NSI-189

"Permanently eradicated the majority of my anhedonia and depression from only 5 doses"

Summary

[Disclaimer: Not medical advice. Purely a research article.]

Atypical anti-depressant, nootropic.

Induces hippocampal neurogenesis. This is the same mechanism of neurogenesis that psychedelics like LSD or psilocybin have.

Similarly to psychedelics, it produces the child-like feeling. Very interesting.

Either it's possible that (hippocampal) neurogenesis literally produces a child-like feeling, or there's a shared mechanism for the neurogenesis and the child-like feelings, that both psychedelics and NSI-189 activate.

I wonder if other neurogenesis agents, like Lion's Mane, cause this feeling. Ketamine also causes neurogenesis and has a similar feeling on high doses.

• If not, then the hypothesis above is false, and it's just a mechanism unique to psychedelics (indirectly) and NSI-189 (directly or indirectly)

Personal effects

Also a lot of people report a general novelty feeling. I didn't necessarily get that effect very strongly, I mostly got the child-like feeling.

It's like a third of LSD's effects. Then you add modafinil, get the entactogenic body load and it's two thirds (child-like feeling + entactogenic euphoria). Without the third part, the trippiness.

We don't know what receptors NSI-189 binds to. It doesn't bind to any of the most known receptors.
It probably uses some deep mechanism that we don't yet understand — again because it uses the same neurogenesis effect that's downstream of serotonergic psychedelics.

Dosage

• 20mg phosphate daily
• 40mg freebase daily

Freebase allegedly works well sublingually and for oral administration phosphate is preferable.

Anecdotal reports

Promising reports

permanently eradicated the majority of my anhedonia and depression from only 5 doses

NSI made me feel like a kid again. Brought me back to 100%. Stress is really, really bad for our brains, particularly our hippocampus.No side effects for me.I got it through back channels, can't say anymore and risk the pipeline.It will be on the market in five years and will in my opinion revolutionize the treatment of depression, ptsd and other neurodegenerative disorders.

Feels like I’m experiencing all the emotions again like when I was a kid wtf....? Food is tasting new...movies feel fresh...everything feels novel and new like for the first time...How can a drug even make u feel the magic of being a kid again with no other mind altering effects? That’s crazy....how’s this even possible? Wtf?

Feels like I can experience things emotionally like I did when I was a child wtf..? How is this even possible? Makes me literally feel like a kid again....this is crazy, only taken like 40mg too...whoa

I guess I thought something was wrong with me. I guess I thought I was missing something. Turns out I wasn't. Turns out that was some kind of trick I was playing on myself. NSI 189 did make me feel like a kid again. Everything felt new and fresh. I watched [...] on NSI 189, It felt like I was watching [...] for the first time. I mixed weed and NSI 189, It felt like I was high for the first time again. There was some paranoia and anxiety, but as an adult I have more of an inner stillness

Makes Me Feel Like a Kid on Christmas Again

I would also greatly encourage you to do mindfulness meditation and meditation overall while on it - meditation has very positive effects on brain structure, and taking it with a drug that accelerates synapse formation is highly likely to enhance the benefits.

Additional information

NSI-189 is not recreational drug, it works by increasing neuroplasticity and takes 10 days or more for such effects and mostly for people with PTSD, depression etc
- IMO it's not recreational in the traditional sense, but it definitely feels very good and so interesting.

You shouldn't feel instant effects, all studies report effects after three weeks. New neuron pathways take 22 days to form, so it makes sense.
- I think this is factually wrong but I'm still including it to have a more diverse range of reports.
> Some of the effects are definitely instant. I trialled it for 6 months.

It also has an unknown mechanism of action, so be very careful combining it with other substances. Remember that not all interactions can be felt.

Just a heads up: NSI-189, while somewhat antidepressive, especially against depression induced cognitive problems, if used while you're in a bad place mentally, can make that mentality harder to shake off.

Research status

It was being researched for depression (human clinical trials). It didn't pass the required threshold for antidepressant medication, however the results were still statistically significant.

• It's possible that the required results favor drugs like SSRIs that mostly work for everyone. Whereas NSI-189 might be something that works gloriously for some and not much at all for others. That said, seems like its more usual acute effects (child-like feeling, novelty) are very reproducible. Only the things like permanently eradicating anhedonia and depression with 5 doses are outliers.

NSI-189 completed a phase I clinical trial for MDD in 2011, where it was administered to 41 healthy volunteers.[6] A phase Ib clinical trial for treating MDD in 24 patients started in 2012 and completed in July 2014, with results published in December 2015.[1][7] In July 2017, it was announced that a phase II clinical trial with 220 patients failed to meet its primary effectiveness endpoint in MDD.[8] Upon the announcement, Neuralstem stock plummeted by 61%.[9] More detailed analysis of the trial results was released in December 2017 and January 2018. It revealed statistically significant improvements on patient-reported depression scales and in aspects of cognition for the 40 mg/day dose. Of particular note are improvements in memory (effect size Cohen's d = 1.12, p = 0.002), working memory (d = 0.81, p = 0.020), and executive functioning (d = 0.66, p = 0.048) as measured by the CogScreen computerized test.[5]

Overall the drug seems safe for use, since it was in human clinical trials, and the amount of anecdotal reports is vast and consistent.

The only concern would be that we don't know the exact mechanism, but it seems to be the one that's downstream of psychedelics-induced neurogenesis, which is generally viewed positively.

This is one of my ongoing research notes in Roam. On January 15th, 2021 I made this formatted dump for the blog. I always keep adding information to my Roam notes, so this blog is not the primary source of truth for my research. However, I figured it could be useful to some people if they could read this, so this is public for reading.