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Amisulpride — A Multipurpose Drug for ME/CFS

JES

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I would recommend staying far away from anti-psychotics for treating anxiety, not least because these drugs have serious side effects. The way @Hip uses Amisulpride makes sense, as it acts as a dopamine agonist at low dosage. At a normal dosage, this drug will act completely different and most likely be counter-productive for treating any anxiety symptoms. Abilify, I'm not sure if it has this inverse dopamine receptor effect of Amisulpride, so even at low dosage it could be totally useless for anxiety.
 

Hip

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I am using Abilify but wonder if amisulpride would work better.
I tried Abilify (aripiprazole), but found it over-stimulated me a bit, but other than that its effect were similar to very low dose amisulpride. However, I only tried one 1.25 mg tablet of Abilify, which due to the long half life of Abilify (75 hours), had effects that lasted for almost a week. So I don't have that much experience of Abilify, apart from this one test.



Which online site did you purchase amisulpride from?
See the pharmacies in the first post of this thread.
 

Hip

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I would recommend staying far away from anti-psychotics for treating anxiety, not least because these drugs have serious side effects.
Generally speaking what @JES says is good advice. Because of serious side effects (like triggering diabetes), atypical anti-psychotics are only used to treat anxiety if other anti-anxiety medications have failed.

I use very low dose amisulpride because it helps treat the significant irritability symptoms I have, which actually are a very unpleasant symptom, and makes me more sociable (reduces the tendency to social withdrawal). Also, I also find very low dose amisulpride is one of the few antidepressants that work for me. And it does a good job in reducing the ME/CFS sound sensitivity symptom. So for me offers a number of very useful benefits.


The atypical anti-psychotics can be classified in relation to their risk of triggering diabetes. The ones with the highest risk of inducing diabetes are Clorazil (clozapine) and Zyprexa (olanzipine). Medium risk are Seroquel (quetiapine) and Risperdal (risperidone).

But Abilify (aripiprazole) and Geodon (ziprasidone) are low risk (they are not considered a diabetes risk). Ref: here.
 
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My worst anxiety symptom is irritability. I'm not sure if that's actually anxiety, but it's a frustrating symptom nevertheless. And regular anxiety drugs, like the ssris, don't seem to improve it that much. And abilify at 2 mg is helping, but a lot of it is being cancelled out by the "overstimulation" effect that Hip mentioned. I feel kind of manic, although I'm not bipolar, but I'm just guessing that's what it would feel like... I'm also concerned with sexual function. Abilify seems to be increasing the drive, but sexual function isn't better and might be worse. But abilify has worked better than any other med on one symptom that's rather annoying....obsessing over health problems. While it's important to find answers, it's counterproductive to actually finding them if you can't stop obsessing.

That's really interesting that abilify has that long of a half-life. That explains why when I ran out and had to skip a day or two I didn't feel much different for most of the time. That gives me an idea that I might try cycling the abilify or maybe the amisulpride if I decide to try that. The one thing that sounds more intriguing about amisulpride is that it helps you enjoy being around people more, and I don't notice much improvement with that on abilify. Being drained by people is depressing. The most useful things abilify's helped me with are overthinking and focus.
 

Jill

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Thank you for your insights @Hip . I describe my brain as being constipated when coming back from social interactions and it takes days to undo no matter how hard I've tried to let things flow over me. I completely 'get' what you are saying. I also find it easier to do things by myself for the same reason. It's like forced isolation is the only way of getting anything done and I hate it !! It bizzaire . I'm glad to have stumbled onto this . Thanks again
 

flitza

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I'll think about integrating it into my regimen. Just getting started with SMP, NAG (and the others recommended in your thread about anxiety) and trying not to start too many things at once.

Hate the anhedonia though.
 
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What's the difference between the mechanisms of amphetamine and amisulpride. I'm asking because amphetamine almost makes me more stress/depressed. Could be some sort of sensetivity to norepinephrine. Also, does amisulpride increase norepinephrine?
 

