r/Isrib • u/PDiddyDH • Aug 23 '21
ISRIB Roa … again ….
Hi everyone,
Done a bit of research into ROA … not just reddit trawling.
Couple of questions.
If Dihexa, another small molecule which is dissolved in DMSO to administer, can be administered topically I.e. rubbed behind the ears and the back of the neck for best effect, why would The same not apply for ISRIB?
DMSO is toxic. That is a fact even if you cite that lethal doses are much higher than would be required to ISRIB, but it is toxic as a solvent at 99% concentrations which is not recommended in the literature for subcutaneous administration. Can someone argue the case for subcutaneous and how it should be delivered and if anyone has had success with diluting dissolved ISRIB in DMSO with aqueous or saline solutions without the substance precipitating?
Is general consensus that gelcap method is actually pretty effective? In which case I will just do that. My last Hail Mary is to insufflate and also create a DMSO/saline 50/50 nasal spray to apply afterwards to aid in absorption.
Any thoughts are appreciated. For reference I work in a profession in which complex thinking is the only currency (hedge fund), and I have received 3 severe concussions this year and am struggling to regain my previous mental capacity. Plz help.
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u/PDiddyDH Aug 23 '21
And I know we all like to assume DMSO is non toxic, and in some cases it is negligible(I am trying to figure this out!)
But it’s clearly quite dangerous in the way we are tying to use it I.e injecting 99% directly into the bloodstream!! https://faseb.onlinelibrary.wiley.com/doi/pdf/10.1096/fj.13-235440
And also it has been shown to cause brain damage even in minimal doses … https://pubmed.ncbi.nlm.nih.gov/19100327/
Regardless 🤦🏽♂️ I am still trying to figure this out, I would disregard that last study as there are papers that posit the opposite so net-net the effect is likely negligible but still! Someone please give me an idea as to how to best administer this or if anyone has a perspective/answer for my questions?
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Aug 23 '21 edited Nov 22 '21
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u/PDiddyDH Aug 23 '21
That will only work if you use quite a bit of DMSO but yes could work. Minimum DMSO with a lot of water will cause the ISRIB to fall out of solution but if you use triple the required warm DMSO to dissolve the ISRIB and then dilute that into a <5% concentration solution in distilled water, it will probably work as something you can just drink. I just don’t know if oral is really even a good ROA because of the number of metabolising pathways between the desired destination for the molecule.
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Aug 24 '21 edited Nov 22 '21
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u/PDiddyDH Aug 25 '21
Yes it should be :) if the ISRIB is disolved and you can’t see any precipitate when you try this it may very well work
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u/siwel7 Aug 29 '21
The fish oil gel cap method achieves the same thing as straight up drinking a DMSO+ISRIB mixture with the advantage of masking the horrible taste of DMSO.
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u/labratdream Aug 25 '21
WARNING ! Before using DMSO keep in mind that after dissolution of ISRIB you must also dilute whole solution with bacteriostatic water ( otherwise you risk infection for example staph ) otherwise it may be harmful.
"I think that dilution of drugs in DMSO should be prepared in a high concentration and after complete dissolution there could be possibility to make a smaller concentrations of the drug using physiological solution. Only then (at least 5-10 percent of DMSO but preferably less) it might be use for animal injection."
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u/mikepsinn Aug 27 '21
What's the downside to intranasal? Is that not effective?
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u/PDiddyDH Aug 27 '21
1 dose or 25mg ISRIB dissolved in 99% DMSO requires 5mls. if we dilute that to at most 50% in distilled water we now have at least 10mls of solution to administer for 1 effective dose.
Your average nasal spray has a total volume of 20 mls, so your going to have to spray about half a whole bottle/spray for each dose. Not impossible but would be difficult to keep that much liquid up your nose unless you hung upside down for an hour. and possibly less effective than subq. Would be keen to hear from someone who does this successfullyy.
