I'm glad I could help. Now it's time for my update.
Every theory presented in this thread has now been tested and ruled out. There is no reason to test drugs endlessly as the chances for some random choice to help are minimal, and recently we've encountered some research that is pointing to a cause that is anyway inaccessible with systemic drug administrations: highly localized dysfunctions. These two articles have given us a lot of insight into the mechanisms that generate pleasure in the brain:
Hedonic Hotspots: Generating Sensory Pleasure in the Brainhttp://www.smith-lab...es-of-Brain.pdfVentral Pallidum Roles in Reward and Motivation http://www.ncbi.nlm....les/PMC2606924/Even though it's not clear where and how exactly my pleasure pathways have become dysfunctional, it appears that the pleasure generation is a highly localized process, and that the only way to block pleasure from occurring (like in CA) is to disturb the function of certain very specific and small sites inside the basal ganglia. Indeed, even very widespread lesions have not been able to induce CA, so for CA to occur some very specific and unique dysfunction is required.
What puzzles me though is how my mu-opiod as well as GABA-B receptors seem to be extremely non-responsive. How can a local issue prevent the function of mu-receptors that are distributed all the way down in the intestines? Also, it is puzzling how the only clear symptom I have is CA (and possibly some less severe sleep and stimulatory issues) and yet my drug reactions are much more extensively disturbed. For example, I would assume that the kind of total mu-opioid dysfunction I have would also cause pain hypersensitivity, but no, all I have is CA and some small sleep and stimulatory issues.
Figuring out the exact pathogenesis by ourselves has proven to be quite the challenge, and thus I'm instead trying to look at the big picture now and to sum up the essentials of the condition to make it easier for others to chime in. So the essential features of my condition are:
Consummatory anhedoniaThis is the symptom that I'm trying to treat. It is complete lack of pleasure as a response to pleasurable stimuli such as sex, sugar and music. It has pretty much nothing to do with the normal anhedonia seen in psychiatric disorders and in several neurotransmitter, hormone or even dietary deficiencies.
Rewarding drugs fail to induce pleasureI also lack pleasure as a response to drugs. Stimulants are capable of inducing some pleasure, but even very big doses induce only very little pleasure. I suspect that other rewarding drugs might have the same effect at high doses, but I have mostly stuck to low to moderate dosages.
Opioids have zero effectOpioids do not induce any effect in me. At this point it is unclear whether huge doses could induce some effects.
GABA-B agonists have extremely diminished effectsPhenibut induced some hypnotic effect at 10g but nothing else. GHB threshold is around 2,5g, 3,5g produces a short lived and non-euphoric intoxication.
On/off natureThe consummatory anhedonia has on occasion switched off and I have felt all the pleasures to the fullest extent for anything from one hour to two days. It is unclear whether opioids and GABA-B agonists would have worked normally during these "windows", I suspect at least opioids would have as they appear to be of such critical importance for pleasure. It is noteworthy that even though systemic opioid antagonism does not induce CA, opioid antagonism at certain "hedonic hotspots" ie small specific sites implicated in pleasure generation does indeed cause CA. Coupled with this lack of opioid response of mine, it is clear that opioids and the mu receptor play a central role in natural pleasure.
Some have suggested that my condition could be due to lesions, organic brain damage or neurodegeneration of specific sites and/or mechanisms pertaining to pleasure generation. I think that the on/off nature of my condition proves that this is not the case: a damaged brain is not capable of switching back to healthy function for a while just to go back to dysfunction soon again.
Genetic causesMy brother also has this condition. He has severe consummatory anhedonia and like me, has diminished response to opioids. He does have some response however so it appears that his CA is slightly less severe. As we were already living separately when the CA started to occur (it came first for me, then later for him), it appears that environmental factors do not play critical role.
Other symptomsIn addition to CA, I do suffer from certain circadian rhythm and stimulation related issues too. I generally feel hot and alert during night time and find it difficult to fall asleep before morning. This does severely impair my everyday functioning. Sometimes I also get over excited about something and find myself behaving and feeling like I would be on stimulants. This is a minor trouble. Interestingly, the typical antipsychotic perphenazine corrected both my sleep/circadian and stimulatory symptoms. I haven't tried other antipsychotics.
I do not have any other symptoms that could in any way be related to the CA (ie be related to brain function) which makes my condition seem to be extremely specific instead of being a widespread dysfunction.
GABA-B agonist use causes the same conditionApparently, in some rare cases the excess use of the GABA-B agonists phenibut and GHB has induced the same condition. Consummatory anhedonia, lack of opioid response, lack of drug pleasure and high tolerance to GABA-B agonists have all been present for anything from one month to one year following the cessation of GABA-B agonist use.
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To sum up all of the above, it seems to me that it is certain that there is no
damage in my brain but a mere signalling mistake. The role of genetics is pretty obvious. Even though viewing the endorphins as the pleasure generators is simplistic, it is clear that the opioid system is involved in the pleasure generation and therefore modulating it is a good strategy. GABA-B probably plays some central role in this.
