NSI-189 is an investigational drug currently undergoing clinical trials to treat depression. Read articles such as “A Better Pill to Swallow” and “The Pill That Could Cure Depression by Growing Your Brain” to see this is not just another drug to treat depression but an entirely new beast altogether. NeuralStem, the company sponsoring research for NSI-189, is hoping that this molecule can not only treat depression, but conditions ranging from Alzheimer’s disease to traumatic brain injury as well as reversing the natural aging process.
During preclinical research involving animals, it was found that NSI-189 can grow the hippocampus by up to 20%. Even the rats that were not stressed grew larger hippocampi. This begs the question, “If the hippocampus is related to memory and cognitive function, and NSI-189 can increase hippocampal size, can it also increase intelligence?”
There are some other issues specifically regarding attention and learning that I would like to bring up. Dr. Barkley has said that children with SCT have difficulties with selective attention and are possibly more likely to have math disorders. Indeed, I struggled with math since early childhood and wonder if there is a solution to math difficulties. Interestingly enough, math ability has been liked to hippocampal size.
A Stanford study found that the size of the hippocampus predicted math learning ability in children. A popular science article worded it best:
“When it comes to math, MRIs may be better than IQs — and even past math scores — at showing whether a tutor can help a child master everything from trapezoids to trigonometry. A new study from the Stanford University School of Medicine says that the size and circuitry of certain parts of children’s brains are excellent predictors of how well they’ll respond to intensive math tutoring.
The researchers’ most surprising finding was that children’s IQ and math scores had no effect on tutoring outcomes, yet brain scan images “predicted how much a child would learn,” said Vinod Menon, a Stanford professor of psychiatry and behavioral sciences who was the study’s senior author.”
I find this so fascinating because it is one scientific validation of what I had an intuitive hunch about all along – that some people who excel at math do so because of some innate architecture in the brain and not necessarily because of extraordinary amounts of effort. I know this because of careful observance of people I know such as my brother who are good at math and seem to do so naturally and effortlessly but are actually quite lazy otherwise– but I digress.
This makes me wonder, “Can taking NSI-189 increase math abilities?” It is a curious question, but it may be a while, possibly decades or more, before such issues can be studied. The above study found that it wasn’t just size of the hippocampus, but the hippocampus’ connections to other brain regions that predicted math abilities.
There are other numerous studies linking hippocampal size to various other human abilities such as “Hippocampal size positively correlates with verbal IQ in male children”, “Hippocampal size predicts rapid learning of a cognitive map in humans” and “Size does matter: Hippocampal and cortical volume predict recall across weeks.” Again, these are all correlations and a causal link between hippocampal size and function has yet to be determined.
In late 2013, Richard Garr CEO of NeuralStem, predicted that it would take at least five years before NSI-189 would make it to market for general availability. That’s right, NSI-189 is a drug that will come out closer to the year 2020 than not. But if there is a will, there’s a way and all it takes is a small group of determined people to find a workaround to get what they want – and that is exactly what happened with NSI-189. (See the enormous 99+ page NSI-189 Longecity thread.)
“After all, who doesn’t want to grow their HIPPOCAMPUS?!” writes Longecity member ScienceGuy who is a respected member of online community known for his in-depth discussions and previous experience with custom synthesized research chemicals.
Headed by ScienceGuy’s expertise, a group of about 40 – 50 people scattered all over the globe from Australia to China to Canada participated in a group buy to obtain a small sample of NSI-189 for personal research purposes. Usually, purchasing large custom quantities of research chemicals is an act reserved for businesses and may cost upwards of $10,000 or more per batch. However it is possible, as is the case with Longecity group buys as they are called, for an organized team to split the costs making it affordable for individuals to purchase research chemicals.
I know what you are thinking. For outsiders reading in on “group buys,” it may seem insanely preposterous for individuals to purchase and then ingest mysterious research chemicals that may have little to no toxicology reports on humans and then put it all under the guise of “research.” Essentially, such people are self-appointed guinea pigs as one member put it.
There are different angles of approaching this issue though. For one, if a person is autonomous, he or she is able to make informed decisions after an analysis of the information at hand. This analysis includes reviewing what information is available and doing a mental checks and balances to see whether the perceived benefits outweigh the perceived risks.
While some may have strong prejudgments, some people really do not have a choice. When I say “really do not have a choice,” what I mean is that some people’s difficult circumstances make it so that by not acting on an opportunity, they may be making their situation worse.
