it I  became tired and I believe took a nap on two out of the three days. 

So far I'm a bit disappointed that i'm not experiencing those positive acute effects people seem to have with the drug. 

 

 Perhaps you can try lowering the dose a little bit? How much did you take on the days you got the fatigue?

 

I used to get extremely tired at times when I was on NSI. It felt like my whole body was filled with lead. I even had some people comment on how oddly I carried myself around because of that. Lowering the dosage as little as 5mg per dose took all the tiredness away.

[Junk Master]

I have experienced tiny sparks or flares in my vision fyi.  Just once.

 

Also, man does NSI do a number on benzos!  I find I nearly have to triple the dose of Clonazepam for it to have the same effect, and THAT is not a good thing.

 

On the flip side, I find I don't have the same anxiety with NSI.   Notice I didn't say NO anxiety, but the anxiety caused at times by NSI seems somehow different then the anxiety I've dealt with my entire life-- and much more manageable.

 

Now if I could just find a way to mitigate my insomnia!  Too bad my doc will not cough up my old Ambien script. Nothing worked as well for me.  What a relief knowing I would be able to sleep once it kicked in, even if it mean I might eat 1/2 a gallon of ice cream every once in a while in the middle of the night and not remember it.  Lol.

[Strangelove]

Has anyone else here tried NSI in conjunction with Tianeptine?  I seem to recall one post about the two not playing well together, but Tianeptine sure removes those little aches and pains referenced above.

 

I've tried the two together on a number of occasions and thought the combo was quite synergistic.  That said, I just find it too easy to take too much Tianeptine and the resultant constipation and stomach bloat just isn't worth it.

 

I'm about to start another cycle of NSI but this time I won't be adding Tianeptine, so I'll report on the aches and pains issue-- which as a longtime weight lifter and football player for the age of 10-23, I have PLENTY of.

 

There are more than a few reports in reddit and here, describing a synergy, this is my experience also, its a good combo.

 

Anyone interested I received NSI-189 freebase from the same source I am getting the phosphate just today, same price from $24 to $16/gram depending on quantity.

[Junk Master]

Thanks as always, Strangelove.

 

 

[Solitude]

 

Has anyone experienced any joint pain on NSI-189?  I find it to be great, except for this issue, and I have read about several similar experiences before I began taking it as well.  
 
All the joints that I use frequently in sports are quite sore - wrists and elbows in particular.  My muscles are also considerably stiffer than usual, even after minimal exertion.  This happened to a minor extent a year ago when I tried NSI-189, but is much more pronounced this time, presumably because I am more active now.

Yeah it's weird. I had a sudden flare up of tendonitis on the outside of my foot and was on crutches for days. Obviously there was a preexisting tendon issue but I didn't notice it at all before and NSI probably is the culprit to bringing it out. Never had any issues like this before NSI; it happened the first week in the trial.

Still worth it though IMO.

I wonder the mechanism behind this. Is it coincidence? Negative placebo effect (overly vigilant to perceived side effects)? Or if it's NSI-related, how would its MOA cause this?

Or maybe it's indirectly related for the more mild aches and pains, where NSI promotes greater clarity and thus awareness of preexisting ached and pains. My first time on stimulants for ADD made me aware of all the aches and pains in my body I was either neglecting or simply unaware of prior. At first tho it seemed adderall was causing it

  

I'm fairly certain it's more than just coincidence.  I have been doing the same sports for over a year now, and the day after I started, both my elbows and both my wrists have become fairly sore.  Usually, I train 4 times a week - I have been doing this for a long time, and I don't get sore muscles after training anymore.  Yesterday, I had a very light training session due to joint pain, and today I'm so sore that I had to take the day off.
 
Although it is possible that it makes you more aware of injuries, I seriously doubt it would do so to the extent that you get tendinitis, end up on crutches, or become unable to exercise.
 
