6219 replies to this topic

[MichaelTheAnhedonic]

"When i first started i did notice old memories rushing in randomly at different times, mostly childhood ones, as others have described, but this effect faded."

Yes exactly the same thing, like random memories pop up of unimportant stuff like me making a coffee that i made half hour ago etc. This effect came after quiting NSI not in the time I consumed NSI. In the time of the "flashback" i cant focus on other thoughts.

 

To the guy with blank mind, you could ask your doc to give you something that affects dopamine system (L-Dopa). Seems to me related. I kickstarted my brain with Ethylphenidate and it still runs fast and good. You could also try my nr.1 tipp rhodiola rosea and if that doesnt help test lowdose NSI and inrease dosage in little steps.

 

Huh. Ethylphenidate was very effective in my case (blank minder here) but it didn't kickstarted my brain. You're lucky.  

[Mind_Paralysis]

Second day of 20 mg NSI-189 once daily.

 

And it's been a pretty good day! : D I'm a lot happier, and my activity-level has been increased notably - today marked my return to actual Jogging instead of short walking for the first time in two months!

 

It's also taken longer to fall asleep and I've had some more anxiety than normal as well, so several forms of activity have already been increased.

 

This is certainly in line with the hypothesis of Dopamine-agonism, since dopaminergics do give me anxiety, and causes slight insomnia.

 

I am going to keep the dosing at low doses this time though - no more fooling around with 40 mg, and no more taking the drug in the afternoon - gotta' protect my sleep.

 

Might actually be lowering the dose after this initial week as well, hmm - might go with more like 10 mg, in the long run, and use it as an adjunct to other antidepressants even.

[Hyperflux]

Second day of 20 mg NSI-189 once daily.

 

And it's been a pretty good day! : D I'm a lot happier, and my activity-level has been increased notably - today marked my return to actual Jogging instead of short walking for the first time in two months!

 

It's also taken longer to fall asleep and I've had some more anxiety than normal as well, so several forms of activity have already been increased.

 

This is certainly in line with the hypothesis of Dopamine-agonism, since dopaminergics do give me anxiety, and causes slight insomnia.

 

I am going to keep the dosing at low doses this time though - no more fooling around with 40 mg, and no more taking the drug in the afternoon - gotta' protect my sleep.

 

Might actually be lowering the dose after this initial week as well, hmm - might go with more like 10 mg, in the long run, and use it as an adjunct to other antidepressants even.

 

Phosphate?

[Mind_Paralysis]

 

Second day of 20 mg NSI-189 once daily.

 

And it's been a pretty good day! : D I'm a lot happier, and my activity-level has been increased notably - today marked my return to actual Jogging instead of short walking for the first time in two months!

 

It's also taken longer to fall asleep and I've had some more anxiety than normal as well, so several forms of activity have already been increased.

 

This is certainly in line with the hypothesis of Dopamine-agonism, since dopaminergics do give me anxiety, and causes slight insomnia.

 

I am going to keep the dosing at low doses this time though - no more fooling around with 40 mg, and no more taking the drug in the afternoon - gotta' protect my sleep.

 

Might actually be lowering the dose after this initial week as well, hmm - might go with more like 10 mg, in the long run, and use it as an adjunct to other antidepressants even.

 

Phosphate?

 

 

Definitely Phosphate.
 

[dreamedm]

Irishdude, bugsbunny and Lunast, thanks for the input guys.

 

bugsbunny, i'm just curious - why test NSI in low dose? jaiho recommended I start with 40 mg and keep taking that.

[jaiho]

I don't see any reason starting @ 20mg.

The trials all start @ 40mg QD.

This isn't like an SSRI where it's good to start low & slow.

[bugsbunny]

Irishdude, bugsbunny and Lunast, thanks for the input guys.

 

bugsbunny, i'm just curious - why test NSI in low dose? jaiho recommended I start with 40 mg and keep taking that.

 

Its a safer use rule to try to minimize risks when trying new compounds. There were some ppl having negative sideeffects that can cause a lot social problems since it can induce anxiety. Every body is different and there are different types of metabolizers. 50mg might be perfect for one guy but complete overdose or another one. Generalizing a dosage isnt working in real life. You can safe a lot of trouble and time if you find the perfect dosage for you and can except hypersensitivity to NSI.  If you dont have any negative side effects you still can raise the dosage.

[Twindaddy37]

Anyone ever make a selank nasal spray or use one with NSI? First time using it today and not terribly impressed with this one. 600mcg dose, if any effect, ever so slight sedated, heavy head type feeling that is it. Using for gaba a and opiate receptor modulation/healing. Maybe best to use before bedtime and let it do its work overnight? Does not seem to have daytime benefit.  

Edited by Twindaddy37, 10 February 2017 - 03:42 PM.

