#5521
Posted 28 July 2017 - 09:21 AM
To those of you that have sought to treat similar non-MDD symptoms with NSI-184, would you recommend it for a short-term course? Why/why not? Are there other nootropics that you'd recommend more for this? (ie N-acetyl semax amidate, P-21, etc?)
I'd really appreciate your anecdotal intel!
«βμ»
#5522
Posted 28 July 2017 - 02:10 PM
#5523
Posted 28 July 2017 - 07:36 PM
Considering NSI-189 effectiveness, let's not forget the following:
1. Virtually all antidepressants ever developed are proven to be no more effective than active placebos ( https://www.ncbi.nlm...les/PMC4172306/ ).
NSI-189 is a non-psychotropic drug essentially devoid of any side-effect. That means that it doesn't get the psychological "its working" boost in the test subjects. That's a considerable disadvantage in such a short trial. You have taken it, you know that the difference to Prozac, Ritalin and even Aspirin is obvious: you can't tell it apart from an inert pill at all. In a blinded trial any small effectiveness over regular placebo, no matter how small, has a whole lot more weight than it has with any other antidepressant.
2. The Neuralstem trial is merely 12 weeks long.
How long does it really take to recover from depression, and why is inert placebo so effective (over 50% to remind you)? What is the actual cause of any particular depressive episode? The answer is, that its all just not that simple, as that it could be answered by 12 weeks of observation and some before/after test score. Really recovering from depression might be up to changing habits, switching jobs, sleeping it off while in inpatient therapy, changing your diet, changing your lifestyle, getting your partner, friends and family to be more considerate. Busted thyroid, adrenal glands, or getting adapted to, or rid of god knows which bacteria or toxins you were exposed to for some time. Does a 12 week trial consider all that? No. Its only concerned with some kind of patient-deceiving, mind-numbing booster pill that, as we already know from SSRI, wreaks some havoc in your system (weight gain, diabetes, etc.) and by all chances causes the reverse of the initial effect on the long run ( https://www.madiname...antsdepression/ ). If it even had a positive effect to begin with.
A drug like NSI-189 designed to fundamentally improve cognitive functioning and thereby outcomes on the very long run - vs. drugs specifically designed by the constraints of timeframes and questionnaires which are so simplistic that they have to be unreal to people's actual lives?
Surely that's rather a hard nut to crack.
People reporting on the internet may suffer from placebo, testing new drugs they order themselves online. But really: what kind of delusions if not mental retardation do people suffer from, who blindly swallow pills which they can't even remember the name of, that consistently make them obese, tired, diabetic, suicidal, plus possibly otherwise mentally and physically damaged for life - while its long proven that those increase relapse rates of their disorder by two to three fold at least over the years? Think about that. If you research and buy your own drugs, you will be born a critic at least, and a whole lot more wary and aware of anything that might go wrong. Common sense tells. If NSI-189 would make me gain 8 kilograms within 6 month, it would have long hit the garbage can. No matter if it all just happened by chance or not.
3. In my eyes, NSI-189 is essentially not even an antidepressant
No more than that a CPU upgrade would qualify as improving the code of a chess program. But of course it most likely increases its chances of winning. To me, its a drug that can provide very valuable cognitive advantages. Such as increased learning speeds, better memory and faster adaptation to new situations and new knowledge. It increases the speed at which you can comprehend and deal with new things, new ideas, new circumstances, new mindsets, whatever the shit it is. That doesn't mean that it makes you "less sad" by default. Or that works against some fucked up mental garbage machinery, that you have constructed in your mind while trying to keep your head over water, in some huge river of shit at the bottom of human existence, for the past 5 years. Really its just another tool, like psychedelics can be. It doesn't mean that you understand the meaning of life, nature and the universe just because you swallow them.
Edited by AOIministrator, 28 July 2017 - 07:59 PM.
#5524
Posted 28 July 2017 - 08:04 PM
While some of the side notes are a bit far off and the general tone can be off putting, i agree for the most part with the sentiment. It's a cognitive enhancer first and foremost. I just switched job to a fast paced one on logistics and everyone, including me, is impressed with my rate of learning. Concepts and data just stick on my mind.
#5525
Posted 28 July 2017 - 08:08 PM
It's odd that suddenly people are all screaming "Placebo! Placebo! We always knew it!" or even accuse responders as being shills for nutraceutical companies! As of now, there is hardly any hard data available about the phase 2 trial. From what is available we can gather that NSI-189 DOES HAVE antidepressant effects and it showed across multiple depression scales even though it failed to reach statistical significance on the MADRS. By how much we don't know. This fact alone doesn't make it a poor antidepressant, just like performing well on the MADRS doesn't automatically make a drug a good antidepressant. You guys should read up on the problems of measuring the outcomes of depression treatments with scales.
For instance, a drug that elevates mood and overall positive affect (the core property of a true antidepressant), but at the same time worsens sleep and anxiety will probably fare not so well on depression scales even though the patient might feel much improved.
Likewise, a drug like Mirtazapine, whose pharmacological profile isn't indicative of any antidepressant effects whatsoever, has somehow managed to receive approval as antidepressant probably by virtue of improving sleep and anxiety and thereby indirectly increasing wellbeing. Since anxiety is a notorious companion of most depressive states, treating it rather than the actual depression can lead to statistically significant outcomes on depression rating scales. IMO this is also what SSRI and SNRI, which are useful anxiolytics, do for most people who are responders (not too many).
ALSO, most people failed to realize that NSI-189 did reach statistical significance on one of their secondary enpoints which was the self-reported SDQ questionnaire! So from a patient's perspective it did offer real benefits for depression even though it didn't show up on the MADRS. So yes, officially the trial was a failure, but looking closer at the data could still lead to a happy end. Let me explain:
IMO Neuralstem was overly optimistic with reaching a large effect size of p = 0.5. When using item rich depression scales like the Hamilton17 (HAM-D17) or the MADRS10 the effect size will always decrease. Even reference antidepressants like venlafaxine and escitalopram typically don't reach p = 0.4 on such scales in clinical trials. So setting the bar at 0.5 made me feel uneasy from the very beginning.
With that in mind, I can still see the study taking a positive spin if the effect size turns out to be at around p = 0.4 or slightly less, especially if cognition data will meet or even exceed its efficacy endpoint. Neuralstem would then own a drug with good antidepressant properties, crowned with being a potent cognitive enhancer. Since cognitive impairment is a debiliating state for any sufferer, people can imagine how much sought after a drug would be that cleared up your head from brain fog, memory and concentration issues.
