If you're still getting high off of CB1 activation you might take that as a sign you have dopamine in your vesicles, could localize whether dopamine is responsible or not for the high with a dopamine antagonist (should also make your anhedonia much worse should it be lack of dopamine related).
This might sound retarded but play along.. theoretically you could try to tell the difference between receptor problems and lack of dopamine problems with pre-synaptic vs. post synaptic binding right?? Pre synaptic binding would depend on having dopamine in the vesicles to fire where as post synaptic binding the dopamine cell could fire regardless of dopamine in vesicles? The problem with this would lie in the post synaptic binding not having much effect with the action potential connecting to the cells on down the line because those cells either wouldn't have dopamine in vesicles or the post synaptic drug wouldn't have bound there.. Am I retarded?
If you are feeling spendy there is the DAT scan... Will likely become cheaper with time. It could help you pin down whether you are having lack of synapse problems in the pre-frontal cortex etc. or dopamine producing cell body problems/dopamine projection problems. Would love to know if there was really a way to figure out what was going on with the receptor down regulation..
COMT is important as well, MAOB is something else to consider but inhibitors of COMT are a mainstay of Parkinsons treatment, "In the brain, COMT-dependent dopamine degradation is of particular importance in brain regions with low expression of the presynaptic dopamine transporter (DAT), such as the prefrontal cortex. This process is supposed to take place in postsynaptic neurons, as, in general, COMT is located intracellularly in the central nervous system"
I think if there is a significant shortage of dopamine coming from the substantia nigra itself this could be revealed with some temporary drug induced Parkinsons (insert neuroleptic here) but Parkinsons is similar to liver failure in the sense that it only really becomes apparent clinically once you are almost there (many of the cell bodies in the SN are gone). Some symptoms can precede others by many years, REM sleep disorders are typically the first and can appear more than a decade before onset of clinical Parkinsons, loss of smell is another one.
But dopamine is not the only matter, dopamine can fire through heterodimers and through 5-HT2A for example, so serotonin is something else to look into. 2A is implicated all over the place in depression, whether or not you want to use the word depression or anhedonia could change views on things regarding whether it's lack of dopamine or too much 2A etc. Theoretically if someone's 2A is firing off a lot of dopamine this could lead to dopamine receptor down regulation in those associated cells. Then a psychostimulant that releases dopamine through a 5-HT2 pathway may not have as much dopamine effect because those would be the specific dopamine receptors that are down regulated. And then in that case a more global dopamine increase would work better (to reach beyond the cells that are down regulated from 5-HT2 interactions). Anhedonia can be from lack of many things and too much of some things me thinks.
There is of course the psychological side of things, if you're interested in that I recommend mindfulness meditation which if you develop Parkinsons down the road will be useful anyways. Vipassana/meditating on the breath is wonderful. It will help your sleep which can improve mood regardless.
Family history wise, was there anything environmental (pesticides in particular) that your fam was exposed to that could explain the Parkinsons or has it been isolated to genetics? Much neurodegenerative disease other than Parkinsons?
Sorry for wall of text