[Mind_Paralysis]

Could we please get some discussion going around the potential metabolism of NSI-189?

Many of us have combined it with various compounds, and many of us want to combine it with damn near anything between heaven and earth, all in the hope of getting the right effect. To do this, we need SOME idea about how the molecule is broken down in the body, and whether or not plasma-levels could be affected by other compounds.

 

As such, I've started looking at the close relatives of NSI-189, and so far these are the compounds I find listed:

 

Nicotinamide

Pyrazine

Momelotinib

 

So, what do we know about the metabolism of these compounds?

 

 

Nicotinamide

Seems to be a compound which can be metabolized in a number of ways.

 

Nicotinamide doesn't become toxic in any way until you go past ridiculous dosing-levels - 3 grams + are the levels where toxicity have been reported.

 

Nicotinamide can be oxidised to nicotinamide-N-oxide, methylated to N-methyl-nicotinamide or hydroxylated to 6-hydroxynicotinamide.

N-methyl nicotinamide is oxidised in the liver, a process that is saturated at high circulating concentrations, and the end products are
N-methyl-2-pyridone-5-carboxylic acid amide 2 pyr )and N-methyl-4-pyridone-3-carboxylic acid amide 4 pyr).

In humans, 2 pyr is formed exclusively

 

Hmm... what does this mean, enzymatically? Which CYP2D6-enzymes are involved in the metabolism of Nicotinamide? Seeing as it's metabolised in the liver, it MUST be affected by CYP2D6.

 

 

 

Pyrazine

Once more, not much is known about it's metabolism it seems. Which is strange, since it seems to be widely used for different things, and sythesizing other compounds.

 

I found a review of its metabolism in microorganisms though - not sure if anything can be gleaned from this regarding its metabolism in humans, but it's all I can find.

 

 

Momelotinib

Super-f***ing hard to find any info on this drug - it's more obscure than even friggin' NSI-189! Anyways, there was a toxicity-listing in one of the recept trials of the drug for the treatment of Myelofibrosis.

 

 

The safety and tolerability of MMB, based on assigned dose, was previously reported with a maximum tolerated dose of 300 mg QD and dose limiting toxicities of elevated lipase and headache at 400 mg QD.

 

 

Ok, that's interesting?? Elevated Pancreas lipase levels?? I believe the Pancreas produces enzymes for FOOD DIGESTION? Does this mean Momelotinib is metabolised by... err... by the PANCREAS? Seems unreal... I must be misinterpreting the data.

 

I just found some info from another trial of Momelotinib as well - apparently, use of strong CYP3A4-inducers prior to trialling Momelotinib is strictly forbidden - does this imply that CYP3A4 is highly involved with Momelotinib's metabolism?
 

---

 

UNGH! I cannot write a single line more. I'm actually feeling quite dysphoric today - the day started out good, but then I had waves of fatigue which really seems to give me anxiety, but they're also making me super-pissed!! I am SO tired of being tired already...! The fact that I have to wait another two f***ing weeks before I get even the possibility of Modafinil, is simply put, beyond painful. Jesus...

 

Hmm... still at 20 mg NSI-189 - have ordered some Magnesium-L-Threonate to help with this god-damn anxiety - that will take about two weeks to get here as well, however...

 

---

 

 

References:

-------------------

Safety of high-dose nicotinamide: a review

http://link.springer...7/s001250051536

 

 

Dose-Response Analyses Of Momelotinib (CYT387), a JAK1 and JAK2 Inhibitor, From a Phase I/II Study (CCL09101) In Treatment Of Myelofibrosis

http://www.bloodjour...so-checked=true

 

 

Momelotinib in Transfusion-Dependent Adults With Primary Myelofibrosis (PMF) or Post-polycythemia Vera or Post-essential Thrombocythemia Myelofibrosis (Post-PV/ET MF)

https://clinicaltria...how/NCT02515630

Lipase -  Common Questions

https://labtestsonli...lipase/tab/faq/

 

 

Microbial metabolism of pyrazines

http://www.tandfonli...41X.2010.512267

[dramachiavellian]

 

 

 

Borderline (yes, BPD is such a disorder - read up on the newest data)

Could you elaborate. Aside from the obvious about why BPD leads to depression, what new data are you referring to ?

 

Thanks !

 

 

Well, I was mainly referring to the fact that BPD is a neuropsychiatric disorder* , instead of the old model currently in effect - that it's strictly an acquired set of traits - a personality disorder.

 

That's incorrect - BPD is almost fully proven to be a disorder of mostly genetic and neuro-anatomical nature. You're born with the disorder, but the symptoms isn't necessarily readily visible until a certain age.