Furthermore, NSI-189 appears to have an excellent safety and side effects profile. It's seems to be a highly tolerable drug unlike the majority of antidepressants ou there!
For this reason, nobody should discard self treatment with NSI-189 solely based on Neuralstem's latest PR about failing to reach statistical signifiance on the MADRS. Measuring antidepressants with these scales is a tricky, complex business that requires thorough analysis of all trial data before drawing any firm conclusions. We need to have some patience until we see the first comprehensive paper about the trial being published. Could be weeks or months.
Until then, don't forget: NSI-189 reached statistical significance on the self-reported SDQ! It's just another scale, but:
"the SDQ represents a valid and novel measure that assesses a more complete spectrum of physical and cognitive depressive symptoms than previous scales, and will be a valuable new tool in efforts to better characterize depression and identify and administer more targeted interventions."
Edited by focus83, 28 July 2017 - 08:11 PM.
#5526
Posted 28 July 2017 - 10:53 PM
I don't know if I qualify to have too much of an opinion, having no first-hand experience with NSI-189, but my reaction to the somewhat poor (or at least more poorly than anticipated) performance of this novel chem on MDD is similar: that, more than likely, Neurostem was trying to put a square peg in a round hole. This is surely because the round hole is a crazy-profitable one--antidepressants are huge business (I can't help but remember scenes from the movie Brain Candy as I write this: "it reaches into your head--chemically...") and the way the system works is that you've got to choose a disease/disorder to have "on label" for your new drug. The more prevalent the disorder, the higher chances of you recouping your research costs & turning a profit, right? From a purely pharma business standpoint, MDD makes sense as a target for NSI-189--but even if the drug was an abject failure in the metrics of the trials, it can still have have great worth to certain individuals with specific challenges & goals, some of which might be overcoming some manner of depression.
If you're trying to rebuild an engine (let's say.. on a 1966 International Scout mmm yes) using only a 7/16th inch hex key, you're an idiot doomed for failure. If you're trying to rebuild that engine with every tool you have, along with the knowledge that you will certainly have to not only buy tools not yet in your collection, but talk to people who know more about certain procedures than you & learn some new skills--then that 7/16th hex key could very well be your most essential tool. I'm here to talk about the tool, not my grand mechanical strategy, so Fuzzmonkey & co, try to 1) stay on topic, and 2) avoid being condescending. Thanx!
«βμ»
Edited by br1n3dm1nd, 28 July 2017 - 10:58 PM.
#5527
Posted 29 July 2017 - 10:26 AM
I have to say, this has been quite sobering news - it's easy to become enamored with a drug, if it just so happens to give YOU some kind of effect - then you think it will be the same for everyone... obviously not.
There are many causes for depression, and I do think NSI-189 could, and IS, useful for treating some of the aspects of the disease. However, not necessarily for everyone.
There's of course also the question - what does this mean for the Neurogenesis-hypothesis of Depression? Is it just that NSI-189 is too friggin' WEAK to affect human brains to the extent necessary? Or is it just that neuroplasticity in the hippocampus does not play as big of a role as some of us started to believe?
Personally, since I didn't use NSI-189 to treat traditional depression, but OCCUPATIONAL BURNOUT, which is a fairly different disease, just comorbid with depression and anxiety, I still think there is potential in the drug - I'd be very interested in seeing the drug trialled as an adjunct to antidepressants, focusing on the treatment of OB, not depression.
Howdy, all. Brand new Longecitite here =) hoping for a little help. Here's my situation: I work 13-15+ hr night shifts in a high-stress hospital environment 3-4x/wk, and am continuously on the verge of burnout... was very interested in NSI a few days ago, joined Longecity to seek a vendor, etc. Of course, I've since read about Neuralstem's failed phase II trials for MDD--and while that is discouraging, I'm not suffering from MDD. Rather, as mentioned above, it's burnout from SWD and sustained stress response, causing chronic fatigue with increased anxiety and recurring anhedonia.
To those of you that have sought to treat similar non-MDD symptoms with NSI-184, would you recommend it for a short-term course? Why/why not? Are there other nootropics that you'd recommend more for this? (ie N-acetyl semax amidate, P-21, etc?)
I'd really appreciate your anecdotal intel!
«βμ»
I've used NSI-189 to great effect in treating the symptoms of occupational burnout - my OB-symptoms come from the fact that I have multiple neurodevelopmental diagnoses, a former abusive Borderline girlfriend, and a terrible wish to prove myself in my particular field.
I eventually ended up so burnt out that I could not even get out of bed - had a hard time feeding myself, talking to anyone, my memory was shot, and the fatigue was through the roof.
NSI-189, in combination with Magnesium-L-Threonate, started working after but a few days! After the first two weeks I already felt about 40% recovered! HOWever... I was too sensitive to the anxiogenic effects of NSI, so I couldn't really use the regular dosage, so I had to lower it - still, some good effects was felt, when I added Tianeptine to the mix as well.
After about a month+ on the drug though, I noticed how the positives, the improvements on memory, cognition, and mood, had begun to flatten out - it was actually eventually, I felt, starting to impair other parts of my mind... it's kind of hard to explain.
But yes, I saw some definitive results from NSI-189 - and for a small note, I was, prior to finally using a combo of NSI-189, Mag-LT and Tianeptine using a combo of Duloxetine and Mirtazapine - "Limerick ROCKET fuel" as it's called - and, IMHO... my own combo, which focuses on the Hippocampus, which is theorized to be damaged to excessive cortisol-exposure in OB, worked a H*LL of a lot better than my prescribed medications.
I shall henceforth call my combo... HIPPO Rocket Fuel! ^^
Cause they all effect the Hippocampus, get it? Just imagine a medicine-box with a colourful hippo, clad in three different colours - inside, the pills are divided into these colours, to be taken together.
NSI-189
Tianeptine
Magnesium-L-Threonate
References for my reasoning, using these combined:
-------------------------------------------------------------------------
Chronic stress, such as OB, causes cortisol-exposure in the hippocampus, to the point that the brain-cells are eventually damaged. As such, neurogenesis, such as that caused by stress-relief and then low-intensity, long-exposure, exercise then reverses the symptoms - but this effect will take YEARS! Unless you cheat...
