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What does it mean when dopaminergic drugs don't work on you or rapidly increase tolerance?

anehdonia

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#1 BrankLucas

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Posted 26 November 2018 - 03:11 PM


I have had some sort of issue where my brain is degenerating somehow, ever since I was born, most of the threads I have found through searching note that people have become like this via something like stress. As a minor I grew up with my emotions mostly disappearing, to the point where my default state at 18 was suicidal depression, and then years from that point I lost even the ability to feel sadness. I have tried all of the categories of prescription drugs, tons of nootropics. I was never abused or neglected as a child, this is not from chronic stress, I was born like this. I have the symptoms of someone who has been smoking meth for 30 years and has done damage to their dopaminergic system, and complete anhedonia as my baseline. None of the categories of prescription drugs work, I have tried TMS as well. The only drugs that have given me temporary relief and extended my life for the last few years have been dopaminergic substances, but for the last few years they've all rapidly built up tolerance, even brand new substances I never used before. I will read about someone using uridine for a year with slowly increasing tolerance, but in my case within weeks I had to build start using 20x the dose per day to feel even a normal baseline. I have lived off of BPC-157 for a while, and even that stopped having positive effects for me after a year.

 

Can someone give me a theory as to what might be occurring when someone can't get a buzz or even stimulation from dopaminergic drugs like nicotine, vicodin, amphetamine, etc and so on? I feel like this might be an important clue, but I don't know enough about neurology to find that answer on my own. I have recently attempted a course of 9-ME-BC, and my experience was different than everyone else, the effects actually rapidly decreased and I had to increase my dose within a week, the effects decreased the more I took it, whereas normal people report and increase in effects the more they take it. I survived off of citicoline for a while, some people report that the effects actually got more severe as they continued to take it(shown to increase dopamine receptor density), yet for me it got less effective The only thing that ultimately might have stayed with me would be the twitchy sort of dopaminergic effects. If I keep taking it I will end up with tardive dyskensia. I realize the standard response is that the brain and especially the dopaminergic system is complex and not understood, and you depression is not that simple, which is true. But the fact that only dopaminergic drugs where the thing to ever provide relief, even for a short time must mean something. I'm looking for a theory, possibly a new direction of things to try, because I'm probably all out of options at this point.


Edited by BrankLucas, 26 November 2018 - 03:14 PM.


#2 jack black

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Posted 26 November 2018 - 04:45 PM

I don't have any good answers, but did you see this: https://www.longecit...o-stop-working/

or other threads by that poster? His issue seems similar, maybe you can compare your notes?



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#3 BrankLucas

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Posted 26 November 2018 - 09:32 PM

Thanks for your response. I don't have any physical health issues for the most part, not any he described anyways. There is some similarity, such as gabergic drugs not working for both of us. I find those drugs actually have zero effect on me unless I add some sort of additional dopamine to my brain with something like citicoline. And of course, the fact that stimulants don't work either. SSRI's worked for me for 6 months the first time I took them, after that, no. I originally had OCD symptoms such as wanting to do things in odd numbers, and thinking about things hundreds of times a day(which the SSRI was effective at), wasn't really disruptive but annoying. After everything seemed to downregulate dopamine wise those symptoms went away, and thus SSRI's were no longer helpful. I have looked into the possibility of it being bacteria based, but the research I've done so far has not indicated that it's necessarily possible to easily colonize bacteria in the stomach so easily. There is a strain I've found that actually produces dopamine that you can buy, but the issue is other dopaminergic drugs for whatever reason are only giving me the physical stimulation as far as how the cells are responsible for muscle control and I get more twitchy, for whatever reason maybe there is something with the pathways where the other sort of manic effects aren't coming through



#4 MichaelTheAnhedonic

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Posted 27 November 2018 - 11:53 AM

It's so frickin unfair that we feel like meth heads even we didn't do drugs...

