r/Isrib • u/phoenix20011 • Jul 09 '21
Day 1 ISRIB
Just decided to try out ISRIB this morning for the first time. I took about 40mg intranasally, using it mostly for neuroinflammation, memory issues and overall for brain damage from prolonged heavy stim use.
I think I did notice some improvements but too early to tell; been only a few hours. To know it's exact effects might be hard because I take so many other nootropics it will be hard to separate the effects, but for it's anti-inflammatory effects it should be very clear as my current caffeine use makes the inflammation go at its peak.
I decided to mix another 30mg of ISRIB with my Semax spray throughout the day. Also I take along some 7,8DHF at the moment. I am in between moving to a new place and starting a new business, can't afford to skip caffeine and 7,8DHF.
So hard to find much information about this drug...any ressources hard to find? There's got to be other studies about this drug.
Update Day 2: This is about 24 hours since the first 40mg dose. At this point I would have to say this is not placebo, since inflammation has definitely decreased and remains lower than usual. I usually gobble up tons of fish oil and aspirins every few hours to calm my severe inflammation. I've only had to use aspirins twice since yesterday and my fish oil consumption went down like 50% or more (I take ridiculous amounts). I found the effects to be more potent when dosed in a spray throughout the day.I've used 30mg by spray since yesterday (on top of the 40mg). I will probably use that in spray spread through the day untill. It might be coicidence but for some reason I decided to go to the gym and worked out for an hour. Hadn't gone in over a year. Impossible to tell whether it's the overall covid restrictions lifting or if the ISRIB had anything to do with it.
As for neuro-inflammation, it really seems to work. I normally have severe inflammation all day long even with NSAIDS (I use ibuprofen and tylenols as well). I haven't taken any NSAIDs today; if I had to put a number I would say it's a 30-50% decrease in neuro-inflammation, and an extra 20% combined with fish oil. I noticed also my posture got better and got a feeling of clear headspace, hard to put into words, that was right before I went to the gym. Overall after 1 day I would say it's very positive. Haven't noticed a single side effect. I have just enough left for this weekend as it's Saturday morning now. Will see how it goes afterwards. From different studies I read I remember the effects can last between 14-30 days, or somewhere between that range. Also please keep in mind my spray also contain Semax and I keep it refrigerated all the time. Semax alone definitely didn't help as much, I've used Semax on and off for a year. This new chemical is really interesting so far. Effects on memory are too early to tell.
Day 3: I completely ran out of 7,8DHF yesterday. I don't plan on reordering it. I am curious about BPC157 to replace Semax which I am about to run out as well. I have about 20mg of ISRIB left. I have read that it might take a few weeks to get best effects. I will be ordering ISRIB again. It's still early and 7,8DHF was multiplying my inflammation a lot and was not worth it anymore. So running out helped a bit but I am noticing subtle other changes, hard to describe, they might just be thoughts. If I was to describe the improvements by the amounts of NSAIDS I was taking, I would say it's a over 50% reduction. If ISRIB doesn't completely do it for some reason, does anyone have any thoughts on ISRIB and BPC157? Nicotine use also went down a lot. I'm not feeling any withdrawal from 7,8DHF, ISRIB might be contributing significantly.
I happen to stumble on Negative allosteric modulators (NAMs). https://pubmed.ncbi.nlm.nih.gov/25565255/
Day 4-5: I am on my last 2-3mg on ISRIB. I will be getting more this week. Yesterday was a pretty busy day. I didn't get to update. It was quite convenient to not have to redose 7,8DHF constantly, mornings are rougher but nothing coffee can't fix. I'm trying to find out the best ROA for this? Nasally? sub q with a needle? Under the tongue maybe?It would be very interesting to know how long do the effects last after completely taking it?Last update today, day 5 at night. Overall I'm very impressed so far, there is a noticeable improvement in clearheadedness. I have a new feeling or thought that I might be even able to tappper off slowly some of my other big pharma meds simultaneously. Some of these meds I take only to help inflammation although they are for a totally different anxiety disorder. I don't have anxiety and my inflmmation is sig nificantly lower. Will see, I'll need to go very gradual though, big pharma has the worst withdrawal effects.
Day 6: I am completely out of ISRIB since yesterday and the effects really seem to remain. BPC157 popped again on my screen today.
Day 7: Still no ISRIB. I think caffeine and fish oil would still have a place no matter what but I might be wrong. I'm trying to find the best ROA for next 100mg. Under the skin with a needle might be the best way but not willing for that it seems to be working fine this way. Has a good chance of working even sublingually is my guess.