Chronic Stress Can Damage Brain Structure and Connectivity
https://www.psycholo...nd-connectivity
Stress and glucocorticoids promote oligodendrogenesis in the adult hippocampus
http://www.nature.co...mp2013190a.html
Traumatic stress: effects on the brain
https://www.ncbi.nlm...les/PMC3181836/
Stress Predicts Brain Changes in Children: A Pilot Longitudinal Study on Youth Stress, Posttraumatic Stress Disorder, and the Hippocampus
http://pediatrics.aa...119/3/509.short
Posttraumatic stress disorder: A state-of-the-science review
http://www.journalof...0091-9/abstract
The brain and the stress axis: The neural correlates of cortisol regulation in response to stress
http://www.sciencedi...053811909005837
https://www.ncbi.nlm...les/PMC4911781/
Magnesium has neurogenic, AND anxiolytic effects
Neurogenesis:
Efficacy and Safety of MMFS-01, a Synapse Density Enhancer, for Treating Cognitive Impairment in Older Adults: A Randomized, Double-Blind, Placebo-Controlled Trial
https://www.ncbi.nlm...pubmed/26519439
Enhancement of Learning and Memory by Elevating Brain Magnesium
http://www.cell.com/...47?showall=true
Elevation of brain magnesium prevents synaptic loss and reverses cognitive deficits in Alzheimer's disease mouse model.
https://www.ncbi.nlm...pubmed/25213836
Magnesium Status in Alzheimer's Disease: A Systematic Review.
https://www.ncbi.nlm...pubmed/26351088
Copper delivery to the CNS by CuATSM effectively treats motor neuron disease in SOD(G93A) mice co-expressing the Copper-Chaperone-for-SOD.
https://www.ncbi.nlm...pubmed/26826269
Anxiolysis:
Hippocampal NMDA receptors and anxiety: At the interface between cognition and emotion
https://www.ncbi.nlm...les/PMC2824088/
Hippocampal synaptic plasticity, spatial memory and anxiety
http://www.nature.co...bs/nrn3677.html
This is why it's logical to use the newest, and best formulation of Magnesium to date - MagLT.
Tianeptine - it alters the response to stress, and seems to cause somewhat more hippocampal neurogenesis than SSRI's.
Tianeptine: a review of its use in depressive disorders.
https://www.ncbi.nlm...pubmed/11463130
Tianeptine: An Antidepressant with Memory-Protective Properties
https://www.ncbi.nlm...les/PMC2701287/
Neurobiological and clinical effects of the antidepressant tianeptine.
https://www.ncbi.nlm...pubmed/18072812
The relationship between sluggish cognitive tempo and burnout symptoms in psychiatrists with different therapeutic approaches
http://www.psy-journ...1584-0/fulltext
(just a small article about how ambitious people with SCT often get burnout - which is logical, other neurodevelopmental diseases are also over-represented in OB-patients)
#5528
Posted 29 July 2017 - 01:27 PM
What's the hippocampal neurogenesis of PCP?
It always seems the most fundamental questions in psychiatry remain to be unanswered on purpose. Here, how sudden changes in perception and thought necessarily must influence its growth. No matter if those changes are beneficial or not.
Edited by AOIministrator, 29 July 2017 - 01:35 PM.
#5529
Posted 29 July 2017 - 01:35 PM
I have to say, this has been quite sobering news - it's easy to become enamored with a drug, if it just so happens to give YOU some kind of effect - then you think it will be the same for everyone... obviously not.
There are many causes for depression, and I do think NSI-189 could, and IS, useful for treating some of the aspects of the disease. However, not necessarily for everyone.
There's of course also the question - what does this mean for the Neurogenesis-hypothesis of Depression? Is it just that NSI-189 is too friggin' WEAK to affect human brains to the extent necessary? Or is it just that neuroplasticity in the hippocampus does not play as big of a role as some of us started to believe?
Personally, since I didn't use NSI-189 to treat traditional depression, but OCCUPATIONAL BURNOUT, which is a fairly different disease, just comorbid with depression and anxiety, I still think there is potential in the drug - I'd be very interested in seeing the drug trialled as an adjunct to antidepressants, focusing on the treatment of OB, not depression.
Howdy, all. Brand new Longecitite here =) hoping for a little help. Here's my situation: I work 13-15+ hr night shifts in a high-stress hospital environment 3-4x/wk, and am continuously on the verge of burnout... was very interested in NSI a few days ago, joined Longecity to seek a vendor, etc. Of course, I've since read about Neuralstem's failed phase II trials for MDD--and while that is discouraging, I'm not suffering from MDD. Rather, as mentioned above, it's burnout from SWD and sustained stress response, causing chronic fatigue with increased anxiety and recurring anhedonia.
To those of you that have sought to treat similar non-MDD symptoms with NSI-184, would you recommend it for a short-term course? Why/why not? Are there other nootropics that you'd recommend more for this? (ie N-acetyl semax amidate, P-21, etc?)
I'd really appreciate your anecdotal intel!
«βμ»
I've used NSI-189 to great effect in treating the symptoms of occupational burnout - my OB-symptoms come from the fact that I have multiple neurodevelopmental diagnoses, a former abusive Borderline girlfriend, and a terrible wish to prove myself in my particular field.
I eventually ended up so burnt out that I could not even get out of bed - had a hard time feeding myself, talking to anyone, my memory was shot, and the fatigue was through the roof.
NSI-189, in combination with Magnesium-L-Threonate, started working after but a few days! After the first two weeks I already felt about 40% recovered! HOWever... I was too sensitive to the anxiogenic effects of NSI, so I couldn't really use the regular dosage, so I had to lower it - still, some good effects was felt, when I added Tianeptine to the mix as well.
After about a month+ on the drug though, I noticed how the positives, the improvements on memory, cognition, and mood, had begun to flatten out - it was actually eventually, I felt, starting to impair other parts of my mind... it's kind of hard to explain.
But yes, I saw some definitive results from NSI-189 - and for a small note, I was, prior to finally using a combo of NSI-189, Mag-LT and Tianeptine using a combo of Duloxetine and Mirtazapine - "Limerick ROCKET fuel" as it's called - and, IMHO... my own combo, which focuses on the Hippocampus, which is theorized to be damaged to excessive cortisol-exposure in OB, worked a H*LL of a lot better than my prescribed medications.
