If anyone tries it, please let us know results. Do some double-n-back game testing, or memory testing games, to see how you do before and after dosing.
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Jorj
#22
500 mg of Trans-Isrib – Powder for $60 for “laboratory research” from Science.bio -:Buy Trans-Isrib - Powder, 500mg. MCE offers 5 mg of trans-ISRIB for $60 and more for larger doses -.https://www.medchemexpress.com/isrib.html I don’t know if there is a difference between trans and non-trans ISRIB (not speaking of gender, here!) of if there is a way to purchase ISRIB from these vendors as they don’t sell to ‘patients’. I would have to qualify myself as a ‘researcher’. Aren’t we all at this stage?
Realistic human dosage of ISRIB??. ABBV-CLS-7262 is given once a day, orally, in the Healey trail.but I don’t see how to correlate that to ISRIB. Anyone have data on dosage? .One test on mice administered 0.1 mg/mL at a dose of 2.5 mg/kg by injection (https://www.pnas.org/doi/10.1073/pnas.2209427119) That doesn’t quite get there for human oral consumption.
ISRIB is exciting if it translates well to humans. I don’t see much data in that area after the slew of tests on mice and several articles in 2022.
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tananth
#23
Keep in mind that ABBV-CLS-7262 that is used in human trials is a mix of the phosphate salt of ISRIB ( also known as Fosigotifator) and tromethamine (Tris - Wikipedia) in equimolar (1:1) proportion : without the tromethamine ISRIB is poorly absorbed. The dosage used in studies appear to be 120-240mg per day.
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Lost
#24
The active molecule of ABBV-CLS-7262 / Fosigotifator has quite a few differences to ISRIB. Clearly a derivative, but not just a salt or prodrug. “Umbrella labs” advertises it quite cheaply, but their COA is not available and I in no way vouch for the identity, purity, or even existence of the product.
If anyone knows why ISRIB needed to be modified (oral bioavailability?) or what the equivalent dosing is between the various available compounds in this class, I would be very interested.
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someone advised me to dilute into mg/mL to get more precise dosing way easier.
Though maybe snorting is an option given how little powder you really need
RobTuck
#26
The preclinical research suggests that ISRIB crosses the blood-brain barrier and has a half-life of around eight hours. The compound’s manufacturer, Calico (a subsidiary of Alphabet focused on longevity), continues to investigate ISRIB’s potential in neurodegenerative and cognitive decline contexts, but there is no public data that I could find on human dose.
what’s dif between ISRIB and ISRIB-A15?
Lost
#28
Potency would be my guess. Possibly better BBB transit. The SAR was worked out in
https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/cmdc.201500483
, which I can’t access easily. Note Fosigotifator has a similar modification.
Edit: The article was provided below. Yes, the potency (IC_{50}) is improved by a factor of ~7.
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I think it bears mentioning that ISRIB is not water-soluble and can not be snorted (not water soluble) or taken sublingually (too large). I found this good post on dissolving ISRIB (it needs DMSO): https://www.reddit.com/r/Isrib/comments/r8y2rc/solubility/
There is a max that can be mixed with DMSO which is usually said to be around 4 to 9 mg per mL. The second poster down probably is right in saying that it doesn’t mix very easily. I have seen ISRIB clump myself in DMSO. It needs some more vigorous mixing is all that needs to be kept in mind with that. Anecdotally, I have had a very good response to ISRIB, when I did not have much of a reaction to other nootropics I’ve taken.
4 Likes
Please share more details. Form of ISRIB you are using, dosing level and timing and duration, any way to measure cognitive results (test scores on double-N-back during dosing, etc.)…?
Luminary
#32
I’m currently using trans-ISRIB dissolved in DMSO. I did not use dual-N-back before starting it, and there is some suggestion that it has benefits in a single dose, so I might hold off on doing that for right now. It might have had a subtle effect, but I didn’t feel anything immediately after dosing it.
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Snorting doesn’t work for water insoluble??
Luminary
#34
You might be right that it is absorbed to a certain extent, but most of what I found on the absorption of water-insoluble drugs is negative. Here is one example:
https://www.sciencedirect.com/science/article/abs/pii/S0939641123000504
RapAdmin
#35
What is the dosing (mg) and frequency you are doing?
1 Like
Luminary
#36
My dosing is inconsistent, but I have been gradually ramping up from 10 mg with 1 mL of DMSO towards 20 mg with 2 mL assuming the ratio of ISRIB to DMSO is at the higher end of 9 mg/1 mL. Most on that subreddit use doses ranging from 10-40 mg which I am guessing has something to do with the doses used in animal studies. I have seen studies as low as 0.1 mg/kg in animals which means most human doses are already at a very high level- almost to par with mice dosing.
Here is an average for animal doses of ISRIB:
Inhibition of the ISR abrogates mGluR5-dependent long-term depression and spatial memory deficits in a rat model of Alzheimer’s disease - PMC
At 0.25 mg/kg, there was at least one study saying it penetrated the BBB well. The challenge, though, is that it needing to be dissolved in DMSO makes it a bit rough getting down, even at 10% dilution.
2 Likes
This interesting reading… thanks for pointing towards this reddit group on ISRIB and biohacking:
https://www.reddit.com/r/Isrib/
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I wonder if shelving it would work?
is isrib-a15 the trans form?
is dmso also diluted in water?
They appear to be slightly different. ISRIB-A15 has this data: CAS number:1628478-12-5
and Formula:C22H22Cl4N2O4. Trans-ISRIB has a CAS number: 1597403-47-8 and the Formula: C22H24Cl2N2O4. Neither of the forms are in development anymore, but the only difference they ever appeared to have was absorption-related.
And definitely dilute DMSO. I think I read before that even 50+ percent DMSO is technically safe for oral consumption, but some people on that subreddit were apparently using 99.9 percent DMSO undiluted—probably not the best long-term plan. It is never used in clinical settings above 10 percent as far as I can gather.
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