Author Topic: Dopamine  (Read 76647 times)

Nightingale

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Dopamine
« on: October 10, 2012, 11:21:42 AM »
Ok so I decided to move some of the discussion about neurotransmitter treatments out of my prior thread, and I'm going to label this one 'Dopamine' so we can organize this more.

So I've been fortunate enough to have found a primary care physician AND a psychiatrist who are open to LISTENING to me regarding POIS and my mental health.  Because of this good fortune, I have been able to try 2 drugs that act on dopamine/dopamine transmitters:

  • Mirapex
  • Wellbutrin

Mirapex is a "dopamine agnoist" which binds with many types of dopamine receptors.  It is indicated for treating Parkinsons Disease and Restless Leg Syndrome.  My psychiatrist listened to our theory that low levels of dopamine could be contributing to POIS.  I was prescribed .125mg to begin with to use "as needed."  I took one pill at night for my first time, and very quickly felt sedated.  The following morning I had quite a bit of trouble waking up.  I was disappointed how tired I felt.  But I took another pill in the morning to see where it would take me.  I felt very tired, and I began to experience some strange vague cognitive changes, I couldn't quite name them at that point.  I took another pill that night.  Now, the second day was even harder waking up, and I began to feel "zoned out" or spacey, and my memory recall was worse than normal.  I did not take a pill that morning.  As the day went on, I began to believe this medication was not going to work for me.  I was attending class, but my attention issues had gotten worse, I was sleepy, and I was not feeling like myself.  I consulted with my psychiatrist over Skype (amazing that he is willing to do this!) and he asked me if I would try it another time or two at night only, and try one pill after orgasm (to see if it had any immediate effect, hoping to reduce prolactin levels).  So I did, and things didn't get better, so I stopped it.

He isn't done with exploring the dopamine theory, so he suggested I try Wellbutrin.  Another dopaminergic drug that is indicated for depression, but can affect attention too.  I was prescribed 75mg, and told to take it once a day in the morning.  I have been taking this for 4 days now, and I am not experiencing such tough side effects as from Mirapex.  But again I am not "feeling myself," and I have not noticed any improvements in my attention.  I was also experiencing some edginess today, and I felt slightly irritated for no reason.  I'm not sure if this drug, but I will continue it for at least a few more days.

For me, it doesn't seem like dopamine drugs will help much.  But I would like to keep this conversation here, and document our experiences with dopamine drugs in one easy to find place.  I didn't have much time while writing this, but I have some other strange effects while on Mirapex that I will cover when I have more time.  I just didn't think they were as important as what I've written so far!
Turmeric and Rosemary 30-45 minutes before orgasm for anti-inflammatory and immune support has helped me a lot. Faster and easier than niacin approach.

Nightingale

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Re: Dopamine
« Reply #1 on: October 10, 2012, 01:20:05 PM »
Wow, quick update:  just an hour after posting the original post, I started to experience some serious side effects from Wellbutrin.  With just having heard that asdfdoc had a psychotic episode after a few days on Wellbutrin, I'm starting to wonder whether ANYBODY with POIS should mess around with it.  Luckily I am taking an antipsychotic and an anti-anxiety med (clonipin), because the following symptoms where hitting me pretty strong:

  • Agitation - feeling like i'm going to lash out for no reason
  • Anxiety - a feeling of crawling, or restlessness (akathesia)
  • Tremor - it was mild but I could notice it.  Very unpleasant
  • Hypertension - just took my blood pressure, was 148/94 AND my Raynaud's Syndrome is worse.  Circulation in my hands is really crap, they are freezing right now...

I am stopping Wellbutrin at once.  To review, I took 75mg once a day for 4 days.  That's hardly anthing.  Most staring doses are 100-150mg once a day then after a week increased to 300mg.

I likely could have had some psychotic symptoms today had I not taken 1mg of Clonipin, and I think if I had started on a higher dose this would have been something even worse. 
Turmeric and Rosemary 30-45 minutes before orgasm for anti-inflammatory and immune support has helped me a lot. Faster and easier than niacin approach.

kurtosis

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Re: Dopamine
« Reply #2 on: October 10, 2012, 02:35:49 PM »
Hey Nightingale. The theory isn't that POIS is caused by low dopamine. It's that there's a fundamental imbalance of dopamine and it's metabolites (which include DOPAC, Norepinephrine, and Epinephrine). It's a fault with the catecholamine system. B_Daniel got some really interesting test results today  and I think the idea still has merit. What I'd forgotten was DOPAC. Can you get your doctor to see if your DOPAC levels are low. DOPAC is related to the amount of dopamine made and stored in the presynaptic neuron. You could have high or normal dopamine release but it may not be utilised properly.

