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The use of antidepressants has grown rapidly in recent years. In the United States, the number of people taking antidepressants increased 400% from 1990 to 2008. In addition, 11% of Americans over the age of twelve take an antidepressant medication.
What is a nootropic compound?
NSI-189 is a new generation antidepressant with nootropic properties created by Neuralstem, Inc. that is derived from pyrazine and nicotinamide.
How long does NSI-189 last?
Testing has shown that NSI 189 significantly reverses behaviors associated with depression. In humans, it can counteract hippocampal atrophy seen in disorders such as major depressive disorder. Scientific studies conducted over a 28-day period showed behavioral improvement in 24 patients who were given NSI-189 orally. Efficacy measures showed a clinically significant and persistent reduction in cognitive and depressive symptoms on all measures.
Studies have shown that it stimulates hippocampal cell neurogenesis in vivo and in vitro. The hippocampus is responsible for spatial navigation, along with memory consolidation, and several other processes.
Usual dosage of NSI-189
The daily dose of NSI-189 powder to optimize results is considered to be in the range of 40-80 mg/day. (Between 1 and 2 measuring spoons).
Antidepressants have been a problematic group of drugs due to their side effects. Even the main class of antidepressants, the selective serotonin reuptake inhibitors (SSRIs), have potential side effects such as insomnia, sexual dysfunction, decreased motivation, and even aggravation of depression. These complications have made it necessary to search for more efficient treatment options.
The origin of the NSI-189
NSI-189 is an experimental drug developed by Neuralstem, a biotechnology company that produces neural stem cells for therapy.
Clinical research on NSI-189 has been ongoing since 2011, and phase 1b testing was completed in July 2014. Phase 1 clinical testing focused on discovering the appropriate dose range for the drug, which It was established between 40 and 80 milligrams per day, in the treatment of major depressive disorder (MDD), and cognitive impairment.
NSI-189 is a small molecule, which makes it structurally unique among other antidepressants. Furthermore, it has also attracted interest in terms of its ability to stimulate nerve growth in the hippocampus.
NSI-189 molecule
According to an official statement from Neuralstem regarding phase 1b of the trial, NSI-189 is a unique new compound that stimulates the growth of new neurons in the hippocampus, a brain region believed to be involved in MDD. as well as in other conditions such as traumatic brain injury, Alzheimer’s disease and post-traumatic stress disorder.
In the phase 1b trial of NSI-189, the safety, tolerability, pharmacokinetics, and pharmacodynamics of NSI-189 in the treatment of MDD were evaluated. Now that the study has been completed and the results revealed, the outlook looks encouraging.
The study, which was conducted on 24 patients over the course of four weeks, revealed that administration of NSI-189 reduced symptoms of depression and cognitive decline significantly more than those administered with placebo. The drug was well tolerated and exhibited procognitive properties associated with increases in prefrontal alpha coherence.
Mechanism of action
Selective serotonin reuptake inhibitors (SSRIs) focus on treating depression by increasing serotonin levels in the brain. This model of depression, known as “The monoamine hypothesis”, states that depression is caused by a lack or imbalance of neurotransmitters in the individual, mainly serotonin. However, this model has been drastically discredited in recent years. Many researchers and psychiatrists now recognize that depression is much more complex than a simple chemical imbalance in serotonin.
What is Depression?
In short, depression is a complex intricate network of causes and effects of both psychological and physiological order. Although scientists know from research that SSRIs and other antidepressants do have an effect in relieving depression, the true pharmacology behind these medications is highly uncertain. Why do some people respond negatively to these medications? Why are some people not responding at all? As these responses are deeply intertwined with genetic and biochemical factors, they are very difficult to address in a comprehensive way.
Which nootropic is most like Adderall?
These observations lead us to two important points: First, depression is such a complex disorder that we don’t yet know the best way to treat it with medication. Second, SSRIs are surely effective in relieving certain types of depression, but we don’t fully understand why they work the way they do. As the roots of depression are still uncharted territory, exploring new treatments that work differently from SSRIs is critical.
How does NSI-189 work?
Some researchers, such as those of Neuralstem, have found a correlation between a reduced hippocampal volume, with a higher frequency in the incidence of major depressive disorder. According to this theory, NSI-189 could be a potential remedy for those suffering from depression, contributing to the growth of the patients’ hippocampus. And since the hippocampus is also closely related to memory, NSI-189 also has the potential to impact cognition in a positive way.
