Abilify tolerance

[Hip]

Though why do we not see any such rapid tolerance for other conditions for which Abilify is prescribed?

Yes, good question.

Pure speculation, but it could be along the lines that because ME/CFS patients have trouble acetylating (as the link posted by @wigglethemouse details), that throws out epigenetic regulation a bit. ME/CFS patients would be shifted towards histone deacetylation rather than histone acetylation.

Benzodiazepine tolerance — involving the down-regulation of GABA receptors caused by benzodiazepine use — is driven by histone deacetylation (removal of the acetyl molecule from histone), according to the paper I linked to above.

So if Abilify tolerance was similarly driven, you might expect tolerance to build up faster in ME/CFS patients compared to other people.

 

[YippeeKi YOW !!]

@Push Fwd and @Martin aka paused||M.E. ....
Here;s everything I could find in my files re various tables of inducers and inhibitors, both prescription and 'natural' .... I'll keep looking, since I think I file away another table I couldnt find ....

Hope this yields some helpful information .... the Flockhart table can be a cranky load, but just hang in, it gets there eventually ....

GABA Receptor, Selleckchem.com
https://www.selleckchem.com/GABA-transporter.html

Natural Products, Selleckchem.com
https://www.selleckchem.com/natural-products.html

Drug Interactions Flockhart Table ™
https://drug-interactions.medicine.iu.edu/MainTable.aspx

Flockhart Table ™
https://edswi.org/wp-content/uploads/2018/02/Flockhart-Table-Medication-Metabolism.pdf

 

[leokitten]

Pure speculation, but it could be along the lines that because ME/CFS patients have trouble acetylating (as the link posted by @wigglethemouse details), that throws out epigenetic regulation a bit. ME/CFS patients would be shifted towards histone deacetylation rather than histone acetylation.

Yes it could be, but I wonder if targeting this would even work well. McGregor who proposed this looking at evidence from other recent ME studies said that diminished histone acetylation was quite possibly being caused by the glycolysis metabolic dysfunction found in his study and multiple other studies. So same worry if we aren’t targeting something to improve the metabolism issues then it won’t work long term.

 

[Martin aka paused||M.E.]

I would have to agree with this. I have been taking benzos for a long time and initially it helped my cfs tremendously. But after a while it stopped working. I then decided to take a break but no matter how long i waited during each break, it barely made a dent. Nowadays taking a benzo barely does anything for me.



In my case abilify worked AMAZING for two months and when it started to lose its effect I stopped in order to take a break and restart again. This time around it took me longer than the first time to notice any improvements (more like three weeks, rather than a week). And the benefits have not been like the first time (maybe half). But it has helped pull me out of a major crash and im glad i started it. This time I will stay on it indefinitely.

Note: I am taking 1mg of abilify, I also take cymbalta 40mg. I took a break for about a month and then restarted again. I have been on it for about a month now.

So maybe if you’d take a break for a few months it could kick right in again. My problem could have been that I took pramipexole in the Abilify holidays

@leokitten I can’t follow your overexertion theory on a layman’s biochemical level...though I know that I would be highly cautious the next time sth works

@Hip the problem is: nobody knows how much (Sodium?) Butyrate is needed. And what’s a good source of Butyrate?

@all: and what if we build our own Abilify? Pramipexole as a D2agonist plus drugs that agonist 5-HT1a and 5-HT2a? Whitney mentioned that Ron works on achieving the same or improved results on a much better way ...

Martin

 

[Martin aka paused||M.E.]

Yes, good question.

Pure speculation, but it could be along the lines that because ME/CFS patients have trouble acetylating (as the link posted by @wigglethemouse details), that throws out epigenetic regulation a bit. ME/CFS patients would be shifted towards histone deacetylation rather than histone acetylation.

Benzodiazepine tolerance — involving the down-regulation of GABA receptors caused by benzodiazepine use — is driven by histone deacetylation (removal of the acetyl molecule from histone), according to the paper I linked to above.