Another problem could be low gaba and poor conversion of glutamic acid to GABA.
Perhaps you could get your doctor to check your GABA and DOPAC levels?

kurtosis

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Re: Dopamine
« Reply #3 on: October 10, 2012, 03:52:23 PM »
Fascinating stuff. Reading the papers of  Dr Michael Panneton.
http://medschool.slu.edu/pharmphys/index.php?page=w-michael-panneton-ph-d

He's basically saying that low dopac could indicate high dopal and that the latter could be the cause of cell death in parkinsons.
The problem would be a genetic mutation in the ALDH gene
See http://www.wikigenes.org/e/gene/e/216.html

So why do I think this might be a problem.
1) The body needs a tonne (not literally) of aldehyde dehydrogenase to clear up after an orgasm.
2) intolerance to alcohol is a symptom of aldehyde dehydrogenase deficiency.
2) fatigue, shortness of breath, mental confusion etc are all symptoms of aldehyde dehydrogenase deficiency.
3) A suggested treatment for aldehyde dehydrogenase deficiency is.... (wait for it) NIACIN.
See http://ajcn.nutrition.org/content/75/4/616.full

Nightingale

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Re: Dopamine
« Reply #4 on: October 10, 2012, 09:07:59 PM »
Hey Nightingale. The theory isn't that POIS is caused by low dopamine. It's that there's a fundamental imbalance of dopamine and it's metabolites (which include DOPAC, Norepinephrine, and Epinephrine). It's a fault with the catecholamine system. B_Daniel got some really interesting test results today  and I think the idea still has merit. What I'd forgotten was DOPAC. Can you get your doctor to see if your DOPAC levels are low. DOPAC is related to the amount of dopamine made and stored in the presynaptic neuron. You could have high or normal dopamine release but it may not be utilised properly.

Another problem could be low gaba and poor conversion of glutamic acid to GABA.
Perhaps you could get your doctor to check your GABA and DOPAC levels?


Got it.  I was not familiar with DOPAC til now, and I see it is a significant piece.  I will ask him for those tests.  Maybe we should start a "Glutamate" thread to chronicle our dealings with that side of things?
Turmeric and Rosemary 30-45 minutes before orgasm for anti-inflammatory and immune support has helped me a lot. Faster and easier than niacin approach.

Nightingale

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Re: Dopamine
« Reply #5 on: October 10, 2012, 09:15:10 PM »

3) A suggested treatment for aldehyde dehydrogenase deficiency is.... (wait for it) NIACIN.
See http://ajcn.nutrition.org/content/75/4/616.full


Damn. Sounds promising.  How is ALDH part of the orgasm clean-up process?

Though the alcohol intolerance does not apply to me.  Nor am I of asian decent, half of all asians lack the enzyme necessary to break down alcohol.
« Last Edit: October 10, 2012, 09:30:56 PM by Nightingale »
Turmeric and Rosemary 30-45 minutes before orgasm for anti-inflammatory and immune support has helped me a lot. Faster and easier than niacin approach.

demografx

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Re: Dopamine
« Reply #6 on: October 10, 2012, 10:05:00 PM »

Wow, quick update:  just an hour after posting the original post, I started to experience some serious side effects from Wellbutrin.  With just having heard that asdfdoc had a psychotic episode after a few days on Wellbutrin, I'm starting to wonder whether ANYBODY with POIS should mess around with it.


Some years ago, I had horrible effects after taking Wellbutrin. I quit it immediately. But I hear others say good things about it, so I guess it comes down to each individual's body reaction to Wellbutrin, as is true with most drugs: one man's cure can be another person's poison.
« Last Edit: October 11, 2012, 09:35:14 AM by demografx »
10 years of significant POIS-reduction, treatment consisting of daily (365 days/year) testosterone patches.

TRT must be checked out carefully with your doctor due to fertility, cardiac and other risks.

40+ years of severe 4-days-POIS, married, raised a family, started/ran a business

kurtosis

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Re: Dopamine
« Reply #7 on: October 11, 2012, 03:49:23 AM »

3) A suggested treatment for aldehyde dehydrogenase deficiency is.... (wait for it) NIACIN.
See http://ajcn.nutrition.org/content/75/4/616.full


Damn. Sounds promising.  How is ALDH part of the orgasm clean-up process?

Though the alcohol intolerance does not apply to me.  Nor am I of asian decent, half of all asians lack the enzyme necessary to break down alcohol.

ALDH converts DOPAL into DOPAC. Your body needs to make Dopamine and use that to synthesise NE to have an O. The body needs to efficiently metabolise dopamine into DOPAL and then to DOPAC as part of normal brain functioning. There's more of the dopamine produced during an O and hence more waste product (DOPAL). DOPAL is supposed to hang around for a very short period of time as it's excitotoxic.
http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0015251
The brain, is a very precise mechanism. Metabolising dopamine to produce dopal is a good thing as it's a relatively efficient reaction AND a bit of excitotoxicity is a good thing for a short while. It keeps the neurons stimulated. But only for a short period of time. After that it's bad shit.

Alcetadehyde Dehydrogenase is supposed to mop it up by turning it into DOPAC. If you had low DOPAC it may indicate that this mopping up process is not happening effectively and you're being left with too much toxic DOPAL at the synapses. This could interfere with memory, movement etc. Panneton's research is novel and intriguing. This is not an uncontroversial idea.