Unfortunately, I am seriously considering stopping.  However, since you seem to have responded in a similar way to me, what did you find over the long term?  Did you continue using it?  Do you believe that it had positive effects?

Cortisol suppression. This is a documented effect in humans, unlike hippocampal volume increase, which is speculative (I mean, it's probable, sure, since it does so in the animal model, but still).

I had the opposite effect -- much improved athletic endurance, less soreness, etc. -- but I believe my cortisol was way too high to begin with (I don't know this for a fact, because the doctor laughed in my face when I suggested that testing it might be informative).

 

This makes some sort of sense.  Do you happen to have a link?  I have always suspected that I have quite low cortisol, but obviously my suspicion is to be taken with a grain of salt.

 

I took 20 mg before bed last night (and didn't take any during the day today) and feel much less sore today. It remains to be seen over an extended period, but taking it at night might be an easy way around that.

[playground]

 

Just an update, 3-4 weeks after starting NST I woke up and was depression free, No rumination, negative thoughts fall quickly off. First time in years that I feel really well. I cannot believe how well this works ,my mind is really peaceful. This stuff is unbelievable. I also did lions mane and cerebrolysin, these 2 might also have helped a bit. I hope  the effect is sustainable. Should I cycle this on and off or should I take it without breaks? I got my NSI-189 from Mr. Strangelove.

DST

 

Don't cycle! I was a long term NSI-189 user and i stopped, and i have never been able to regain the anti depressant effects i experienced for 6 months.

I tried multiple genuine sources to ensure it wasn't a bunk supply.

The other thing i could try is increases doses but i dunno.. it feels like its lost its magic

 

 

This seems to be a common report.  A frequently occurring story line:

NSI-189 was effective in the beginning, but not any more (or obviously less effective than it once was).

 

It reminds me of something a friend of mine said about ecstasy (MDMA) : 

The first 30 or 40 pills are the best, but after that, it gets disappointing.

 

The advice to the ecstasy users was, perhaps still is, 'less is more'

Which is short for :  Don't have 6 pills every night you go raving. Stick to 1.
The suggestion is basically that higher dosages promote tolerance faster.

 

I wonder if this means that either:

- people should take 20mg to 40mg dosages (rather than 40mg to 80mg suggested by NeuralStem)

- people should take NSI-189 intermittently.  One week on, One week off. etc.

 

Someone,  somewhere.... is an expert on minimising tolerance effects.

We need that person ...  or we need his/her published articles.

 

Perhaps someone could suggest some tolerance minimising advice / articles ??

[pheanix997]

Has anyone experienced any joint pain on NSI-189? I find it to be great, except for this issue, and I have read about several similar experiences before I began taking it as well.

All the joints that I use frequently in sports are quite sore - wrists and elbows in particular. My muscles are also considerably stiffer than usual, even after minimal exertion. This happened to a minor extent a year ago when I tried NSI-189, but is much more pronounced this time, presumably because I am more active now.

Yeah it's weird. I had a sudden flare up of tendonitis on the outside of my foot and was on crutches for days. Obviously there was a preexisting tendon issue but I didn't notice it at all before and NSI probably is the culprit to bringing it out. Never had any issues like this before NSI; it happened the first week in the trial.

Still worth it though IMO.

I wonder the mechanism behind this. Is it coincidence? Negative placebo effect (overly vigilant to perceived side effects)? Or if it's NSI-related, how would its MOA cause this?

Or maybe it's indirectly related for the more mild aches and pains, where NSI promotes greater clarity and thus awareness of preexisting ached and pains. My first time on stimulants for ADD made me aware of all the aches and pains in my body I was either neglecting or simply unaware of prior. At first tho it seemed adderall was causing it

I'm fairly certain it's more than just coincidence. I have been doing the same sports for over a year now, and the day after I started, both my elbows and both my wrists have become fairly sore. Usually, I train 4 times a week - I have been doing this for a long time, and I don't get sore muscles after training anymore. Yesterday, I had a very light training session due to joint pain, and today I'm so sore that I had to take the day off.

