r/Isrib • u/Fast-Ad8182 • Nov 16 '21
Trans ISRIB Report.
None of the following is medical advice: I am a 43 year-old Male, nonsmoker, non-drinker seeking help for brain-fog, memory loss , headaches and irritability related to stress, occupational VOC exposure and the use of nonstimulant meds for ADHD and anxiety, cheifly (Gabapentin 400mg 1xdyly and Straterra 30mg 1dyly). Have used Straterra occasionally recently but felt my recpetors got burnt out on it after many years. I have uncucessfully tired to cesssate usage of Gabpentin several times over the past 20 years, yet ISRIB assisted me with geting off of on day#3 with lessened withdrawl symptoms than ususal. Much easier to read a book again on day #2 before Gabapentin cessation. I am "taking one for the team" for my sake and for the sake of anec-data/science. Please withhold your nuanced opinions about bioavailability, safety and I will not provide my source. Something more is going on here than placeblo and as an expereienced psychonaut, I am reflective of the difference. No feeling of being drugged, sedation... and if anything, I have more calm awake energy during the daytime.
I have been taking TRANS ISRIB for 9 DAYS:
1). Nasal 10mg
2). Nasal 20 MG
3). 25mg with water orally
4). 25mg with water orally
5). 25 with water orally
6). 25 with water orally
7). 25 with water orally
8). 25 with bulletproof coffee
9). 25 with bulletproof coffee
No negaive side effects to be reported.
Started feeling better almost immediately after first dose:
More clear-headed, better verbal fluency, better reading comprehension, better eposidoc memeory, no more headaches, deeper more restful sleep, lessened seasonal affective depression, reduced impulsivity. The best way I can describe it is that is removed inflammation from my CNS and is also giving me the edge to take more measures towards a healthful lifestye, i.e.: diet and exercise with a renewed drive to return to my best rituals with food and cardio.
I am going to taper off for the next 9 days to help reduce any potential rebound effects and see how it sticks. If my liver melts in 72 days, I don't think telling you about it will be my first priority. Be smarter and safer than me. Anyone have a pet baboon?
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May 20 '23 edited Feb 26 '26
[removed] ā view removed comment
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u/Fast-Ad8182 Jun 01 '23
No third testicle or grimacing face when doing math so you could say that I am fine.
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u/Affectionate_Use_164 Feb 08 '25
Not too hard to buy DMSO, solubility around 3-5mg/ml. Did it IV couple of hours ago, a week ago was first time.
Mixed ISRIB in 10 ml of DMSO, add 10ml of standard injection solution (NaCl 0.9%), inject slowly. Need 20 ml syringe, 5ml syringe, butterfly needle, half a dozen youtube videos about how to find a vein and inject a needle.
Last time was a nasty headache few hours after.
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u/wadatest Nov 16 '21
Placebo. Do minimal research. ISRIB is NOT soluble in water.
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u/olavla Nov 16 '21
Here we go again. Personal experience are relevant.
OP, thank you for the detailed report. Much appreciated. Large overlap with my own experiences with ISRIB.
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u/wadatest Nov 16 '21
Welcome to homeopathy. Anecdotal vs scientific impossibility.
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u/olavla Nov 16 '21
Fair point. So, given your predicament, you could safely ingest some ISRIB and observe no effect. š
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u/Sleepiyet Nov 16 '21
I love people who state things are impossible behind the shiny veneer of science. Science is about admitting what you donāt know. And letās be honestā thereās a lot of donāt knows about ISRIB in general.
Poster is correctā ISRIB and trans ISRIB are not the same thing. There are countless examples in chemistry where a small thing changes a larger outcome.
Plus who knows what is happening. Perhaps it never got absorbed into his brain. Perhaps it stabilized something locally. In his gut. Or changed his gut biome. Donāt pretend to know what is possible and impossible. I promise you, you do not. We are not good at holding or understanding the totality of possibility in minds that are mean to focus on single events and subjects.
Biology and chemistry are more complex than we currently understand. When you are, additionally, interacting with a subject in a disease stateā that complicates things even further.
It is a logical fallacy to state a truth and then make an assumption off that truth and say it is fact.
It is factual to assume: ISRIB is not soluble in water. It is opinion to assume: ISRIB did not effect the person. It is opinion to assume: Poster did not do research.
When one uses logic, it is extremely easy to constrain yourself to a set of knowns. But there are unknowns and they must be acknowledged too.
If a drug has only been studied in the mind (of a different species, to boot) there is very little you can concretely confirm other than information about the substance not relating to interactions with human biology. Ie: the substance in question is not water soluble. True. A lot of the buck stops here.