So if Abilify tolerance was similarly driven, you might expect tolerance to build up faster in ME/CFS patients compared to other people.

The article I linked speaks about differences in low and normal dose for getting tolerant.

 

[Hip]

I'd be interested to see if ME/CFS who have obtained benefits on low-dose Abilify might also get benefits from a very similar antipsychotic called amisulpride.

I've been taking very low-dose amisulpride daily since 2012, and it's benefits have not faded.

The only major difference between Abilify and amisulpride that the former hits several adrenergic receptors, which explains why Abilify can have a stimulating effect; whereas amisulpride does not hit these adrenergic receptors, so is not stimulating.

 

[Martin aka paused||M.E.]

I'd be interested to see if ME/CFS who have obtained benefits on low-dose Abilify might also get benefits from a very similar antipsychotic called amisulpride.

I've been taking very low-dose amisulpride daily since 2012, and it's benefits have not faded.

The only major difference between Abilify and amisulpride that the former hits several adrenergic receptors, which explains why Abilify can have a stimulating effect; whereas amisulpride does not hit these adrenergic receptors, so is not stimulating.

Does it also give you more energy? Abilify took me from very severe to moderate-severe in a very short amount of time

 

[YippeeKi YOW !!]

And what’s a good source of Butyrate?

There are several dietary sources, but the one that comes immediately to mind is butter and cheese. Butyrate is a short-chain fatty acid and its production depends on gut microbiota fermentation of dietary fiber, so legumes, beans, nuts, cereals, and whole grains are good sources as well.

 

[Martin aka paused||M.E.]

There are several dietary sources, but the one that comes immediately to mind is butter and cheese. Butyrate is a short-chain fatty acid and its production depends on gut microbiota fermentation of dietary fiber, so legumes, beans, nuts, cereals, and whole grains are good sources as well.

Ok then this can’t be the answer... I’m on keto for a week (without any effect btw) and eat tons of cheese

 

[YippeeKi YOW !!]

I’m on keto for a week (without any effect btw) and eat tons of cheese

It takes more than a week to retrain your gut microbiome.

Also, remember that fiber sources are a necessary component of conversion of butyrate/butyric acid.

Maybe incorporate something like lentils, which are both high fiber and high protein, as well as full of other potential prebiotic benefics ...

 

[Martin aka paused||M.E.]

It takes more than a week to retrain your gut microbiome.

Also, remember that fiber sources are a necessary component of conversion of butyrate/butyric acid.

Maybe incorporate something like lentils, which are both high fiber and high protein, as well as full of other potential prebiotic benefics ...

I already eat lots of veggies... I think it’s clear that I have to take a long break from Abilify in case it’s receptors... if it’s genetics or plasticity I got a problem b/c I don’t think that would help. But I have to keep in mind that I took another d2 agonist while on Abilify holidays so that might have tanked my success ...

 

[sb4]

@leokitten Do you still eat ketogenic, or is it just low carb now? What happens if you eat high carb meals? Do you feel noticably worse?

 

[bensmith]

I dont have anything to add, just wanted to say i hope omf can shed some light on the topic this year. I am sure they are looking at it closelyX

 

[YippeeKi YOW !!]

I already eat lots of veggies

It's not generic 'veggies' that help with butyrate .... it's specific fibers that the gut needs .... as I stated in my post, lentils, beans, nuts, some fruits, grains, cereals ....

It may not be worth the effort, and I know how dispiriting it can be to have to keep trialing things over and over in a sort of steady stream of " ....maybe this'll work .... or this'll work .... or possibly this'll work .....", but thought I'd post this just in case you wanted to give it a try down the road ...

 

[pamojja]

It's not generic 'veggies' that help with butyrate .... it's specific fibers that the gut needs .... as I stated in my post, lentils, beans, nuts, some fruits, grains, cereals ....

Maybe better start simply with a butyrate supplement?