JES

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What's the difference between the mechanisms of amphetamine and amisulpride. I'm asking because amphetamine almost makes me more stress/depressed. Could be some sort of sensetivity to norepinephrine. Also, does amisulpride increase norepinephrine?
Amphetamine is a stimulant and amisulpride an atypical antpsychotic, I don't think you can compare the two. Amisulpride primarily affects dopamine receptors, and in a different way depending on whether you use a low or a high dose. I'm not aware that it has any effect on norepinephrine.
 

Hip

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Also, does amisulpride increase norepinephrine?
Amisulpride's receptor binding affinity profile is given here (smaller numbers mean stronger binding). As you can see, it does not really bind to norepinephrine receptors, and I don't think it alters norepinephrine levels very much either (it weakly increases norepinephrine; ref: 1).
 

flitza

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I use it every day, and it continues to work well.
With respect to the NAG: I ordered some of the non-shellfish (I hope) from Swanson. Do you recommend starting with a whole capsule or trying to divide it up at first? I'm horribly sensitive to meds and supps and feeling so miserable with the anxiety that I'm nervous about trying anything new.

The cromolyn sodium helps a lot and quickly but doesn't last long. Couldn't tolerate the flaxseed oil (got diarrhea) and not sure if the turmeric is doing much.
 

Stretched

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FWIW, I am an Amisulpride advocate, having followed @Hip's analysis and having similar symptoms.

It does the same for me as above, but I use it in 50mg units once a day in am. (I mistakenly bought the
only size this supplier had, 400mg, and 1/8's are the smallest 'slices' w/o powdering the pill, but divides fine
with a standard, ubiquitous plastic pill slicer.)

With a favorable side effect, it allows me to walk away from Sertraline without titration (take it or leave it), and has a similar effect with clonazepam, which I have taken for 30 years, minimally. I do wonder if there is an
inherent withdrawal potential w/Amis since it is has such noticeable efficacy? No need at present to withdraw - only if something 'non-redundant' falls off...:confused:
 

Kenny Banya

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I have been taking very low doses (12.5 to 25 mg daily) of the drug amisulpride for around a year now, and I have found this drug quite helpful for a number of mental and cognitive symptoms that arise in ME/CFS and its comorbid conditions like depression and anxiety disorder.

At very low doses, amisulpride is know to act as an:

Antidepressant treatment
Anti-anhedonia treatment
Anti-anxiety treatment


I have also found that very low dose amisulpride also:

Reduces ME/CFS noise sensitivity symptoms
Greatly reduces ME/CFS irritability symptoms
Improves sociability
Treats anxiety psychosis symptoms (anxiety psychosis from anxiety disorder)
Improves attention deficit-hyperactivity disorder (ADHD)


I have all the above conditions, and so I found amisulpride particularly useful.

This small scale study of the benefits of amisulpride for ME/CFS found that 25 mg of this drug taken twice daily reduced fatigue and somatic complaints.

Amisulpride is not licensed in the US, but it can be obtained from the usual overseas suppliers. I believe the smallest available size of amisulpride tablets is 50 mg, so you will need to cut these 50 mg tablets in half or in quarters if you want to take the very lowest doses of 25 mg and 12.5 mg.



BUYING AMISULPRIDE:
Amisulpride can be bought prescription-free from any of the following pharmacies:
1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 .

Amisulpride can also be bought in powder form at TrueLife Research.

Amisulpride : A forgotten "Old-School" AntiPsychotic with A Superior Anti-Depressant Profile & Unique Mechanism of Action (Little to no Side Effects)

Amisulpride certainly doesn't carry the wide array of pharmacological actions that most "familiar" or "Atypical Antipsychotics" do, but that doesn't make it any less potent (1).

AMISULPRIDE HAS FAR LESS SIDE-EFFECTS

One distinguishable trait of amisulpride is that lower doses seem to only, or mostly block the dopamine D2S (autoreceptors) (2) - which leads to an actual enhancement in dopamine release (3).

