Dopamine documents

[b_jim]

I will post here some documents about dopamine. I suspect dopamine to be an important element in Pois symptoms.

1/ What is dopamine ?
(very basic)

Dopamine is a neurotransmitter.
Nervous system works by 2 ways :
- "electric wires" (dendrites and axons)
- chemical messangers to pass "bridges" (synapses).
These messangers are called neurotransmitters.

There are many neurotransmitters. Some of them are excitative (like dopamine) and some others sedative depending if they increase or decrease nervous system acitivity.

2/ Dopamine linked to pois ?

Since the start dopamine has be suspected to be linked to Pois symptoms like mental confusion or muscular weakness.

Orgasm : during orgasm, lot of neurotransmitters and hormones are released, like dopamine.

Ejaculation : human semen is rich in catecholamines (dopamine-like molecule) .
https://www.ncbi.nlm.nih.gov/pubmed/11736795

=> We suspect dopamine levels to have abnormal fluctuations after ejaculation !

3/ Let's compare Pois cognitive symptoms to symptoms of low dopamine after specific anti-dopamine drug

from : Subjective Experiences During Dopamine Depletion (2005)

After 7 hours, Mr. A felt more distance between himself and his environment. Stimuli had less impact; visual and audible stimuli were less sharp. He experienced a loss of motivation and tiredness. After 18 hours, he had difficulty waking up and increasing tiredness; environmental stimuli seemed dull. He had less fluency of speech. After 20 hours, he felt confused. He felt tense before his appointment and had an urge to check his watch in an obsessive way.
After 24 hours, Mr. A had inner restlessness, flight of ideas; his ideas seemed inflicted, and he could not remember them. He felt a loss of control over his ideas. After 28 hours, he felt ashamed, frightened, anxious, and depressed. He was afraid that the situation would continue. At that time, blepharospasm, mask face, and tremor were noted. After 30 hours, he was tired and slept 11 hours. After 42 hours, he had poor concentration. In the next hours, he returned to normal.
The striatal-to-nonspecific binding ratio was 27% higher after Mr. A took AMPT compared to the baseline situation, indicating severe acute dopamine depletion (1).

3/ Dopamine and restless legs syndrome

A lack of dopamine is linked to restless legs syndrome :
https://www.ncbi.nlm.nih.gov/pubmed/17566122

The impressive relief from restless legs syndrome (RLS) symptoms provided by levodopa treatment indicates RLS is caused by a dopaminergic abnormality.

Some of us complain of restless legs syndrome after ejaculation. And maybe some symptoms like itchings finger tips pain ...etc could be explained by dopamine.

4/ 50% of the dopamine is released in the gut :

 

More than 90% of the body's serotonin lies in the gut, as well as about 50% of the body's dopamine, which is currently being studied to further our understanding of its utility in the brain.

Some of us complain about intestine problems after ejaculation.

[I have very very few time to write for the moment. I will update this topic very slowly ]

[demografx]

Excellent thread, b_jim!

[koko]

Excellent post. It's a shame that he neglected here and did not continue to discuss dopamine issue this is one of the reasons of pois

[dizzy]

Yes, interesting. In [1] it is noted that niacin helps break down dopamine (by increasing the activity of COMT). I'm wondering if that could be the reason that niacin is effective for a lot of people here?

[1] https://humansystemdebugging.blogspot.com/2013/11/new-potential-ha-niacin-sam-e-and.html

[Unvers]

I think that in my case is not dopamine the problem but opioids, dopamine is released also during masturbation or intercourse but if I don't orgasm I don't have POIS, instead in orgasm there is a release of endogenous opioids, I think that my POIS is a withdrawal syndrome from them which in turn cause a shortage of neurotrasmitters like dopamine.

[b_jim]

Yes, it's a good point of view.

[demografx]

I think that in my case is not dopamine the problem but opioids, dopamine is released also during masturbation or intercourse but if I don't orgasm I don't have POIS, instead in orgasm there is a release of endogenous opioids, I think that my POIS is a withdrawal syndrome from them which in turn cause a shortage of neurotrasmitters like dopamine.

Yes, it's a good point of view.

b_jim, I think you have been consistent about your point-of-view regarding dopamine for many years!

[b_jim]

Yes ! I will go to a PhD before the end of the year for my stomach/fats problems and i hope to have new elements to give

[dizzy]

So if POIS is a withdrawal symptom, would there be any other kind of cure besides a period of abstinence (e.g. nofap)?