I shall henceforth call my combo... HIPPO Rocket Fuel! ^^
Cause they all effect the Hippocampus, get it? Just imagine a medicine-box with a colourful hippo, clad in three different colours - inside, the pills are divided into these colours, to be taken together.
NSI-189
Tianeptine
Magnesium-L-Threonate
References for my reasoning, using these combined:
-------------------------------------------------------------------------
Chronic stress, such as OB, causes cortisol-exposure in the hippocampus, to the point that the brain-cells are eventually damaged. As such, neurogenesis, such as that caused by stress-relief and then low-intensity, long-exposure, exercise then reverses the symptoms - but this effect will take YEARS! Unless you cheat...
Chronic Stress Can Damage Brain Structure and Connectivity
Understanding the burnout experience: recent research and its implications for psychiatry
https://www.psycholo...nd-connectivity
Stress and glucocorticoids promote oligodendrogenesis in the adult hippocampus
http://www.nature.co...mp2013190a.html
Traumatic stress: effects on the brain
https://www.ncbi.nlm...les/PMC3181836/
Stress Predicts Brain Changes in Children: A Pilot Longitudinal Study on Youth Stress, Posttraumatic Stress Disorder, and the Hippocampus
http://pediatrics.aa...119/3/509.short
Posttraumatic stress disorder: A state-of-the-science review
http://www.journalof...0091-9/abstract
The brain and the stress axis: The neural correlates of cortisol regulation in response to stress
http://www.sciencedi...053811909005837https://www.ncbi.nlm...les/PMC4911781/
Magnesium has neurogenic, AND anxiolytic effects
Neurogenesis:
Efficacy and Safety of MMFS-01, a Synapse Density Enhancer, for Treating Cognitive Impairment in Older Adults: A Randomized, Double-Blind, Placebo-Controlled Trial
https://www.ncbi.nlm...pubmed/26519439
Enhancement of Learning and Memory by Elevating Brain Magnesium
http://www.cell.com/...47?showall=true
Elevation of brain magnesium prevents synaptic loss and reverses cognitive deficits in Alzheimer's disease mouse model.
https://www.ncbi.nlm...pubmed/25213836
Magnesium Status in Alzheimer's Disease: A Systematic Review.
https://www.ncbi.nlm...pubmed/26351088
Copper delivery to the CNS by CuATSM effectively treats motor neuron disease in SOD(G93A) mice co-expressing the Copper-Chaperone-for-SOD.
https://www.ncbi.nlm...pubmed/26826269
Anxiolysis:
Hippocampal NMDA receptors and anxiety: At the interface between cognition and emotion
https://www.ncbi.nlm...les/PMC2824088/
Hippocampal synaptic plasticity, spatial memory and anxiety
http://www.nature.co...bs/nrn3677.html
This is why it's logical to use the newest, and best formulation of Magnesium to date - MagLT.
Tianeptine - it alters the response to stress, and seems to cause somewhat more hippocampal neurogenesis than SSRI's.
Tianeptine: a review of its use in depressive disorders.
https://www.ncbi.nlm...pubmed/11463130
Tianeptine: An Antidepressant with Memory-Protective Properties
https://www.ncbi.nlm...les/PMC2701287/
Neurobiological and clinical effects of the antidepressant tianeptine.
https://www.ncbi.nlm...pubmed/18072812
The relationship between sluggish cognitive tempo and burnout symptoms in psychiatrists with different therapeutic approaches
http://www.psy-journ...1584-0/fulltext
(just a small article about how ambitious people with SCT often get burnout - which is logical, other neurodevelopmental diseases are also over-represented in OB-patients)
Man that's great work! I know I got my anhedonia/DP from stress and flooding my brain with dopamine from energy drinks. If Nardil + traneptine doesn't work for me, I'm trying your stuff <3
#5530
Posted 29 July 2017 - 02:39 PM
I have to say, this has been quite sobering news - it's easy to become enamored with a drug, if it just so happens to give YOU some kind of effect - then you think it will be the same for everyone... obviously not.
There are many causes for depression, and I do think NSI-189 could, and IS, useful for treating some of the aspects of the disease. However, not necessarily for everyone.
There's of course also the question - what does this mean for the Neurogenesis-hypothesis of Depression? Is it just that NSI-189 is too friggin' WEAK to affect human brains to the extent necessary? Or is it just that neuroplasticity in the hippocampus does not play as big of a role as some of us started to believe?
Personally, since I didn't use NSI-189 to treat traditional depression, but OCCUPATIONAL BURNOUT, which is a fairly different disease, just comorbid with depression and anxiety, I still think there is potential in the drug - I'd be very interested in seeing the drug trialled as an adjunct to antidepressants, focusing on the treatment of OB, not depression.
Howdy, all. Brand new Longecitite here =) hoping for a little help. Here's my situation: I work 13-15+ hr night shifts in a high-stress hospital environment 3-4x/wk, and am continuously on the verge of burnout... was very interested in NSI a few days ago, joined Longecity to seek a vendor, etc. Of course, I've since read about Neuralstem's failed phase II trials for MDD--and while that is discouraging, I'm not suffering from MDD. Rather, as mentioned above, it's burnout from SWD and sustained stress response, causing chronic fatigue with increased anxiety and recurring anhedonia.
To those of you that have sought to treat similar non-MDD symptoms with NSI-184, would you recommend it for a short-term course? Why/why not? Are there other nootropics that you'd recommend more for this? (ie N-acetyl semax amidate, P-21, etc?)
I'd really appreciate your anecdotal intel!
«βμ»
I've used NSI-189 to great effect in treating the symptoms of occupational burnout - my OB-symptoms come from the fact that I have multiple neurodevelopmental diagnoses, a former abusive Borderline girlfriend, and a terrible wish to prove myself in my particular field.
I eventually ended up so burnt out that I could not even get out of bed - had a hard time feeding myself, talking to anyone, my memory was shot, and the fatigue was through the roof.
NSI-189, in combination with Magnesium-L-Threonate, started working after but a few days! After the first two weeks I already felt about 40% recovered! HOWever... I was too sensitive to the anxiogenic effects of NSI, so I couldn't really use the regular dosage, so I had to lower it - still, some good effects was felt, when I added Tianeptine to the mix as well.
After about a month+ on the drug though, I noticed how the positives, the improvements on memory, cognition, and mood, had begun to flatten out - it was actually eventually, I felt, starting to impair other parts of my mind... it's kind of hard to explain.