Most of the usual antipsychotics we hear about, e.g risperidone, thorazine and Haldol — all have very potent dual action dopamine receptor blockade (4). This leads to many more side-effects, including incidences of depression and high rates of drug-induced tardive dyskinesia (5).

Additionally, most anti-psychotic drugs have extremely potent alpha-1-adrenergic receptor blockade (6) (7), amisulpride lacks this property, as well as the usual anti histamine property of anti-psychotics (8) — which means AmiSulpride is very unlikely to cause any form of sedation (9).

Usually, the anti-histamine properties of other anti-psychotic drugs combined with the alpha-1-blockade — acts as a one-two punch in knocking the patient out cold.... frequently we hear about some of the affected even drooling on themselves or just completely incoherent and lethargic the following day (10)!

While some medical professionals consider this a benefit in hostile or unpredictable patients, I would find it much less than ideal for someone who wants to maintain somewhat of a normal life, not incapacitated but with symptoms controlled (11).

Besides lack of side-effects, or at least lack of sedation, amisulpride has one very notable effect that sets it apart from other drugs in its class — its anti-depressant effects are VERY FAST ACTING, very potent — and generally yield little to no negative endocrine effects (12).

The mechanism of action is totally unique, amisulpride binds to the serotonin 5-HT(7) with 11.5 nanomolar (ki/nm) affinity - this includes in human subjects (14).

It antagonizes the action of serotonin at this receptor — resulting in an anti-depressant effect that cannot only augment other anti-depressants — but can be much more effective alone than many anti-depressants (15).

The additional benefits of 5-HT(7) antagonism are that it will reduce overstimulation and anxiety - as well as treat depression - and lower cortisol levels as well (16).

Because many depressed patients exhibit HPAA (hypothalamic-pituitary-adrenal-axis) dysfunction — and often have elevated cortisol — this unique mechanism of action may benefit the hormonal balance of depressed patients (17), unlike SSRIs which tend to increase stress hormones (18) and oppose other beneficial neurotransmitters such as GABA, dopamine and others (19)!

Thus, in summary...

Amisulpride has the following benefits / advantages over other drugs aiming to do the same.

  • A cortisol reduction, instead of increase.
  • Enhances dopamine at lower doses.
  • Little to no sedation, drowsiness, dyskinesia, tremors , punding or other disturbing side-effects.
  • Doesn't interfere with cognitive function or vigilance.
  • Treats depression quickly , and effectively.
  • May improve anxiety symptoms as well.


Source: TrueLife Research
I started taking 25mg, but only in the morning as agitation is a side effect
Day number 4
 

Tunguska

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Hi @Hip, do you know what kind of dose this represents if they say they test cells with "1 μM"?
To test whether the observed Akt activation was specific to haloperidol, we tested 1 μM amisulpride (Fig. 1E), an atypical antipsychotic drug with a different affinity profile, and found that this concentration of amisulpride also increased phosphorylated Akt and phosphorylated S6, indicating activation of the mTORC1 pathway. Thus, haloperidol and amisulpride activated the Akt-mTORC1 pathway and its downstream effectors of translation within 20 minutes, suggesting a role for the mTORC1 pathway in the acute mechanism of action of typical and atypical antipsychotics.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4063438/
 

Hip

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Hi @Hip, do you know what kind of dose this represents if they say they test cells with "1 μM"?
There is no easy way to reliably convert from in vitro micromolar (μM) concentrations to an oral dose in grams. However, for a rough and ready way, you can use my own "home made" formula: Oral dose = C x M / (B x 250), which is explained in the second part of this post.

But to save you the trouble, by my calculation using that formula, 1 μM amisulpride works out to a human oral dose of around 30 mg.

However, one proviso is that the formula is only valid for water soluble drugs, and amisulpride has poor water solubility (0.293 mg/mL). The 30 mg figure is probably roughly correct, though, as a ballpark figure.
 

Tunguska

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Thanks very much, bad math can ruin a day and then I thought "I bet Hip already figured it out". Right on the money. I'll actually use that later.

I still need to actually try amisulpride (been putting it off for... at least 3 years... but now it's looking a lot better than herbs)