[Muon]

Yes, interesting. In [1] it is noted that niacin helps break down dopamine (by increasing the activity of COMT). I'm wondering if that could be the reason that niacin is effective for a lot of people here?

[1] https://humansystemdebugging.blogspot.com/2013/11/new-potential-ha-niacin-sam-e-and.html

Good point.

Yes ! I will go to a PhD before the end of the year for my stomach/fats problems and i hope to have new elements to give

Can you show the results of this thread to that doctor while you are there?: http://poiscenter.com/forums/index.php?topic=2684.0
I don't know if that PhD is specialized in dopamine metabolism, but if so ask if Habibou's results could have something to do with catecholamine/dopamine metabolism defects, if possible.

[b_jim]

If i will have interresting new datas, i will give them, no problem

[Unvers]

So if POIS is a withdrawal symptom, would there be any other kind of cure besides a period of abstinence (e.g. nofap)?

I think that taking things used for opioids addicts like methadone would be foolish because of the side effects so I think abstinence is better, I use to smoke SSRI antidepressants with tobacco to have a temporary relief from POIS but now I think the body has tolerance of them and the effect is inferior.

[Unvers]

The dopamine has many receptors, just to give you an idea I post the pharmacodynamics of atypical antipsychotics:

The atypical antipsychotics integrate with the serotonin (5-HT), norepinephrine (α, β), and dopamine (D) receptors in order to effectively treat schizophrenia.

D2 Receptor: Hyperactive dopaminergic activity on D2 receptors in the mesolimbic pathway is responsible for the positive symptoms of schizophrenia (hallucinations, delusions, paranoia). After taking an antipsychotic, antagonism of D2 receptors occurs throughout the entire brain, leading to a number of deleterious side effects from D2 receptor antagonism throughout the entire dopamine pathway system. Unfortunately, it?s not possible to affect D2 receptors only in the mesolimbic pathway.[58][Stahl AP Explained 1 - 1] Fortunately, 5-HT2A receptor antagonism reverses these side effects to some extent.[Stahl AP Explained 1 - 2] Reducing D2 dopaminergic activity in the mesolimbic pathway also results in an anhedonic effect, reducing pleasure, motivation, and the salience of one?s life experience. In the mesocortical pathway to the DLPFC and VMPFC, endogenous D2 receptor dopamine activity is sometimes low in schizophrenia, resulting in cognitive, affective, and, broadly, the negative symptoms of schizophrenia. D2 receptor antagonism here further compounds these problems. In the nigrostratial pathway, D2 receptor antagonism results in extrapyramidal symptoms. If this antagonism occurs long enough, symptoms of EPS may become permanent, even if antipsychotic use is discontinued. In the tuberoinfundibular pathway, D2 receptor antagonism results in elevated prolactin. If prolactin levels become high enough, hyperprolactinaemia may occur, resulting in sexual dysfunction, weight gain, more rapid demineralization of bones, and possibly galactorrhea and amenorrhea.[Stahl AP Explained 1 - 1]

5-HT2A Receptor: When serotonin is released on to postsynaptic 5-HT2A receptors, the dopamine neuron is inhibited, thus acting as a brake on dopamine release.[Stahl AP Explained 1 - 2] This brake is disrupted through action of a 5-HT2A antagonist, which cuts the brake cable, disinhibiting the dopamine neuron, and stimulating dopamine release. The result of this is that dopamine competes with antipsychotic D2 antagonistic action at D2 receptors, thereby reducing antagonistic binding there and eliminating or lowering D2 antagonistic effects in several pathways of the dopamine system.[Stahl AP Explained 1 - 2] In the nigrostratial pathway, it reduces EPS. In the tuberoinfundibular pathway, it reduces or eliminates prolactin elevation.[Stahl AP Explained 1 - 3] Dopamine release in the mesolimbic pathway from 5-HT2A antagonism does not appear to be as robust as in the other pathways of the dopamine system, thereby accounting for why atypical antipsychotics still retain part of their efficacy against the positive symptoms of schizophrenia through their D2 antagonism.[Stahl AP Explained 1 - 3] When 5-HT2A antagonistic agent particles occupy 5-HT2A receptors in the mesocortical pathway and in the prefrontal cortex, the negative symptoms of schizophrenia, affective symptoms, and cognitive deficits and abnormalities are treated and reduced.[Stahl AP Explained 1 - 3] Furthermore, 5-HT2A receptor antagonism blocks the serotonergic excitation of cortical pyramidal cells, reducing glutamate release, which in turn lowers hyperactive dopaminergic D2 receptor activity in the mesolimbic pathway, reducing or eliminating the positive symptoms of schizophrenia.[Stahl AP Explained 1 - 3][59][60]

