I have to dethrone pitolisant as the most interesting neuropharmaceutical I have experimented with in a long time.
Usually, I do not use non-FDA/EMA-approved molecules due to the lack of proper safety data (i.e., Is the molecule safe?) and manufacturing quality control (i.e., Do I get exactly what is on the label?). This includes peptides, bromantane, racetams, and a lot of other molecules that are propagated throughout the quacko-sphere.
However, NSI-189 piqued my interest even though it has not yet been approved.
Whenever I take a low therapeutic dose of ketamine, I feel like a kid for about a week. This is presumably due to ketamine cranking up levels of neuroplasticity.
It has long been known that neurogenesis/neuroplasticity is essential to energy levels, mood, and cognition. Things that induce it (such as psychedelics, traveling, or exercise) have powerful effects on energy, mood, memory and cognition whereas things that reduce it (e.g., aging, loss of environmental enrichment, physical inactivity, hypercortisolemia) are depressogenic.
Hence, it would be interesting to find molecules that induce neurons to grow. To do so, researchers were using a brute-force method (high-throughput screening) to induce hippocampal neurons to grow in vitro. Essentially, they were bombarding thousands of petri dishes with around a dozen thousand different molecules and were selecting the molecules that were inducing the most growth. The lead compound they found would later be modified into NSI-189.
While the exact mechanism has not been elucidated, the most likely explanation is an indirect upregulation of neural growth factors (e.g., GDNF, BDNF, etc.). Screening against a number of enzymes, monoamine receptors and transporters and a host of kinases was negative, and as of yet the exact target has not been found. If TrkB is blocked (TrkB is the receptor for BDNF), most of the effects of NSI-189 seem to be blocked as well.
NSI-189 successfully passed preclinical development (e.g., toxicology) and made it as far as a completed phase II study in humans for depression. Unfortunately, it only worked for a subset of people (as is always the case with depression because depression is a catch-all term for a heterogeneous set of syndromes that do not share the same underlying neurobiology).
It did have an effect on depression but it did not reach statistical significance. However, it reached statistical significance on a number of cognition markers, including memory, working memory, and executive functions.
NSI-189 has been further refined by Chinese research groups into even more potent neural growth stimulators but to my knowledge none of these molecules have human data yet.
Anyway, thanks to being an MD, I have access to proper research chemical sites used by medical universities. For roughly 700 euros I bought 10g of NSI-189. I started it roughly 3 weeks ago, along with a good friend. Dosing is 20mg twice daily. Costs me about 3 Euro per day.
Normally, I do not dream much (or at least I do not remember my dreams). Ever since starting the NSI-189, I have daily vivid dreams. I even started a dream journal. Furthermore, my libido is undeniably higher. Normally, I do not go for second rounds, but ever since starting the NSI-189, I often do and I do not feel depleted after. In the first week, I even had a wet dream one day after having had sex twice, which had never happened to me before.
Maybe I am also subtly more emotional as I am moved to tears more often than normal but it is hard to say conclusively.
My friend also notices the vivid dreams. And he also claims that his memory has gotten better. I personally have not noticed anything on the cognition side.
Anyway, NSI-189 is surely one of the more interesting molecules I have experimented with. The only thing I can say for sure is that it has an effect on my dreaming and libido. I do believe that dreaming & libido are expressions of “brain vitality”, of which neuroplasticity may be a feature.
It will be interesting to see whether the effects on libido and dreaming are sustained. Usually, with neuropharmaceuticals, the effects dampen down with time but given the unique mechanism of action, NSI-189 may be different.
Weekly observations
I share two Weekly Observations in my newsletter every week, similar to the one above. You can find the full archive here.
Disclaimer
The content available on this website is based on the author’s individual research, opinions, and personal experiences. It is intended solely for informational and entertainment purposes and does not constitute medical advice. The author does not endorse the use of supplements, pharmaceutical drugs, or hormones without the direct oversight of a qualified physician. People should never disregard professional medical advice or delay in seeking it because of something they have read on the internet.