But yes, I saw some definitive results from NSI-189 - and for a small note, I was, prior to finally using a combo of NSI-189, Mag-LT and Tianeptine using a combo of Duloxetine and Mirtazapine - "Limerick ROCKET fuel" as it's called - and, IMHO... my own combo, which focuses on the Hippocampus, which is theorized to be damaged to excessive cortisol-exposure in OB, worked a H*LL of a lot better than my prescribed medications.
I shall henceforth call my combo... HIPPO Rocket Fuel! ^^
Cause they all effect the Hippocampus, get it? Just imagine a medicine-box with a colourful hippo, clad in three different colours - inside, the pills are divided into these colours, to be taken together.
NSI-189
Tianeptine
Magnesium-L-Threonate
References for my reasoning, using these combined:
-------------------------------------------------------------------------
Chronic stress, such as OB, causes cortisol-exposure in the hippocampus, to the point that the brain-cells are eventually damaged. As such, neurogenesis, such as that caused by stress-relief and then low-intensity, long-exposure, exercise then reverses the symptoms - but this effect will take YEARS! Unless you cheat...
Chronic Stress Can Damage Brain Structure and Connectivity
Understanding the burnout experience: recent research and its implications for psychiatry
https://www.psycholo...nd-connectivity
Stress and glucocorticoids promote oligodendrogenesis in the adult hippocampus
http://www.nature.co...mp2013190a.html
Traumatic stress: effects on the brain
https://www.ncbi.nlm...les/PMC3181836/
Stress Predicts Brain Changes in Children: A Pilot Longitudinal Study on Youth Stress, Posttraumatic Stress Disorder, and the Hippocampus
http://pediatrics.aa...119/3/509.short
Posttraumatic stress disorder: A state-of-the-science review
http://www.journalof...0091-9/abstract
The brain and the stress axis: The neural correlates of cortisol regulation in response to stress
http://www.sciencedi...053811909005837https://www.ncbi.nlm...les/PMC4911781/
Magnesium has neurogenic, AND anxiolytic effects
Neurogenesis:
Efficacy and Safety of MMFS-01, a Synapse Density Enhancer, for Treating Cognitive Impairment in Older Adults: A Randomized, Double-Blind, Placebo-Controlled Trial
https://www.ncbi.nlm...pubmed/26519439
Enhancement of Learning and Memory by Elevating Brain Magnesium
http://www.cell.com/...47?showall=true
Elevation of brain magnesium prevents synaptic loss and reverses cognitive deficits in Alzheimer's disease mouse model.
https://www.ncbi.nlm...pubmed/25213836
Magnesium Status in Alzheimer's Disease: A Systematic Review.
https://www.ncbi.nlm...pubmed/26351088
Copper delivery to the CNS by CuATSM effectively treats motor neuron disease in SOD(G93A) mice co-expressing the Copper-Chaperone-for-SOD.
https://www.ncbi.nlm...pubmed/26826269
Anxiolysis:
Hippocampal NMDA receptors and anxiety: At the interface between cognition and emotion
https://www.ncbi.nlm...les/PMC2824088/
Hippocampal synaptic plasticity, spatial memory and anxiety
http://www.nature.co...bs/nrn3677.html
This is why it's logical to use the newest, and best formulation of Magnesium to date - MagLT.
Tianeptine - it alters the response to stress, and seems to cause somewhat more hippocampal neurogenesis than SSRI's.
Tianeptine: a review of its use in depressive disorders.
https://www.ncbi.nlm...pubmed/11463130
Tianeptine: An Antidepressant with Memory-Protective Properties
https://www.ncbi.nlm...les/PMC2701287/
Neurobiological and clinical effects of the antidepressant tianeptine.
https://www.ncbi.nlm...pubmed/18072812
The relationship between sluggish cognitive tempo and burnout symptoms in psychiatrists with different therapeutic approaches
http://www.psy-journ...1584-0/fulltext
(just a small article about how ambitious people with SCT often get burnout - which is logical, other neurodevelopmental diseases are also over-represented in OB-patients)
Man that's great work! I know I got my anhedonia/DP from stress and flooding my brain with dopamine from energy drinks. If Nardil + traneptine doesn't work for me, I'm trying your stuff <3
Cheers for the praise, friend - glad to see that my reasoning at least seems sensible. = )
Err... it should be noted though... I've read your posts, and my symptoms are, and were, quite different from yours...
My Anhedonia didn't have the same character, and I did not have DP/DR - I had slightly blunted emotions for a little while, but that was not a primary concern to me, they actually seemed to be returning on their own.
My primary issues were with memory - word-recall, and with fatigue - spatial awareness was also shot to h*ll. My symptoms were primarily cognitive, not emotional.
I don't think it's obvious that my stack would have much of an effect on DP/DR - maybe some on Anhedonia. It should also be noted that the MagLT decreased excessive emotional tone caused by NSI-189 - so that might actually be something you should stay away from... especially since it's a known fact that DP/DR can be caused by NMDA-antagonists.
By all means, try NSI-189, but there is no specific evidence that hippocampal damage is the root cause of DP/DR, and anhedonia - instead, there is some evidence that glutamatergic and opioidergic dysfunction is at the core of the disease - remember, stress does more than just damage your hippocampus, it affects multiple systems.
As such, I believe a combo of:
Lamotrigine
CERC-501
Which is a glutamate-modulator and a Kappa-antagonist, could be a better combo for someone like you. I'm surprised you haven't checked out Kappa-antagonism and our CERC-501 thread yet! Aren't you even aware that they're currently trialling CERC-501 as a treatment of anhedonia?? : O I believe other Kappa-antagonists are in trials specifically for DP/DR as well.
#5531
Posted 29 July 2017 - 03:04 PM
BTW... here's something that's been on my mind for a while now - isn't it about time that we came up with our OWN name for NSI-189? Either a cool, sort of snappy marketable one, or a very scientifically accurate one, based on the molecular structure and systemic name of the drug.
So, let's think here... These are a couple, off the top of my head:
Nicazine (because it was derived from nicotinamide and pyrazine)
Pyramide (see above)
Dentgen (the Dentate gyrus is the part of the hippocampus most involved in neurogenesis - NSI-189 should cause most of the increased activity here -regenerating the dentate gyrus - do you get it? = ) )
Neuronine (or neuronin - since it was was created by neuralstem, causes neurogenesis, and has a 9 in it's code-name)
Benzmethylanone (after it's rather complex systemic name: (4-benzylpiperazin-1-yl)-(2-(3-methylbutylamino)pyridin-3-yl)methanone )
I think I'm the most fond of Nicazine and Neuronine myself - they roll off quite well. I'm guessing Benzmethylanone is the most logical one, though.