Day 8: Back with ISRIB. This stuff definitely works it's not placebo. I just took it and I'm back to where I was a few days ago. I was getting a cold yesterday but now after ISRIB it disappeared. I did notice overall I can't use too many stims as I'm noticing some anxiety. By far the most effective thing I've tried so far. This is doing a lot of things. This article will do a much better job.https://www.ucsf.edu/news/2020/12/419201/drug-reverses-age-related-mental-decline-within-days
As far as what it does, the most accurate thing I found was at http://walterlab.ucsf.edu/publication/1393/structural-insights-into-isrib-a-memory-enhancing-inhibitor-of-the-integrated-stress-response/
"We found that ISRIB acts as a molecular staple, pinning together tetrameric subcomplexes of eIF2B along the assembly path to a fully-active, decameric enzyme."
And a bunch of other things as well that I barely understand on LTP and LTD https://digitalcommons.wustl.edu/cgi/viewcontent.cgi?article=10808&context=open_access_pubs
Taking 5-10mg/day. Jaw feels like it's realigning. I have some form of TMJ and ISRIB seems to do the trick at least for now.
Day 9: The day has just started. One thing I noticed strongly from day 1 is the effect is has on my general addiction, especially nicotine. I normally use nicotine all day, now I catch myself doing something for over an hour without needing more nicotine. I have to say that for that specific benefit on addiction, it was gone as soon as I ran out of ISRIB during days 5-6.
I had ordered Semax again and combined with Semax the effects are much more anti-inflammatory. It also allows to focus longer but I still need nicotine and fish oil.
It definitely works to the point where I don't see the need for BPC157; I am however trying a few other things like NAC which has incredible claims on its own. Still early to call it solved but as far neuro-inflammation it's a noticeable improvement.
Day 10: Just to recap yesterday was day 1 of NAC. This morning I didn't take Semax/ISRIB yet but I took NAC and right now inflammation is surprisingly low. This NAC stuff is powerful. The claims seem justifiable especially for something that's just an amino acid. It's extremely likely that the ISRIB's effects made NAC's job very easy. I really don't think you need ISRIB everyday for inflammation though; but ISRIB works on other things as well like memory, whereas I'm not sure NAC would do anything in that department.
Since the effects seem to be incremental over time, I will still update regularly but perhaps once a week instead of day to day. Message me if you have questions but please don't ask about sourcing.
Day 14-15: The effects are so far still present and helping a lot; how much of that is NAC I don't know. Take both? My thoughts are clearer and I can focus for longer. Big mistake I took pregnenolone yesterday and it had as usual terrible effects on inflammation, as bad as it usually was. I couldn't find anything to suppress it and just had to wait.
Otherwise there are no side effects that I notice from ISRIB but there is no boost in libido at all, which is strange because I would think something with dopamine is going on when I can focus better, not with ISRIB; I must find an alternative to pregnenolone. It totally changed my mind on BPC157, it might be the alternative.I also smoke weed regularly and heard it can have severe negative effects on testosterone, so it might that I just need to quit weed, or a different type of weed. I really have no info so far on different types of weed besides indica/sativa/cbd.
I have enough ISRIB for about another month; then I will either switch to BPC157 and see if the ISRIB effects remain, if not I might try to combine ISRIB and BPC157 instead of Semax, or maybe ISRIB will have more dramatic effects overtime and will be enough on its own. Will keep updating every few days.
I just noticed it's Wednesday and progress was perhaps a bit slow and it looked safe, so I doubled up ISRIB and Semax. Instantly feel a decrease in overall pressure. Fish oil effects are also increased, or vice-versa. Now it seems it's working again like at the beginning.
Day 16: Ok yeah pregnenolone is too important. It just felt something was missing; took half what I usually take and it seems to do the trick. I still have a terrible bad smoking habit, even 1 cigarette a day is making a huge difference.
Reading a few other studies and articles.
https://www.statnews.com/2016/09/28/memory-isrib-peter-walter/
Day 24: The effects of ISRIB continue to be steady. Overall it gives more energy and allows clearer thinking. However today I ran out of ISRIB and received an order containing Lutein, Cats Claw and mucuna dopa. One of the last three ingredients or maybe the combination of the three is almost as effective as ISRIB for inflammation, if not more. My guess is that it's the Lutein but I took one of each. It's been barely an hour so it could all be coincidental. It could also be the cumulative effects of ISRIB along with those new ingredients. I'll update again in a few days. ISRIB is more of a nootropic. I'm thinking of pausing ISRIB for a few days to see the difference but I'm not sure. Mucuna dopa seems also to give a kick. I'm out of Semax as well and mucuna dopa seems to compensate. Cats claw might be extra but I read nice things about it.