Although it is possible that it makes you more aware of injuries, I seriously doubt it would do so to the extent that you get tendinitis, end up on crutches, or become unable to exercise.

Unfortunately, I am seriously considering stopping. However, since you seem to have responded in a similar way to me, what did you find over the long term? Did you continue using it? Do you believe that it had positive effects?

Cortisol suppression. This is a documented effect in humans, unlike hippocampal volume increase, which is speculative (I mean, it's probable, sure, since it does so in the animal model, but still).

I had the opposite effect -- much improved athletic endurance, less soreness, etc. -- but I believe my cortisol was way too high to begin with (I don't know this for a fact, because the doctor laughed in my face when I suggested that testing it might be informative).

This makes some sort of sense. Do you happen to have a link? I have always suspected that I have quite low cortisol, but obviously my suspicion is to be taken with a grain of salt.

I took 20 mg before bed last night (and didn't take any during the day today) and feel much less sore today. It remains to be seen over an extended period, but taking it at night might be an easy way around that.

Hey solitude,

Do you sometimes notice a stuffiness? Like a subtle drowsiness when you take NSI? I get that once in a while

[playground]

 

^ Regarding my last post, my foot is better today but I still probably have tendonitis. This is unusual for me. It may just be a coincidence, though, that it occurred 11 days after starting NSI-189. 

 

I haven't noticed many positive effects. The third day or so I had awesome HD vision. I was seeing the details of peoples' faces in the oncoming lane as I was driving. This is NEVER the case with me, so I doubt it was placebo. Usually my vision is vaguely blurry. Adderall, and other nootropic compounds, sharpen up my vision as well. Sadly I only experienced one day of that :(

 

I notice it gives me a sleepy/ dull feeling of brain fog shortly after dosing, which seems to go away a bit as the day goes on. It also gives me a verbal dyslexia. I would sometimes use the wrong words, put words out of place, and speak in halting phrases. I think I've always had some kind of underlying dyslexia though - not in reading but in speech and information processing. So maybe NSI-189 was just bringing it to the surface.

 

While every user report is appreciated and I totally understand that serious depression can make someone take desperate measures, I just wanted to reiterate that people shouldn't interprete too much into this report due to the many other drugs pheanix997 is taking.

 

Leaving out tendonitis, verbal dyslexia and brain fog seem to be very unusual responses based on reviews so far. Most people either report clearheadedness and general pro-cognitive effects or none. Not saying that NSI-189 taken alone couldn't do that (after all we just don't know yet), but I would bet this is a result of a negative interaction with one or more drugs of your current regimen. I've noticed something similar when I took NSI-189 with caffeine. I have a feeling that NSI-189 and psychostimulants don't mix well as NSI-189 itself is very stimulating.

 

Anyhow, thanks for sharing.
 

 

 

You seem very anxious to protect the reputation of NSI-189, focus83.

Are you shilling ?

 

[playground]

Has anyone experienced any joint pain on NSI-189?  I find it to be great, except for this issue, and I have read about several similar experiences before I began taking it as well.  

 

All the joints that I use frequently in sports are quite sore - wrists and elbows in particular.  My muscles are also considerably stiffer than usual, even after minimal exertion.  This happened to a minor extent a year ago when I tried NSI-189, but is much more pronounced this time, presumably because I am more active now.

 

This question about NSI-189 causing pain .... of some form, somewhere on the body... keeps coming up.

 

One poster has suggested that the main effect of NSI-189 is to reduce cortisol.  

Could a reduction in Cortisol cause pain, i wonder ?
 