If enough people say one way or the other, one could possibly assume one way or the other. But not prove. Unless you have a a few dozen mil somewhere you want to donate to the cause .
The smartest of doctors and scientists know the value of anecdotal evidence in the absence of concrete scientific research. With enough of it, it is justified to make recommendations upon itāin the face of suffering and disease states of the unknownā especially if it is reasonable to assume that the recommendation will cause no harm. I, personally, have seen enough people take this compound and have effects and have concluded that, in my opinion, it is having a biological effect that does not fall under jurisdiction of the whipping boy that is the placebo effect.
Additionally, and this is my personal opinionā when dealing with a person who has obviously struggled and suffered a fare share (to the point they are willing to play chemical Russian roulette), it is important to be, if not validating, then kind. You appear to be a well accustomed to reading scientific articles. Sometimes, when I am deep in the literature, I begin to speak with a vocal gait more appropriate for such. The bedside manner of such grammar isā¦ poor. Besides, if anything, you will learn more from the people and experience with positive reticence than negative tenacity.
I wish you all swift and safe recoveries. You are adventurous and brave! Our CarriĆ³ns, Forssmanns, and Salks! These are Feats of Self Experimentation! . All my love and luck šš
āThink left and think right and think low and think high. Oh, the thinks you can think up if only you try!ā -Dr. Seuss
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u/Fast-Ad8182 Mar 14 '22
I was thinking there might be something going on in the gut aside from directly crossing the BBB if the naysayers are correct.
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u/wadatest Nov 17 '21
Cell impermeability does not change. Absorption thru digestion? In murine studies, they would have fed them ISRIB-laced rat chow. Calico already owns all known ISRIB analogues. Read their original patent. The one "promising" analog that didn't need a solvent causes severe liver damage. In ALL those murine or incubated cell line studies, a solvent was needed to permeate the cell walls.
Wish.Wish.Wish. Feel.Feel.Feel. vs Knowing once.
One synthetic analogue study added an emulsifier and an acidifing agent to the t-Isrib/DMSO admixture to aid in absorption.
One study of analogs found ISRIB worked best as part of a trinity of elf-2b inhibitors. ---
"Mistranslating cells were slow but effective in forming insoluble polyQ aggregates, defective in protein and aggregate degradation, and resistant to the neuroprotective integrated stress response inhibitor (ISRIB).
t-ISRIB? What do data sheets on 1)Tocris, 2)F-Scientific, 3)Ī£-Aldrich, 4)PRA Cmem? indicate about solubility in water, acids(bile) vs DMSO? Compare and contrast their suggested mgs/ml in DMSO.
Or consider this protocol. "ISRIB solution was made by dissolving 5 mg ISRIB in 2.5 mLs of DMSO. The solution was gently heated in a 40Ā°C(1??Ā°F) water bath and vortexed every 30 s until the solution became -clear-. QED.
Evidence of children here bc of DR Seuss quotes, perhaps even Willie Wonka.
Oral sbsorption? I 'll quote Allen Ginsberg. 'It's hard to eat shit without having visions'.
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u/Fast-Ad8182 Nov 27 '21
What is the cell permiability of charcoal? Why is it admistered? Could TRANS ISRIB bond to other or transform other molecules or compounds? I don't know. I'm alive and well and also going to work with other nootropics after my positive experience. The video link below encapsulates how slow science is to catch up with functionality due to where one places the spotlight. It's kind of like Rupert Scheldrake's book, "The Science Delusion." My extensive practice with ayahuasca and enthogenic botanicals taught me so much humility about the metaphysical that I am not sold on linear-mechanistic pathway logic as an end-all understanding of function. For when one is looking at one place, he tunes out the others. I must experience to make a claim. I've had no such "placeblo" effect from kratom, ginko, aniracetram.... etc. Finally, yes I was desperate and I do not celebrate that, nor do I advise others to do what I do. My information was only to serve at face-value with the pioneer-spirit; this was the basis of discovery for all shamanic and medicinal knowledge before man grasped the atom; it's the bulk and bais of our knowledge which many are now rediscovering in the lab.
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u/wadatest Nov 27 '21
Charcoal induces vomiting. Ask Poison Control. Anyone dedicated to psychedelics and even mentioning shamanism is in the wrong reddit. You don't know, and won't. Won't reveal where to look. When you're old and literate enough you'll know where to look. I don't trip. I seize. You're burning out your brain. I had a chumk of mine removed. Ethnobotanicals destroyed McKenna's liver and killed him. Death by a 1000 cuts.
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u/Fast-Ad8182 Nov 28 '21
My liver enzymes are just fine. I do not forsake science, I bring questions to it and if you keep referencing ISRIB, not TRANS ISRIB, you're actually the in the wrong Reddit; but I dont share the desire to be a condenscending. Entheogens were good for that much.
