Finally Found a Treatment...Can Anyone Please Explain This?

[Alvin2]

You may be right.Here it states 1% risk for such side effects while some studies state 16%.16% is certainly not low but for me is low enough and I think if it was going to happen it would have happened already.At least this is a neuroprotective drug and I can feel that for what is worth.Also it doesn't affect hormones, especially male hormones, negatively like atypical antipsychotics, so that's another plus.

1%? That is incredibly unbelievable.
16% is still unbelievable.
Frankly its considered a bonus if you don't come down with behavioural side effects as its expected patients will.

That said if you are not having issues that is great to hear.

If I find a solution in another drug or supplement yes, I'd rather quit it.It helps with mood too but I don't have a problem there so it's not a big boost for me.I'm gonna try NADH injections, helminthic therapy and a couple of peptides next.Hoping for the best.

I understand, sometimes its worth living with high risk of side effects, but nonsense about their prevalence needs to be avoided.
Do bear in mind that they can happen over longer periods. Some patients do fine for a while then start to slowly change without their realizing it as it can be subtle and cumulative. Gambling, sexual side effects and grandiose planning can start small and very slowly build. I highly recommend having someone who can monitor you long term and has Power of Attorney in case you become self destructive or worse.

 

[bthompsonjr1993]

I’ve had several longer breaks in symptoms the past 10 months (2x 7-10 days) and thought it was due to something I was taking but couldn’t replicate it.

I finally did replicate it however and have been pouring over literature trying to decide what exactly is happening and the most likely mechanism.

ITPP - I posted a thread a few days ago about ITPP (myo inositol trispyrophosphate) which is an almost Eric effector of hemoglobin that can increase oxygen release up to around 50%. Incredible performance enhancer. By itself this helps with physical fatigue a fair amount 40-50% and mental fatigue

Cabergoline - this is a dopamine (primarily selective D2) agonist. Also has some affinity at other DA receptors and Alpha receptors. By itself this drug doesn’t seem to do a whole lot...maybe a very tiny mood elevation.


Neither of these drugs make an enormous difference by themselves is the weird thing (ITPP much more so than the caber but still not a lot). COMBINING them, however, makes an enormous difference and I had almost all my symptoms fade over the course of 12 hours after taking them both.

Energy is back, sense of humor is back, brain fog is gone, mental clock speed is much faster, sex drive and function is back strong, and an overall general feeling of wellbeing is back.

Can anyone try and help postulate why? Been looking at every angle non stop to try and figure out what about this combination is elliciting 100% improvement, and in such a short time period

WOW that’s interesting. Can you tell me what brand of ITPP you take, and at what dosage per day? I am trying to buy some but not sure which one to but. And the cabergoline has to be prescribed by a doctor, correct?

 

[lateM98]

I really wish if people who experience improvements from some kind of intervention elaborate some more, for example: Before I couldn't do X, or I could only do Y for a certain number of minutes per day, now I can do X, or now I can do Y for a larger number of minutes per day..etc It really helps people who goes back to read these threads, and it adds to the credibility of the claims. Much better than vague statements "HUGE improvements".

 

[Frunobulax]

Oh yeah, Mirapex is well known for causing obsessive and compulsive behaviour, hallucinations, dyskinesias and has quite the reputation as a drug to be avoided.

All dopamine agonists do this. Mirapex just has a higher rate than others.

All those mentioned are quite rare.
Either way I'm willing to take the risk to be permanently dependant on this drug because the benefits worth it so much I don't even see a dilema.

Risk of impulse control disorders is between 15% and 35% depending on which study you read. And there is the risk of adapting to the drug, that is, you'll need increasing dosages with time. Most studies are short term (up to a year) so they will vastly underestimate the risk.

They most certainly are not. Its typically a last resort medication in Parkinsons because the behavioural side effects are that insidious.

Exactly. Patients are known to self destruct within months. This is common knowledge for restless legs, where patients have no brain damage and psychiological disorders, yet they still behave like they're taking some serious narcotics. So it's very obvious that it's the drugs and not PD. And the patients don't realize this themselves, mind you. They think it's perfectly normal what they're doing, throwing away their relationships, gambling away all their money (including money they haven't got) and whatnot.