[Bukujutsu]

My dosage schedule so far: 1/26 started NSI-189 5mg 2x, 1/30 7mg 2x, 2/1 10mg 2x, 2/10 15mg x2, 2/16 40mg 2x

 

Some things I've noticed:

 

I noticed a significant increase in hunger. Before I was only eating one meal a day (intermittent fasting) and not really feeling any particular hunger until then. Now I'm up to two, although I still keep them within an 8 hour period. Loss of appetite, food tasting bland, is a common symptom of significant depression, although I don't know what the mechanism of action is. Cortisol could be effecting this as well.

 

I've also noticed that it causes me to wake up much earlier than usual. For a time after starting I would wake up feeling sweaty and somewhat anxious, which I suspect was from a cortisol rebound: https://en.wikipedia...kening_response

IIRC it was recently found to significantly reduce cortisol (commonly referred to as a stress hormone) levels, which was found to be the determining factor for whether subjects were responders. IIRC about half of those with (major) depression were found to hyper-secrete cortisol. Other conditions, such as anxiety, which has a high cormobidity with depression, and I suspect autism spectrum disorders, due to an enhanced fear response, which may be in part due to differences in the amygdala and the effect of memory formation and conditioning from negative events, and anxiety being a common part of it (there seems to be a deficit in the GABAergic system and an imbalance between glutamate and GABA). I have all three.

 

I also recently noticed the hypomanic effect after strenuous exercise, which I had experienced consistently before after heavy weight lifting sessions when I was using it over a year ago. IIRC in rats the greatest period of neurogenesis was found to occur during periods of highest physical activity. It was after a strenuous 5-6 hour hiking session in a regional park, with much of it very off trail (rough), and steep climbs. Should have been exhausted afterward, but I experienced a very noticeable boost in physical and cognitive energy that lasted about 4-5 hours. I was even able to run back and forth part of the way between a train station and grocery store, on the way back with a backpack loaded with food and some gear, and more food in a reusable grocery bag under the other arm, then running part of the way home after that as well, making good time on all. Energy continued at home.

 

One last thing I noticed after leaving Tilden park, starting from when I was in Downtown Berkeley, was that I could smell things! I noted before that I seemed to have an unusually weak sense of taste and smell, and this may be reversing. It was the scent of flowers I noticed multiple times while walking, and food. It was definitely a marked change, I hadn't noticed how dulled my sense of smell had become. As I mentioned before, loss of appetite, food tasting bland, is a common symptom of significant depression, although I don't know what the mechanism of action is, and taste is strongly tied to smell.

[Bukujutsu]

 

Has anyone experienced any joint pain on NSI-189?  I find it to be great, except for this issue, and I have read about several similar experiences before I began taking it as well.  
 
All the joints that I use frequently in sports are quite sore - wrists and elbows in particular.  My muscles are also considerably stiffer than usual, even after minimal exertion.  This happened to a minor extent a year ago when I tried NSI-189, but is much more pronounced this time, presumably because I am more active now.

Yeah it's weird. I had a sudden flare up of tendonitis on the outside of my foot and was on crutches for days. Obviously there was a preexisting tendon issue but I didn't notice it at all before and NSI probably is the culprit to bringing it out. Never had any issues like this before NSI; it happened the first week in the trial.

Still worth it though IMO.

I wonder the mechanism behind this. Is it coincidence? Negative placebo effect (overly vigilant to perceived side effects)? Or if it's NSI-related, how would its MOA cause this?

Or maybe it's indirectly related for the more mild aches and pains, where NSI promotes greater clarity and thus awareness of preexisting ached and pains. My first time on stimulants for ADD made me aware of all the aches and pains in my body I was either neglecting or simply unaware of prior. At first tho it seemed adderall was causing it

  

I'm fairly certain it's more than just coincidence.  I have been doing the same sports for over a year now, and the day after I started, both my elbows and both my wrists have become fairly sore.  Usually, I train 4 times a week - I have been doing this for a long time, and I don't get sore muscles after training anymore.  Yesterday, I had a very light training session due to joint pain, and today I'm so sore that I had to take the day off.
 
