5HT-2A and JC polyomavirus

Kobold

Member
I have been suffering from ME for 19 years and 5 months. I was always curious why escitalopram and amisulpride help me despite the fact that I don't suffer from any mental disease. Now I found something interesting: 5HT-2A acts as a receptor for JCV. Amisulpride blocks this receptor and chronic use of SSRI desensitize and diminishes density of these receptors. Other medications that block this receptor include mianserin, risperidone and others.
 

Hip

Well-Known Member
I don't think JC virus has even been connected to ME/CFS, though.


Very low dose amisulpride activates the dopamine D2 and D3 receptors. There's one theory that lack of dopamine can cause increased neuroinflammation.
 

Kobold

Member
Yes, amisulpride starts to have antipsychotic effect only in the doses above 200mg or 400mg. I am taking 50mg so it should increase dopamine levels in the synaptic cleft. But in the past I was taking various NDRIs without any positive effect.
 

Hip

Well-Known Member
Yes, amisulpride starts to have antipsychotic effect only in the doses above 200mg or 400mg. I am taking 50mg so it should increase dopamine levels in the synaptic cleft. But in the past I was taking various NDRIs without any positive effect.
I also take very low dose amisulpride, 12.5 mg daily, and find it has a mild mood-boosting effect, as well as helping various ME/CFS symptoms (have a thread about this drug here).

But when I take the dopamine booster selegiline (deprenyl), I don't get any benefits, even though before getting ME/CFS, I used to use selegiline regularly as a cognitive enhancer, and I found it always had great mood and libido boosting effects, and would increase creativity and lateral thinking abilities as well. But now this same drug does nothing for me (if anything, selegiline now seems to increase my depression slightly).

So that suggests that the dopamine system gets altered as a result of ME/CFS, and does not respond as normal to dopamine drugs. One study found that 5% of ME/CFS patients have dopamine D2 receptor autoantibodies, so that might in part explain why the dopamine system behaves strangely.


I also tried the NDRI Wellbutrin, and got amazing results for the first two weeks, with my ME/CFS brain fog being greatly improved; but then these very strong positive effects disappeared after two weeks, and thereafter Wellbutrin completely stopped working for me. I've never been able to get it to work ever since. So that's quite odd as well.


But very low dose amisulpride seems to work consistently for me, perhaps because its mechanism of action (working at the dopamine autoreceptors) is an unusual one.

I am quite interested in the dopamine system, because the virus that triggered my ME/CFS (like coxsackievirus B4) also triggered severe anhedonia (the inability to experience reward or pleasure from enjoyable activities), and dopamine plays a key role in the reward circuitry of the brain.

I compiled a list of drugs and supplements that work on the dopamine system here.
 

Kobold

Member
Kobold, in what way's, symptoms do they help?
My ME/CFS started like an infection, first I was diagnosed with infectious mononucleosis. My illness is predominantly a brain disease: In the left parietal part of my brain I have a constant pain, pressure and a feeling of an inflammation. My main symptoms are cognitive deficit and exhaustion--they all seem to stem from the "inflammed part" of my brain. (But I don't know if real brain inflammation is really present, or what infectious or neuro-immuno-pathological process it is, it's a feeling similar to when a healthy person has a fever or as if an acid was in this part of the brain)

Amisulpride reduces this feeling of "brain inflammation".

I am the type of ME/CFS patient with: Sudden, flu-like onset, catch every virus or cold, no substantial pain in joints or muscles, no photosensitivity, best in summer, worst in winter

But my younger brother who also developped suden onset ME/CFS on the contrary never catches a virus or cold.

(My older brother also developped suden onset ME/CFS but after just one year he recovered completely. Now triathlon and anaesthetist in London)

I hope it helps.

Sorry for my English. I have never been to an English speaking country, even if I would love to. :)
 

Kobold

Member
Thanks! This is amazing. I also tried many of the medications from your list. Memantine, pramipexol, selegiline, methylphenidate, bupropion, modafinil, tianeptine etc. but none of them was as effective as amisulpride.

Unfortunatelly amisulpride does to me quite pronounced side effect of hyperphagia. So now I am taking it only sporadically--but it always works.
 

rebar

Active Member
Thanks Hip and Kobold, I just finished reading the thread on PR, a question. How does lamotrigine, (lamictal) compare. It too is an antipsychotic.
I take low dose lamictal (12.5) to stabilize my mood, and does amisulpride also help with sleep?
 

Kobold

Member
Thanks Hip and Kobold, I just finished reading the thread on PR, a question. How does lamotrigine, (lamictal) compare. It too is an antipsychotic.
I take low dose lamictal (12.5) to stabilize my mood, and does amisulpride also help with sleep?
If I remember well lamotrigine is primarily used as an antiepileptic medication and it probably also has some mild mood stabilizing properties.

Amisulpride is the least sedative neuroleptic of all those that I know. To the contrary it can be quite stimulating. It was specifically designed to be activating to treat also the negative symptoms of schizophrenia.

There is also one chemically related compound sulpiride. It also block the dopamine autoreceptors and it would be interesting to find out if it also blocks 5HT2A. If not I could test my hypothesis. :)
 

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