I can only strongly advise to stay far away from all dopamine agonists. Or at the very least have long breaks in treatments, several weeks for cabergoline.
I did experience all this shit myself (being a Restless Legs sufferer that was on Mirapex for a while, unfortunately), and while I can't prove it, I'm quite convinced that dopamine agonists caused my ME/CFS as I had my first crash shortly after coming off them. They are like narcotics: They appear to do good at first, but boy will they burn you eventually.

 

[Wishful]

I really wish if people who experience improvements from some kind of intervention elaborate some more,

Details are good when they're available, but a lot of the things that did provide noticeable benefits for me simply reduced overall symptom severity, which is hard to quantify. Even if it's only a general reduction, details of how long it took to start working, how long it lasted, etc, can be useful.

 

[lateM98]

Another drug that work similarly to ITTP is Trans Sodium Crocetinate and is currently developed for some form of brain malignancies by Diffusion Pharma. It should be cheap to obtain from chemical manufacturer.

 

[stefanosstef]

I don't know if that 15-35% risk of impulse control is realistic and if it is the same for PD and non PD patients.I am n=1 but I am taking a high dosage and I don't have a gambling problem.I don't gamble, I am not overspending at all, I put money aside, I haven't dropped any kind of relationship recently and I don't have impulse control problems over sexual urges or masturbation.I think it's crazy to assume that I cannot count how much money I have in my account, how many times I have sex or I initiate it, or how many times I masturbate.

Yes, my mood is a little better, especially at night, IF I manage to get enough sleep AND have a midday rest.I know my case is N=1, but I am just providing my own experience with honesty.Another detail that could be relevant is that I was most likely low dopamine.Got all the symptoms and the 2-3 psychiatrists I have seen all agreed with this.And it makes sense as it is a direct consequence of neuroinflammation.

 

[Alvin2]

Another detail that could be relevant is that I was most likely low dopamine.

How was this determined?

I don't know if that 15-35% risk of impulse control is realistic and if it is the same for PD and non PD patients.I am n=1 but I am taking a high dosage and I don't have a gambling problem.I don't gamble, I am not overspending at all, I put money aside, I haven't dropped any kind of relationship recently and I don't have impulse control problems over sexual urges or masturbation.I think it's crazy to assume that I cannot count how much money I have in my account, how many times I have sex or I initiate it, or how many times I masturbate.

Yes, my mood is a little better, especially at night, IF I manage to get enough sleep AND have a midday rest.I know my case is N=1, but I am just providing my own experience with honesty.Another detail that could be relevant is that I was most likely low dopamine.Got all the symptoms and the 2-3 psychiatrists I have seen all agreed with this.And it makes sense as it is a direct consequence of neuroinflammation.

I deal with several Parkinsons neurologists and have had this Dopamine agonist talk repeatedly, they prescribe these pills when they have no other choice and often have to take patients off them. They are prescribed assuming there will be a problem later because is so common.
Also its not a one shot deal, because your fine today does not mean it will stay that way. It requires constant vigilance, preferably by a third party.
And you don't know your having the problem, patients argue like crazy that they are fine even after they have ruined their lives, there is nothing wrong, they need the motor control, they made all the right moves, it was just bad luck, it was caused by an external force (paranoia is not uncommon) and so forth.
I'm happy you are not having any issues and i sincerely hope you never do.
Dopamine agonists are not drop in replacements for dopamine, they are chemical activators that work indiscriminately. Just like Amphetamine which is a dopamine stimulant is not a drop in replacement for Dopamine, its a stimulant which is highly addictive and can cause behavioral side effects over time.

 

[Swim15]

How was this determined?