Xenix, one member who was part of the NSI-189 group buy, discusses his low quality of life:
“I had a brilliant future ahead of me — all ripped apart from chronic carbon monoxide poisoning; everywhere I look about getting treatment from my situation I hear and read the words “irreversible brain damage” again and again. This substance is the ONLY thing in the whole world that MAY provide me some hope with dealing with the endless headaches, NO short-term memory, infinite fatigue, nausea and all the other loveliness I experience every waking moment caused my HIPPOCAMPAL ATROPHY and anoxia from CO poisoning. My plan B is suicide, what is yours?”
A dire tragedy is someone in the United States commits suicide every 30 minutes so if some “mysterious” powder such as NSI-189 or another research chemical can reverse these tragedies –even if it’s all speculation – then it’s obvious, at least to me, whether such gray-area lengths are justified.
Aside from the nootropics community who obviously are a small unique online niche with their own biases, another more mainstream group of people who knew about the NSI-189 Longecity trials were business investors discussing Neuralstem’s stock as the company is publicly traded as CUR.
So as such the regular mainstream business folks are skeptical and are scratching their heads. On the Yahoo Finance forums, one user named omeg4 asks, “So who’s running this lab… Walter White?” Other users say downright “scam.”
Here’s what user imamisanthrope has to say:
“The Longecity “trial” has no control, no defined endpoints, and no credibility. It’s nothing more than a group of idiots taking an unapproved drug and posting anecdotal evidence. You shouldn’t pay attention to it one way or the other.”
Another user alex1444:
“I realize that a bunch of people taking “bootleg NSI-189” in an uncontrolled “trial” is nearly worthless from a scientific perspective. However, it is mildly interesting that many of those posting on the Longecity website seem to love whatever it is they have taken. This might or might not bode well for CUR as the owner of NSI-189, but if future trials of the real deal are anywhere close to what the Longecity people have claimed, I think we are looking at a multi-billion dollar drug.”
What may not be immediately apparent was that unlike purchasing substances from “cheap Viagra” websites where you could be taking “who knows what” this was a joint non-profit community effort to receive a genuine, high quality product. Every step of the process, from logistics to synthesis stages, was made completely transparent. ScienceGuy would chime in with posts from the supplier such as “We are very busy purifying the PIPERAZINE intermediate – the one with two N atoms on opposite sides of ring.” On top of knowing the supplier ScienceGuy even independently did a third party analysis test confirming the quality and purity our batch and posting the technical documents online in post 953. I have no doubts in my mind about the nature of what I was consuming. Having said that, NSI-189 itself is indeed investigational.
My experiences with NSI-189
I started taking NSI-189 in August 2013 making me perhaps one of the first 100 people or so to try it; of course, there are risks and unknowns involved in this but I was educated and informed. Yes, I fully accept being a lab rat. When you have chronic, treatment resistant depression as well as untreated ADD making hard to work and support yourself and even to think and communicate, then the benefits seem so bright and obvious and the drawbacks seem so dim and insignificant.
I am going to quote myself as user h2o discussing my initial reaction to NSI-189. In summary, I did experience acute anti-depressant effects on day one, but ultimately it was not a “cure.”
Here is my write-up on September 20th, 2013:
“Today is my 30th day on NSI-189 and this is my first real update since starting my trial. I originally was *very* interested in NSI because I have chronic treatment resistant depression. I pretty much have had dysthymia with some occurrences of major depression all of my adult life. But why I really wanted to try NSI is because of the worsening memory/concentration that occurs with long term depression and so the mechanism of action of NSI seemed spot on. Actually, I can relate to a lot of what OpaqueMind has experienced (which he describes wonderfully) about how early onset, long term depression destroys autobiographical memories.
I am female and in my mid 20s. I remember MizTen saying that she was surprised that people half her age are experiencing positive effects, but I don’t think it has anything to do with age but more to do with onset and duration of symptoms (among other issues). In fact researchers have found hippocampal shrinkage in depressed kids as young as five.
For the first week on NSI, I noticed a clear reaction right away. I started being aware of small environmental details that I usually would not notice. I especially was keen on noticing nuanced facial expressions. Some of my experiences were similar to taking Noopept at least at first. NSI also gave me a mild stimulating effect that was not quite like a stimulant. I also have ADD so that effect was welcome. In general I was just more focused and felt some sort of inner peace.
Overall, I would say that the strongest effects for me were the first week and then the effects tapered a bit and then strengthened after the third week. For the first week, I was taking 40mg once a day and that was more than enough, but I did notice an obvious come down effect about 12 hours later. The second week I dosed 30 mg 2 x a day but strangely I felt less of an effect even though I was dosing more overall. The following weeks I have been doing 40mg x twice a day which is the standard middle range dose.