#5532
Posted 29 July 2017 - 03:15 PM
Well... my anhedonia is annoying but I believe I can cure it someday. What frightens me is my weirdly shitty memory. It's probably much worst than what you had. Basically, all my memories feel like they never happened. I have absolutely zero connection to them, but it's not amnesia. Memories of a week ago, and of a year ago are equally hard to remember, they feel the same. I know those could be symptoms of DP, but I barely have any anxiety since my anhedonia set in and so it doesn't make sense to me that I would have such a disorder. Especially since I don't feel disconnected to my body. Concerning my surroundings, I don't feel awake/in the present but maybe that's correlated to my memory issues. I don't feel so dissociated from the outside as I remember being a while ago after a strong panic attack. If my memory problems are from DP, how can I fix them if I'm not anxious... I'm worried I may be suffering from some type of brain damage that might develop into dementia :( I still haven't had any other explanation till this day and it's hard to live with this constant distress + anhedonia that doesn't help either in staying hopeful :/
Anyway... I vote for Nicazine
Edited by Deaden, 29 July 2017 - 03:22 PM.
#5533
Posted 31 July 2017 - 09:08 AM
Reporting back after a two month cycle of NSI 189. Zero effects for me on MDD, burnout or anything else.
Likewise for every nootropic I've tried too. Seems like fluff. Effects of an extra half hour sleep, excercise or caffeine are far more pronounce for me.
#5534
Posted 08 August 2017 - 10:00 PM
I'm so fucked!!!!!!! I've been taken off the Nardil because I told the psychiatrist I was going to add adderall to it because he wasn't answering and I wanted to make him react. I knew he would take it as a threat even though it is safe I just wanted wanted him to answer!! Now he said he wasn't comfortable prescribing me any medication anymore just for that what do I do oh my god?? I fucked up so hard... made one mistake and he made me regret it instantly when we had a good relationship wtf?? Can I order some online??? Can I fake a prescription?? FUCK
It will take so long and so much money finding another psychiatrist that is willing to prescribe an MAOI!!
Edited by Deaden, 08 August 2017 - 10:07 PM.
#5535
Posted 09 August 2017 - 04:50 AM
I'm so fucked!!!!!!! I've been taken off the Nardil because I told the psychiatrist I was going to add adderall to it because he wasn't answering and I wanted to make him react. I knew he would take it as a threat even though it is safe I just wanted wanted him to answer!!
How it is safe? Just 20 mg of dexamphetamine sulfate combined with Nardil has caused a death.
When people are talking of "safe" combination of MAOIs and stimulants, they are usually referring to methylphenidate.
Not all stimulants are the same.
Methylphenidate acts as a norepinephrine–dopamine reuptake inhibitor (NDRI) while amphetamine is both a releasing agent and reuptake inhibitor of dopamine and norepinephrine. DRA, NRA, SRA, MRA
MAOIs are strongly contraindicated with amphetamine (Adderall) because amphetamine is releasing agent.
Monoamine releasing agents (MRA) take advantage of monoamine transporter to get inside the area, where they initiate the release, some MRAs can diffuse directly across the cell membrane, but taking a ride on transporter is much easier and faster.
NRI + NRA:
NRI mechanism decreases the reuptake of newly released extra NE, but the NRA also has harder time to get inside the area where they need to get to release NE, since most NE transporters are occupied. This balancing makes this manageable combo. Similarly, Adderall's serotonin release doesn't cause serotonin syndrome in proper use with SSRIs.
MAO-A inhibition + NRA:
There is no similar balancing as in the previous case. The interesting question when combining MAO-A inhibition with Adderall is whether you get hypertensive crisis first from way too much NE or serotonin syndrome from way too much serotonin.
MAO-A inhibition + NRI:
The risk of life threatening hypertensive crisis is a lot smaller than risk of life threatening serotonin syndrome in case of MAOI + serotonin reuptake inhibitor. NRI mechanism actually hampers tyramine's effort to act as releasing agent, some have advocated for non selective irreversible MAOI + NRI combo to reduce risk of food tyramine induced hypertensive crisis, plus possible therapeutic benefits for some people for this combo.
Because of these factors, MAOI+ methylphenidate can be ok, MAOI+ amphetamine is not ok.
This is why there has been recorded deaths with just a dose of 20 mg of dexamphetamine combined with Nardil, records of just 10 mg Adderall and Nardil increasing bloodpressure to over 200, etc, whereas there hasn't been reports of normal dose of methylphenidate and MAOI causing deaths.
Edited by Finn, 09 August 2017 - 05:13 AM.
#5536
Posted 09 August 2017 - 06:58 AM
How it is safe? Just 20 mg of dexamphetamine sulfate combined with Nardil has caused a death.
As has any drug due to adverse allergic reactions.
Amphetamine can be used with MAOIs but doses must be titrated low & slowly, and should only be combined if necessary as there is definitely a risk there.
http://psychotropica...g-amphetamines
#5537
Posted 09 August 2017 - 02:45 PM
How it is safe? Just 20 mg of dexamphetamine sulfate combined with Nardil has caused a death.
As has any drug due to adverse allergic reactions.
Amphetamine can be used with MAOIs but doses must be titrated low & slowly, and should only be combined if necessary as there is definitely a risk there.
http://psychotropica...g-amphetamines
Perhaps, although I have my doubts - but why take ANY risk? Why not just try MAOI + Methylphenidate, or for that matter, Modafinil, FIRST? Why go for the riskier option as a start?
#5538
Posted 09 August 2017 - 04:43 PM
Reporting back after a two month cycle of NSI 189. Zero effects for me on MDD, burnout or anything else.
Likewise for every nootropic I've tried too. Seems like fluff. Effects of an extra half hour sleep, excercise or caffeine are far more pronounce for me.
interesting how the post got 2 negative rating.
is it from the vendors of this?
#5539
Posted 09 August 2017 - 05:09 PM
There are many people here who have done like 5 or 10 cycles plus occasional use over 2-5 days. You get to know the effect better then.
Edited by AOIministrator, 09 August 2017 - 05:12 PM.
