NSI-189 is a compound that may increase the birth of new neurons (neurogenesis) in the brain area known as the hippocampus. It has been studied in humans for its potential anti-depressant effects. Recently it has been gaining popularity among healthy self-experimenters who are trying to feel and perform better. Some people say it is a creativity-boosting, memory-enhancing, and mood-lifting nootropic. But is it effective? Read on to find out what the science says.
Read about the effects of NSI-189 in relation to the amount of evidence we've found
NSI-189 for improved mood
In one study in patients with major depressive disorder, 6 people received a placebo, 6 people received 40mg NSI-189, 6 people received 80mg NSI-189, and another 6 people received 120mg NSI-189 for 4 weeks. 
NSI-189 improved depression symptoms to a significantly greater degree than placebo in two of the four depression outcome measures. The study also found that some people were responders, some were partial responders, and others were non-responders. 
Baseline biochemistry of the participants was successfully used to create a model for the prediction of who is likely to respond well to the drug.
The beneficial effects of NSI-189 lasted more than 2 months after discontinuation of use. The long-lasting effects were especially prominent in the groups receiving 80mg and 120mg NSI-189 daily.
In another larger study on the effects of NSI-189 in patients with major depressive disorder, 220 depressed people were randomized to 12 weeks of 40mg, 80mg, or placebo. 
NSI-189 improved depression symptoms only in depressed people who did not respond to a placebo. It only improved some test scores and had no significant impact on other mood tests.
The evidence from this larger study suggests people with moderate depression had more beneficial effects from use of NSI-189 than people with severe depression.  This finding is promising for healthy humans looking to improve their already okay mood, since NSI-189 doesn't appear to exert the usual restoration-only effect of many other nootropics, which is when a substance brings a person closer to normal if impaired, but not above normal if starting from normal. However, data on the effects of NSI-189 in healthy people is still severely lacking.
NSI-189 for cognitive enhancement
In a small study in people with major depressive disorder, 40-120mg NSI-189 was given to the patients daily for 4 weeks. A self-report inventory was used to assess memory, attention, and executive functioning difficulties at the start and end of the study period.
NSI-189 significantly improved symptoms of memory, attention, and executive functioning difficulties compared with placebo.
Confident valid conclusions cannot be made as regards the efficacy of NSI-189 as a cognitive enhancer in healthy people, because the evidence available consists only of data from people with clinical depression.
In a larger study in which 220 participants received 40mg or 80mg NSI-189 or placebo for 12 weeks, it was found that 40mg effectively improved self-rated cognition, but that 80mg daily did not. 
This study didn't only include subjective measures of cognitive performance but also measured cognition objectively with the help of two test batteries.
NSI-189 improved various aspects of cognition in some people, but not all.
The patients who received 40mg experienced improved processing speed and executive functioning. The patients who first received placebo, didn't respond to it, and then received NSI-189, experienced beneficial effects from NSI-189 on working memory and long term memory, with the most prominent effects amongst participants who received 40mg NSI-189.
Neither 40mg or 80mg NSI-189 improved cognition as measured by another test battery which tested learning, working memory, and other aspects of cognitive functioning. 
Moderately depressed patients likely have more cognitive benefits to expect from the use of NSI-189 than severely depressed patients.  It is not known whether NSI-189 might be even more powerful in mildly depressed people, or even in healthy people without depression.
The legality and side effects of NSI-189
Frequently asked questions about NSI-189
Studies conducted on the effects of NSI-189 in healthy humans
Last updated Saturday, June 10, 2023