melange
Bluelighter
like cocaine?
I wonder how different the high would be in someone with full blown Parkinson's.
I wonder how different the high would be in someone with full blown Parkinson's.
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N&PD Moderators: Skorpio
people with parkinsons using dopanergic drugs
- Thread starter melange
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Ham-milton
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Would it probably cause a temporary decrease in symptoms, followed by an increase?They probably woudn't even get high as the mechanism of a high is striatlal dopamineric ennervation, a separate dopamineric "compartment". They may experience mild to effective peripheral affects due to dopamine reuptake in the substantia nigra, and probably a decrease in dopa efficacy after the drug event is worn off.ziddy
Yes DAergic activity is decreased in PD, apparently by loss of DA producing neurons in the substantia nigra, and receptor malfuntion iin associated stuctures like the pars compacta in the lower brainstem. But have you ever wondered why a PWP does not get a powerful high (a few cases have been known where subjects got high taking up to 25 grams!!! of L-Dopa) by taking L-Dopa, they only get relief from the symptoms of slowness and stiffness? That's because dopamine synthesis , packaging in vesicles, and release, has it's priorities of where the dopamine is to be used. In the dopamine compromised human, a reuptake inhibitor doesn't flood the higher striatal dopamine compartment, it is directed towards movement control. I'm not real sure on this because i'm not an expert on anything, but i have heard reports of stimulant drugs not really affecting the PWP in a way which would make the rest of us run a 3 minute mile
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This is a very interesting question, and i would like to know the "real truth" behind what i am speculating. Thanks
Groovy guru
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Bondmaker
I can assure you from personal experience that PD sufferers do get quite high from MDMA. There is a thread in the archives somewhere about this too. I did not notice any difference in the symptoms afterwards either. Don't know about cocaine or methylone.
Regarding L-Dopa, it does have side effects in PD patients. Hallucinations, involuntary muscle movements, mood changes, increase in sexual appetite are common side effects. PD patients are not affected as much as you or I would be, since L-Dopa is only the precursor and the conversion to dopamine is of course much less efficient in PD patients. Unfortunately it becomes even less efficient over the course of time (otherwise, PD would be like diabetes - mostly controlled).Groovy Guru..
I never said PWP didn't get high on MDMA, i'm sure they would get high but that high would be slightly different from a non-PWP because the high of MDMA relies partially on the transport of dopamine to the DA receptors in the striatum, as well as being an uptake inhibitor in the dopamine producing structures. I said that they probably wouldn't get as high on cocaine, as a non-dopamine deficient person would, as the activity of cocaine is mostly from ennervation of DA receptors in the striatum. See the activity of MDMA thread where it's activity is determined from tweaking various DA, 5-HT and NE receptors as reuptake inhibitors.Groovy guru
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Well, I'm not sure that the receptors are affected that much, otherwise agonist therapy wouldn't work very well. Certainly, they become desensistized with prolonged agonist treatment.
However, I think you are correct about the effect of cocaine. Ritalin has been used to treat PD experimentally for several of the symptoms including depression. Unfortunately, it seems that PWP are much less sensitive to the euphoric effects of ritalin than healthy controls. However, these people were depressed and likely in a fairly advanced state of PD so I don't know how that extrapolates to other PWP who form a notoriously diverse population.
My personal observations have involved early stage PD where with medication the symptoms are barely noticeable. And at least for MDMA, the high doesn't appear to be any less intense. If I get any new data on more dopaminageric drugs, I'll let you know...
Ham-milton
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That's partly not true. The vast majority of MDMA's activity stems from it's effect on SE transport, not reuptake inhibition.I went back and read the "how does MDMA work" thread, and in my first response I said what I had been taught, that MDMA acts at 5-HT2 SE sites, stimulating SE release (a presynaptic agonist). Then Ham-milton told me (us) that it acted as a reuptake inhibitor of SERT, DA and NE. Above Ham-milton says "That's partly not true. The vast majority of MDMA's activity stems from it's effect on SE transport, not reuptake inhibition." So then, is the correct answer for that question, to say that MDMA acts mostly as a 5-HT-2 receptor agonist, stimulating SE release, but also blocks reuptake sites, along with weak DA and NE reuptake, further enhanced by VMAT-2 "pumping"? This would account for the intense SE depletion that occurs after a dose of MDMA wears off.
Vector implied that 5-HT2 agonism is not as important as reuptake and MattPsy gave some IC50 receptor binding at various receptors, along with further stressing the VMAT-2 "pumping" of whatever SE left in the cell is actively pumped out.
Sorry to get so off topic from the original question, melange.Last edited:
fastandbulbous
Bluelight Crew
MDMA works by putting serotonin reuptake into reverse, causing an efflux of serotonin from the cells into the synaptic cleft. Actual reuptake inhibition plays only a minor role in MDMA's effects and agonism at 5HT2a (or other 5HT receptors) effectively has bugger all influence on it's activity; if it did, then the R isomer of MDMA would have a bigger role in the eventual effects of the drug. As well as that, N-alkalated PEAs/amphetamines have an even lower affinity for the 5HT2a receptor than the corresponding primary amine and MDA doesn't have that great an affinity for the receptor in the first place (although it has enough to make S-MDA feel somewhat different to R-MDA, the racaemic drug having a bit of both (S isomer is the one with most entactogenic activity whereas R isomer is the more trippy - with all optically active PEA psychedelics, the R isomer has the greater affinity for 5HT2a)
Er, could you go through and change where you used NMDA when meaning MDMA as it doesn't help with the clarity and some of us are confused enough individuals as it is!