Common Pathways of Abused Substances; All Lead to Dopamine

There is an excellent diagram in Nature Neuroscience that shows how the various drugs of abuse share a common pathway, usually starting in the ventral tegmental area and progressing to the dopamine neurons in the nucleus accumbens.

This highly technical article accentuates the point that all substances of abuse increase dopamine, remove pain and promote pleasure. The PURSOR protocol also increases dopamine but rather than increasing it very rapidly, does it relatively slowly, seconds vs. milliseconds. PURSOR relieves the psychic pains of low dopamine but provides no rush of pleasure. It therefore is not addictive.

Introduction to Immune disorders and their treatment with PURSOR

GLOSSARY

In my opinion, the neurotransmitters dopamine (DA) and serotonin (5-HT) are the primary regulators of life. These two similar substances control in a reciprocal fashion not only human beings but also all other animal species. More than two millennia ago both the Chinese and the Greeks recognized that "balance is health; imbalance is illness and pain." In summary, DA greatly resembles the Yang and 5-HT the Yin. Western medicine started to recognize this antipodal action in 1957.

Multiple articles in the current medical literature discuss imbalance in the T helper cells. T helper cells are simplistically divided into two major divisions, Th1 and Th2 cells. Harvard's Dr. Kimball summarizes this far better than I can. I would strongly recommend this link. Let's focus on the two major components.

• The cellular immune system (Th1 driven, Th2 opposes) (increased by DA, suppressed by 5-HT) goes to work when it senses a foreign cell threatening our well-being. These foreign cells can arise from the outside, from viruses and bacteria whose survival inside our body is at the expense of our health or even our survival. This cellular system can also be activated to fight our own cells that have mutated and threaten us with cancer and similar diseases.

• The humoral system (Th2 driven, Th1 opposes) (increased by 5-HT, suppressed by DA)   becomes activated when it senses that there are foreign proteins threatening to overwhelm us. The humoral system produce antibodies that can safely engulf these foreign chemicals and dispose of them safely.

Interestingly enough, each system controls the other. The cellular system reins in the humoral and the humoral keeps the cellular in control. Th1 suppresses Th2 and Th2 suppresses Th1

Unfortunately, when we are diseased, one or the other system can break out of control and start to overact. If the cellular system excessively dominates, doing its job too well, It starts to attack our own good cells and autoimmune diseases such as lupus, rheumatoid arthritis, psoriasis and Lyme disease ravage our bodies. In the brain, the cellular system running amok can cause neurodegenerative conditions such as Lou Gehrig/s disease or multiple sclerosis that rot our brain and spinal cord.. This is Th1 excess.

Th2 excess conditions, when the humoral system is too vigilant and the body reacts to unimportant levels of foreign protein, are allergic in nature. Asthma, allergic shock, hives and food allergies can cause us woe.Th2 excess.

By the year 2002 there had been already 200 patent applications to bring such imbalances under control. Those folks were looking to create a harmonious equality of the humoral and cellular immune systems or, in fancy terms, a Th1/Th2 balance. The treatments covered in these patent applications shared, in most cases, three qualities. They were toxic, expensive, and ineffectual.

Fortunately, It is apparent when one reads the medical literature that brain dopamine and serotonin controls the Th1/Th2 ratio and can restore it to balance.

• Dopamine increases TH1 and controls Th2 
• Serotonin increases Th2 and diminishes Th1. 

Why not, you may ask, don't we correct the Th1/Th2 imbalance and remit illness by increasing the brain levels of dopamine and serotonin?

The administration of the PURSOR protocol which permits our own brain to bring dopamine and serotonin into balance permits us to control either immune system that is overeager and bring us into balance. It is not surprising that when we bring the Th1 and Th2 under control that autoimmune, neurodegenerative, and allergic conditions can remit and stay away as long as the treatment is given.

Immunodeficient conditions are a bit, just a bit, more complicated. In such conditions both the cellular and humoral systems are damaged. I believe, however, with the restoration of proper dopamine and serotonin levels, these conditions  will also improve. I have seen a phenomenal success with an AIDS patient, but that is another story.

Technical section below. Click on title to get full text.

The Restoration of ImmuneTh1/Th2 Balance with Combined Dopamine and Serotonin Agonists

Pietr Hitzig, M.D.
phitz96@gmail.com 
443 231-6240

The YIN YANG (DA/5-HT) duality

the Monoamines Dopamine and Serotonin are Antipodal in Nature.

Yin (陰 or 阴 "shady place, north slope, south bank (river); cloudy, overcast"; Japanese: in or on; Korean: 음, Vietnamese: âm) qualities are characterized as soft, slow, substantial, water, cold, conserving, tranquil, gentle, and corresponds to the night.

Yang (陽 or 阳 "sunny place, south slope, north bank (river), sunshine"; Japanese: yō; Korean: 양, Vietnamese: dương) qualities are characterized as hot, fire, restless, hard, dry, excitement, non-substantial, rapidity, and corresponds to the day.