Some effects of 5-HT1A receptor activation include decreased aggressive behavior/ideation,[61] increased sociability, and decreased anxiety and depression.[non-primary source needed] 5-HT2C activation blocks dopamine and inhibits norepinephrine release. Blockade of the 5-HT2C receptor increases serotonin, releasing norepinephrine and dopamine within the brain.[58] But neuronal reuptake of norepinephrine is limited sharply by some antipsychotics, for example ziprasidone. Increased norepinephrine can cause increased glucose levels, which is to say blood sugar levels.[62][63][64] Increased blood sugar levels by increased norepinephrine causes hunger in many humans, which is why weight gain occurs with some antipsychotics if the norepinephrine is not inhibited.[65][66][67][68][69] Inhibition of norepinephrine stabilizes mood in humans.[70] 5-HT6 receptor antagonists improve cognition, learning, and memory.[71] The 5-HT7 receptor is very potent for the mitigation of bipolar conditions and also yields an antidepressant effect. The antipsychotics asenapine,[72] lurasidone,[73][74] risperidone,[75] and aripiprazole[76] are very potent at the 5-HT7 receptor. Antagonistic affinity for the H1 receptor also has an antidepressant effect. H1 antagonism blocks serotonin and norepinephrine reuptake. Patients with increased histamine levels have been observed to have lower serotonin levels.[77] However, the H1 receptor is linked to weight gain. To have partial agonism at the 5-HT1A receptor can yield absence of weight gain in an antipsychotic. This is very relevant for ziprasidone,[78][79] but it creates a risk for a prolonged QTc interval.[80][81] On the other hand, blockade of the 5-HT3 receptor removes the risk for a prolonged QTc interval,[73] but then creates a larger risk for weight gain. Relation to the 5-HT3 receptor increases caloric uptake and glucose,[82] which is seen in clozapine and olanzapine.[83][84] Other ways for dopamine to resolve is to have agonism at both the D2 receptor and 5-HT1A receptor, which normalizes the dopamine level in the brain. This occurs with haloperidol and aripiprazole.

Whether the anhedonic, loss of pleasure and motivation effect resulting from dopamine insufficiency or blockade at D2 receptors in the mesolimbic pathway, which is mediated in some part by antipsychotics (and despite dopamine release in the mesocortical pathway from 5-HT2A antagonism, which is seen in atypical antipsychotics), or the positive mood, mood stabilization, and cognitive improvement effect resulting from atypical antipsychotic serotonergic activity is greater for the overall quality of life effect of an atypical antipsychotic is a question that is variable between individual experience and the atypical antipsychotic(s) being used.[58]

Maybe the cognitive POIS result in a shortage of dopamine at the D2 receptors and in the prefrontal cortex where it cause impaired cognition and maybe brain fog while in the D2 cause anehdonia and loss of pleasure.

[b_jim]

Important study :
https://www.cell.com/trends/cognitive-sciences/fulltext/S1364-6613(19)30066-X

Inflammation decreases dopamine levels and it is a cause of lack of motivation feeling.

I think this is exactly what happens in Pois.

One side, dopamine is activated by orgasm, loss in semen.
And possible inflammation causes decreased synthesis.

If we can't avoid infllamatory mechanism afet ejaculation, we can make a stock of tyrosine and follow an anti inflammatory diet.

I've strated to take L-Tyrosine caps all mornings on an empty stomach.

[b_jim]

Damn, It seems diet can have a REAL influence on dopmine !?

Hyperkalemia and hyperdopaminemia induced by an obsessive eating of banana in an anorexia nervosa a

.dolescent

I DON'T recommand to eat 20 bananas a day. Potassium can be a POISON


https://www.sciencedirect.com/science/article/abs/pii/S0387760406002464

[drop247]

I've strated to take L-Tyrosine caps all mornings on an empty stomach.

How is the Tyrosine working for you?