#5540
Posted 09 August 2017 - 05:26 PM
Jack Black "zero effect" is obviously a pretty biased opinion. There is always something happening in your life and psyche that correlates with drug use. Why do you thing they test against inert placebo? The most you can be is to be unsure about the effect. All the more so if you did just one cycle.
There are many people here who have done like 5 or 10 cycles plus occasional use over 2-5 days. You get to know the effect better then.
"Getting to know the effect" sounds like more of a bias than saying saying it had no effect on me. My situation is stable and did not fluctuate during the test period. That it is not to say NSI doesn't produce measurable results for anyone, but it didn't for me unfortunately.
For example, in my experience:
Coffee = measurable result
SSRIs = measurable result
Excercise = measurable result
Modifinal = measurable result
NSI = no measurable result
I would love to be given a reason to revisit NSI 189 by more compelling data. Just posting my honest experience, so far, for posterity.
#5541
Posted 09 August 2017 - 06:46 PM
I took the freebase nasally a few month back and I got some very prominent side-effects from that. I am guessing that the nasal route is maybe 10 times something more potent. Now high-dosed NSI-189 isn't the brightest idea, so I am sticking to the 40mg phosphate sublingually. If it even absorbs in the mouth properly. It surely doesn't taste like that.
#5542
Posted 09 August 2017 - 07:00 PM
Glad you are achieving results.
Could you expand on your dose, cycle and effects?
I did 40mb sub lingual, with b12.
#5543
Posted 10 August 2017 - 11:15 AM
Perhaps, although I have my doubts - but why take ANY risk? Why not just try MAOI + Methylphenidate, or for that matter, Modafinil, FIRST? Why go for the riskier option as a start?
Because treatment resistant depression or Anhedonia when suicide is a real risk, the combination of MAOI & Amphetamine must be an option.
At this stage i think Deaden is so desperate for his Anhedonia to be treated as quickly as possible, that he wants the most effective option regardless of risk.
Edited by jaiho, 10 August 2017 - 11:16 AM.
#5544
Posted 10 August 2017 - 05:11 PM
Sorry for freaking out last time, I'm surprised I didn't get down voted for it like the usual. I wanted to answer sooner, but was busy.
Sooo honestly the Nardil is doing something, it hasn't brought my emotions and pleasure back, but I feel like I'm in a better mood, more patient, calm. When before it's true I would be desperate and would get really frustrated/hopeless some days like: "I want this over now!". Really a shitty feeling, I don't get that anymore. I think I scared my psychiatrist showing him all this research he doesn't know about and when he didn't answer I said I would try adderall so he would react. Since then he doesn't want to work with me anymore. I was only half serious when I spoke about that, but I believe it is safe... I was going to paste the same link as Jaiho did and some others. Thankfully, my GP made some mistakes and my mother scared him for his license, so he agreed on giving me additional 150 pills of Nardil so I don't stop cold turkey and have the time to find another doctor. I have been taking this MAOI for five weeks now, I don't think it will be enough to treat my anhedonia, but I feel like adding Nortriptyline to it might me. Unfortunately, I think it will take luck, or time and money to find another psychiatrist that is willing to combine both. So I'm considering buying this drug online, read there is some websites that sell those without the need of a prescription. I think I'm just going to have to take the matter in my own hands... do what it takes to get appropriate treatment. Do you guys think I would have chances of buying real NTP without getting scammed online?
Also, I would like to thank Jaiho and all users of Longecity for helping each other, I think it's great.
Update: nvm I don't think I can get some online...shit
Edited by Deaden, 10 August 2017 - 06:11 PM.
#5545
Posted 12 August 2017 - 10:51 PM
I took it myself at a dose of 80mg a day from two sources: Strangelove and IRC.bio
IRC.bio actually stopped selling it due to the damage I suffered from their product and that i threatened to sue them for selling a patented product under a password protected page.
I took it six weeks and I can fully relate to the dullling that FuzzMonky experiences from NSI-189 neurotoxicity.
I tried it for a full six weeks and got progressively slower, anxious, started suffering akathisia, my movement became stiff and I developed parethesias with strong tingling and prickling sensations all over my body, especially in my cheecks, nose, hands and feet. My perception changed as well as my eyesight and since I took NSI-189 everything has become blurry but at the same time very bright, almost like I am permanently tripping on shrooms.
My body is stiff now and I walk slowly and my movement and higher cognitive functions like body language hve been damaged.
My cognitive abilities also declined and I started suffering memory loss. I also have sever shooting pains and constant abdominal pain since Strangeloves NSI-189. I hve so far talked to over 15 people whos lives have forever been changed and in many cases ruined by NSI-189.
Due to the NSI-189 induced brian damage i can no longer work and barely even play video games.
None of the neurotoxic brin damage from Strangelove and IRC.bios NSI-189 has gone away and I am still crippled almost eight months later. People like Strangelove selling dangerous, untested and toxic substances like nSI-189 should be ashamed of themselves and should be held accountable for anyone who is damaged by what they sell and advertise on this forum. The moderators of this forum should do something about the black market on this forum and Strangelove and people like him making a living on this forum off selling poisonous, unsafe and life ruining chemicals should be banned. The studies show it doesnt work and it has many permanent side effects. It permanently changes and damages the structure of the human brain. Now that we know it doesnt work anyone continuing to sell it here needs to be banned. I am considering reporting them personally but I will give them some time first to disappear.
If nothing changes and counterfeit NSI-189 continues to be sold on this forum I will contact Neuralstem personally with Strangeloves personal details which I still have from the purchase I made last november.
#5546
Posted 12 August 2017 - 11:00 PM
When you decide to experiment with untested and unproven substances, it is assumed you do your homework and are willing to accept the risk. This is just full-on tard and melodrama, expecting others to pay the price for your own carelessness. The NSI-189 that either one sell is not "counterfeit," and parasthesia is a widely documented side effect in the Neuralstem trials. Good luck pursuing litigation. I highly suspect you have underlying health issues that have been exacerbated and are just picking the nearest target.
Edited by Puppalupacus, 12 August 2017 - 11:03 PM.
#5547
Posted 12 August 2017 - 11:10 PM
-Stroke
-Alzheimers
-Resistant depression
-Opiate and alcohol withdrawal syndrome
-Alcoholic encephalopathy
-Parkinsons
-Extrapyramidla symptoms
-Cognitive decline
and many more indications.
