Strong case for dopamine

This is for hypothesis and even educated speculation.
CirqueduSoleil90
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Strong case for dopamine

Unread post by CirqueduSoleil90 »

Some time ago I took a DNA test and found out I have a gene called gs224 (https://www.snpedia.com/index.php/Gs224). This gene leads to low levels of dopamine. Let's follow the dopamine trail.

There are at least two recovery stories for Inositol, which increases dopamine receptors (https://pubmed.ncbi.nlm.nih.gov/11267629/). I've read about people taking 18g of Inositol a day, but I can barely tolerate a few hundred milligrams. Even at that level I go completely anhedonic. I read somewhere although I've lost the reference, that Inositol initially blunts dopamine release. Perhaps my low initial levels of dopamine make me susceptible to this effect in a way that people without this gene aren't. But that's a side track. Even if Inositol affects dopamine and I apparently have an issue with dopamine, Inositol also has has a host of other effects, any of which might be the real reason for the recoveries. Let's keep digging.

There are also recovery stories for St Johns Wort (SJW) which also increases dopamine (https://pubmed.ncbi.nlm.nih.gov/15148244/). Of course, SJW also has a host of other effects, but at least dopamine is common theme for SJW and Inositol.

There are also recovery stories for various anabolic steroids and subsequent post cycle therapy (PCT). The connection between steroids and libido does not seem to be well understood, but it seems that testosterone does not directly affect libido. Testosterone does however affect dopamine (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3949980/). Now we have three compounds, all with wildly different effects, but with the common denominator that they affect dopamine.

Finally, at least one person has recovered using pramipexol which directly activates dopamine receptors and another using dextroamphetamine, which also activates dopamine receptors. These two last compounds are the clearest link to dopamine since these compounds don't do much except activate dopamine receptors.

The likely culprit: dopamine.
BlackCat
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Re: Strong case for dopamine

Unread post by BlackCat »

Dopamine agonists are known to cause hypersexuality as a side-effect. Dopamine lowers prolactin (a hormone that inhibits sexuality). Whether you have PSSD or not, a drug that increases dopamine is likely to make you more horny.
rmichaelballow
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Re: Strong case for dopamine

Unread post by rmichaelballow »

CirqueduSoleil90 wrote: Thu Jun 23, 2022 2:33 am Some time ago I took a DNA test and found out I have a gene called gs224 (https://www.snpedia.com/index.php/Gs224). This gene leads to low levels of dopamine. Let's follow the dopamine trail.

There are at least two recovery stories for Inositol, which increases dopamine receptors (https://pubmed.ncbi.nlm.nih.gov/11267629/). I've read about people taking 18g of Inositol a day, but I can barely tolerate a few hundred milligrams. Even at that level I go completely anhedonic. I read somewhere although I've lost the reference, that Inositol initially blunts dopamine release. Perhaps my low initial levels of dopamine make me susceptible to this effect in a way that people without this gene aren't. But that's a side track. Even if Inositol affects dopamine and I apparently have an issue with dopamine, Inositol also has has a host of other effects, any of which might be the real reason for the recoveries. Let's keep digging.

There are also recovery stories for St Johns Wort (SJW) which also increases dopamine (https://pubmed.ncbi.nlm.nih.gov/15148244/). Of course, SJW also has a host of other effects, but at least dopamine is common theme for SJW and Inositol.

There are also recovery stories for various anabolic steroids and subsequent post cycle therapy (PCT). The connection between steroids and libido does not seem to be well understood, but it seems that testosterone does not directly affect libido. Testosterone does however affect dopamine (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3949980/). Now we have three compounds, all with wildly different effects, but with the common denominator that they affect dopamine.

Finally, at least one person has recovered using pramipexol which directly activates dopamine receptors and another using dextroamphetamine, which also activates dopamine receptors. These two last compounds are the clearest link to dopamine since these compounds don't do much except activate dopamine receptors.

The likely culprit: dopamine.
What you're seeing here is one part of the way to recover, and that's addressing dopamine. As seen on the thread about cabergoline (a dopamine D2 agonist), and a temporary full recovery (or window), addressing dopamine helps substantially, not just for libido and erectile function, but for sensation as well. But it seems to be a bit more complicated than just agonizing receptor sites, and the entire dopaminergic system as a unit, needs to be restored.