Another possibility is that you have or have had chronic exposure to external acetaldehyde which steals the acetaldehyde dehydrogenase needed by your nervous system. It's nasty stuff.

Quote
Acetaldehyde is an irritant of the skin, eyes, mucous membranes, throat and respiratory tract. Symptoms of exposure to this compound include nausea, vomiting, headache. These symptoms may not happen immediately. It has a general narcotic action and large doses can even cause death by respiratory paralysis. It may also cause drowsiness, delirium, hallucinations and loss of intelligence. Exposure may also cause severe damage to the mouth, throat and stomach; accumulation of fluid in the lungs, chronic respiratory disease, kidney and liver damage, throat irritation, dizziness, reddening and swelling of the skin.

Also from the wikpedia entry
Quote
People who have a genetic deficiency for the enzyme responsible for the conversion of acetaldehyde into acetic acid may have a greater risk of Alzheimer's disease. "These results indicate that the ALDH2 deficiency is a risk factor for LOAD [late-onset Alzheimer's disease]

It may also increase the risk of parkinsons for similar reasons.
See http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0015251

Acetaldehyde Dehydrogenase needs NAD to work. See mechanism of action at http://en.wikipedia.org/wiki/Aldehyde_dehydrogenase
So the conclusion of the paper I linked in my previous post is that by increasing the amount of NAD, you make the most of either a reduced supply or a faulty AD transcription (genetic problem). There are several genes in the ALDH set. Different POIS sufferers may have more than one modification. You may not necessarily have the flushing when  you take alcohol but you may feel bad and non-specific fatigue effects.

Chronic alcoholics (and I've known 2 in my life) develop a range of symptoms that can resemble POIS. They get tremors and have compromised immune systems. The following things are known about the build up of AD.
- it causes the immune system to activate leading to an elevated white blood cell count.
- it can combine with cell proteins and may cause the bodies immune response to attack good cells. (i.e. autoimmune)
- it increases sensitivity to anaesthetics, fumes, spores and anything which requires a healthy immune system. It leads to non-specific symptoms of a compromised immune system.

Gee, it may even make someone allergic to their own sperm :)

So acetaldehyde poisoning will actually cause allergic responses to things that you have no inherent allergy to. But problems in the efficient production of AD in the body will also produce symptoms of acetaldehyde poisoning. Do you see where I'm going here? Something that gives the appearance of lots of allergies.

The potential treatment for this is sort of simple.
Take P5P (active b6), NADH (active b3), methionine (by themselves, not as part of a complex) and try not to smoke cigarettes or drink alcohol.
Drink some vitamin c as it's helpful for eliminating acetaldehyde. That's it.
Any treatment that suggests giving up beer is not going to make everybody happy but... :)

Starsky

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Re: Dopamine
« Reply #8 on: October 11, 2012, 07:17:19 AM »
Where comes acetaldehyde from?

kurtosis

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Re: Dopamine
« Reply #9 on: October 11, 2012, 08:08:14 AM »
Where comes acetaldehyde from?

Just being alive. It's a byproduct of energy creation via glucosis in cells. More complex compounds which contain acetaldehyde are found throughout the body including the brain. DOPAL is one of them. As I said, it should be just quickly converted to DOPAC in the same way the aldehyde resulting from processing alcohol is converted to vinegar. (acetic acid) But if it's not then DOPAC levels would be low and it would indicate DOPAL wasn't being cleared fast enough.

There's an extreme form of aldehyde dehydrogenase deficiency called Sjorgen Larsson Syndrome. Rather than just a mild malfunction or an environmental overload, the person is not capable of producing fatty AD. This leads to mental retardation, vision problems, illness due to a compromised immune system and stunted growth.

So none of us are at that end of the scale obviously but it seems that other mutations of the gene affecting the creation of this important enzyme are possible and that they may not be that problematic until some environmental factor changes and aldehyde increases. Only some of these can be detected by 23andme genetic testing. I already checked :)

You can't stop producing acetaldehyde but you can give your body less to deal with if you reduce your exposure to smoke and alcohol. Taking in more medium chain triglycerides (e.g. coconut oil) might be useful too as this is a different mechanism for fuelling cells than burning glucose. It may reduce acetaldehyde load.
It seems you might also be able to improve the efficiency of breaking down acetaldehyde using supplements that work with the enzymes that break it down - Acetaldehyde Dehydrogenase.

For example, methionine and the coenzyme Nicotinamide adenine dinucleotide (also known as NADH). Your body can make the latter from niacin but NADH is more efficient it seems. Both of those should help clear acetaldehyde and related compounds.
I took some NADH this morning. A very small amount but it appears to provide significant amounts of energy. I'll keep taking it for the rest of the week along with my favourite eye medication / nootropic and see how I get on.

You could get a similar effect by taking a good slow release niacinamide (which is cheaper) every day and methionine every 2nd day. The total cost of the experiment would only be a few dollars. An effective dose of NADH isn't that expensive itself.

kurtosis

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Re: Dopamine
« Reply #10 on: October 12, 2012, 04:19:58 AM »
So I took NADH and piracetam yesterday. I had an O last night and then another. Just curious. Almost no POIS. I woke up this morning and had more ideas about this theory and why it might fit. So I'm laying these out as a kind of questions and answers section.