This hippocampal model of depression is still in its infancy, and NSI-189 is one of the first drugs developed to target this specific form of treatment. Although NSI-189 is known to increase hippocampal volume, the exact mechanism causing this effect is still unknown. Results from the phase 1b trial even suggest that the effect of NSI-189 on hippocampal volume was not as dramatic as that seen in animal studies.
Can nootropics cause brain damage?
Whether or not the increase in hippocampal volume persists after drug discontinuation remains to be determined. As research and testing with NSI-189 continues, further research will focus on this model of depression, and the medical community will be better able to understand the correlation between depression and hippocampal volume.
Potential Benefits of NSI-189
- Improvement in behavioral responses associated with depression.
- Reversal of hippocampal atrophy.
- Stimulation of neurogenesis, which could improve memory and cognition.
- Positive results persist, even after stopping treatment.
Experiences
Since NSI-189 is still in its infancy as a clinical treatment for MDD and cognitive disorders, anecdotal information is important for those considering trying NSI-189.
The following testimonials were reported by users of the reddit.com site:
“ I have been taking the NSI-189 phosphate for three weeks. I take 40 milligrams orally, once a day. (…)
I began exploring this substance hoping to counteract my chronic brain fog, slight depersonalization, anhedonia, a generalized feeling of fog, and slow cognition.
Most notably, I have noticed an intensification of emotions, as well as pleasure. (…) Although it’s only been three weeks, I’ve noticed that I’m more inclined to make plans. I’m quicker to laugh and socialize.
Before NSI-189, every emotion I experienced felt like just background noise. Now, all my emotions feel more genuine, like they’re at the forefront of my brain.
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When I experience anxiety, I no longer feel dissociated from it. When I feel joy, it tends to last longer. Although these new perspectives are scary, I welcome the change. My default state of mind also tends to be slightly more upbeat.
I admit that I feel more guided by my emotions, as I have not felt in years (…), this substance is bringing me closer to my long-forgotten inner feelings. (…)
Lastly, I dare to say that I have better mental acuity and I am less likely to “get stuck” when I have to speak. (…)
Overall, I am motivated to stay on this drug for a while. My mental symptoms are nowhere near gone, but I see enough benefits to continue.”
Here, the experience of another Reddit user:
“Personally, I have found the NSI-189 very useful. I take 50 mg once in the morning daily. The effects for me are a gentle wave of calm, an improvement in long-term memory, and a noticeable improvement in vision.
What medication works like Adderall?
The improvement in memory is the strong point in this substance. I see myself having vivid memories of when I was less than ten years old. This has also allowed me to remember times when I encountered the same difficulties that I am currently having, and what I did to resolve them back then. I feel better equipped to face them with a better memory of what worked and didn’t work in the past.
When it comes to side effects, there are childish emotions that come quite strong. This turns out to be both good and bad. The good thing is that that feeling of amazement that we experience when we are children, is present again. The downside is the initially immature emotional responses. For example, jealousy on a very childish level. It is not incapacitating you, but it is something to be aware of.
And speaking of being mindful, it has become much easier for me to practice meditation and I retain the experiences I get from it in my longer-term memory.”
Conclusion
If NSI-189 proves to be an effective treatment for major depressive disorder, it could have a potentially big impact on the direction of antidepressant medications for years to come. The long dominance of SSRIs in the treatment of depression has left many wondering how long it will take for the next big breakthrough in antidepressants to arrive.
A novel drug like NSI-189 could be the answer, and studies on it also give us a useful look at the correlation between depression, hippocampal volume, and cognition. As we move into the twenty-first century, the scientific community will undoubtedly continue to more carefully map the territory of the human mind.
NSI-189 Review
NSI-189 is an experimental, potential antidepressant that modulates the function of the brain’s serotonergic system. The purpose of this review is to highlight the potential pharmacodynamic mechanisms and clinical utility of a 5-HT1A receptor antagonist in the treatment of depression. While preclinical data suggest that the potential efficacy of NMDA receptor antagonism in depression is limited, an antidepressant profile similar to that of tricyclic antidepressants may be achieved with a novel 5-HT1A antagonist. The potential for synergy in treatment of depression is suggested by the observed therapeutic effects of NMDA receptor antagonists when combined with the SSRI, desipramine, and the 5-HT1A agonist, buspirone. In summary, the NMDA antagonist, ketamine, a 5-HT1A antagonist, and an SSRI may each be useful in the treatment of depression, but only a 5-HT1A antagonist appears to have an antidepressant profile similar to that of tricyclic antidepressants. A 5-HT1A antagonist, such as NSI-189, may hold promise for the treatment of depression.