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Amisulpride — A Multipurpose Drug for ME/CFS

Discussion in 'General Treatment' started by Hip, Dec 18, 2012.

  1. Hip

    Hip Senior Member

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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. I am writing up my experiences, as I think this drug may benefit other people suffering a similar range of symptoms.

    At very low doses, amisulpride acts as an antidepressant, anti-anhedonia and anti-anxiety drug.

    I have found that very low dose amisulpride also helps with attention deficit-hyperactivity disorder (ADHD), reduces noise sensitivity, which is useful, improves sociability, reduces irritability, and treats anxiety psychosis symptoms (anxiety psychosis can arise if you have extreme anxiety disorder).

    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.
    Last edited: Feb 27, 2014
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  2. Hip

    Hip Senior Member

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    Amisulpride, the Wonder Drug from France!

    The following text was copied from here.

    Amisulpride is a new antipsychotic drug that was invented in France. It is so new, it is still in the USA’s final testing stage for release here, but can still be obtained now legally from Europe.

    Amisulpride is a very safe drug with few, if no side effects, and can be used for three different purposes.

    In normal doses, 400mg-1200mg, it is used for symptoms that include and excess and/or disruption in cognition and emotional functions.

    In lower doses, 50mg-200mg, it is used for symptoms that include a diminution or loss of normal cognitive and/or emotional functions.

    In even lower doses, 12.5mg-200mg, it is used for minor depression, attention-deficit/hyperactivity, and emotional imbalances.

    It was discovered by accident that amisulpride, originally created as an antipsychotic drug for schizophrenia, has the antidepressant effect when taken in minuscule doses as compared to what was originally intended. The drug appears to have an opposite effect depending on if small or larger doses are taken.

    Originally designed to be taken at 400mg to 800mg a day, when you take Amisulpride instead at just 12.5mg to 100mg a day combats LOW MOOD, CONSTANT NEGATIVE THOUGHTS, SOCIAL ANXIETY, ANHEDONIA (inability to experience pleasure), and FATIGUE. These are the symptoms of atypical depression or dysthymic disorder, which is a mild but continuous form of depression. The symptoms are characterized by blahness, lack of motivation, lack of interest, and social withdrawal. While combating these problems in an amazing way that no other drug seems to do, the low, low dose also makes amisulpride almost completely free of side effects, so it is tolerated by more people, more often than other anti-depressants.

    In a day, or a week or two, depending on the person, on amisulpride one feels renewed interest, renewed motivation, social comfort, more confident, and less emotional anxiety. You’ll notice a very strange blunting of ONLY the emotional triggers that seem to be the ones you’d want to get rid of. It’s difficult to explain, but a strange yet wonderful experience!

    It feels as if you’ve been freed of mental issues that have held you back from doing things you wish you would be doing.

    Each person that has responded to the effect is immediately amazed. Others who see the transformation of their friends have been equally amazed.

    Because amisulpride has an opposite effect at higher doses, for depressive treatment, you must prepare yourself to cut back on the dose if you feel any negative effects like sedation. Rather than immediately giving up, be aware that this is exactly what it’s supposed to do, and it simply means that your body is so sensitive that a lower dose is the appropriate one for you.

    Most drugs don’t have the opposite effect the moment the dose is too high, so this unique quality should be known before you start on your journey.

    Every person is different and it takes a unique milligram dose for each person that could be anywhere between as little as 12.5mg to 100mg so you need to understand that it’s not a bad thing if you don’t feel the correct effect; you simply adjust the dose and continue to find the exact amount that is right for you. DON’T GIVE UP!

    Specifically, a the low doses, Amisulpride is a “selective dopamine antagonist” which stimulates specific types of dopamine receptors (D2 and D3) on their presynaptic side. D2/D3 limbic system pathways are thought to be involved in regulating mood, anxiety and motivation. Unlike many other medications, it exclusively acts in the mesolimbic brain, which is unusual, because this is the site where emotional mood states and memory storage and retrieval takes place in your brain. This is great because it doesn’t unnecessarily stimulate other dopaminergic receptors elsewhere in the brain, so locomotion and general attention/arousal systems are largely bypassed, eliminating sleep disturbances, anxiety exacerbations, the jitters, and scattered and/or hyper-attentiveness. For this specific purpose, it is used in very low doses (12.5-100mg/day).

    Since it was designed to be used at much higher doses, there are few side effects at these low doses. Keep in mind it may take up to two weeks to feel any effects from amisulpride, so try it for at least 2 weeks! It seems to have a very unusual ability to tone down a person’s unwanted emotional outbursts in a very precise clean way, while preserving the drive to accomplish important matters in their life. Strangely enough, it actually seems to shut down the part of the brain that spends time worrying about other people’s problems or going in circles about personal emotional issues. The emotional spin cycle simply disappears!

    It’s such a wonderful feeling to have emotional baggage simply lifted from you within the course of 2 weeks without therapy!