As my trial went on, my emotions became reminiscent of how I felt like when I was younger so it felt like I was going back in time a bit. Also I am a very withdrawn person and keep to myself almost to the extreme and I found myself having small talk with store clerk which was interesting. I also wasn’t as self-conscious. I noticed that some people here have had opposite effects though and started becoming more withdrawn. Perhaps NSI is turning on a switch of some sort with regards to social interactions.
One remarkable feat of NSI is that it comes with little to no side effects, at least for me. I experienced no headaches which seem to be the number one common side effect. Occasionally, I experienced a mild, transient head pressure or tingling but it was not really bothersome to me and I have a low tolerance for pain and discomfort. People take anti-depressants to feel better not worse, right? On a scale from 0 (none) to 5 (severe) I would rate the side effect profile of NSI of being a 1 for being mild and infrequent.
Thirty days into I would say that NSI is promising and can help many people, especially those who do not respond to other treatments like SSRIs. Having said that, I still have a long way to go before I can be completely relieved of depression. No, I am not “cured” just yet of depression despite the hype that NSI can “cure” depression. No matter how good a drug is, one still needs to develop good habits over the long term. That is why I think at least 3 – 6 months of NSI is needed before real life changes happen instead of just subjective feelings of well-being.
Also, I want to add that I really appreciate everything ScienceGuy has done and am thankful that he gave me the opportunity to try NSI as well as setting the precedent for future group buys. I would also like to acknowledge VLK for his generosity in setting up the second group buy so many will actually be able to try NSI for longer periods of time. Last but definitely not least, let’s not forget NeuralStem (and Darpa) who funded and developed the compound.”
I later posted another update on June 23, 2014:
“My NSI update: I have been cycling NSI-189 for 10 months now and have only continued to see steady improvements. Approximately how much NSI have I taken so far? About 18 grams over 1-2 month on/off cycles with the NSI cycle that I’m currently on being a full 3 months by the end of this week. As a comparison, the highest dose from the 1B clinical trial was 40mg three times a day for 28 days or 3.36 grams total for the entire trial.
I will always remember my initial reaction to the drug back when I took it August of last year. What I will say is this: I was a very strong responder to NSI and felt the anti-depressant effects within the first two hours. I took 40mg orally the first week. Within a certain population, NSI-189 can have a very quick onset just like ketamine is reported to have. I am fully certain that the initial effects were not at all placebo, because placebo effects are vague and abstract while I felt a clear physical uplifting reaction to NSI-189 somewhat similar to how stimulants are fast-acting and energy boosting. Also, if placebo effects do occur, they are usually short lived. My improvements have been stable and I never reverted back to my original pre-NSI depression even during off cycles.
No doubt I still have better days and “less better” days but this is simply within the normal range of human behaviors and my symptoms are very manageable. Before I have had some cognitive and memory symptoms that were very severe/problematic such as forgetting where I parked my car and difficulty reading in such a way that by time I finished reading a single long sentence I would have forgotten the beginning of the sentence and therefore losing grasp of the entire meaning (disastrous working memory). Keep in mind I am in my 20s, not 80s and I have always had ADD since childhood, but these symptoms associated with depression only compounded these problems further. I personally think I have much more room for improvement so I plan on continuing to take NSI-189 to see how the effects max out.
There is also so much I more I want to talk about such as how I am much more improved socially and more optimistic about the future. I am in the early stages of starting an online business and I’m currently learning a foreign language. I may provide further updates in the future about these subjects.
Other notes: For the first 6 months of my trial, it was NSI-189 which was the only pharmaceutical I was taking along with some general health supplements and vitamins that I had always taken previously with only modest improvements. I wanted to see the effects of NSI-189 i.e. “untested experimental drug” at the time, without conflicting factors. Once I was comfortable with my NSI reaction, more recently (last 2 months) I was on low dose selegiline (2.5mg) and then TA-65. Intriguingly enough, TA-65’s effects, at least for me, were similar (though not exactly the same) to the same effects as taking NSI-189 the first time including improved motivation, energy, and mild head pressure in the beginning. TA-65 might actually be a potent anti-depressant for some people even though it’s marketed as an anti-aging supplement. There are other anecdotal reports and research (shortened telomeres relating to very chronic depression) that point in this direction as well.
Also shout out to MizTen and paul because to my knowledge, we three have been the first human lab rats to have taken such a large amount of NSI over the long term. So here you go, although NSI-189 has been officially proven safe in humans in 28 days, it has “unofficially” been proven safe and effective over a course of nearly a year. (Wow, has it already been this long?) What a journey this has been!
I will end with a very interesting study (actually one of my favorite studies ever). I can’t believe no one has ever mentioned this study in these 70+ pages!”