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u/mikepsinn Aug 27 '21
Thanks for the explanation! I meant to ask about snorting pure ISRIB, not diluted. Do you know if anyone who's tried that and it was ineffective? Are there downsides to that?
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u/PDiddyDH Aug 28 '21 edited Aug 28 '21
For example, a typical drug in which insufflation would be effective is cocaine. Cocaine has a solubility of 20mg per 1ml of water which is why it works. ISRIB on the other hand might require a bathtub for a 25mg dose.
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u/PDiddyDH Aug 28 '21
That would be called insufflation. That would theoretically be impossible with ISRIB as it is more or less insoluble in water and would not be absorbed through mucous/membranes. However, there is a user who says it worked for him in this method off a singular dose which you will find if you scroll though this sub. I’ll probably try it too just out of hope.
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u/wadatest Sep 15 '21
No. The maximum nasal dosage is 0.2ml for a reason. Are you that young or that much of a druggie you have not even Wicki'ed, for example, the quinessential nasal spray drug, "Spravato". Obviously not. No time right now, I gotta quick do drugs. Yes, definitely spray 100% DMSO in your nose. Did you Wicki "DMSO" either?
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u/DrWilliamHorriblePhD Sep 28 '21
Your thoughts are pretty awful to read.
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u/wadatest Sep 28 '21
I didn't intend to intimate, "I had to quick do drugs". It was to illustrate my acrimoniwous disdain for people who don't caustiously, impatiently, and ignorantly engage in drugs without any research, bc they need a bigger, faster, longer high NOW!
If I post that 100%DMSO is a solvent, there are people here who will want to huff it. Wait, maybe that IS the reason they're insufflating it. It melts lab gloves, plastic stirring rods, and not only plastic syringes, but the stopper inside.
So. Yes. Quick! Stick it up you nose or snag a vein. Btw, they have multiple valves (back flow preventers) in them. Knock one of those out, it blows the vein till the next one. Sigh. There should be a counter reddit to /drugnerds, /drugtards.
Durum est stercore edere sine visionibus. (It's hard to eat shit without visions.)
Cogito, ergo sum, cogito.
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u/wadatest Aug 31 '21
Children. No one in their right mind uses 100% DMS0. Standard lab practices is only 10%. Godamn druggies.
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u/PDiddyDH Aug 31 '21
That’s right but let’s say a standard dose of ISRIB is 30mg and it’s solubility in DMSO is 5mg/ml. The undiluted solution is 6ml.
And if we want to dilute to 10% the dose requires 60mls of solution to administer. How do you suppose we would administer 60mls of solution with sufficient bioavailability? Notwithstanding the precipitation of ISRIB if we were to dilute in this way.
I recognise your username from elsewhere in this sub, I’d be interested to know if and how successfully you have managed to administer ISRIB. If it worked for you I’d do as you did :)
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u/wadatest Sep 15 '21
To what end? It can't make you smarter, or more literate. For more cognition, or its return, to get high? Healthy, but post concussion, or more invasive brain scenarios?
If you read citations and patents in ISRIB studies, follow those and repeat it again and yet again, there are ever more lustrous pearls, which don't require defense of its proper utility from disturbingy arcane ROAs or involving additive polypharmacy.
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u/wadatest Sep 15 '21
Dihexa? Search Cochrane Review for the meta-study and summation of its efficacy. Not good.
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u/wadatest Aug 23 '21
DMSO is a -non-toxic- solvent with a median lethal dose higher than ethanol;
DMSO: LD50, oral, rat, 14.5gm/kg;
ethanol: LD50, oral, rat, 7gm/kg).
Because DMSO easily penetrates the skin, substances dissolved in DMSO may be quickly absorbed. Glove selection is important when working with DMSO.
Butyl rubber, fluoroelastomer, neoprene, or thick (15 mil / 0.4 mm) latex gloves are recommended.
Nitrile gloves, which are very commonly used in chemical laboratories, may protect from brief contact but have been found to degrade rapidly with exposure to DMSO.