 

Here, check out my prototypical paper on the subject, and judge for yourself if a redefinition of the disease is in its order:

 

 

Disturbances in the Cholinergic system in Borderline Personality Disorder - possible avenues of treatment, and a plea for a change of ethiology and name

 

1. fMRI studies prove that BPD is a neuropsychiatric disorder - suspected pathology is a faulty Fronto-amygdal loop. (compare to ADHD: Fronto-Striatal, or SCT: Fronto-Parietal)

 

2. Study proves that BPD-ers have abnormally high choline-production.

 

3. Another study shows that the Alpha-7-nicotinic acetylcholine receptor is a very important site in the Amygdala - controlling outward traffic to other networks. (like the PFC!)

 

4. The effects of Alpha-7 modulating compounds like Memantine and Lithium is found.

 

5. Piracetam reports of effects on BPD is found.

 

6. aCh-modulation hypothesis is born - combining knowledge from several sources! It ties everything together nicely...

References:

------------------- PFC and Amygdala:

 

 

Borderline personality disorder is a heritable brain disease

http://www.mdedge.co...order-heritable

 

Brain structure and function in borderline personality disorder
http://link.springer...0429-012-0379-4

 

Orbital frontal and amygdala volume reductions in obsessive-compulsive disorder.

https://www.ncbi.nlm...pubmed/10530633

 

Evidence of abnormal amygdala functioning in borderline personality disorder: a functional MRI study.

https://www.ncbi.nlm...pubmed/11522264

 

Amygdala-prefrontal disconnection in borderline personality disorder.

http://www.ncbi.nlm....pubmed/17203018

 

Neural Correlates of Disturbed Emotion Processing in Borderline Personality Disorder: A Multimodal Meta-Analysis.

http://www.ncbi.nlm....pubmed/25935068

 

Behavioral Inhibition System activity is associated with increased amygdala and hippocampal gray matter volume: A voxel-based morphometry study

http://www.sciencedi...05381190600797X

 

Acetylcholine connection:

 

Aberrant DNA Methylation of rDNA and PRIMA1 in Borderline Personality Disorder

http://www.ncbi.nlm....les/PMC4730312/

 

 

α7-Containing nicotinic acetylcholine receptors on interneurons of the basolateral amygdala and their role in the regulation of the network excitability.

http://www.ncbi.nlm....pubmed/24004528

 

Depressive response to physostigmine challenge in borderline personality disorder patients.

http://www.ncbi.nlm..../pubmed/9326751

 

Possible varenicline-induced paranoia and irritability in a patient with major depressive disorder, borderline personality disorder, and methamphetamine abuse in remission.

http://www.ncbi.nlm....pubmed/19011454

 

Possible connection between aCh and NAA

Neurochemical alterations associated with borderline personality disorder.

http://www.ncbi.nlm....pubmed/25817526

 

Basal forebrain moderates the magnitude of task-dependent amygdala functional connectivity

http://europepmc.org...cles/pmc4381234

 

N-Acetylaspartate in the CNS: From Neurodiagnostics to Neurobiology

http://www.ncbi.nlm....les/PMC1919520/

 

Fluctuations in Acetylcholine-levels as a result of fluctuations in sex-hormones

 

Dietary choline requirements of women: effects of estrogen and genetic variation1,2,3

http://ajcn.nutritio.../92/5/1113.full

 

Menstrual cycle-related brain metabolite changes using 1H magnetic resonance spectroscopy in premenopausal women: a pilot study.

http://www.ncbi.nlm....pubmed/11231099

 

 

 

The Alpha-7-receptors role as primarily a behavioural regulator, and not of peripheral activity:

Alpha7-nicotinic acetylcholine receptor subunit is not required for parasympathetic control of the heart in the mouse.

http://www.ncbi.nlm....pubmed/15797970

 

Role of central nicotinic and beta-adrenergic receptors in the onset and further development of tail-tremor induced by repeated nicotine administration to rats.

http://www.ncbi.nlm..../pubmed/9151294

 

Evidence of Piracetam, a modulator of the Cholinergic system for the treatment of excessive emotionality.

 

Double-blind, placebo-controlled trial on the effect of piracetam on breath-holding spells.

http://www.ncbi.nlm....pubmed/22302459

 

Anecdotal evidence from self-professed sufferers of BPD regarding the effects of Piracetam on the disease:

 

http://be-a-betterma...brain-drug.html

"My wife who has Borderline Personality Disorder (BPD), finds that Piracetam helps her tremendously. It helps keep her wild mood swings and perceptions under control."