The reason is because the fibers consumed are only half of the equation, it alse needs the specific gut-bacteria. Here the examples given in my ubiome-test of some of them:

Anti-Inflammatory Microbes:

- Butyrate-producing microbes:
>2x than Selected Samples (These are samples from individuals who report no ailments and high levels of wellness; Anaerostipes, Faecalibacterium prausnitzii, Eubacterium, and Roseburia..)

- Propionate-producing microbes:
0.28x than Selected Samples (Akkermansia muciniphila, Eubacterium, Roseburia, and Ruminococcus..)

- Polyamine-producing microbes:
1.23x than Selected Samples (Bifidobacterium..)

Those bacterial species aren't even available in commercial probiotics. Would love to trade some of my overabundance in butyrate-producing microbes via a conscientous company doing FMTs, against some of the propionate-producers. But also seems not available here in Central Europe yet.

However, when analysing my food-intake, I indeed found I get about 50 g/d of fibers from my diet (the average intake is less than half of that). None from grains or cereals though, and addtionally consume probiotic suluble fibers in form of inulin, konjak, gum arabica, pectin or resistant starch.

In this forum the basics of Prebiotic Fiber Sources, and a more basic Gut Flora Resource Overview. Also consider many psychotropic drugs addtionally have antibiotic acitivity.

Here a more complete list of butyrate-producing microbes: https://microbiomeprescription.com/Library/EndProductProducers?epid=22&sampleId=0

 

[jaybee00]

Does anyone have the chapter from Jay Goldstein’s book on tolerance that they could post here?

Thanks.

 

[jaybee00]

inositol is reported to reverse desensitization of serotonin receptors,

https://www.sciencedirect.com/science/article/abs/pii/S0924977X97004094

 

[Hip]

Does it also give you more energy? Abilify took me from very severe to moderate-severe in a very short amount of time

I did not notice any energy boost from amisulpride.

I wonder if it is that actual stimulant action of Abilify which is providing energy, as stimulants do tend to boost energy levels in ME/CFS.

If that is the case, then it may be a stimulant tolerance which is building up with Abilify, causing its effects to diminish over time.

To prevent such stimulant tolerance, I've seen some suggestions that NMDA receptor antagonists can be used.

The drug memantine is an NMDA receptor antagonist, and also if you take high dose transdermal magnesium, that acts as an NMDA receptor antagonist (oral magnesium doses are usually not high enough due to bowel flushing, but transdermally you can absorb more magnesium). My method of applying magnesium sulfate transdermal is here.


Have you ever tried the vitamin B1 derivative sulbutiamine, in doses of around 300 mg? This supplement I find produces a potent stimulant and energizing effect, and other ME/CFS patients have found this also. But I heard some stories of sulbutiamine losing its effect after some months of use, in a similar way to Abilify.

 

[Hip]

Regarding the stimulant action of Abilify (you can see that this drug binds to several α and β adrenergic receptors in the pharmacodynamics diagram on the right of its Wikipedia page):

Well "β-adrenergic receptor activity has been shown to modulate mitochondrial metabolism", it says here.


So possibly the energy obtained from Abilify may not just be "false" energy resulting from a stimulant action on the brain and mind, but may be real energy arising from improved mitochondrial metabolism.

This paper says that the β2-adrenoceptor agonist formoterol stimulates mitochondrial biogenesis. Some other β2 agonists listed here.

 

[Martin aka paused||M.E.]

Regarding the stimulant action of Abilify (you can see that this drug binds to several α and β adrenergic receptors in the pharmacodynamics diagram on the right of its Wikipedia page):

Well "β-adrenergic receptor activity has been shown to modulate mitochondrial metabolism", it says here.


So possibly the energy obtained from Abilify may not just be "false" energy resulting from a stimulant action on the brain and mind, but may be real energy arising from improved mitochondrial metabolism.

This paper says that the β2-adrenoceptor agonist formoterol stimulates mitochondrial biogenesis. Some other β2 agonists listed here.

I can tell you it’s not false energy... before Abilify I couldn’t move in bed, after Abilify taking the stairs