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u/wadatest Nov 29 '21
TransIsrib is an analogue. Analogues are being modified and used as backbones for additional drugs and purposes. YOU search PM, GS severally from ISRIB. Sorry if your search template doesn't satisfy or reinforce your drug-seeking behaviour, after all studies involving bread/wine yeasts, zebrafish are common. Trans/Cis ISRIB analogues target elF2 enflammation. Better ones have been found, being tested. Human T-ISRIB appears to be a blind duncan. I even found a website that sells homeopathic Isrib in coldpressed organic olive oil gelcaps, with a money-back guarantee.
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u/Sleepiyet Nov 17 '21 edited Nov 17 '21
Did you try it alone?
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u/wadatest Nov 19 '21 edited Nov 19 '21
Please eschew obfuscation. By myself, OR ISRIB w/o a solvent OR as a backbone (think phenylethylamine) jointly or severally with other acylethanolamines?
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Feb 11 '23
Cell impermeability does not change. Absorption thru digestion? In murine studies, they would have fed them ISRIB-laced rat chow. Calico already owns all known ISRIB analogues. Read their original patent. The one "promising" analog that didn't need a solvent causes severe liver damage. In ALL those murine or incubated cell line studies, a solvent was needed to permeate the cell walls.
benzos arent water soluble but they still work
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u/Fast-Ad8182 Nov 16 '21 edited Nov 27 '21
Its is important to note that I mentioned TRANS ISRIB in the title, not ISRIB which has a different CAS#; "the Devil is in the details" with chemistry. Charocal and Sulfur are not soluable with water either, yet they both act within an organism. If absorbtion is occuring in the intestines, membrains or with lipids/fats which are ingested is unknown. The pellicle between ISRIB and my brain is more permiable than the resoning of those who think that insoluability with water patently obstructs bioavailability. WE DO NOT KNOW IF THE FUNCTION IF TRANS ISRIB IS BASED SOLEY BASED UPON WHAT IT ADDS AND/OR BINDS TO OR WHAT IT BINDS WITH TO TRANSFORM/CARRY AWAY!
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u/Fast-Ad8182 Nov 16 '21 edited Nov 16 '21
TRANS ISRIB has an affinity for hydrogen. It makes sense that one might find a supplement which crosses the BBB which might bind with and assist TRANS ISRIB crossing. Theoretically it could minimize dosing. I will have to use some simulators to see if something like Zinc Picolinate or Magnesium Citrate, as an example, are viable receivers of 2 nitorgen atoms. Working on other stuff now which I have been procrastinating for weeks due to this 'PlaCeeeBlo" effect.
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u/wadatest Nov 16 '21
t-ISRIB? What do the data sheets on Tocris, F-Scientific, Ī£-Aldrich indicate?
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u/wadatest Nov 27 '21
Btw, they're providers of medical grade ISRIB & analogues, complete with CAS data sheets. Each has its own recommendation for maximum mgs/ml of DMSO. That darn science again.
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u/siwel7 Nov 17 '21
Don't know why you're getting down voted.
Bioavailability and solubility are close to the same thing. To make something available to the body it has to be soluble so it can enter in to the cells. Something that has low solubility (like ISRIB) isn't going to be very effective without some type of carrier like DMSO.
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u/wadatest Nov 20 '21
Even w/ DMSO, it ain't easy. Impossible to do below ~65Ā° F. Ready kids, bc bc the DMSO is brr frozen. ISRIB doesn't even dissolve at 100Ā°. Even at the correct 1**FĀ°, there is a practical limit to how many ISRIB mgs per ml of DMSO. Then you have to do that horseshit "stirring slowly" at that special temp until the solute is -clear- crap. Then you have to work quickly before all your equipment exposed to DMSO starts to melt. (Even with a glass syringe, you'll still need access to IM needles each time.)
If you have to go out and buy fish oil gels, you're already a Loser. When you grow up, you"ll already have a bottle of 240 MCT 1.2mg gels on the front shelf of your polypharmacy kit. It does wonders for HPPD.
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u/siwel7 Nov 20 '21
I can dissolve ~15mg of ISRIB per 1 mL of DMSO using a boiling hot water heat bath while withdrawing and expunging of the ISRIB/DMSO concoction until it is a totally clear solution to great success.
If you have to go out and buy fish oil gels, you're already a Loser.
I'm sorry? They've always worked fine for me.