 

https://www.reddit.c...tam_kicking_in/

"Immediately. When I first took piracetam I didn't notice anything, but that was before I had anxiety/borderline issues... piracetam was sort of a last ditch effort since I had it on my shelf, really helped me get back on track!

edit I take ~800mg when I need it now, been having good luck with other stuff though like L-phenylalanine"

 

http://nootriment.co...for-depression/

“When I started to use Piracetam, I noticed some stimulating effects like increased mental and physical activity, decreased fatigue and trouble sleeping. Later on my severe mood swings (because of BPD), impulsivity and inadequate behavior started to disappear. I became more active, very productive, no more sluggish in the morning, positive and noticed that depressive symptoms are gone. – Parapsychiatrist"

 

http://www.depressio...total-recovery/

"I'd like to share my experiences and thoughts what could have caused my recovery (from bipolar, insomnia and severe manifestation of bpd)

Piracetam course was supposed to last only month, but because of such 'magical' effects, my doctor allowed me to continue using it."

 

http://forum.bodybui...d.php?t=5185783

"I've shown symptoms ranging from bipolar disorder, borderline personality disorder, ADD, depression and obsessive compulsive disorder.

Well odd thing is that when I cut back on the choline bitartrate, I actually started to feel better. - Random907"

 

Potential candidates for treatment: novel antidepressants with Alpha-7-nicotinic antagonistic properties

 

HNK and DNK

Sub-anesthetic concentrations of (R,S)-ketamine metabolites inhibit acetylcholine-evoked currents in α7 nicotinic acetylcholine receptors

http://www.ncbi.nlm....les/PMC3534778/

 

 

 

 

As for BPD-ers being depressed, well, that's common health-care knowledge! They're at the top of the suicide-numbers, sadly.
 

 

*I just realized that I've been using Scandinavian definitions, and as such, what I should REALLY be saying, is "Neurodevelopmental Disorder"

 

http://dsm.psychiatr...890425596.dsm01

 

 

References:

-------------------

Borderline Personality Disorder

http://focus.psychia...journalCode=foc

 

 

I find this very interesting as I'm diagnosed with Histrionic Personality Disorder, which shares a few traits with Borderline. It's not beyond the realm of possibility that they could just be different presentations of the same neurological deviations.

 

On a related note, is anybody here familiar with the theory of Reward Deficiency Syndrome or similar genetic deficits in D2 and possibly other dopamine receptors?

 

A bit of background info: I was basically born with anhedonia. The positive effects of achievement based reward - in addition to motivation, delayed gratification, goal-oriented behaviour and excited anticipation - are completely alien to me. Quite simply, I have never not been bored, which could easily have progressed into pathological Histrionic behaviour in a compensatory sense (theoretically).

 

I was wondering if anybody here who suffers from extreme anhedonia, suicidal boredom and/or a Cluster B (Borderline, Histrionic, Narcissistic, Antisocial) Personality Disorder has benefitted from NSI-189. I'm very interested in its reported effects and to be honest, my mental health situation is getting desperate. I'd love to hear how NSI has affected people with a similar symptomatic profile to myself, if such a person exists on this forim.

 

The only other substance I've found that has the potential to close the metaphorical Grand Canyon of my Reward Deficiciency is Selegiline, but because I'm currently taking SSRI medication, that really is a last resort. Modafinil gives me complete insomnia at just 50mg. Tianeptine Sulfate is mildly beneficial, but my scales recently broke and volumetric dosing with the Sulfate salt is out of the question.

NSI-189 is my only remaining basket. I have no choice but to put all my eggs in it. If you started taking this substance to ameliorate issues even slightly similar to mine, then your input and feedback would be beyond valuable. Thank you in advance.

 

✪ EDIT: StinkorNinjor, isn't Bupropion proven to be quite an effective antagonist at Alpha-7-nicotinic receptors? Would you say it has any potential to ameliorate symptoms of emotional instability found in Borderline (and Histrionic) patients?

 

D R A M A C H I A V E L L I A N

X

Edited by dramachiavellian, 10 February 2017 - 08:04 PM.

[jaiho]

 

I was wondering if anybody here who suffers from extreme anhedonia, suicidal boredom and/or a Cluster B (Borderline, Histrionic, Narcissistic, Antisocial) Personality Disorder has benefitted from NSI-189. I'm very interested in its reported effects and to be honest, my mental health situation is getting desperate. I'd love to hear how NSI has affected people with a similar symptomatic profile to myself, if such a person exists on this forim.

 

Yep that would be me. My condition is more an extreme Anhedonia than depression symptoms, with avoidance/anti social behaviors.

NSI-189 helped it more than anything i've tried, except perhaps a trial of Ketamine, which is more a short term solution.

Though it isn't 100% relief, it definitely helps me become more immersed in life.