The sex steroid recoveries are interesting. The affect on dopamine that testosterone has, is limited to the state of the dopaminergic system (I believe). Some people do quite well w/ Clomid, and or actual TRT, and managing estradiol, and some do not. The ones that do not, seem to have a more "broken," if you will, dopaminergic system.

But ALL of this plays a role and more. The system of sexual function is too complex to be mediated or controlled exclusively by dopamine. You've got approach every angle. Sex hormones + dopamine, I've seen be a successful route to take, that has landed people in long stints of recovery.

And what's important for people to understand is that merely taking Tyrosine or phenylalanine, both dopamine precursors, isn't going to solve the dopamine issue, if the conversion enzymes and gene regulation of dopamine creation/synthesis are malfunctioning, which I believe is the case in some. Working on up-regulating the expression of Tyrosine hydroxylase, should be one particular target, in these situations. Another would be attempting to restore the way the brain actually makes dopaminergic neurons. We actually have evidence that TH gets down-regulated in the presence of SSRIs. This study (https://pubmed.ncbi.nlm.nih.gov/1977162/) was with long term/chronic use, but who's to say this doesn't happen in shorter term use as well.
Joao Paulo Brasil
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Re: Strong case for dopamine

Unread post by Joao Paulo Brasil »

There is another 10 year pssd recovery case using pramipexole. I believe he never posted his success story anywhere, after he got better he walked away from our group. He was part of our pssd group in our country. What I know from his story is that she had pssd and anhedonia, and it only got better after 2mg a day. And all I know.
Impermanence
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Re: Strong case for dopamine

Unread post by Impermanence »

Joao Paulo Brasil wrote: Mon Nov 14, 2022 10:22 am There is another 10 year pssd recovery case using pramipexole. I believe he never posted his success story anywhere, after he got better he walked away from our group. He was part of our pssd group in our country. What I know from his story is that she had pssd and anhedonia, and it only got better after 2mg a day. And all I know.
Thank for this post.
I have been using Pramipexol with some moderate success (libido mostly) but only until 0,7. I was planning to do it again until 2,1/day. So you confirm me it has sense..
Joao Paulo Brasil
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Re: Strong case for dopamine

Unread post by Joao Paulo Brasil »

I've already tried pramipexole and the maximum dose I tolerated for a few weeks was 1.5mg. Ai decides to stop due to collateral damage. Came back again last week now I'm on 0.25mg starting over. I'm on my second attempt.
Impermanence
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Re: Strong case for dopamine

Unread post by Impermanence »

Joao Paulo Brasil wrote: Tue Nov 15, 2022 11:00 am I've already tried pramipexole and the maximum dose I tolerated for a few weeks was 1.5mg. Ai decides to stop due to collateral damage. Came back again last week now I'm on 0.25mg starting over. I'm on my second attempt.
Did you notice benefits at 1,5mg/day?
6-Eggs!
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Re: Strong case for dopamine

Unread post by 6-Eggs! »

Although this is all speculation. My neurologist which is regarded as one of the top ones in the Asia Pacific area said serotonin systems do fully recover but take months to a few years. Dopamine neurons take significantly longer and in some rarer cases only partly recover or not at all.

It's very easy to mess them up when taking any dopamine targeting drugs so I wouldn't risk it. Most people suffer issues long term from post ssri and other drugs due to trying to fix it with other treatments when the CNS is already hyper-sensitized and just prolongs the recovery and the cycle continues.
lukejimmy
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Re: Strong case for dopamine

Unread post by lukejimmy »

6-Eggs! wrote: Thu Nov 17, 2022 8:26 pm Although this is all speculation. My neurologist which is regarded as one of the top ones in the Asia Pacific area said serotonin systems do fully recover but take months to a few years. Dopamine neurons take significantly longer and in some rarer cases only partly recover or not at all.

