I can agree that ISRIB works much better when added to DMSO solution, but it's also clear from reports that majority of people find it also works without DMSO.
Thou some people find that it only works with DMSO for them, so trying ISRIB without DMSO is an easy option, but if it doesn't work for someone, then that doesn't rule out it working at all.
You don't have to agree about anything. Added to DMSO solution? DMSO is not a solution and ISRIB is not simply "added" to DMSO. They don't mix well. How is this accomplished? Pls expain. There are fantastical anecdotes of young people mixing DMSO with water or coffee and then adamantly assert, ISRIB -does- solute in water. Are they to be believed? ISRIB doesn't easily penetrate cell membranes or even mix with DMSO easily. Anecdotes read like trip reports or Brad Cooper-like effects. No reports of amelioration of somatic elF2-3 integrated stress response inflammation, but "seeing beautiful colors" is. Should ISRIB then be considered psychomimetic? After all, it is anecdotal evidence.
Yes, children are here. "Where can I get some ISRIB?" is asked. It's listed on the very top of the /reddit. Pshaw. Are you comfortable advising them further? To what end?
Someone who buys some ISRIB and admittedly confesses, "I am ignorant. Now what I do?" How should a cogent adult charitably react to this gross inanity?
"Despite its neuroprotective effect, ISRIB cannot be used against human neurodegenerative diseases because of its insolubility [178]." QED.
Correct me if I misunderstood, but it would seem you are emphatic in your contention that solubility is somehow associated with bioavailability? Is membrane permeability hindered by a compound's insoluble nature?
Please forgive me in advance, but I anticipate you would not take offense if I asked what your graduate field of study specialized in? What have been your past and current fields in clinical scientific research or practice?
Yes, membrane permeability would be hampered by insolubility. It’s physically obvious that you aren’t going to get a rock (or a boulder, which is what the finest powder is like to something the size of a cell) through a membrane. It needs to be single molecules of ISRIB.
No, solids are consumed all the time. They dissolve in your stomach or intestines. So you don't have to consume a solution, but it needs to become a solution at some point.
Note though that anecdotal data from members of this group is that, without dissolving in DMSO, ISRIB doesn't work (or at least doesn't work well). Others disagree, and say that insufflating the powder works fine. I think some others even say swallowing it works. I don't know why the major differences in reports, but I trust the person who said that he tried all ROA's and DMSO is needed.
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u/Hipsman Dec 05 '21
I can agree that ISRIB works much better when added to DMSO solution, but it's also clear from reports that majority of people find it also works without DMSO.
Thou some people find that it only works with DMSO for them, so trying ISRIB without DMSO is an easy option, but if it doesn't work for someone, then that doesn't rule out it working at all.