It is just a hypothesis but one I'm becoming increasingly excited about as you can see.

What is this acetaldehyde stuff?
Acetaldehyde (systematically ethanal) is an organic chemical compound with the formula CH3 CHO, sometimes abbreviated by chemists as MeCHO (Me = methyl). It is one of the most important aldehydes, occurring widely in nature and being produced on a large scale industrially. Acetaldehyde occurs naturally in coffee, bread, and ripe fruit, and is produced by plants as part of their normal metabolism. It is also produced by oxidation of ethylene and is popularly believed to be a cause of hangovers from alcohol consumption Pathways of exposure include air, water, land or groundwater as well as drink and smoke.

So this stuff is everywhere, how could it be harmful?
Most of us are familiar with other aldehydes but we don't recognise them as such. Think "Formaldehyde" and you'll realise that you're already aware of a toxic yet relatively common substance.

Acetaldehyde is toxic when applied externally for prolonged periods, an irritant, and a probable carcinogen. It is an air pollutant resulting from combustion, such as automotive exhaust and tobacco smoke. It is also created by thermal degradation of polymers in the plastics processing industry. Acetaldehyde naturally breaks down in the human body but has been shown to excrete in urine of rats

Acetaldehyde is an irritant of the skin, eyes, mucous membranes, throat and respiratory tract. Symptoms of exposure to this compound include nausea, vomiting, headache. These symptoms may not happen immediately. It has a general narcotic action and large doses can even cause death by respiratory paralysis. It may also cause drowsiness, delirium, hallucinations and loss of intelligence. Exposure may also cause severe damage to the mouth, throat and stomach; accumulation of fluid in the lungs, chronic respiratory disease, kidney and liver damage, throat irritation, dizziness, reddening and swelling of the skin.

Surely our bodies can deal with this? Otherwise we'd be sick all the time
Yes, the quote did say it breaks down in the human body but the degree of efficiency of this breakdown is the key point. Also objectively 1) We are sick all the time and 2) due to a several possible genetic defects of the gene that breaks down acetaldehyde in the body, there is an increasing amount of people who cannot efficiently break it down.

I'm intolerant to alcohol and have POIS, does this offer an explanation as to why?
Yes. Consuming alcohol increases the amount of acetaldehyde that the body has to clear.

I'm not intolerant to alcohol
Perhaps but you have POIS symptoms and you don't know where they came from! Acetaldehyde buildup contributes to hangovers. POIS would in affect be like another hangover but caused by a latent acetaldehyde disposal problem in your body that is exacerbated when you release lots of neurotransmitters at once. This happens when we're stressed and when we have an O.

I have allergies, does this explain that?
Yes. One of the noticed symptoms of acetaldehyde poisoning is a compromised immune system. The body will actually to attack its own cells that acetaldehyde binds to. This is a problem as it's everywhere so it may give rise to fatigue like symptoms and allergies throughout the body.

I get POIS symptoms when I exercise, does this explain that?
YES. Exercising increases the load of acetaldehyde as it's produced as a byproduct of energy consumption in cells. 
There is another group of people who get bad symptoms when they exercise and they have Chronic Fatigue Syndrome. The 2 things may be related.
To reduce your acetaldehyde load during exercise you should try to get Medium Chain Triglycerides instead of sugars. Coconut oil is a good example but there are others. I've been putting coconut oil in my whey (B_Daniel is probably fed up of me telling him about coconut oil) :) and it definitely increases stamina.


Why does niacin work?
Simply, Niacin and Niacinamide are used to make NAD which is a coenzyme used by the body to turn acetaldehyde's into non-toxic substances.
These are combined with acetaldehyde dehydrogenase to make acetaldehyde into safe acetic acid (vinegar). Some researchers have shown that supplementary niacinamide (or precursors) or indeed its related metabolised enzyme (NADH) can improve the efficiency of acetaldehyde clearance in people who have a genetic problem producing "correct" acetaldehyde dehydrogenase (the enzyme that breaks the nasty stuff down)

Why might niacin not be working for me?
You may not be taking enough. If POIS is related to aldehyde poisoning then it is an ongoing problem that is only exacerbated by the chemical cascade following an O. The problem would always exist and you'd need to take niacin or niacinamide every single day. Quantities of at least 200mg / day of niacin depending on age and the severity of POIS, at least until symptoms improve. Niacinamide may be a better option as it can be bought in time release form.

What else might be useful to help treat this
Vitamin C and methionine taken every day with the niacinamide. Coconut oil or exercise supplements which are low in sugar and high in MCT's.
If you had lots of money or severe impatience you could try the most efficient forms of niacin and methionine for turning these toxins into safe compounds. These are SAM-e and NADH. However, even if they were 100% effective it would take some time to start feeling really good.