It's very easy to mess them up when taking any dopamine targeting drugs so I wouldn't risk it. Most people suffer issues long term from post ssri and other drugs due to trying to fix it with other treatments when the CNS is already hyper-sensitized and just prolongs the recovery and the cycle continues.
I agree with you on avoiding taking more drugs, but if dopamine targeting drugs caused long-term damage years post-discontinuation, then wouldn't there be a Post-Amphetamine Syndrome with 100'000's of people complaining about Numbed Positive Emotions, Anhedonia and Pleasureless Orgasm's, considering it's by far the most widely abused Prescription Medicine? I suppose there is a higher percentage of the Population on SSRI's but why isn't there a forum for an Amphetamine Post-Drug condition?
I also don't think SSRI's affect Dopamine Neurons in the same context where your Neurologist claims takes years or doesn't even recover at all, I assume the Hypersexuality/Porn addiction prevalence in PSSD victims would have a higher potential to do that given that it would be a more potent and direct effect on dopamine neurons vs SSRI's.
6-Eggs!
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Re: Strong case for dopamine

Unread post by 6-Eggs! »

lukejimmy wrote: Fri Nov 18, 2022 11:08 am
6-Eggs! wrote: Thu Nov 17, 2022 8:26 pm Although this is all speculation. My neurologist which is regarded as one of the top ones in the Asia Pacific area said serotonin systems do fully recover but take months to a few years. Dopamine neurons take significantly longer and in some rarer cases only partly recover or not at all.

It's very easy to mess them up when taking any dopamine targeting drugs so I wouldn't risk it. Most people suffer issues long term from post ssri and other drugs due to trying to fix it with other treatments when the CNS is already hyper-sensitized and just prolongs the recovery and the cycle continues.
I agree with you on avoiding taking more drugs, but if dopamine targeting drugs caused long-term damage years post-discontinuation, then wouldn't there be a Post-Amphetamine Syndrome with 100'000's of people complaining about Numbed Positive Emotions, Anhedonia and Pleasureless Orgasm's, considering it's by far the most widely abused Prescription Medicine? I suppose there is a higher percentage of the Population on SSRI's but why isn't there a forum for an Amphetamine Post-Drug condition?
I also don't think SSRI's affect Dopamine Neurons in the same context where your Neurologist claims takes years or doesn't even recover at all, I assume the Hypersexuality/Porn addiction prevalence in PSSD victims would have a higher potential to do that given that it would be a more potent and direct effect on dopamine neurons vs SSRI's.
Probably because illicit drug users don't know or care they have issues as altered state of mind is their norm. One of my family members is really messed up from years of drug use and doesn't acknowledge or realize he's messed up, but to everyone else it's very obvious. And I mean really messed up, disability and mental/neurological issues such as schizophrenia, poor reasoning/cognitive abilities,scattered thought patterns, negative motivation, 0 sexual function or interest, constant anger etc... He's been mostly illicit drug free for years now but now has to be on a number of neuoleptics due to the aggressive behavior that his psychosis brings about.

My partner has a number of drug users on her cousin/s side of the family and they are the same, messed up but they think it's normal. They also have sexless relationships from what I heard and think me and my partner are weird for having sex 1-2 times a day most days.

I was also put on ADHD drugs as a teen becasue I had learning difficulties and was miss diagnosed as ADD/ADHD and then I ended up failing a year as the drug killed all my energy and motivation and that persisted for about a year or 2 after stopping the drug.

At least for me, dopamine system disruption hadn't really caused orgasm issues, maybe dulled them a bit while I was on ADs and APs. For me libido, erection and arousal difficulties were the most obvious symptoms for the sexual stuff, but the paranoid thoughts and movement issues were the obvious ones while tapering off.

The serotonin symptoms are primary sensory and sexual and autonomic issues, sensory being the biggest by far.

I suppose it also depends on the Dopamine agents being used too, if they are mild and intermittent does then recovery should be fine, but some agents like full agonist or antagonists can and will cause long term damage and are cumulative. The longer you take them, the longer it takes to recover and recovery is always slow and can be only partial. The AP I was taking and still tapering is a partial agonist so from my research they are less likely to cause up/down regulation but they will still do it to far smaller degree. I still felt the effects of altered Dopamine system but seems quick to recover and mild compared to cases I have read. The seritonin alterations were far worse and are very persistent and slow to recover due to the large changes that occurred to me, norepenephrine receptors are likely involved too as the AP I used is extremely potent antagonist of a heap of alpha receptors.
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