 

[dramachiavellian]

 

 

I was wondering if anybody here who suffers from extreme anhedonia, suicidal boredom and/or a Cluster B (Borderline, Histrionic, Narcissistic, Antisocial) Personality Disorder has benefitted from NSI-189. I'm very interested in its reported effects and to be honest, my mental health situation is getting desperate. I'd love to hear how NSI has affected people with a similar symptomatic profile to myself, if such a person exists on this forim.

 

Yep that would be me. My condition is more an extreme Anhedonia than depression symptoms, with avoidance/anti social behaviors.

NSI-189 helped it more than anything i've tried, except perhaps a trial of Ketamine, which is more a short term solution.

Though it isn't 100% relief, it definitely helps me become more immersed in life.

 

 

it took me a long while to figure out that i don't have depression - at least not in the classical sense - and that my inertia is due to the severe anhedonia you described.

 

As for StinkorNinjor's case that Personality Disorders are linked to high levels of Acetyl/Choline, i wish to add my further research on Selegiline, which yielded conclusive evidence that its MAO-B inhibiting properties elevate levels of Acetylcholinesterase, the enzyme responsible for breaking down Acetylcholine. Furthermore, selective MAO-B inhibition prevents the breakdown of dopamine with comparatively minimal D2 receptor downregulation, I would be inclined to believe that using Seligiline in conjunction with NSI-189 promises significant potential to improve quality of life for those who suffer from Anhedonia and/or Personality Disorders.

 

I've noticed many members on this forum claiming to get positive results combining NSI-189 with non-selective MAOIs such as Moclobemide, so i presume co-administration is relatively well tolerated. As for my personal situation (being on an SSRI), I am very aware of the propensity to develop Serotonin Syndrome here. My current plan is to stick to an oral dose of 2.5mg selegiline per day. If adverse reactions resembling Serotonin Syndrome manifest in any way, I thankfully have a few weeks' supply of atypical antipsychotic medication to hand. I wish to announce very clearly that I would not advise others to take these risks. To put it bluntly, allowing the current severity of my mental state to continue poses equal, if not greater risks than taking this stack. It would be unnecessary to go into much more detail about this, but in my current, personal situation, this is where I am at the moment. I can assure anyone reading this that I have deliberated on the matter extensively.

 

D R A M A C H I A V E L L I A N

X

 

 

 

Edited by dramachiavellian, 11 February 2017 - 02:10 AM.

[muntjac]

I've developed a possible side effect after 19 days of 20 mg phosphate BID, all spicy food - black pepper, ginger, jalapenos, curries - cause intestinal pain. The first time it happened was after a particularly spicy meal, the pain was so intense I thought I had food poisoning. This has never happened to me before, I don't know what else could have caused such a dramatic intolerance.

[Mind_Paralysis]

I've developed a possible side effect after 19 days of 20 mg phosphate BID, all spicy food - black pepper, ginger, jalapenos, curries - cause intestinal pain. The first time it happened was after a particularly spicy meal, the pain was so intense I thought I had food poisoning. This has never happened to me before, I don't know what else could have caused such a dramatic intolerance.

 

Curious...!

 

You are the first such case I've seen mentioned - however, it does play into the greater puzzle of the drugs effects - heightened senses, or sensoric sensitisation, certainly seems to be a feature of the drug - PAIN in particular seems to be commonly mentioned - so it's not unreasonable to attribute it to NSI-189 - especially when you take into mind that capsaicin and other spices work through direct effects on the nerves - increases activity by way of the neurotransmitters which register heat does, I believe - hence the "hot" sensation.

 

Have you noticed any increased sensitivity to ACTUAL heat as well? Like, do you not shower as hotly, or does a hot bath bother you now, wheras it wouldn't have before?

Edited by Stinkorninjor, 12 February 2017 - 09:11 PM.

[Turnbuckle]

I've developed a possible side effect after 19 days of 20 mg phosphate BID, all spicy food - black pepper, ginger, jalapenos, curries - cause intestinal pain. The first time it happened was after a particularly spicy meal, the pain was so intense I thought I had food poisoning. This has never happened to me before, I don't know what else could have caused such a dramatic intolerance.

 

 

Maybe your body knows something--Capsaicin impairs proliferation of neural progenitor cells and hippocampal neurogenesis in young mice.

[Mind_Paralysis]

 

✪ EDIT: StinkorNinjor, isn't Bupropion proven to be quite an effective antagonist at Alpha-7-nicotinic receptors? Would you say it has any potential to ameliorate symptoms of emotional instability found in Borderline (and Histrionic) patients?

 

 

I think Bupropion has potential, but so does Memantine and Ketamine-metabolites (in particular) as well.

Last I checked, the Alpha-7-antagonistic properties of Bupropion was considered fairly weak though? As I understand it, the other nAch-receptors have prominence before Alpha-7 - there's also the fact that we don't know what happens when the modulating properties of Alpha-7 is interrupted by nAch-1-6 and NRI as well as DRI -actions - could be that this interferes with efficacy.

