are you talking about HU-211 or GAT211?
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Gat 211…glad to see you picked up like that.
The PAM effect of GAT 211: think of it as altering the radar plot, more than just an increase in THC action.
A brief review of GPCR bias and representation a “radar”plots: Receptors | Free Full-Text | Biased Agonism or “Biaism” for Dummies: A Commentary
Cut and paste
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Gat 211
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Just a thought…I know CBD has been shown to reduce insulin resistance significantly. I also have been reading about type 3-4 diabetes which many believe to be the underlying cause of alzheimer and dementia. Maybe there is a causal link between the CBD and insulin resistance and battling alzheimers.
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Sure – and i’d say, maybe you might want to do that for like 6 months – 1 week is crazy small when you’re talking about breaking down what’s become a substantial portion of their brain mass…
I should also point out just “removing plaques” isn’t really as good as it sounds. Cause it’s not like when you remove plaque suddenly there’s healthy tissue in it’s place. No, you’re just left with a big honking hole. That’s why these recent amyloid antibodies like aduhelm all reduce total brain volume. The idea that removing plaque actually will improve cognitive function in my view is totally unproven… the most I would expect is that it could slow further progression but not actually undo any damage already done, and even that does not actually have hard data supporting it. Hell, it could make things worse if it leads to some kind of regional structural collapses…
By the time you’ve got so much plaque that your brain volume drops 10% when it’s removed, your brain is freaking swiss cheese. I don’t see any sort of medications fixing that one, not in 100 years. What we need is a handle on the actual causative factors and treat it preventatively. Nothing i’ve seen convinces me “curing” or “reversing” alzheimers is a realistic goal. Something is fundamentally wrong with the mouse models that every lever that changes their outcome, generates null results in humans. The mouse models simply mutate them to secrete more beta-amyloid. Seems like the human disease has causative factors going at least one step deeper than that that keep on trucking no matter what you do to the amyloid production process.
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I absolutely see your logic here, my only counter is how miraculous the human brain is. Have you heard of the gentleman who had 90% of his brain mass missing and still lead a completely normal life? The brain has been shown to do amazing things in the wake of extreme trauma.
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6 months …if you really think you can reverse plaque formation? How about rapid cognitive improvement? You can observe such improvements using cholinergic agonists.
Cognitive capabilities are emergent phenomenon. None regard such actions a “curative” in an manner.
Yes “ Rescue Memory Deficits and Reduce Amyloid-Beta and Tau”. Is a very shocking claim! Certainly, your criticisms if the topic/field are needed. I have not read the paper in sufficient detail to offer any specific critique of their experimental design or interpretation of results. Just mostly interested in the CBDA/THCA protocols. Which if my memory serves me seemed high 1-10 micromolar using Tween?
The Wnt signaling pathway most interesting .
There is anecdotal evidence that CBDA/cbd can interact with these signaling pathways.
You might also look closely at the History of “humanized mice” as a tool in preclinical studies. Try wikipedia for a start. A lot has changed over the past “50 years”…
It sort of explains why there are 100s of mouse models.
Best
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I have heard about that and I confess I don’t have any explanation for it. But if anything, it seems like it just casts further doubt on plaques being the real causative factor, since they don’t disrupt nearly the brain volume that man’s hydrocephalous did. There was a similar case involving someone born with little more than a brain stem but at least managed to live (though I think in that case they were completely disabled).
At any rate, this point should be clear – we have drugs that effectively remove plaque in humans now but still don’t affect cognitive decline. These same drugs also remove plaque in the best mouse models and do affect cognitive decline. So we can’t consider either plaque removal or reversal of cognitive decline in mice, to be valid proxies for it working in humans. Only true human trials can do that, and ones that test cognition DIRECTLY, not act like “amount of plaque removed” can be used as a proxy endpoint. It was essentially that last point, by the way, that led the FDA’s advisory board to resign over adulhelm’s approval. Plenty of amyloid reduction but nothing when it comes to actually helping people.
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“Making sure everyone is on same page when it comes to “amyloid proteins”.