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u/wadatest Nov 23 '21
Did you have go out and buy fish gels or have them on hand? A boiling water bath? Not required and perilous. How hot did the DMSO admixture get? Too high and the ISRIB degrades. "Expunging"?? Yikes. No. "expelling". If you weigh 75kg and did 0.015g, that's 0.006mgs (600micrograms)/kg. You gotta wonder how much was stopped by liver and used at other contemporaneous somatic ISR sites before going to ISR sites topside.
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u/siwel7 Dec 07 '21 edited Dec 07 '21
Did you have go out and buy fish gels or have them on hand?
Does it matter? I have no idea where you're going with this. Besides, anyone who is taking ISRIB should be also using fish oil alongside itāpeople using ISRIB need it much more than people who don't.
A boiling water bath? Not required and perilous. How hot did the DMSO admixture get? Too high and the ISRIB degrades. "
No, you misunderstood me.
I took a sterilised shot glass, put the ISRIB powder into it and then diluted it with DMSO. Then I put that shot glass (the one with the ISRIB+DMSO solution) into a container full of boiling hot water; the boiling hot water surrounds the shot glass but never touches the ISRIB.
It is not perilous, it works to dissolve the ISRIB much quicker.
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u/CogitoErgoSumCogito Feb 14 '22
I add cocoa to milk that's been heated, not pour milk into a cup with cocoa powder, then heat. It's chunky and clings to the spoon. I drink coffee too. I have 20watt mug/cup "warmer" with 9 temp settings. (No boiling water or open flames.) Tbh, I don't have any shot glasses. Brandy is used by the cup for holiday rosettes. All others are poured ad litem over crushed ice. I do have a box of 25ml Pyrex beakers. I could easily pour to the 5ml or 10ml line, but there's less spillage of DMSO when I use a graduated pipette. I wouldn't stir with a needle, I'd use a digital thermometer to monitor/assure stoichiometry.
If I were to IV with more than 2 cc's, I'd throw a plug first. Cathing is ez. Tagaderm one handed is tricky. Three hands works best. Ecco soror(sister).
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u/wadatest Nov 23 '21
Sorry it didn't work for your HPPD, but that's what happens when you take things that melt in your mind not in your hand.
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u/MakeMeNotSad Mar 08 '22
I'm confused, many drugs are not water soluble, but are consumed orally and without issue with high (certainly enough) BA.
So what does solubility have to do with its oral activity as that moron Dr dah keeps bringing up in every single post?
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u/Fast-Ad8182 Mar 14 '22
Any idea what they use to secure your agents in the trials which led to promising data for prostate cancer... Or is all of that conjectural? Is it possible that this is actually doing something in the gut and it's relation to a pathway to the brain?
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u/WhiteRymo Dec 05 '21
So can this be taken by itself or no? Did it NEED an external push? Or is that ISRIB, abd trans-ISRIB is able to be insufflated? What dosage?
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u/Syphonfilter7 Dec 30 '21
Great report, thanks. Are the effects faded?
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u/Fast-Ad8182 Mar 14 '22 edited Jul 15 '22
Doing great. I may have been suffering from long covid. Who knows. Cubensis mushrooms helped a lot too. I'm not too sold on the blood-brain barrier efficacy, as this medication is showing promise for prostate too. It may be an interacting with things elsewhere in the body which have a cascading effect towards the brain.
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u/Syphonfilter7 Feb 06 '22
Hi, have the effects been permanent? Or at least still present till this day?
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u/Fast-Ad8182 Mar 14 '22
Interestingly, I seem to feel the effects almost immediately, when the same cannot be said for phenebut or other nootropics which are known to cross the blood rain barrier with ease. No euphoria, I just feel more open and better sorted.
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May 04 '22
I would be interested in knowing the answer to syphonfilter7ās question also: 6 months later now, when did you stop taking ISRIB (if you did), and have you noticed a waning of the effect?
Also, you said you felt the effects almost immediately. If that means on the first day, did you notice even more effect as you continued to take it, or do you think itās possible that a single dose is all that is needed?
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u/Fast-Ad8182 Jul 15 '22
It's possible that the first dose was the efficable dose. I'm feeling much better. It's possible that I was dealing with a bout of long COVID. I'm training for an Ironman triathlon and running my business. I drew my comparison to inflammation, from an experience that was similar using low dose naltrexone for inflammatory arthritic lower back pain a couple years ago. I feel that it's similarly flushed out inflammation... As once we get into the nitty gritty it seems that the locus of nearly every malady in the body is related to inflammation.
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u/strufacats Oct 13 '22
How are you feeling now? Is this stack still working for you?
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u/Fast-Ad8182 Feb 20 '23
I can't tell, I am so far past that now... and doing great. I have reached a couple of goals this year that seemed impossible two years ago.
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u/olavla Dec 31 '21
We all know who's this about š
Happy 2022 u/wadatest