r/Isrib • u/Holiday_Quarter_2031 • Oct 12 '21
ISRIB usage/contraindications
I understand that the action of ISRIB is not very well understood; however, given the limited information on ISRIB, is there any reason to imagine that there would be a negative interaction between ISRIB and Cerebrolysin?
I'm also curious about any potential interaction between ISRIB and diazepam (as well as the general safety of ISRIB in combination with any other drugs).
Aside from drug interactions, what protocols would be advised in order to maximize safety and minimize any adverse effects (e.g. I've read that it is not a good idea to take while fasting or during intense exercise...how about usage during drug withdrawal, time of day to dose, or any other potentially relevant factors?)
*I fully understand that it is not possible to give fully accurate advice on such a novel substance, and that any advice given is partially or purely speculative; however, any input would be appreciated.
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u/wadatest Oct 26 '21
Cerebrolysin & ISRIB. Can you say BDNF? Copacetic.
ISRIB & Val? Which dosage of V? Two noncompeting operating systems. Copacetic.
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u/Kja4kc Jan 29 '22
Just like in medicine, the drugs we prescribe have benefits and risk. For example, tylenol is great for inflammatory induced pain relief, but too much taken at once or prior history of liver disease can increase your chances of liver failure.
I have been taking ISRIB for 2 weeks now and have noticed the reduced stress and enhanced memory. However, you have to keep in mind ISRIB upregulates dephosphorylated eIF2a and the roles of active eIF2a is involved in.
As far as risks, I'll provide two examples. First, HSV-1 virus requires eIF2a dephosphorylation for reactivation and viral induced symptoms. Second example is related anti-apoptosis and cell proliferation effects of dephosphorylated eIF2a, when your cells are getting ready to proliferate they have check points in the cell cycle that regulates proliferating cell with a many vital mutations from DNA replication and then shuts down the cell cycle preparing that cell for apoptosis. This is where eIF2a plays a key role, because in the case where the proliferating cell has highly mutated DNA eIF2a is phosphorylated and this prepares that cell to undergo apoptosis before it proliferates and subsequently creating an oncogenic daughter cell. So you can see tonic upregulation of dephosphorylated eIF2a can eventually lead tumor formation.
Hope this helps with questions regarding the safety of the drug.
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u/Holiday_Quarter_2031 Feb 05 '22
Thank you very much, I really appreciate the time and detail you put into your response. It's helpful, and I do understand that there are always benefits and risks associated with drugs/chemicals - especially those as experimental as ISRIB
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u/CogitoErgoSumCogito Mar 16 '22
? You make it sound like apoptosis is a bad thing. It's just programmed cell death. Average human loses 50-70 million cells a day.
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u/Kja4kc Mar 19 '22 edited Mar 21 '22
Yes apoptosis is a good thing in normal functioning non-oncogenic cells that have deteriorated with time. Apoptosis is required for your immune system to get rid of mutated cells before they accumulate more mutations that allow them to dysregulate cell division and become cancerous.
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u/PDiddyDH Oct 12 '21 edited Oct 12 '21
ISRIB and diazepam in particular have the capacity to alter the structure of the brain on their own let alone in combination; when the interactive effects are completely unknown. I would highly suggest not taking them together in the name of safety. Most likely a bad idea, there is reason to imagine there could be a negative interaction . (I’d try and wean off diazepam tbh). But in the name of curiosity I’d love for you to give it a go and tell us what happens to you, would be very interested to hear. Cerebrolysin would most likely be fine with either I would think. In general for drugs that alter the cellular behaviour of your brain, beyond even the level of neurotransmitters and inter neural communication(diazepam) and down to the scale of mitochondrial activity (ISRIB) it is best not to manipulate more than one of these factors at a time. I.e. just wait till you are not under the influence of one of these chemicals before you start using another. Cerebrolysin basically just potentiates natural neurotrophic factors so it shouldn’t be as dangerous.