I deal with several Parkinsons neurologists and have had this Dopamine agonist talk repeatedly, they prescribe these pills when they have no other choice and often have to take patients off them. They are prescribed assuming there will be a problem later because is so common.
Also its not a one shot deal, because your fine today does not mean it will stay that way. It requires constant vigilance, preferably by a third party.
And you don't know your having the problem, patients argue like crazy that they are fine even after they have ruined their lives, there is nothing wrong, they need the motor control, they made all the right moves, it was just bad luck, it was caused by an external force (paranoia is not uncommon) and so forth.
I'm happy you are not having any issues and i sincerely hope you never do.
Dopamine agonists are not drop in replacements for dopamine, they are chemical activators that work indiscriminately. Just like Amphetamine which is a dopamine stimulant is not a drop in replacement for Dopamine, its a stimulant which is highly addictive and can cause behavioral side effects over time.

This is a little over the top - I’m all about caution with DA agonists and the long term side effects should definitely be accounted for and known by the patient.

That said, a lot of people do use them without issue. For a condition as severe as CFS, I don’t see an issue if people find them helpful. Hell people are using monoclonal antibodies for CFS and I’d use a DA agonist well before one of those

 

[Alvin2]

This is a little over the top - I’m all about caution with DA agonists and the long term side effects should definitely be accounted for and known by the patient.

That said, a lot of people do use them without issue. For a condition as severe as CFS, I don’t see an issue if people find them helpful. Hell people are using monoclonal antibodies for CFS and I’d use a DA agonist well before one of those

I have not posted any falsehoods.
Sometimes the behavioural side effect manifest after months, or even years.
These are very risky drugs.

As i mentioned i am very glad there are no side effects currently, and i hope it stays that way but having a third party monitor is essential.
I could get into worse stories but if you think this is over the top you don't want to hear about the self injury behaviour or those who do things and later when taken off the drug say it seemed like they were watching someone else do it as if it was on TV.

 

[Swim15]

I have not posted any falsehoods.
Sometimes the behavioural side effect manifest after months, or even years.
These are very risky drugs.

As i mentioned i am very glad there are no side effects currently, and i hope it stays that way but having a third party monitor is essential.
I could get into worse stories but if you think this is over the top you don't want to hear about the self injury behaviour or those who do things and later when taken off the drug say it seemed like they were watching someone else do it as if it was on TV.

No, you aren’t wrong per se but I have also seen patients on DA agonists for 10+ years and not have those side effects. They are common, are most likely to develop over long periods of time like years, and DA downregulation is very real that can leave someone worse off than they are.

That said, the PT has been informed of the risks

 

[Alvin2]

No, you aren’t wrong per se but I have also seen patients on DA agonists for 10+ years and not have those side effects. They are common, are most likely to develop over long periods of time like years, and DA downregulation is very real that can leave someone worse off than they are.

That said, the PT has been informed of the risks

I have not claimed 100% of patients have these side effects. But i do say all should be kept an eye on, have a signed Power of Attorney and never become complacent because it does sneak up on people.

I sincerely hope this is an overabundance of caution and @stefanosstef never has a problem

 

[stefanosstef]

@Alvin2 I am not in denial, I understand what you are saying.I wrongly assumed these side effects either occur or not in the first months.That was my conclusion by briefly reading about these and by my experience with it, which so far seems to be stable.I don't feel tolerance or reverse tolerance to it.

@Swim15 It seems to be a disagreement between experts on this.What do you mean downregulation exactly?Permanent adaptations that, if I quit, could set the environment for developing Parkinson's?
Or the temporary downregulation of the presynaptic receptors which in turn increases dopamine flow to the metasynaptic ones?

So far this adaptation is very responsive to dosage changes:

When you increase there is a temporary period that it makes you more tired because you activate the autoreceptors and the reduce the dopamine flow, before they downregulate.
When you decrease it's the opposite, because they are already downregulated from previous high dosage, you get stimulated.

Edit:I also wanted to say that I was out of options when I decided to take pramipexole.I still am but I have a few treatments in mind to try.If anything proves successful I will consider quitting it.

But also take into consideration that pramipexole isn't just a behaviour changing drug that acts on dopamine, it's a neuroprotective and antiinflammatory drug and I can really feel that.I feel that it protects from the long term every day damage that low grade inflammation causes.

It feels like a constant mild/medium storm that is taken away until it's just clouds.