Dopamine is Yang while Serotonin is Yin

DA and 5-HT have been antipodal in their activities for more than a billion years. Here, for example, the prostostomes, who according to Dawkins, went their particular way and parted from us 500M years ago are using the monoamines to decide whether to move or not.

The effect of dopamine on [snail] command neurons is significantly reduced in the presence of serotonin. In the presence of dopamine, the efficacy of serotonin action on the size of the response elicited in command neurons is reduced. Based on the data obtained, it was concluded that the interrelation of dopamine and serotonin concentrations could be the basis for the formation of behavioral choice in snails

Dopamine is the Reward Neurotransmitter

When the cortex has received and processed a sensory stimulus indicating a reward, it sends a signal announcing this reward to a particular part of the midbrain–the ventral tegmental area (VTA)–whose activity then increases. The VTA then releases dopamine not only into the nucleus accumbens, but also into the septum, the amygdala, and the prefrontal cortex.The nucleus accumbens then activates the individual’s motor functions, while the prefrontal cortex focuses his or her attention.
These regions are connected by what is called the pleasure or reward bundle. In neuroanatomical terms, this bundle is part of the medial forebrain bundle (MFB), whose activation leads to the repetition of the gratifying action to strengthen the associated pathways in the brain.
First described by James Olds and Peter Milner in the early 1960s, the MFB is a bundle of axons that originates in the reticular formation, crosses the ventral tegmental area, passes through the lateral hypothalamus, and continues into the nucleus accumbens as well as the amygdala, the septum, and the prefrontal cortex.
The MFB is composed of ascending and descending pathways, including most of the pathways that use monoamines as a neurotransmitter. The mesocorticolimbic dopaminergic system is one of its main components.

But Serotonin inhibits Reward and Stops Excessive Behavior

Serotonin plays a major role in the behavioural inhibition system (BIS).

This system was identified by Henri Laborit in the early 1970s. It is associated with the septo-hippocampal system, the amygdala, and the basal nuclei. It receives inputs from the prefrontal cortex and transmits its outputs via the noradrenergic fibres of the locus coeruleus and the serotininergic fibres of the medial Raphe nuclei.
The BIS is activated when both fight and flight seem impossible and the only remaining behavioural option is to submit passively. The pathological consequences of this behavioural inhibition have provided an understanding of how destructive chronic stress can be to people’s health.

Substantial evidence suggests that the functional status of the mesocorticolimbic dopamine (DA) system originating in the ventral tegmental area is under a phasic and tonic inhibitory control by the 5-HT system that acts by stimulating 5-HT(2C) receptor subtypes. Serotonin within the nucleus accumbens may play an important role in mediating incentive motivation by modulating dopaminergic neurotransmission.

Several hypotheses regarding physiopathology of major psychiatric diseases exist. Attention has been focused on cerebral monoaminergic systems, the dysfunction of which is thought to underlie various aspects of their symptomatology. There are reports describing the involvement of serotonergic and dopaminergic systems in the mechanism of action of psychotropic drugs. This article reviews current knowledge on interaction between 5-hydroxytryptamine (5-HT), acting at 5-HT2C receptors in the central dopamine (DA) systems. Since 90s, a growing body of behavioural, neurochemical and electrophysiological evidence from animal studies have demonstrated a clear role for 5-HT2C receptors in modulation of activity of dopamine neurones.

The blockade of serotonin receptors potentiates behavioral effects of dopamine agonists. It is concluded that central serotonin may play an inhibitory role, antagonistic to that of catecholamines

Increasing 5-HT activity in the nucleus accumbens inhibits dopamine-dependent behaviour, and further indicate that activation of 5-HT(1B) receptors is particularly important in this regard

T helper cell I and II Duality of the Immune System are under the Control of Dopamine and Serotonin

Devoino wrote seminal articles in the early 1980s that dealt with the monoamines regulation of the immune system. She wrote prior to the discovery of the T helper cell and its differentiation into Th1 and Th2 subsets. However, interpolating her articles forward she was clearly stating that DA promotes Th1 and suppresses Th2 cytokines and serotonin does the converse. She wrote in 1984:

The monoamine systems take part in the mechanisms of immunomodulation: the dopaminergic one accelerates and the serotoninergic system inhibits the development of immune response, the final result being determined by their interaction.

The combined use of a combined dopamine and serotonin agonist protocol (CODAS) such as PURSOR can titrate DA and serotonin into sufficiency and balance and remit addictive craving and immune disorders.

Does depression decrease cholesterol? Apparently

In the CODAS model, depression is associated with a decrease in DA/5-HT. One would, therefore, postulate that depression would be associated with decreased cholesterol.

Biochemical markers of anxiety and depression

The results of research into a biochemical marker for depression are presented. The research was carried out on a normal population in a primary care setting. Cholesterol levels were identified as the blood marker for anxiety and depression. The Hamilton Rating Scale for Depression was chosen to identify depression. Those with low cholesterol scored significantly higher on the Hamilton Rating Scale for Depression