But B vitamins make me sick
No they don't. B vitamins are necessary BUT if you have acetaldehyde poisoning then some b vitamins will actually make you sicker until enough of the acetaldehyde is cleared from your body. In particularly B1 would be a disaster. You might feel initially better as it will combine with acetaldehyde and reduce the acetaldehyde load but it produces another toxic substance. The same for Betacarotene See http://www.ncbi.nlm.nih.gov/pubmed/11468125
Vitamin A is also off the list. Treatment using anti-acne medication which contains vitamin A derivatives would be terrible for acetaldehyde poisoning.

B-complexes may work for some people but only if they got enough supplementary niacin and methionine first to reduce the acetaldehyde load.
By the way, this is a known phenomenon. People sometimes recommend taking a b vitamin tablet after a hangover but what you need are b6, b3 and b12. Taking thiamin and betacarotene to cure a hangover just makes it worse!

So there's stuff I should avoid also
Yes, betacarotene and vegetables that contain it. Thiamin in b supplements. Smoking cigarettes. Smoking marajuana which has even more of the nasty stuff and drinking alcohol. Avoid getting lots of sugar. Also, make sure you don't have a yeast infection as this could be producing alcohol inside your body. Some new office environments are full of it and there's little that can be done about that except trying to get outside into the hopefully less polluted air for a walk every now and again. There's no way not to be exposed to acetaldehyde so all you can do is responsibly reduce the amount of acetaldehyde you're contributing with lifestyle decisions.

You've said this is genetic but POIS just happened to me. I wasn't born with it
Yes but defects in acetaldehyde dehydrogenase are recessive AND the amount of external acetaldehyde we're exposed to on a daily basis has increased MASSIVELY in the past 50 years. It's in so many different things (including modern office furniture) and all on the assumption that people can break it down easily into a harmless substance. There is no point getting paranoid about this. It's entirely possible that, if this is the problem, we could clear it effectively using niacinamide and methionine.

From Wikipedia http://en.wikipedia.org/wiki/Acetaldehyde
Quote
Although a relatively weak sensory irritant, acetaldehyde is a common contaminant in workplace, indoor, and ambient environments. It is also a potential carcinogen. Moreover, we spend more than 90% of our time in indoor environments, hence increasing any exposure and consequently the risk to human health.[22]
In a study in France the mean indoor concentration of acetaldehydes measured in 16 homes was approximately seven times higher than the outside acetaldehyde concentration. The living room had a mean of 18.1?17.5 μg m−3 and the bedroom was 18.2?16.9 μg m−3, whereas the outdoor air had a mean concentration of 2.3?2.6 μg m−3.
It has been concluded that VOCs such as benzene, formaldehyde, acetaldehyde, toluene and xylenes have to be considered as priority pollutants with respect to their health effects. It has been pointed that in renovated or completely new buildings, the VOCs concentration levels are often several orders of magnitude higher. The main sources of acetaldehydes in homes include building materials, laminate, linoleum, wooden varnished, and cork/pine flooring. It is also found in plastic water-based and matt emulsion paints, in wood ceilings, and wooden, particle-board, plywood, pine wood, and chipboard furniture.[23]

I have some symptoms of pellagra, does this explain that?
Yes, because the body uses b3 in the detoxifying reaction with acetaldehyde dehydrogenase in greater amounts to achieve the same or less effect. You'd need supplementary b3.

This is different to the kurtosis method, why should I believe you?
All these ingredients were in the kurtosis method together with herbs that have a neuroprotective effect. However, I was also taking piracetam for my eye wobble / nystagmus. In tests on rats, piracetam reduces the effects of acetaldehyde on brain cells. The racetams seem to be able to help brain cells live longer and function better while under significant acetaldehyde load. In someone without acetaldehyde poisoning, this improves the effectiveness of their dopaminergic system as it can fire faster and better under the buildup of toxic DOPAL produced by "thinking" :) So the racetams actually help protect brain cells from damage by acetaldehyde and,hence, have been prescribed to alcoholics to help them recover their mental faculties. Incidentally, nystagmus shows up in alcoholics. The ophthalmologist was surprised I had it despite not drinking anything or taking any dopaminergic drugs. This should have been a clue to me.

This piracetam stuff sounds good, where can I get some?
Piracetam was the first nootropic yet it is remarkably safe. This is not my opinion, there is literally decades of research to back this up. Once it went out of patent it was widely available on the Internet and was fabricated by companies ranging from very reputable health food organisations with their own testing and manufacturing facilities to guys in basement labs. Despite the variety of production methods, there is not a single case of someone dying by taking piracetam. It is particularly useful in preventing or delaying the death of neurons due to external toxins, including alcohol and acetaldehyde. Many many white mice and rats have been killed to prove this is the case and there have been human studies also. There are more powerful derivatives of piracetam out there.
However, this stuff makes people smarter. Not massively smarter but it does improve memory and enhances creativity. So, it has effectively become a controlled substance. Some colleges have banned it and describe it as academic doping.

