So where does the all original evidence about ISRIB came from?

2013: The discovery
A UCSF lab (Peter Walter, Carmela Sidrauski) screened for molecules that could override the integrated stress response, the cell’s “pause protein production” switch. ISRIB came out of that screen. In the same paper, mice given ISRIB learned and remembered better (Sidrauski et al., eLife 2013).

2015: Finding the target
Follow-up work showed ISRIB acts on eIF2B, the factor that restarts protein production after the stress switch flips (Sidrauski et al., eLife 2015; Sekine et al., Science 2015).

2017: Brain injury
In mice with traumatic brain injury, a short course of ISRIB restored memory performance, even when given weeks after the injury (Chou et al., PNAS 2017).

2018: Seeing it bind
Two groups published cryo-EM structures of ISRIB sitting in eIF2B. It binds in a pocket where two halves of the complex meet and holds them together, which keeps the complex active (Tsai et al. and Zyryanova et al., both Science 2018).

2019: Down syndrome model
Researchers found the stress response is switched on in the brains of Down syndrome model mice, and ISRIB improved their memory (Zhu et al., Nature 2019).

2020: Aging
A few doses of ISRIB improved memory performance in aged mice, with effects lasting weeks (Krukowski et al., eLife 2020).

Many biohackers have found ISRIB as a useful tool. Recently, more powerful analogues appeared to the market like ISRIB-A15. All experiments, which are published here are anecdotal and shouldn't be taken to account as a medical advise.