Deposits of aggregates of particular proteins are specific hallmarks of a wide range of neurodegenerative diseases [1]. Aggregates of misfolded proteins with altered degradation can be located intracellularly and/or extracellularly. The most important primary intracellular proteins include:*
Hyperphosphorylated protein tau in Alzheimer’s disease (AD) [2], tauopathies including frontotemporal lobar degenerations with tau pathology (FTLD-tau) [3];
Alpha-synuclein in Lewy bodies in Parkinson disease (PD) and dementia with cortical Lewy bodies (DLB) or in oligodendroglial inclusions in multiple systemic atrophy (MSA);
Phosphorylated TDP-43 in frontotemporal lobar degeneration with TDP-43-positive inclusions (FTLD-TDP) [4];
Ubiquitin in frontotemporal lobar degeneration with inclusions positive for ubiquitin-proteasome system markers (FTLD-UPS) [4,5];
Fused in sarcoma (FUS) inclusions in FTDL-FUS [6].
Primary extracellular protein aggregates, in optical microscopy called “plaques,” can be observed in cortical locations in:
The frontal temporal stuff is the hardest on the families. I have read that the afflicted cycle through 2-3 entirely different personalities all of which none can put up with…
So it is all not just losing your marbles. The Parkinson’s and MSA conditions…are somewhat worse…the aspects of latter include loss of autonomic functions…like wide awake and experiencing your own decrepitude…and fully aware …
Everyone has so much to look forward to …
Dealing with an elder family member who has passed through such states leaves a lasting impression. There is something to say about “live fast, die young and have a beautiful corpse”…
‘’BTW”. One of those hydrocephalus men in England taught math at a local community college…something like that.
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Asking for a friend with Parkinson’s
What would one recomend
Cannabinoids or psilocybin (dmt)
Personally I would think that the psylo and dmt give beter plasticity to the brain than noids but honestly not sure what to recomend
A low dose of Delta 9 is there some consensus about in relation to Alzhemeirs, that it somehow can be helpfull in retaining myelin and slow progress.
That is a horrible disease, Alzheimers.
If i theorise i cant see any hinders in microdosing Mushrooms, beware medications and interactions.
You are a good friend
Its partly about plasticity, that is the brains abillity to re construct the damaged pathways and networks to.circumvent the damaged connections.
Plasticity drops dramatically after 35-45 years of age, there are a lot of ways to cement the brain .
The brain cant use its plasticity after enough progress of disease.
And holding down symptoms on palliative care is all there is as treatment.
I beleive that he will find some relief with a low dose D9, it is the active inflamation and antibodies that needs to be releived of duty.
And next.best is reducing, . but its shooting dart in the dark. Not even sure.there is a dart.board left
FILE_3878.docx (407.1 KB)
Perhaps a couple of additions
DOI 10.3389/fphar.2022.1048259
Int. J. Mol. Sci. 2020, 21, 3067; doi:10.3390/ijms21093067
I have a couple Liters of some jars labeled CBDa. I should homogenize them all together and send off for a test to @kcalabs
Personally I would dose 1mg per lb of body weight with a 1:1 CBDA:THCA full spec terpene rich multi carrier oil tincture daily. Mix avocado, olive oil, grape seed oil, for a variation of LCT’s for potentially increased uptake. not medical advice. a lil d9 in it isn’t gonna hurt either.
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If they are stored in EtOH, in about 6mon to a year refrigerated, I find the CBDA slowly converts to a solution of CBDA/CBD …which is not such a bad combo elixir itself.
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How slow ?
My cbd-a shelf life trails where very positive
Biggest conversion noted was 3% in 12 months under harsh conditions
Visor of the car all year slight discoloration to yellowing but little decarboxilation and a little increase of thc-a wich I attribute to analytics deviance since it was 0.015% when started
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Are you storing in ethanol?
No this cbd-a was in crysteline form pebblles in a sandwich bag with a knot om the drivers visor in the car a whole year treu all seasons hot in summer cold in winter etc
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