    At doses above 400mg, amisulpride stimulates the same dopamine receptors but on their postsynaptic side. At this dosage, amisulpride treats disorganized symptoms including thought disorder, confusion, disorientation, and memory problems.

    This drug was invented in France, and is still in Phase III FDA testing here in the USA, therefore it is only available by mailorder from Europe. It is not a scheduled substance and is legal to import in personal use quantities. Amisulpride works in a novel way, it doesn’t affect seratonin at all, it affects only dopamine, so it works when SSRI antidepressants don’t. Specifically, it increases the dopamine in the synaptic cleft of the D2-D3 receptors in the limbic system and to a lesser extent the striatum. It improves mood, concentration, energy, and sense of pleasure while decreasing social anxieties.


    More info

    Amisulpride: A Review of its Clinical Potential in Dysthymia
    Amisulpride in medium-term treatment of dysthymia


    Amisulpride dosage

    One half 50mg tablet (25mg) once a day (use a razor blade to cut pills in half).

    The effect is generally seen in 7-14 days.

    If you feel sedation, cut back to 12.5mg/day ¼ tablet.

    Since amisulpride has the OPPOSITE effect at higher doses, you should realize a dose too high will cause an effect opposite of what is desired.

    Alternatively, if you feel no effect at 25mg/day, you can raise the dosage by 25mg increments to 100mg day maximum to get the best effect for you.

    Wait at least a week after each 25mg increment; keep in mind 12.5mg-50mg should be sufficient.

    Not available in the USA.
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  3. adreno

    adreno 3% neanderthal

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    One problem with the drug is that prolactin levels often go through the roof. Did you experience this?
  4. Hip

    Hip Senior Member

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    I haven't developed any "man boobs" (gynecomastia), which I believe is a symptom of high prolactin in men. Though I do notice my libido is significantly reduced on days when I take amisulpride — and reduced libido can result from high prolactin.

    I usually take a very low 12.5 mg daily dose of amisulpride; and every week or two, I take a break from amisulpride for a couple of days. So at this very low dose, perhaps I am not raising my prolactin levels too much.

    Even so, I wish I could find a workaround to prevent the low libido induced by amisulpride.
  5. adreno

    adreno 3% neanderthal

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    Pantethine should be an inhibitor of prolactin, by the way. I use it with pregnenolone and DHEA. I haven't done any tests, but libido is good.
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  6. Hip

    Hip Senior Member

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    I might try that. I read that pantethine may have some neuroprotective effects, plus it seems to treat fatty liver, which I have.
  7. FunkOdyssey

    FunkOdyssey Senior Member

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    Doesn't look like there is much hope for resolving sexual sides, aside from a switch to aripiprazole, which may or may not provide any of the same benefits:

  8. FunkOdyssey

    FunkOdyssey Senior Member

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    Actually, it looks like maybe you can add aripiprazole to another antipsychotic and its partial d2 agonism is able to keep prolactin down. It isn't clear how that would affect the benefits of amisulpride though, seems to me if it can overpower the d2 antagonism of other antipsychotics at the pituitary, it would be able to do it throughout the brain:

  9. Hip

    Hip Senior Member

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    That is very interesting. So, if I understand correctly, the reason for excess prolactin release by amisulpride (and other anti-psychotic drugs) is because it blocks the dopamine D2 receptors in the pituitary gland.

    And aripiprazole has the reverse effect, as it stimulates the pituitary dopamine D2 receptors.


    One of the things I find the most useful with very low dose amisulpride is that this drug noticeably reduces my irritability and annoyance symptoms.

    Irritability seems to be a fairly common symptom in ME/CFS (and in autism). On bad days, I find myself irritable with everything: people, places, opinions — anything that moves! Irritability is a very unpleasant symptom — especially because you always have the urge to express your irritability and annoyance to people; and yet you know that your irritability is generally not warranted; it's just a ME/CFS mental symptom that makes you that way; so you have to try to bite your lip and suppress expressing your irritability.

    Interestingly, it seems that aripiprazole is good for treating irritability in autism, with doses of 2 mg and higher, so I wonder if aripiprazole may work for ME/CFS irritability too. Ref: 1.
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  10. Hip

    Hip Senior Member

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    By the way, Funk, would you have any idea of how aripiprazole treats irritability, in terms of its actions at receptors. I would like to understand the neurochemistry of irritability.

    Amisulpride not known for its ability to treat irritability (or at least I have not seen any literature on this), but I have personally found that amisulpride reduces irritability symptoms. It makes me a little more tolerant of things, and also makes me more tolerant of sound and noise.
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  11. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    Sorry to go off topic but adreno have u found preg and dhea increase prolactin?
  12. adreno

    adreno 3% neanderthal

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    Pantethine is a precursor to cysteamine, which depletes prolactin:

  13. adreno

    adreno 3% neanderthal

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  14. adreno

    adreno 3% neanderthal

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    They do from the studies I have seen, IIRC. They also gave me tingling nipples in the beginning, but it went away (with pantethine, I presume)
  15. Pachequín Bombín

    Pachequín Bombín Just a daydreamer in all aspects.