 

[Alvin2]

@Alvin2 I am not in denial, I understand what you are saying.I wrongly assumed these side effects either occur or not in the first months.That was my conclusion by briefly reading about these and by my experience with it, which so far seems to be stable.I don't feel tolerance or reverse tolerance to it.

My apologies.

could set the environment for developing Parkinson's?

Its hard to say, its possible Parkinsons is caused by an ongoing infection of some type according to circumstantial but not conclusive evidence. However secondary Parkinsons is also possible (Parkinsons caused by another method, downregulation, genetics, brain tumors, brain damage, epilepsy, etc). The symptoms between both types of Parkinsons can be similar but the treatment and prognosis can be the same or different depending on the cause.

So far this adaptation is very responsive to dosage changes:

I am very reminded of this line from the Amphetamine Wikipedia article
"Amphetamine and other dopaminergic drugs also increase power output at fixed levels of perceived exertion by overriding a "safety switch""
https://en.wikipedia.org/wiki/Amphetamine

 

[stefanosstef]

My apologies.

I am very reminded of this line from the Amphetamine Wikipedia article
"Amphetamine and other dopaminergic drugs also increase power output at fixed levels of perceived exertion by overriding a "safety switch""
https://en.wikipedia.org/wiki/Amphetamine

I don't see how this is related.I meant to say that the brain adaptations seem fast and elastic, short term at least.But yeah, amphetamine used to work, now I can't handle it because I do more than I can and migraine is almost 100% certain afterwards, which oddly feels like the peak of neuroinflammation to me.

 

[Alvin2]

I don't see how this is related.I meant to say that the brain adaptations seem fast and elastic, short term at least.But yeah, amphetamine used to work, now I can't handle it because I do more than I can and migraine is almost 100% certain afterwards, which oddly feels like the peak of neuroinflammation to me.

You have said that Mirapex helps you. This could be why.
But we have no way to know if it is because of this or because of something else.

You did mention you had low Dopamine, i am curious how you figured that out?

 

[percyval577]

So you find ITPP plus cabergoline greatly improve your ME/CFS symptoms, but these drugs do not do a great deal on their own. Interesting.

Indeed interesting.

If you look at possible combinations, you will find that there are many many many (a matter for combinatorics). Here Ron Davis was wrong, when saying that treatment with supps would already had been found out, if this were possible.

Cabergoline - this is a dopamine (primarily selective D2) agonist. Also has some affinity at other DA receptors and Alpha receptors. By itself this drug doesn’t seem to do a whole lot...maybe a very tiny mood elevation

I had after having discovered my first rather big influence for quite some time good success with tyrosine, though now detrimental effects, which should have been in charge in the past too, as I evaluate my feelings. I think that the typically dopamine containing structures are an excelent candidate for MECFS symptoms. It might be only a deregulation of synaptic connections, so to say a geometrical trap.

 

[gregh286]

Seen it for.sale in a few sites

https://rechemco.to/en/myo-inositol-trispyrophosphate-itpp-powder-1000mg.html

 

[stefanosstef]

You have said that Mirapex helps you. This could be why.
But we have no way to know if it is because of this or because of something else.

You did mention you had low Dopamine, i am curious how you figured that out?

No way to prove low dopamine.It is diagnosed for me from the common psychiatrist to professors, all agree.I also have mutation on dopamine related genes (DAT?DRD? I cant remember but I can check it out) that predisposition me for low dopamine and ADHD.

 

[Alvin2]

No way to prove low dopamine.It is diagnosed for me from the common psychiatrist to professors, all agree.I also have mutation on dopamine related genes (DAT?DRD? I cant remember but I can check it out) that predisposition me for low dopamine and ADHD.

Interesting. But actually there is a way, there was a very interesting study about a drug trial with Nilotinib for Parkinsons, it did amazing and is in phase 2 or 3 trials iirc. They developed a way to determine if the body was creating Dopamine endogenously, and they explained the tests in their phase 1 study, though i don't know if you can find a lab to run those tests.
That said if Mirapex is helping you has anyone tried giving you Sinemet, which would give your brain L-Dopa from which to create Dopamine as needed? That could also help determine if you have low Dopamine or if the dopamine agonist is working in some other fashion.