Although it is possible that it makes you more aware of injuries, I seriously doubt it would do so to the extent that you get tendinitis, end up on crutches, or become unable to exercise.
 
Unfortunately, I am seriously considering stopping.  However, since you seem to have responded in a similar way to me, what did you find over the long term?  Did you continue using it?  Do you believe that it had positive effects?

Cortisol suppression. This is a documented effect in humans, unlike hippocampal volume increase, which is speculative (I mean, it's probable, sure, since it does so in the animal model, but still).

I had the opposite effect -- much improved athletic endurance, less soreness, etc. -- but I believe my cortisol was way too high to begin with (I don't know this for a fact, because the doctor laughed in my face when I suggested that testing it might be informative).

 

 

 

 

Blackkzeus: >Does NSI-189 make any of you tired? I've been taking it for the past few days. The first day I took about 25- 30 mg and felt mildly uncomfortable and anxious. 

 

>I think it may have enhanced my vision slightly too. Besides those effects I felt nothing. Then on the second day I took about 20 mg

and felt nothing. Third, fourth, and fifth day I took it I  became tired and I believe took a nap on two out of the three days. 

So far I'm a bit disappointed that i'm not experiencing those positive acute effects people seem to have with the drug. 

 

 

Playground: >This question about NSI-189 causing pain .... of some form, somewhere on the body... keeps coming up.

 

>One poster has suggested that the main effect of NSI-189 is to reduce cortisol.  

Could a reduction in Cortisol cause pain, i wonder ?
 

 

Yes! Cortisol is the answer to all of these!

 

http://www.longecity...124#entry760587

 

https://en.wikipedia...Immune_response

 

 

"Cortisol prevents the release of substances in the body that cause inflammation."

 

Low cortisol can cause fatigue as well. Levels decline throughout the day, IIRC.

[focus83]

 

 

^ Regarding my last post, my foot is better today but I still probably have tendonitis. This is unusual for me. It may just be a coincidence, though, that it occurred 11 days after starting NSI-189. 

 

I haven't noticed many positive effects. The third day or so I had awesome HD vision. I was seeing the details of peoples' faces in the oncoming lane as I was driving. This is NEVER the case with me, so I doubt it was placebo. Usually my vision is vaguely blurry. Adderall, and other nootropic compounds, sharpen up my vision as well. Sadly I only experienced one day of that :(

 

I notice it gives me a sleepy/ dull feeling of brain fog shortly after dosing, which seems to go away a bit as the day goes on. It also gives me a verbal dyslexia. I would sometimes use the wrong words, put words out of place, and speak in halting phrases. I think I've always had some kind of underlying dyslexia though - not in reading but in speech and information processing. So maybe NSI-189 was just bringing it to the surface.

 

While every user report is appreciated and I totally understand that serious depression can make someone take desperate measures, I just wanted to reiterate that people shouldn't interprete too much into this report due to the many other drugs pheanix997 is taking.

 

Leaving out tendonitis, verbal dyslexia and brain fog seem to be very unusual responses based on reviews so far. Most people either report clearheadedness and general pro-cognitive effects or none. Not saying that NSI-189 taken alone couldn't do that (after all we just don't know yet), but I would bet this is a result of a negative interaction with one or more drugs of your current regimen. I've noticed something similar when I took NSI-189 with caffeine. I have a feeling that NSI-189 and psychostimulants don't mix well as NSI-189 itself is very stimulating.

 

Anyhow, thanks for sharing.
 

 

 

You seem very anxious to protect the reputation of NSI-189, focus83.

Are you shilling ?

 

 

 

What the heck is your problem? Do you know which user review I was refering to? This guy was taking Lexapro, Adderall and Wellbutrin alongside the NSI-189. Would you rate that as a good setting for evaluating the effects and side effects of NSI-189? Please think before you post.

 

Also, read my own review and you will notice that I am not shilling, but merely describing my own very positive experience. Would you prefer I downplay all the good things NSI-189 did to me?