 

Anyways, Bupropion isn't known to be any more useful than SSRI's for Borderline personality-disorder, so hence another reason why I have my doubts. On the other hand, it hasn't been trialled as a mono-treatment for BPD, so it does warrant at least a trial to determine efficacy.

 

 

It should be noted btw, that I've only researched aCh-activity in Borderline - there's nothing, as far as I know, implying that aCh-irregularities is a potential core-symptom in Histrionic and Narcicisstic Disorders - so I don't really claim that it would be useful in those disorders as well.

 

In fact, from what little I can find regarding the neuroanatomical pathology of Histrionic Disorder, it would appear as if there are some implications of abnormally heightened NOREPINEPHRINERGIC, or Adrenergic, activity in that disorder.

 

This could certainly explain the somewhat more explosive, and panicky traits which come with that disorder, in comparison to NPD and BPD. But it's really hard to tell - there's hardly any research on HPD for some reason - at least not to the same extent as the other Cluster B -disorders.

[muntjac]

I haven't noticed heat intolerance or increased feelings of pain elsewhere. I can live without capsaicin, but no black pepper or ginger?   About two years ago I was treated aggressively for Lyme disease, there might be some damage to my gut that is flaring up. 

[tdmonster99]

tdmonster99,

 

thank you for the input. Did/do you by any chance also have the "blank mind" dp? This, along with the other symptoms that come with it, is the most devastating for me. With blank mind, I suffer from flat affect, complete disconnection from others, no pleasure in anything, and no drive/motivation to do anything. If NSI-189 can reverse this and give me back my "internal monologue," it would be a miracle.

 

As some of the following replies mentioned, I do not think NSI-189 in isolation will have the magnitude of effect you are looking for with respect to internal monologue and flow of thought.  The combination of NSI-189, regular anaerobic and especially intense aerobic exercise, improved diet and nutrition, combined with an enriched environment of peers I enjoy and work I feel challenged by has had the most profound effect. 

[Twindaddy37]

 

tdmonster99,

 

thank you for the input. Did/do you by any chance also have the "blank mind" dp? This, along with the other symptoms that come with it, is the most devastating for me. With blank mind, I suffer from flat affect, complete disconnection from others, no pleasure in anything, and no drive/motivation to do anything. If NSI-189 can reverse this and give me back my "internal monologue," it would be a miracle.

 

As some of the following replies mentioned, I do not think NSI-189 in isolation will have the magnitude of effect you are looking for with respect to internal monologue and flow of thought.  The combination of NSI-189, regular anaerobic and especially intense aerobic exercise, improved diet and nutrition, combined with an enriched environment of peers I enjoy and work I feel challenged by has had the most profound effect. 

 

 

Well said, and may I also add in that a healthy meditation practice is key. I have also found that elimination of all social media (aside from this forum), in isolation, has allowed me to reconnect with people on a real level. I found at first with its elimination, to feel a bit disconnected, perhaps a little "out of the loop" or lonely, followed by a natural yearning to connect with people as we used to do, with phone calls and face to face encounters. In my opinion its all about reversing the damage modern culture has done to our own intuition by bombarding it with constant stimulus. The idea is to decrease as much stimulus as possible, get uncomfortable in the silence, create more mental band-with, reconnect with self- then reconnect in a healthy fashion to the outside world again. I imagine this has a similar effect giving up porn does to the ability to connect to women/girlfriends and wives. We must take it back to the basics. NSI is just a little icing on the cake.

 

 

Edited by Twindaddy37, 13 February 2017 - 08:54 PM.

[Twindaddy37]

I haven't noticed heat intolerance or increased feelings of pain elsewhere. I can live without capsaicin, but no black pepper or ginger?   About two years ago I was treated aggressively for Lyme disease, there might be some damage to my gut that is flaring up. 

 

Very interesting, i noticed this exact same thing after i enjoyed a ginger beer, specifically with capsacin in it the other night (incredible acid burn type feeling in gut). But it was an isolated incident that i have not noticed with any other spices. I have noticed the gut being slightly more sensitive since NSI, perhaps more gas than usual, more likely to get stomach upset. But i also have been consuming MCT oil since the start of NSI, which is supposed to heal gut damage. 

[aperson444]

I'm curious, I have read some anecdotal evidence (i.e. on Reddit) of NSI-189's ability to enhance cognition and I know that NSI-189 promotes neurogenesis in the hippocampus, but has anyone here had experience with improved memory following a course of NSI-189 treatment? I acquired some moderate brain damage from a lack of oxygen to the brain (via an opioid overdose) about six months ago and MRIs showed that the damage was primarily focused on my hippocampus. I've been taking NSI-189 phosphate from Strangelove at 40 mg a day for 8 days now. At what point should I be looking for improvement in cognition if it happens at all? I understand that it's too soon to tell if there is any cognitive improvement, but I've noticed that my Lumosity scores have stayed the same or decreased slightly (though this may be due to a lack of sleep). Moreover, what other nootropics should I look into to improve my memory (which was impacted the most by the injury)?