Its not a toxic research chemical in phase 2 development by a tiny company with a few dozen employees. The phase 2 trials failed. Even the real, legitimate NSi-189 produced by neuralstem and not in some dirty Chinese Lab DOES NOT WORK. So imagine what these counterfeit chemicals mass produced in some sketchy lab will do to your brain.
Cerebrolysin has actually repaired some of the brain damage that Strangeloves and IRC.bios poison caused me. Less than half and im still crippled by neurotoxic symptoms and peripheral nervous symtom damage/severe neuropathy but since I did 30 infusions of 30ml of Cerebrolysin IV/day which I got directly from a pharmacy in Vienna I have noticed some improvements. My body is less stiff, the monotone voice and dullness NSI-189 gave me has gotten a bit better, and some of my the pressure on my forehead caused by NSI-189 is gone.
Its not a cure but its the best substance for stimulating neurogenesis and regeneration of damaged neurons/ brain tissue that exists for now.
I would also advise to not order it from nootropic websites or online pharmacies and to get a prescription and order it directly from Austria where it is made in a huge manafacturing facility on the Lake Attersee. I realize though that this will likely be difficult for most people who do not live close to Austria or speak german.
#5548
Posted 12 August 2017 - 11:31 PM
When you decide to experiment with untested and unproven substances, it is assumed you do your homework and are willing to accept the risk. This is just full-on tard and melodrama, expecting others to pay the price for your own carelessness. The NSI-189 that either one sell is not "counterfeit," and parasthesia is a widely documented side effect in the Neuralstem trials. Good luck pursuing litigation. I highly suspect you have underlying health issues that have been exacerbated and are just picking the nearest target.
I can understand the points you made but I can assure you that NSI-189 has caused me a lot of health issues. Not that I was in perfekt health before it but I had a decent life which has now been largely detstoyed. People on this forum saying that NSI-189 works and has no side effects are clueless morons. I was also a moron for taking this untested, ineffective poison and thats why I am warning others. I will add that I may have taken to high a dose, but I doubt 80mg of neuralstems real product would have caused the same neurotoxic reaction.
Try and understand that Strangelove is selling counterfeit NSI-189 and other research chemicals produced in some sketchy lab soley to earn money and not with your wellbeing in mind. Much like a common tactic Big pharma uses when adverse reactions and toxicity to a drug is reported, Strangelove has attempted to market NSI-189 as safe and I have read on this forum how he has downplayed the risks and even tried to deny peoples negative testimonies and experiences with his product.
I see now after this happened to me how ridiculous it is to try some untested ineffective counterfeit chemical when safe , proven neuroprotective, neurotrophic/neuroregenerating substances like Cerebrolyson exist which work against almost all psychiatric and neurological ilnesses in clinical trials, including treatment resistant depression.
Cerebrolysin has huge benefits for every brain, its even given to tens of thousands of babies in Russia to enhance brain development and treat even the most mild developmental delays with success.
A interesting study in detoxing heroin addicts I read showed that only 20 injections of 10ml Cerebrolysin ameliorated almost all opiate withdrawal and abstinence symtoms, cured their depression and increased their IQ from 88 to 107 points whereas the Placebo groups IQ increased only three points after withdrawal and all suffered severe absitence symptoms.
I havent personally noticed as huge of an effect from Cerebrolysin as reported in those studies but it has helped me more than anything else from recovering from psychiatric drugs and NSI-189 toxicity.
#5549
Posted 12 August 2017 - 11:47 PM
When I first started NSI-189 the perceptual change and brightness in my vision hapened overnight but the side effects of paresthesias, anxiety, sever cognitive dullness and worsening anheodnia, shortness of breath, stiff robotic mivement, severe shooting pains and pain all over my body did not start until about two weeks in. As I read many people here and on Reddit say that these are just initial side effects that should subside before the full benefits manifest themselves I decided to continue taking it. Which was the biggest mistake of my life. Not only did the toxicity grow worse the longer I was taking it, NONE of the symptoms I described above have subsided fully even eight months later depsite a full course of Cerebrolysin.
I knew I was taking a risk when I purchased NSI-189 but I didn't know it would ruin my life.
As it is clearly toxic and Neuralstems product free of impurities and byproducts doesn't even work.. My advice is
Don't risk it.
Just take Cerebrolysin instead. It works, will help you and there is no chance of it ruining your life.
#5550
Posted 13 August 2017 - 03:04 AM
One more thing..
When I first started NSI-189 the perceptual change and brightness in my vision hapened overnight but the side effects of paresthesias, anxiety, sever cognitive dullness and worsening anheodnia, shortness of breath, stiff robotic mivement, severe shooting pains and pain all over my body did not start until about two weeks in. As I read many people here and on Reddit say that these are just initial side effects that should subside before the full benefits manifest themselves I decided to continue taking it. Which was the biggest mistake of my life. Not only did the toxicity grow worse the longer I was taking it, NONE of the symptoms I described above have subsided fully even eight months later
I'm not here to point fingers or complain. NSI-189 changed my life for the five months I was on it. I battled through the paresthesia until it became unbearable, and then I lowered my dose. This worked for good for two months until shooting pains developed and I also developed a vague fatigued feeling (lactic acid feeling?) in my arms. Then, I had to stop. Issues seemed to mostly subside in two weeks. After trying to reintroduce the drug months later, pain side effects came back in two days. From what I recall, it was the shooting pains specifically. Again, they went away after quitting. I do not experience the shooting pains anymore.
However, I now intermittently deal with the vague fatigue feeling in my arms. I also have the feeling in my jaw. The sensation feels exactly like I have left my arms (and jaw) outstretched for too long. When this pain flares, it feels effortful to talk, text, type, and lift anything. This pain is influenced more by motion than it is weight. It's an annoyance. Has anyone else felt more prone to odd pains AFTER quitting NSI-189? In looking at my Reddit browsing history, it seems I have experienced some types of "burning" pains fairly easily doing everyday things before ever using NSI-189. However, it was never as invasive as this. The only other thing I can imagine that could be causing this is Tianeptine. I have been on it a long time now. Opioids are known to cause neuropathic pain in some. So I plan to quit it for a while and see how I feel. I am ambivalent to the possibility NSI-189 has caused/exacerbated this issue. I just want more feedback. Thanks.
Edited by Code_of_error, 13 August 2017 - 03:19 AM.
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