ISRIB to treat ME/CFS

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I checked my nootropics box and found that I still have 2 ISRIB vials (50mg each) that I bought from reachgenius. I had tried ISRIB on myself long time ago after I posted about it on reddit: https://www.reddit.com/r/Nootropics/comments/ef4jti
In my experience, I tried maybe 2-5mg dosage via DMSO, and as far as I remember, the name of the drug "integrated stress response inhibitor" pretty much describes the effect. For me it felt like strong anxiolytic, like the anxiety mechanism got disabled. My attention I remember was much better. But I stopped after maybe 3-4 attempts because I did not like the anxiolytics effect (which felt like I'm satisfied with everything). Also it felt pretty scary to be probably one of the first humans trying this (I did not find any other reports online on its effect on humans).
I think it can be a miracle for someone with GAD, but I don't want to make any claims, but it would be cool to see what happens on a person like that.

I can sell 1x50mg vial for 90€ + shipping from Europe.
Do you still have this available? If so, I would like to purchase.
 

Hip

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Do you still have this available? If so, I would like to purchase.
Note that IRSIB has never been tested on human beings, apart from a handful of people who have tried it (like this person).

ISRIB researcher Professor Susanna Rosi has stated that "ISRIB is still far from being used to treat humans. Our lab only focuses on preclinical models and more research really needs to be done." See here.

So trying it may expose you to unknown risks. Just so that everyone is aware and informed.
 
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Hip

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I would be very wary of taking a substance that has been tested on animals, but yet to be tested on humans.
 
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I am also interested in joining the order for this. The discord link was expired for me. Could somebody please PM me about this?
 

Hip

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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.

These above reports come from a Telegram ISRIB group and a Discord ISRIB channel.


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.
 
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mitoMAN

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RESULTS SHOW IFB-088 IS SAFE AND WELL TOLERATED IN HEALTHY VOLUNTEERS DATA SUPPORTS INITIATION OF PHASE 2 TRIAL IN CHARCOT-MARIE-TOOTH DISEASE January 7, 2020 Nantes, France – InFlectis BioScience SAS, a drug discovery company committed to the development of innovative therapeutics harnessing the Integrated Stress Response for the treatment of a broad range of diseases, today announced the results of its Phase 1 study of IFB-088, an oral small molecule targeting the stress-induced PPP1R15A/PP1c phosphatase complex, in 72 healthy volunteers. Results of this randomized, double-blind, placebo-controlled, single- and multiple-dose escalation study (SAD/MAD) demonstrated that administration of IFB-088 was safe and well tolerated. No serious adverse events, dose-limiting toxicities, or clinically significant abnormalities were observed. The pharmacokinetic parameters were consistent with data derived from extensive studies in animal models. Anne Visbecq, Chief Medical Officer of InFlectis BioScience SAS, said: “We are very pleased with the outcomes of the IFB-088 Phase 1 trial, which confirm the good tolerance profile of IFB-088 even in high dose groups. No safety concern has been identified and pharmacokinetics were as expected.” “Results from this study provide the first clinical data for IFB-088 and creates a path forward for its evaluation as a potential first-in-class oral therapeutic treatment of CMT disease,” commented Philippe Guédat, Ph.D., President and Chief Executive Officer, InFlectis BioScience. “We look forward to working towards a U.S. and EMA IND filing in the coming months.” http://www.inflectisbioscience.com/wp-content/uploads/2020/01/IB-PR-InFlectis-Phase-1-Final.pdf



https://www.reddit.com/r/MultipleSclerosis/comments/aha934 Sephin1 was isolated from Wytensin/guanabenz a blood pressure medication. This is probably good news, adding to the already established safety profile of Sephin1 in healthy volunteers!
 
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Wanted to give an update with our ISRIB use: We have given my mother 7 doses as of yesterday. We started at 30 mg for 4 days, took 1 day off and then the last 3 days have been at 15mg doses. She crashed and slept a lot on the day off. We have noticed her ability to engage in conversation has increased...she is actually picking up on what we are saying. She has gone from being barely able to walk, to about 60 % of the time she is quite mobile and on day 4 she actually was very hyper and ran to my dad when he came in the door. The 30 mg was way too much for her after 4 days, so we cut back for a bit and will try again at a higher dose this week for a few days and see how it goes. She said my name for the first time in months last Saturday and she asked to go to the chiropractor. These are all significant improvements in only 1 week. She has also not been holding her head in pain at all this week...so we are assuming little to no headaches. I will keep you posted as this progresses.
 

mitoMAN

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Wanted to give an update with our ISRIB use: We have given my mother 7 doses as of yesterday. We started at 30 mg for 4 days, took 1 day off and then the last 3 days have been at 15mg doses. She crashed and slept a lot on the day off. We have noticed her ability to engage in conversation has increased...she is actually picking up on what we are saying. She has gone from being barely able to walk, to about 60 % of the time she is quite mobile and on day 4 she actually was very hyper and ran to my dad when he came in the door. The 30 mg was way too much for her after 4 days, so we cut back for a bit and will try again at a higher dose this week for a few days and see how it goes. She said my name for the first time in months last Saturday and she asked to go to the chiropractor. These are all significant improvements in only 1 week. She has also not been holding her head in pain at all this week...so we are assuming little to no headaches. I will keep you posted as this progresses.
This is extremly wonderful news! May I ask what illnesses your mother was diagnosed or suspected with?
ME/CFS?
 
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This is extremly wonderful news! May I ask what illnesses your mother was diagnosed or suspected with?
ME/CFS?
That is a loaded question as her case is quite complicated. She has a hx of 39 surgeries and missing significant inner body parts and under anesthesia each time, severe head injury from a car accident as well as lyme disease, fibromyalgia, chronic fatigue, anxiety/depression....then we now have a dementia "dx". So many factors!
 

mitoMAN

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That is a loaded question as her case is quite complicated. She has a hx of 39 surgeries and missing significant inner body parts and under anesthesia each time, severe head injury from a car accident as well as lyme disease, fibromyalgia, chronic fatigue, anxiety/depression....then we now have a dementia "dx". So many factors!
One last question. How did you administer the isrib? Did you mix it with dmso?
 
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One last question. How did you administer the isrib? Did you mix it with dmso?
We just gave her the powder with no DMSO since she cannot swallow capsules.
We have seemed to hit a stall in progress this past week with some regression of movement/spacial awareness and people recognition, so as of today we went back to the 30mg divided into 2 doses. I will update in another week and give progress.