[IP3]

I am on my second day on nsi and i feel extremely tired. Will it fade with time? Caffeine lost its stimulant properties.

[Water Buffalo]

I'm curious, I have read some anecdotal evidence (i.e. on Reddit) of NSI-189's ability to enhance cognition and I know that NSI-189 promotes neurogenesis in the hippocampus, but has anyone here had experience with improved memory following a course of NSI-189 treatment? I acquired some moderate brain damage from a lack of oxygen to the brain (via an opioid overdose) about six months ago and MRIs showed that the damage was primarily focused on my hippocampus. I've been taking NSI-189 phosphate from Strangelove at 40 mg a day for 8 days now. At what point should I be looking for improvement in cognition if it happens at all? I understand that it's too soon to tell if there is any cognitive improvement, but I've noticed that my Lumosity scores have stayed the same or decreased slightly (though this may be due to a lack of sleep). Moreover, what other nootropics should I look into to improve my memory (which was impacted the most by the injury)?

Well, in the 1b study they didn't see a significant improvement in hippocampal volume in 28 days. They are conducting the 90 day Phase 2 study right now. Hopefully, they'll see significant changes at that time. I've been taking NSI-189 for about 13 months. I think that the improvement in memory becomes more profound with more initial damage, and, of course, time of treatment. My memory has definitely sharpened, but I can't give you specifics on the time interval when it became statistically significant. Maybe 90 days? 

 

NSI-189 was shown in animal models to not only increase hippocampal volume, but, also, synaptogenisis. It was also recently found to improve LTP and STP in mice that were bred to exhibit deficits in learning and LTP. http://investor.neur...&d=1&id=2179002

 

I also added in bacopa about 6 months into my treatment with NSI-189. I was looking to proliferate my dendrites https://www.ncbi.nlm...pubmed/21892534. I started with bacognize for roughly 6 months, but I just recently switched over to Synapsa. I haven't noticed a huge difference in sleep inducing effects between the two, but, then again, I've also been taking 40-80 mg of NSI-189 phosphate without any side-effects past the first few days of headaches. Synapsa is supposed to be more energizing than Bacognize. It will take around 6 weeks to notice any changes in memory, but there have been numerous studies on healthy humans to corroborate increases in cognition.

https://www.ncbi.nlm...les/PMC5075615/

https://www.ncbi.nlm...pubmed/24252493

https://www.ncbi.nlm...pubmed/22747190

Edited by Water Buffalo, 17 February 2017 - 08:37 AM.

[Giles Westwood]

Hi Peeps,

 

I have purchased some NSI-189 and I'm also thinking about investing in Neuralstem. FYI this was announced:-

 

http://investor.neur...rint&ID=2246615

 

I've been following the thread and it appears beneficial to some people but others complain of fatigue. Is there a way we could collect together a poll of all the symptoms or something?

 

Personally I'm holding off taking NSI myself until I've fully investigated the potential of improving my methylation situation because I have multiple defects in that area so I'm going to try some specific b12 forms in liquid form.

[Mind_Paralysis]

I am on my second day on nsi and i feel extremely tired. Will it fade with time? Caffeine lost its stimulant properties.

 

It's far too early to tell - for many it does fade, but for others it does not.

 

Give it at least a week before you start changing your dosing-regimen - perhaps you're on too high of a dose? How much are you taking? Are you weighing it up, so you actually know the dosing?

 

For me, the fatigue never quite goes away - I'm on it again now, and I've started noticing a bit of it - but it's mostly at the higher dosages - 40 mg+, so I'm only doing 20 mg once daily right now, and both fatigue and anxiety is markedly improved from 40 mg.

 

On another note - yesterday was the first day that I noticed hyper-emotionality - at 20 mg for about 7 days - I started weeping from reading a book yesterday, which is unusual for me. I do not notice any such effects today, but today I am also on 35 mg Atomoxetine, which does dampen emotions to some extent, in me at least.

 

Also got Magnesium-L-Threonate today! They had a special for 40% off on iHerb so I nabbed some up a week or so ago! = ) With this in hand, I am considering increasing the dosage to 40 mg tomorrow, to get some sh*t going! ; )

 

Still, I might hold off on doing that until I have Armodafinil (ordered two days ago! from modafinil bank - hopefully they will come through) or Modafinil.