Think about it. A safe substance that makes people smarter and more creative with no damaging side effects (modest level of blood thinning) and governments are going out of their way to ban it? Yet you can get drunk and damage your brain in almost every country in the world. OK, that's my political speech done with. I'm leaving politics now ! I'm just trying to raise awareness of one of the dumbest decisions the FDA has ever made and all the dumb politicians and lobbyists in the way. In no way can Piracetam be compared to Marajuana but you get headlines like this..
http://phys.org/news173560595.html
This stuff is so cheap and safe, it should be available to everyone in which case it would help people remain smarter for longer.

OK done with politics moving on :D

If you want some you have to be prescribed it by a medical doctor. Up until recently I had to buy it online from a company that officially wasn't producing the stuff. Now I have a prescription and can pay more than 3 times the amount for stuff that is exactly the same (I had it analysed in a lab).

However, even if you can't get piracetam, you can definitely get extra b3 and methionine and you could definitely try not drinking for a week or so. The racetams are good but the energy boost from NADH was astonishing yesterday and seems just as wild today.

Ccconfucius

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Re: Dopamine
« Reply #11 on: October 12, 2012, 10:27:15 AM »
kurtosis have you been using piracetam with your  method. Piracetam works for you, it didnt do anything for me, it can skew the results of your method.
« Last Edit: October 12, 2012, 10:48:04 AM by CertainlyPOIS »

kurtosis

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Re: Dopamine
« Reply #12 on: October 12, 2012, 12:22:45 PM »
kurtosis have you been using piracetam with your  method. Piracetam works for you, it didnt do anything for me, it can skew the results of your method.

Only intermittently. Yes I'm aware it can skew the method. I bought lots of the stuff in powdered form at the end of last year and found it worked intermittently. I also wasn't sure whether it was working at all. However, I was only taking it around an O and rarely. Mostly I was just taking the stuff I described in the kurtosis method. The ingredients changed every now and again.. Like I'd take methionine and p5p at night instead of ZMA  - Zinc Methionine Aspartate & Magnesium Methionine Aspartate (which are quite similar)

 A few weeks back I noticed it improved the eye wobble and started taking it more often. I talked to my doctor about getting prescribed it for nystagmus as I read it could be used to treat that. The eye doctor was quite interested and wondered if this would be applicable to other patients. I was advised I wasn't taking enough and that the studies on using it to treat jerks, involuntary eye movements etc. required a longer time period and more of the drug.  I now take at least 2g a day (1 800 and 1 1200 mg). I've been doing this for 2 weeks and I had been taking about 1.5g / day of the online powdered stuff for the previous 2 weeks. This is the first time I've taken it consistently in decent dosages. Contrary to what I'd read on many forums, the effect for me is getting better with repeated use. I may be able to move to ampanet (aniracetam) and take less.

CP, I said in the past that I found the effects of piracetam interesting but not compelling. I've changed my mind. With repeated and consistent use and with additional niacinamide and b6, it seems to be much better. The other thing I was doing was I was using a Soya choline source. From what I've read about acetaldehyde poisoning  this was a big mistake and may have actually reduced the effect of the piracetam for me.  I have very little soy in my diet now and no fermented soy products. This appears to have been a good move.

It's a pity as I really like chinese food but I think the dogma that piracetam and choline must be taken together is largely a myth based on 2 studies showing choline depletion in rats when given an extraordinary amount of piracetam / kg and one showing that other rats were smarter when given choline & piracetam together. I don't think it's as easy as saying 1+1=2 and, for me, it appears that choline supplementation was a mistake. I felt a bit weird in the first few days of large dose piracetam but I've adjusted. One of its affects is repairing (improving sensitivity) of acetyl choline receptors in the frontal cortex. This could take weeks of continued use to achieve. This stuff is marketed by some online retailers like it's the pill from the movie limitless but it's nothing like that. Slow, subtle changes that sort of creep up on you.

So I now have at least 2g of piracetam / day and no lecithin / soy-derived choline and it's working much better.
I can still take ginkgo and I can take niacinamide and methionine. No contra-indications.

If you have some piracetam and it's not out of date then I suggest trying it again at reasonable dosages every day. Take it with niacin or a decent amount of niacinamide (a few hundred mg) and see what happens.

B_Daniel

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Re: Dopamine
« Reply #13 on: October 13, 2012, 03:09:19 PM »
A few thoughts in response to all the posts above.

1.  I posted my Neurotransmitter labwork on NSF, if you care to check it out.  Habibou's is also posted just above mine.
2.  Kurtosis, I'm always confused when you say NE.  We've used it on the forums for so long to abbreviate Night Emission, that I keep forgetting it can also mean NonEpi
3.  If our ALDH was low, then our faces would turn red with alcohol consumption.  That's not the case, so I tend to not think that's the problem.
4.  Wellbutrin is one of the only medications that has ever helped me consistently.  It doesn't make me 100% better, so I don't think it touches upon the exact neurotransmitter that I'm struggling with.  But it's likely hitting upon something immediately upstream or downstream from my problem because it makes me feel significantly better.  The morning after taking it, I wake up with ease.  Looks like my experience is completely contrary to yours, Nightingale.  I only take mine for 2 days on, then 2 days off, because once it builds up in my system it stops working for some reason.   I take the 150mg XL dosage.
« Last Edit: October 13, 2012, 03:17:02 PM by B_Daniel »

