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Dr Mariano posts - l dopa, dopamine

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by , 09-10-2012 at 05:32 PM (2428 Views)
http://www.definitivemind.com/forums...read.php?t=591


Velvet bean (Mucuna pruriens) is a tropical medicinal plant that is a member of the legume (bean) family. The bean of the plant contains a substantial amount of L-dopa, the precursor to dopamine (7-10% of the beans is L-dopa). Serotonin can be found in the bean pod, leaf and fruit. The bean contains numerous other substances which may be also active in affecting the nervous system. Because of these properties, I doubt it would be carried by Whole Foods.

Dopamine is one of the signals that can increase growth hormone release.

Dopamine has numerous signaling functions in the nervous system and body. It is produced either in a continuous manner (such as to permit muscle movements, to stimulate libido circuit activity) or in an as needed/pulsatile manner (as in stimulating motivation and a positive sense of well being, stimulating memory storage, etc. ). Dopamine reduces norepinephrine signaling. In the kidney, dopamine is produced to control blood pressure, to allow the kidney to release excess salt.

Pleasure, happiness, laughter, etc. is produced by a combination of signals including dopamine and norepinephrine, acting on numerous circuits in the nervous system. Norepinephrine production is important to promote excitement and a heightened sense of awareness when one is in a positive mood. Without norepinephrine, dopamine does not give pleasure or enjoyment.

Norepinephrine signaling has numerous effects - both positive and negative. In excess, the negative effects may predominate. Norepinephrine, for example, is also the signal for stress, distress, danger, fear, anger, that something is wrong. When the sympathetic nervous system produces norepinephrine, it will also put the immune system on alert. This may lead, however, to an increase in inflammatory signaling as the immune system attempts to protect the body.

When both the nervous system and immune system sense and excessive amount of stress, numerous signaling changes occur in a cascade that will shut down various systems in a defensive maneuver. For example, adrenal activity is suppressed. Thyroid signaling is suppressed. Seeking, problem solving, libido, nurturing, social circuitry activity is suppressed. Dopamine signaling is suppressed. Serotonin signaling may be suppressed. These result in sickness behaviors or defensive postures. One experiences a feeling of being ill, of depression, of lack of motivation, lack of libido, social isolation, lack of energy, lack of pleasure, etc. When chronic, one has dysthymic or chronic depression, or a chronic feeling of un-wellness or unhappiness. Under certain circumstances, when stress is extreme, even sensations, can be shut down so the person feels nothing.

The use of L-Dopa (which penetrates the blood brain barrier and dopamine hardly does) or dopamine agonists are treatments used in psychiatry in an attempt to improve mood. These are also used frequently to reduce restless legs or akathisia - side effects of antipsychotics or serotonin medications. They do not often give happiness or pleasure (other than sometimes improving libido) because other signals (such as norepinephrine) have to be present in the right amounts. But they are useful tools given their potential to reduce stress, improve activity in some circuits.

But again, rarely do they give the feeling of happiness. A combination of signaling changes needs to occur. Some of these are stimulated by one's activities including physical activities and interactions with others. Happiness doesn't usually occur when one is limited to lying in bed or sitting on a couch all day. Part of the problem is that increasing Dopamine using L-Dopa or a dopamine agonist increases the continuous dopamine signal, not the pulsatile signal. Strong dopamine reuptake inhibitors (such as cocaine) are probably best in improving the pulsatile signal - but they tend to be illegal, addicting, and due to their short half-lives cause many problems.

Antidepressants, all to a certain extent but weak extent, also block dopamine reuptake. In clinical use (except for the antidepressant that was banned because it blocked reuptake too strongly, causing addiction), the dopamine increase from antidepressants is too weak and is overwhelmed by the increase in serotonin or norepinephrine signaling.

Dopamine in excess can cause fatigue, excessive sleepiness, falls due to low blood pressure or sudden attacks of sleep. It can cause abnormal muscle movements such as jerking movements, called dyskinesias. Under some circumstances, it can trigger hallucinations.

Stimulants are one of the oldest medications in psychiatry. Amphetamine has been used for nearly 100 years in psychiatry. Stimulants, such as the Adderall, Dexedrine, Provigil, Methylphenidate, Focalin, etc. all increase both dopamine and norepinephrine signaling. When they stop working or lose their effectiveness, it is because the norepinephrine signaling is triggering the negative effects and the negative conditions (such as inflammation, adrenal dysregulation, stress responses, etc. are already present).

Generally, one useful way to predict whether or not a stimulant will produce a negative effect is to measure adrenal signaling. When adrenal signaling is too low (e.g. if cortisol is < 10) - meaning adrenal dysregulation is occurring already, generally, I hesitate to give a person a stimulant since it will tend to produce the the negative effects. Many people cannot tolerate a stimulant under that circumstance. Kids with ADHD, for example, will become irritable, tired, angry, if given a stimulant is given and adrenal dysregulation is present.

In summary, dopamine and dopamine agonists and stimulants are useful tools in psychiatry. They may not work under some circumstances. Dopamine alone, in general, does not give happiness or even pleasure - a combination of signals is necessary as well as activities. They are not a panacea. They can have significant adverse effects. Use in the right circumstance - e.g. when the foundation for their use is established by addressing concurrent problems, they can have a beneficial effect.


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Central nervous system dopamine signaling is difficult to monitor with commonly used lab tests.

The plasma fractionated catecholamine test is not a good test for dopamine signaling in the nervous system. The dopamine in the test is generally dopamine that escapes from norepinephrine producing cells, not dopamine produce by dopamine producing cells. As such, it isn't a dopamine level that corresponds to nervous system signaling. From my point of view, it isn't clinically useful. The norepinephrine and epinephrine levels are clinically useful.

Urine dopamine also is problematic when trying to estimate central nervous system dopamine signaling. Most of the urine dopamine is produced by the kidney, itself. Renal dopamine is used to maintain salt balance. It doesn't correspond or correlate with central nervous system dopamine signaling.

Increasing dopamine signaling may lead to an increase growth hormone production and testosterone production. The amount of increase depends on the individual given the numerous interactions between signaling systems and cellular metabolism involved. In my experience, in many cases, the increase in testosterone production is small or insignificant.
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