 

Modafinil is at least two weeks away though, so perhaps it's better to wait... It's hard for someone like me to wait though - I've been incapacitated by Burnout for 6 months now! God-damnit... In theory, NSI-189 should repair the damage, but I gotta' be on it consistently to get neurogenesis going - and that's damn hard, when it gives me fatigue and anxiety.

[Twindaddy37]

I'm curious, I have read some anecdotal evidence (i.e. on Reddit) of NSI-189's ability to enhance cognition and I know that NSI-189 promotes neurogenesis in the hippocampus, but has anyone here had experience with improved memory following a course of NSI-189 treatment? I acquired some moderate brain damage from a lack of oxygen to the brain (via an opioid overdose) about six months ago and MRIs showed that the damage was primarily focused on my hippocampus. I've been taking NSI-189 phosphate from Strangelove at 40 mg a day for 8 days now. At what point should I be looking for improvement in cognition if it happens at all? I understand that it's too soon to tell if there is any cognitive improvement, but I've noticed that my Lumosity scores have stayed the same or decreased slightly (though this may be due to a lack of sleep). Moreover, what other nootropics should I look into to improve my memory (which was impacted the most by the injury)?

 

Can you explain the extent of this event that happened to you? How long were you out for? Were you revived or narcaned?

[aperson444]

 

I'm curious, I have read some anecdotal evidence (i.e. on Reddit) of NSI-189's ability to enhance cognition and I know that NSI-189 promotes neurogenesis in the hippocampus, but has anyone here had experience with improved memory following a course of NSI-189 treatment? I acquired some moderate brain damage from a lack of oxygen to the brain (via an opioid overdose) about six months ago and MRIs showed that the damage was primarily focused on my hippocampus. I've been taking NSI-189 phosphate from Strangelove at 40 mg a day for 8 days now. At what point should I be looking for improvement in cognition if it happens at all? I understand that it's too soon to tell if there is any cognitive improvement, but I've noticed that my Lumosity scores have stayed the same or decreased slightly (though this may be due to a lack of sleep). Moreover, what other nootropics should I look into to improve my memory (which was impacted the most by the injury)?

 

Can you explain the extent of this event that happened to you? How long were you out for? Were you revived or narcaned?

 

I woke up the next morning without having to be revived or treated with naloxone, but I was suffering from significant memory impairment. A trip to the ER and a subsequent MRI showed damage to the tails of my hippocampus (hippocampi?). They defined this "damage" as decreased BOLD diffusion in the tails of the hippocampus indicating severely decreased blood flow to those regions. My assumption is that I ODed for long enough to sustain brain damage but was able to resume breathing within the time frame required before brain death or extremely severe brain damage occured, so I must've consumed just enough opioid to depress my respiration for a short period of time. I can't be sure, but I think what happened was I fell asleep rapidly after ingesting the opioid and stopped breathing for a certain period of time in my sleep, hence I woke up the next morning on the floor of my room, alive, but with severely impaired memory (I couldn't remember what I'd had for breakfast for at least a month if not 2-3 months afterwards). With this information, I believe that the damage was restricted to the hippocampus, which is particularly sensitive to oxygen deprivation.

[Hyperflux]

What's the equivalent of 40mg phosphate to freebase?

[aperson444]

What's the equivalent of 40mg phosphate to freebase?

40 mg of the phosphate salt is around 32 mg of freebase (31.77 mg). Calculated based on a molar mass of 462 g/mol for phosphate and 367 g/mol for freebase.

[Mind_Paralysis]

 

What's the equivalent of 40mg phosphate to freebase?

40 mg of the phosphate salt is around 32 mg of freebase (31.77 mg). Calculated based on a molar mass of 462 g/mol for phosphate and 367 g/mol for freebase.

 

 

That's some good calculation there! = ) We could definitely use a sort of conversion-table for this stuff.

 

A note though, you should probably include how the oral bioavailability is drastically lower for Freebase when compared to Phosphate - hence Sublingual is the preferred administration-route of NSI-189 Freebase.

 

When looking at the reports in the thread and on Reddit, it seems as if the actual THERAPEUTICAL dosing-equivalent is different from the calculated one - you actually seem to need a lot more oral freebase than you need oral phosphate, even though in theory, freebase should be dosed lower. Well, seems like there's a reason Neuralstem is going with phosphate for their trials...

 

As to what that the therapeutic equivalence is... well, beats me! Maybe one should go with a halving of the oral equivalent, when comparing? Sublingual freebase seems to be about twice as strong though, compared to oral phosphate. (dunno' what this means for sublingual phosphate though...)
 

So, perhaps something like this?

 

 

a) 40 mg oral Phosphate = 20 mg sublingual freebase

 

b) 40 mg oral phosphate = 32 x 2 mg oral freebase = 64 mg oral freebase