B_Daniel

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Re: Dopamine
« Reply #14 on: October 13, 2012, 03:20:27 PM »
good picture i found to show the pathways that are being discussed about throughout this thread

B_Daniel

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Re: Dopamine
« Reply #15 on: October 13, 2012, 03:38:08 PM »
There is a drug disulfiram (also known as antabuse) which has been used for more than 50yrs in the treatment of alcoholism.  Disulfiram inhibits ALDH, which results in the accumulation of acetaldehde on ethanol ingestion.    This toxic metabolite produces aversive symptoms sums as flushing, nausea, vomiting, etc.

Basically, disulfiram inhibits ALDH, resulting in Asian Flush when you drink alcohol - so some alcoholics take it to help them resist the urge of drinking.  It's kinda like putting on that bad tasting nailpolish so you wont bite your fingernails.

Anyway, if your theory were accurate Kurtosis, wouldn't Disulfiram make us feel significantly WORSE?  Isn't that an easy way to check it?   I might be able to ask my doctor to write me a prescription to try it. 

Daveman

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Re: Dopamine
« Reply #16 on: October 13, 2012, 03:58:31 PM »
A few thoughts in response to all the posts above.

1.  I posted my Neurotransmitter labwork on NSF, if you care to check it out.  Habibou's is also posted just above mine.
2.  Kurtosis, I'm always confused when you say NE.  We've used it on the forums for so long to abbreviate Night Emission, that I keep forgetting it can also mean NonEpi
3.  If our ALDH was low, then our faces would turn red with alcohol consumption.  That's not the case, so I tend to not think that's the problem.
4.  Wellbutrin is one of the only medications that has ever helped me consistently.  It doesn't make me 100% better, so I don't think it touches upon the exact neurotransmitter that I'm struggling with.  But it's likely hitting upon something immediately upstream or downstream from my problem because it makes me feel significantly better.  The morning after taking it, I wake up with ease.  Looks like my experience is completely contrary to yours, Nightingale.  I only take mine for 2 days on, then 2 days off, because once it builds up in my system it stops working for some reason.   I take the 150mg XL dosage.

Can you post them over here?

That thread is hostile toward our promotion of research, and the more people that stay over there the less we ACTUALLY advance.

As I said before, even IF we find an outright cure, that ONLY cures those who share the given forums. MOST of the POIS sufferers (2, 3 10 times our numbers and MORE) go to doctors who don't have a clue.

Research can change that! It will clue the doctors in.

CARE about POIS sufferers around the world. not just us here! Donate to research.
WITHOUT RESEARCH THERE WILL BE NO CURE!
Sessions 5 to 9 days, mostly Flu-like, joints, digestion problems, light cognitive.
Niacin has changed my lif though, now 1 day MAX.
Somewhere in this interaction with Niacin is the answer!

B_Daniel

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Re: Dopamine
« Reply #17 on: October 13, 2012, 06:13:35 PM »
Neurotransmitter test results.

kurtosis

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Re: Dopamine
« Reply #18 on: October 13, 2012, 06:30:18 PM »
A few thoughts in response to all the posts above.

1.  I posted my Neurotransmitter labwork on NSF, if you care to check it out.  Habibou's is also posted just above mine.
2.  Kurtosis, I'm always confused when you say NE.  We've used it on the forums for so long to abbreviate Night Emission, that I keep forgetting it can also mean NonEpi
3.  If our ALDH was low, then our faces would turn red with alcohol consumption.  That's not the case, so I tend to not think that's the problem.
4.  Wellbutrin is one of the only medications that has ever helped me consistently.  It doesn't make me 100% better, so I don't think it touches upon the exact neurotransmitter that I'm struggling with.  But it's likely hitting upon something immediately upstream or downstream from my problem because it makes me feel significantly better.  The morning after taking it, I wake up with ease.  Looks like my experience is completely contrary to yours, Nightingale.  I only take mine for 2 days on, then 2 days off, because once it builds up in my system it stops working for some reason.   I take the 150mg XL dosage.

2) OK, I say NE for norepinephrine as it takes less time to type :)

In response to 3), not true. There a multiple genes that control synthesis of ALDH. http://ghr.nlm.nih.gov/geneFamily/aldh

I can't drink myself. I get a bad skin reaction when I drink beer and I'll feel sick for a few days after I drink. However, the red face modification to the ALDH2 gene is one of the few that's readily testable. 23andme can test it for instance.

There are all kinds of modifications possible and only some are associated with diagnosed conditions (e.g. the ALDH2 disease you mention). It's impossible to rule out POIS as an ALDH gene mutation without doing extensive genetic testing on POIS sufferers. Some may have one mutation, others may have more. That's not as much a stretch as it sounds and may explain why POIS appears so rare.

