Potential Dangers of ISRIB
Is ISRIB Dangerous for the Heart?
There is a report of one person who tried just two small doses of ISRIB (total of 15 mg intranasally) passing out and collapsing two days later. This is a young person with no previous history of passing out or having heart issues.
On going to hospital, the cardiologist performed an ECG (electrocardiogram), and found the heart was out of whack. Heart rate was erratic, varying form normal to extremely low (20 bpm). Heart arrhythmias in the form of atrial fibrillation were diagnosed. Electric shock to the heart (cardioversion) was planned, to knock the heart back to a normal rhythm; but then heart returned to normal rhythm on its own. On release from hospital, no further heart problems were observed, and heart enzymes were fine, suggesting no permanent damage.
Another person who took 110 mg of ISRIB over 4 days (partly intranasally, partly orally dissolved in DMSO), reported getting some chest discomfort, modest chest pain, and some shortness of breath lasting several days, which appeared one week after their last dose of ISRIB. This person had no previous heart issues, and and ECG and ultrasound performed by a cardiologist 6 months prior showed a healthy heart.
Other people have reported a slow heart rate while on ISRIB.
Can ISRIB Precipitate Psychosis and Hallucinations?
There is also a report of a high functioning autistic woman who suffered brain injuries as a child experiencing a short period of psychosis and hallucinations episode while taking ISRIB. She had experienced episodes of psychosis previously, but never with hallucinations. She previously had also taken ISRIB previously without such adverse effects.
The above adverse effect reports come from a Telegram ISRIB group and a Discord ISRIB channel I am in.
ISRIB-Like Compound Shown to Cause Anomalies in Dog Hearts
A compound called 2BAct, which works similarly to ISRIB, was found to cause significant cardiovascular anomalies in dogs.
To quote the paper:
The molecule was well-tolerated in the animal studies described here, and did not elicit any relevant effects in a rat cardiovascular (CV) safety study; however, significant anomalies were observed in a dog CV model. This CV safety liability makes this particular molecule unsuitable for human dosing.
Another paper found that the integrated stress response (ISR, which ISRIB inhibits) affects the heart. The paper states that the ISR regulates the autophagy and apoptosis (cell death) of cardiac progenitor cells. So taking ISRIB will have an affect on these cardiac cells.
And this paper says there is a connection between activating the ISR and arrhythmias. If there were a rebound effect on the ISR when you stop ISRIB, you might get higher levels of ISR after stopping, which might trigger arrhythmias. This rebound might explain why the heart issues experienced by the two people above only appeared some days after they stopped ISRIB.
ISRIB Shown In Vitro to Cause Accelerated Cell Death When ER Stress is Present
In cell culture studies where ER-stress was artificially induced, 24 hours of ISRIB treatment in vitro accelerated cell death (Sidrauski et al, 2013). This suggests that in diseases characterized by increased ER stress, UPR or ISR modulators such as ISRIB might be toxic. Ref: here.
Conditions which involve endoplasmic reticulum (ER) stress include viral infection, type 2 diabetes, atherosclerosis, metabolic syndrome, cardiovascular diseases, obesity and fatty liver disease. Ref: here.
ISRIB has never been tested on humans in any clinical trial, and although it can be bought at some research chemical and peptide suppliers, and is being researched by Google's Calico, to me, after learning more about ISRIB, it does not look like a safe substance to experiment with.
Indeed, ISRIB researcher Professor Susanna Rosi, who is exploring the potential benefits of ISRIB, stated "ISRIB is still far from being used to treat humans".
I was looking into ISRIB to se if it might be useful to help repair the mild brain damage I sustained from the viral encephalitis which triggered my ME/CFS; but after these reports of possible cardiac ill effects, I am not going to risk it.
Other ISRIB Observations and Facts
ISRIB can have potent nootropic effects (improved cognition). Some report these nootropic effects cease to appear after some months of ISRIB use.
More than one person has reported that ISRIB increases brain fog, but if you eat a lot of food, then the brain fog dissipates. So it requires eating a lot to keep brain fog at bay. Strange phenomenon.
Several people have reported blunted emotions while on ISRIB.
One report from a person trying ISRIB is here and here.
ISRIB appears to have a strong anti-cancer effect against aggressive fast-growing prostate cancers (though no effect against normal cancers).
One anecdotal report of a short course of ISRIB permanently fixing some prefrontal cortex brain damage in a Russian guy, caused by a car crash when he was a child. The repair to the brain was confirmed by MRI scans taken before and after the ISRIB treatment.
One report of a person who gave ISRIB to their grandmother who had terminal stage Alzheimer's. She began to remember everyone. But died after 4 months (this may have been from old age and her type 1 diabetes).
Some people have reported the inability to get drunk on ISRIB.
People have reported faster wound healing while using ISRIB.
ISRIB half-life in mice is 8 hours. Ref: here.
I first posted the above here.
Edited by Hip, 17 October 2022 - 12:19 AM.