 

I tested positive again for H. Pylori. Dunno if it's connected to my issues with drugs efficiency. But I am sure that I feel worse than ever. I'm gaining rapid tolerance to every drug even thou I always was resistant to tolerance. 

 

Last time I had to take 2x 0.5mg of alprazolam to feel anything. The thing is that 1,5 year ago I could feel 0.25mg. Another thing is that there's no way I could develop tolerance because I wasn't taking it constantly. 

 

Methylphenidate works in higher doses but it's very weak and short compared to what I was gaining 1,5 yrs ago. 



#5 BrankLucas

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Posted 27 November 2018 - 03:43 PM

It's so frickin unfair that we feel like meth heads even we didn't do drugs...

 

I tested positive again for H. Pylori. Dunno if it's connected to my issues with drugs efficiency. But I am sure that I feel worse than ever. I'm gaining rapid tolerance to every drug even thou I always was resistant to tolerance. 

 

Last time I had to take 2x 0.5mg of alprazolam to feel anything. The thing is that 1,5 year ago I could feel 0.25mg. Another thing is that there's no way I could develop tolerance because I wasn't taking it constantly. 

 

Methylphenidate works in higher doses but it's very weak and short compared to what I was gaining 1,5 yrs ago. 

 

You can try what I tried, which is to use additional dopaminergic substances to get something for those drugs to release dopamine, or at least I think that's what happened. I had the best success with BPC-157. Or citicoline worked too. Like for example I enjoyed DXM as an antidepressant for a while, it did absolutely nothing for me to take it, unless I used BPC-157 at the same time. I was able to live off BPC for at least a year

 

On the other hand, I just tried some of the dihexa powder I had last night, in spite of likely purity issues, I don't have a choice, and it may or may not be bringing effectiveness back to the tyrosine. I was taking tyrosine multiple times a day for barely any relief, and it would have almost no effect. Easy to write it off as a placebo, if not for the fact that I also had involuntary muscle twitching in addition to the signs of the tyrosine working again from the increased dopamine in my neurons after taking it. And  felt great emotionally. I'm ordering DMSO and seeing how this works out.

 

If the drugs work on releasing dopamine and they don't work for us then...it means something with no dopamine to release, but I don't have any education to be able to even guess what. I'm having an MRI for an unrelated medical issue soon, 99% chance it won't reveal anything, but maybe.


Edited by BrankLucas, 27 November 2018 - 03:53 PM.


#6 jack black

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Posted 27 November 2018 - 09:18 PM


I tested positive again for H. Pylori.

 

you need to treat that. what therapy did you get the previous time?


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#7 BrankLucas

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Posted 28 November 2018 - 07:30 AM

So I took some dihexa today again, orally, and again I felt the effect of the tyrosine gaining some effectiveness again. I actually got mildly psychotic from tyrosine in my system that was now suddenly affecting me to even a higher degree, had to take some phenibut. Naturally I can take something like dxm in a dose that would have normal people laid out and immobile and feel nothing, or even now tyrosine doesn't even do anything without the dihexa for me. I have no reason to believe this won't just be a short term fix that won't last, but hopefully I'm wrong.



#8 CWF1986

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Posted 29 November 2018 - 06:41 AM

Have you tried sulbutiamine?

It's been observed to increase dopamine receptor in the prefrontal cortex.

 

Uridine does something similar.  I know citicholine  has some in it, but it might not be the ratio that's right for you.  I would still recommend taking a choline supp and fat with it.  Fish oil is real easy since you can go your local corner store and pick it up in capsule form.  

 

Mostly, I'm suggesting looking at this issue at a different angle.  That of the receptors as opposed to raw material and release of dopamine.  

 

And I seconded the advice to get the H Pylori thing sorted out.  Gut health and brain health are closely related.  



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#9 BrankLucas

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Posted 29 November 2018 - 09:19 AM

Yes, sulbutiamine didn't particularly help. Substances like uridine etc directly adding dopamine double tolerance extremely rapidly, but are the only thing that even remotely help







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