@Hip, I have this anhedonia too. I don't know what hascaused allthis mess. It gradually set in.Some symptoms were accute, others were gradual.
In my case, my anhedonia, and also my blunted affect (emotional flatness), were both trigger by the virus I caught, which also precipitated my ME/CFS. And it was not just me; several acquaintances who caught the virus from me also developed some anhedonia and blunted affect. I detail the symptoms produced by my virus
here.
Prior to catching this virus, I definitely did not have anhedonia; I found lots of everyday things in life very rewarding.
It is interesting that in ME/CFS, a small percentage (5%) of patients develop autoantibodies to the dopamine D2 receptor (ref:
here), so possibly this may help explain my anhedonic symptoms.
I have here methylphenidate and ropinirole. The first one seems to work as NRI and DRI and the last one as D2 agonist.
I'd like to try methylphenidate, because I suffer from quite severe ADHD (my ADHD appeared after I had a nasty episode of viral meningitis). However, I read that in the UK, it is hard to get a doctor to prescribe this drug, if you are an adult. And being a controlled drug, it hard to find for sale online (and where it is for sale, it tends to be very expensive).
Uridine has impact on the D1-D2 heteromer as a modulator (i think). Don't know if that could help you.
I did do a brief trial with uridine monophosphate recently, at a dose of 120 mg sublingual daily. I found uridine had a good mental focusing effect, but in a subtle way (not like a strong stimulant), which allowed me to work on the computer more effectively. However, it caused a side effect of increase sound sensitivity, so I stopped it for the moment, but will be trying it again soon.
Interestingly, I found amantadine also causes this side effect of increased sound sensitivity, but usually after several days taking amantadine, this side effects gradually diminishes.
By contrast, very low dose amisulpride greatly reduces my sound sensitivity, which is one of the reasons I find this drug a great ME/CFS treatment.
i didn't know amilsupride blocks presynaptic receptors, I wonder if it could help me, as according to that Taq1A1 A1, I have too much L-Dopa at the presynaptic vesicles, which is lowering the D2 receptors.
The thing I like about very low dose amisulpride is that no tolerance builds up; it works as well for me now as when I first started taking it a few years ago.
Also, for me this drug feels very "natural." I have some depression as well as anhedonia, and I have tried out various antidepressants. Some, like tricyclic antidepressants (eg: amitriptyline), kind of alleviate my depression, but they feel unnatural and imbalanced in terms of how my mind feels. The mood is improved, but the minds feels a bit disturbed. Whereas amisulpride feels nice and balanced, more like a supplement than a drug.
Do you feel high prolactin sides from amilsupride?
Very low dose amisulpride does lower libido, I find, which may be a result of increased prolactin. However, the dose I use, just 12.5 mg daily, is about 100 times smaller that the full amisulpride dose (of 1200 mg) used for treating schizophrenia. So I would think that compared to the full dose, the very low dose I use will cause much less of a problem with prolactin.
Though note that with any anti-psychotic, even these second generation atypical anti-psychotics like amisulpride, there is a significant risk of developing diabetes. But again, using a very low does, I assume that the risk will be correspondingly reduced.
Have you tried any SERMs (estrogen receptormodulators) or steroids at some point, anabolic or other ?
I have seen selective estrogen receptor modulators (SERMs) for sale on body-building websites, but I am not sure what benefits these might have for my symptoms. Was there any benefit you had in mind?
On the subject of estrogens: a while ago I was trying low doses of transdermal estriol, the weakest of the three estrogens. Estriol has potent anti-autoimmune effects, and is being investigated as a treatment for multiple sclerosis. The very high levels of estriol found in pregnancy might also explain why some female ME/CFS patients find their symptoms significantly better during pregnancy.
Anyway, at the low doses I used (0.3 mg estriol daily), I found no specific benefits for ME/CFS, but I did find estriol noticeably improves my blunted affect (flat emotions), and makes me less irritable, more tolerant of people, and more inclined to social banter.
So now I use estriol now and then for this purpose. I don't take it all the time, because even though it is a very weak estrogen, it does still have some feminizing effects, and I don't really want to grow breasts.
Have you tried memantine?
Have not tried it, but I should do really. I often use high-dose transdermal magnesium (magnesium cream applies to the skin from head to toe), which like memantine is also an NMDA blocker. I definitely notice a calming, anti-anxiety effect from high-dose transdermal magnesium (anxiety may be linked to NMDA receptor over-stimulation).
But I guess you are referring to memantine's agonism of the dopamine D2 receptor.