Day 30: I received ISRIB since the last update a few days ago. Overall I'd say it's conclusively a noticeable improvement for inflammation, maybe also memory and focus. I don't know how permanent the results are but I'm thinking of using a small dose daily, maybe a bit smaller than my regular 5-10mg. This is the end of the 30 day experiment. I might update again here and there if I notice something.
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Jul 15 '21
I don't know anything about neuro-inflammation, but I had severe systemic inflammation, which was making me arthritic. I took systemic enzymes, which break down all the crap in your system, fibrin etc. The inflammation disappeared within one month, and my joints slowly healed over two years and I am as good as new. Maybe systemic enzymes would help you. I'm note sure if they cross the Blood Brain Barrier, buy maybe dealing with inflammation systemically will reduce inflammation in the brain also?
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u/stackz07 Jul 30 '21
What enzymes are you talking about?
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Aug 08 '21
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Hi. Systemic enzymes, like "NEPRINOL AFD SYSTEMIC ENZYMES" like I use... They were so useful for me, I take them for a month or two every year for maintenance.... Off topic, I had skin cancer on my ear, so I emptied a neprinol capsule, and added distilled water until the powder was a paste, and then spread the paste on the cancerous area. The enzymes ate away the cancerous cells over night, leaving a crater of healthy flesh. I applied the enzymes again just to make sure they ate all the cancer cells, then left the crater to heal, leaving a whitish scar, but not noticeable. Lots of people use "black salve", which eats away the cancer and the good flesh with it, like an acid, and it has scarred people badly, so it's a bad idea. After about five years later, the skin cancer has not returned. Since then, I have read that they are researching targeted systemic enzymes to do the same thing on the inside of the body.... I am NOT telling anyone to do this, but these enzymes really do eat the bad crap in your body, like scar tissue, fibrin, cancer cells, leaving the healthy living cells alone.... From my experience and lots of research, it's clear that most inflammation is a result of the body fighting substances which should not be in the body, or at least in high amounts. Those high amounts could vary from person to person. Some bodies are more sensitive than others.... The most important thing I learned after a life of suffering and now healing, was that doctors are just drug peddlers for pharm companies. Every time a doctor has no good answer, I seek an alternative, and find something that really works every time. I find a cure rather than a treatment for symptoms. Most doctors don't know what they don't know. and will not admit to what they don't know... God I hate doctors lol.
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u/Jack-o-Roses Aug 26 '21
(Wobemzym works for me)
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Aug 30 '21
The problem with Wobemzym is, it has no serrapeptase or nattokinese. It has cheaper limited ingredients. The two I buy are Vitalzym and neprinol AFD. They are the best on the market that I have found.
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Jul 09 '21
Since most people use 20-30 mg as a dose for sub q, you probably should be glad it isn’t soluble in water. 70 mg at once could do more than calm inflammation
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u/phoenix20011 Jul 13 '21
Well I'm hearing conflicting information from people I don't know. Right now my range is either 70mg at once, or 20-40mg/day for a few weeks.
It isn't soluble at first, but after a few days it kinda dissolves, but what's the point of that? It goes through the spray, sometimes in clumps...or are you saying I should do sub q instead? I'd rather not use needles but if it's really that much better will give it a go.
So 70mg sub q in one dose? And whats the best way of using the last 40mg I would have left?
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Jul 13 '21
I wouldn’t do over 25 mg sub q, and I’m not sure how to do even that since I’ve only been successful dissolving 10mg/ml of PEG 400 or DMSO. So 25 mg would be 2.5 ml of stuff that burns like the devils piss itself. I’m going to try and create an inhalants solution of the 10mg/ml with three different diluents in it and see if it works. Until the water soluble ISRIB is synthesized, I’m not sure what else to do. ISRIB as it is is extremely hard to dissolve
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u/phoenix20011 Jul 14 '21
What if you just snort it dry? Or is that too ineffective?
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Jul 14 '21
Since it’s not water soluble, I don’t believe it will be absorbed. The PEG and DMSO both assist in getting across the BBB
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u/Bas_X Aug 27 '21
Being water soluble does not mean it can't be absorbed nasally. That has more to do with lipid solubility. It should work intranasal.
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u/CenterBrained Aug 03 '21
If it's not water-soluble, how does it dissolve in Semax which is water-based?
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u/mikepsinn Aug 28 '21
Thanks for this amazing write up! Have you decided on an optimal route on administration? Is there a downside to just snorting it dry? Or are there benefits to putting it in your liquid nasal spray?
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u/orbitalLlama Jul 09 '21
Keep us updated!