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    Hi Hip. I'm also taking amisulpride for my ADHD, but I haven't seen any result that just somnolence since three weeks ago Does it help for concentration? I'm taking 50 mg now, but as you say, I must cut back to 25 mg. What is the best dosage? 25 or 12.5 mg? Does it depend on my weight? Thank you so much.
  16. Hip

    Hip Senior Member

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    I usually take 12.5 mg daily. What I personally find is that taking 25 mg gives a stronger effect, but I get the impression this higher dose reduces my motivation and reduces my focus on doing things. So this is why I usually stick with 12.5 mg.
  17. Hip

    Hip Senior Member

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    I just found this thread on Phoenix Rising on using the above-mentioed atypical antipsychotic drug Abilify (aripiprazole) for treating ME/CFS:

    Abilify and energy

    I have just ordered some Abilify, and will compare its benefits to those of amisulpride.

    I have a good opinion of atypical antipsychotics as a treatment for ME/CFS (based so far on my experience with amisulpride) and I urge others to try these drugs.

    General Note:
    Don't be concerned about using an antipsychotic drug for ME/CFS. Atypical antipsychotics are not just used for psychosis and schizophrenia: atypical antipsychotics are also used off-label for many other conditions, such as: depression, ADHD, anxiety disorder, bipolar disorder, PTSD, OCD, dementia, etc (reference: here).

    Atypical antipsychotic drugs alter levels of neurotransmitters in various part of the brain; the only thing that really matters is whether the changes these drugs make to neurotransmitter levels translates to a benefit for ME/CFS patients; it is of no importance at all that these drugs are labelled as antipsychotics — that is just part of their function.

    In any case, the doses of these drugs used for ME/CFS treatment are much, much smaller than the dose used for psychosis and schizophrenia.
  18. adreno

    adreno 3% neanderthal

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    Even atypical antipsychotics potentially have some very nasty side effects (diabetes, tardive dyskinesia etc), so just be careful. Personally I won't touch them, not even Abilify. I also believe that modulating the glutamate/GABA balance is more effective than blocking dopamine.
  19. Hip

    Hip Senior Member

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    Point taken. I would definitely say that to help minimize the possibility of side effects, take the lowest does you feel is offering benefits. In my case, my daily dose of just 12.5 mg of amisulpride is very much lower than the 400 to 800 mg doses used for treating schizophrenia and psychosis. So I hope that this makes the risk of side effects much lower. I have been taking amisulpride for a year now, and have seen no real side effects.
  20. Hip

    Hip Senior Member

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    One of my main reasons for taking amisulpride is because I find it increases my social motivations; that is to say, amisulpride increases my desires to engage in social activity.

    I find that it it not just the fatigue of ME/CFS that draws you away from socializing; there seems to be an increased need for peace and solitude in ME/CFS, with too much social activity perturbing the mind. I sometimes feel my mind has been almost "mentally raped" after too much social activity. I think this feeling of being "mentally raped" is actually caused by a weakened "mental firewall" — that is to say, a weakness in the mind's sensory stimuli filter, which allows stimuli to enter into consciousness, when they really should have been filtered out. This weakened "mental firewall" I think is also the reason for noise sensitivity in ME/CFS.

    I am pretty sure this "mental firewall" itself is located in the reticular formation of the brainstem. The reticular formation's functions are known to include filtering out irrelevant or repetitive stimuli, so that the rest of the mind is not overloaded with unnecessary information. So for example, for a normal healthy person, if they hear a car alarm go off in their street, at first this noise rouses their consciousness attention, but then they soon forget about it, and after a few minutes, it does not enter consciousness anymore. This filtering out is called habituation, and is the reticular formation's "firewall" springing into action, and blocking irrelevant, repetitive stimuli from reaching consciousness and thereby overloading the brain.

    However, I find that in ME/CFS, repetitive noises such as car alarms are constantly aggravating, because you do not seem to habituate to the noise, and so the noise continually deeply penetrates into your conscious mind and becomes unpleasant; this repetitive noise is not properly filtered out by your "mental firewall".

    I suspect a weakened reticular formation "firewall" is the norm in ME/CFS, and this leads to the feeling of being overwhelmed or "mentally raped" when exposed to too many stimuli, as you tend to get in hectic social situations. These stimuli are penetrating deep into the mind, whereas they should have been stopped by the "firewall", stopped by the brain's bouncer at the door: the reticular formation.

    Anyway, what I have found is that amisulpride seems to make this "mental firewall" stronger, so that you are more able to cope with the maelstrom of social environments; and with amisulpride I find that sounds and other sensory stimuli are not so mentally intrusive.
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