This also means that, while someone being intolerant to alcohol including red face reactions or getting drunk very quickly, would only be indicative that they have one particular ALDH gene mutation. Other reactions are possible such as bad hangovers, stomach upsets continuing for a while after alcohol consumption and brain fog etc. What POIS sufferer can say that never happens to them considering the litany of problems associated with POIS?

It is correct that if the theory is correct then continuing to take disulfam over a few weeks should make the POIS sufferer sicker and exacerbate their symptoms of anxiety, brain fog, fatigue etc. Disulfam has been shown to block metabolism of DOPAL (or at least that's what I've read, I'll check).
If you'd like to try it and not take any niacin or other supplements that may counteract it then go ahead but it seems like it could be a very rough few weeks...
Counteracting supplements include anything that reduces inflammation, stimulates NGF or helps protect neurons in anyway. So pregnenolone, DHEA and testosterone are out also.

Re. 4, This would explain why wellbutrin works intermittently for you. The presence of dopamine metabolites that are uncleared in neurons would reduce those neurone's ability to use dopamine. Wellbutrin would increase the amount of circulating dopamine and would stimulate more dopaminergic neurons into functioning. However, that would just increase the amount of uncleared DOPAL in the brain as a whole and make you sick every few days.
As you know, DOPAL clears to DOPAC.

It would also explain why "the kurtosis regime" worked for Jon for a while and eventually made him feel sicker. It didn't have that effect on me and I think it may be because I occasionally took piracetam and or pregnenolone (which is neuroprotective) and because I've been taking niacin and methionine in other supplements for so long. I'd take the piracetam on rare days when my eyes got really bad but what if that was because of DOPAL buildup & I was actually medicating POIS.

This toxic DOPAL idea is the key theory from Dr Panneton's work anyway. He believes that the dopamine boosting medication given to sufferers with MS and Parkinsons actually makes them sicker in the long term. He's not the only one. Dr Birkmayer who discovered that NADH may have potential to treat alzheimers and parkinson's found that the patients that responded worst to NADH were those that had been treated with external DOPA medication for a longer time.
This is a really controversial idea. There's billions being made on drugs to treat Parkinson's that some scientists are now suggesting might be ultimately making patients sicker. Don't expect too many doctors to go along with this.

Put together, his and Panneton's work suggests that raising dopamine artificially is a bad idea and that clearing dopamine metabolites to DOPAC using supplementation would give the best results. What if POIS is similar?

All ALDH which is synthesised will need an NAD (essentially Niacinamide) to reduce aldehydes to safe metabolites. So even if you don't have an obvious alcohol metabolism problem, there'd be less NAD for use by the less efficient ALDH pathway resulting from whatever mutation you had. So treating POIS would be about helping the clearing process through supplementation and reducing aldehyde load on the body.

All I'm suggesting is niacinamide, methionine and not drinking alcohol for a while to see if it reduces POIS.
I mentioned NADH and there's some interesting literature out there about it being used to help treat parkinson's. It's also worth remembering that despite years of research, the cause of Parkinson's is still unknown. It is only treated, not cured.

Daveman, I'm not against research at all. But I've got to be honest here. I don't think POIS is caused by allergy. I think that the underlying cause of POIS causes multiple allergies. I've got a few. The allergist I'm seeing is dubious symptoms are being caused by one allergy.
If POIS is caused by an ALDH mutations (and there are multiple mutations possible with individual sufferers having 1 or more) then the best doctors to contact would be neurologists who are involved in treating parkinsons and alzheimers.

I'm very fearful that POIS is not an allergic condition but part of a family of neuro-degenerative disorders caused by cellular energy dysfunctions. (e.g. like Parkinsons) but that the symptoms are most obvious when we have an O and dump a crap load of dopamine into our neurons which cannot be effectively metabolised.
You yourself are using niacin at high dosages to treat it and are suffering from few symptoms. We may be on to something here...

kurtosis

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Re: Dopamine
« Reply #19 on: October 13, 2012, 06:47:14 PM »
There is a drug disulfiram (also known as antabuse) which has been used for more than 50yrs in the treatment of alcoholism.  Disulfiram inhibits ALDH, which results in the accumulation of acetaldehde on ethanol ingestion.    This toxic metabolite produces aversive symptoms sums as flushing, nausea, vomiting, etc.

Basically, disulfiram inhibits ALDH, resulting in Asian Flush when you drink alcohol - so some alcoholics take it to help them resist the urge of drinking.  It's kinda like putting on that bad tasting nailpolish so you wont bite your fingernails.

Anyway, if your theory were accurate Kurtosis, wouldn't Disulfiram make us feel significantly WORSE?  Isn't that an easy way to check it?   I might be able to ask my doctor to write me a prescription to try it. 

Yes, Disulfiram blocks DOPAL to DOPAC metabolism.
http://www.ncbi.nlm.nih.gov/pubmed/15019299
If your doctor sees you already have low DOPAC and goes along with prescribing you disulfiram as part of a hypothesis test, they'd want to monitor it closely. At least I hope they would. With no other medication to counteract it, it could make you feel awful.
Also, it takes a while to clear your system so you could continue to feel awful for a few days after you stopped.