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NeuroResearch Clinics, Inc. |
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AMA Category 1
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Continuing Medical Education |
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NEUROTRANSMITTER |
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(Serotonin,
Dopamine, Norepinephrine, Epinephrine) |
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Written by:
Marty Hinz,
MD |
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President
Clinical
Research |
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NeuroResearch
Clinics,
Inc. |
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Low
levels of the serotonin and the dopamine neurotransmitter molecules are not the
primary cause of chronic
neurotransmitter disease
such as depression, ADHD, etc. In reviewing
urinary serotonin and dopamine laboratory assays from many thousands of
patients it is clear that all patients
with and without disease such as
depression, ADHD, etc. have
virtually the same serotonin and
dopamine neurotransmitter
levels prior to treatment. |
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Chronic disease
such as depression, ADHD, etc. symptoms
is caused by
damage to the electrical system of the
brain (neurons). The real problem is
decreased electrical flow due to damaged
neurons. The only way to increase
electrical flow is to increase the
serotonin and dopamine neurotransmitter levels in the brain,
drugs can't do this they deplete
serotonin and dopamine neurotransmitter molecules.
Serotonin and dopamine neuron damage is
caused by neurotoxins, trauma, and
biologic insult. |
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Some
labs advocate baseline serotonin and
dopamine neurotransmitter
testing prior to treatment of
depression, ADHD, etc. Baseline urinary
serotonin and dopamine neurotransmitter
testing is a
waste of time and money. There is no
correlation between baseline urinary
serotonin and dopamine neurotransmitter testing and
urinary serotonin and dopamine test
results once the patient is taking
significant levels of tyrosine aka
L-tyrosine, 5-HTP aka 5HTP or 5 HTP, and
L-dopa aka dopa. The only thing baseline
urinary serotonin and dopamine baseline
testing practices do is to line the pockets of the lab
with money at
the expense of a patient who is already
suffering with disease
such as depression, ADHD, etc. These same
baseline urinary serotonin and dopamine
promoting labs
also claim that the serotonin and the
dopamine neurotransmitter
molecules cross the blood brain
barrier, which they don't (see
above).
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Drugs
do not increase serotonin and dopamine neurotransmitter levels
in the brain, they work by moving
serotonin and dopamine neurotransmitter molecules from one place to
another and in the process the deplete
the serotonin and dopamine neurotransmitter molecules instead
building
serotonin and dopamine neurotransmitter levels. The only way to
increase serotonin and dopamine neurotransmitter levels in the
brain is by giving the body the
5-HTP aka 5HTP or 5 HTP, tyrosine aka
L-tyrosine, and L-dopa
aka dopa that it needs to build neurotransmitter
molecules. |
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Everywhere you look in the body the
neurotransmitter molecules serotonin, dopamine,
norepinephrine, and epinephrine are in
balance and compete with each other.
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Serotonin, dopamine, norepinephrine, and
epinephrine are the master
neurotransmitter molecules they directly
and indirectly control every process in
the body. Only by optimizing the
serotonin, dopamine, norepinephrine, and
epinephrine neurotransmitter molecules
will the patient feel optimal and
optimal function be facilitated.
Hormones, cortisol, GABA, PEA,
melatonin, blood pressure and a host of
other things are controlled by the
serotonin, dopamine, and norepinephrine
neurotransmitter molecules. There is
nothing in the body that exerts as much
force on the system as a whole as the
serotonin and dopamine
neurotransmitter molecules do. |
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The
reuptake inhibitor depression drugs do nothing to
increase serotonin and dopamine neurotransmitter levels they
work by moving serotonin and dopamine neurotransmitter
molecules from
one place to another in the brain. In
the process these drugs deplete
serotonin and dopamine neurotransmitter molecules and can make clinical
symptoms of depression or ADHD worse increasing risk of
suicide. |
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Antidepressants deplete neurotransmitter
molecules |
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From The Formal |
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"Effexor Prescribing Information" |
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For
Physicians |
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THE REAL VALUE |
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OF BASELINE
URINARY |
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NEUROTRANSMITTER
TESTING |
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Baseline
urinary serotonin and dopamine neurotransmitter testing prior to
treating with 5-HTP aka 5HTP or 5 HTP, tyrosine
aka L-tyrosine, and L-dopa aka dopa is of no
value. Even thought the practice of baseline
urinary serotonin and dopamine
neurotransmitter testing is
promoted by some labs it is not effective,
it is a waste of time and a waste of money.
The only thing it does effectively is line
the lab bank account with money. |
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As noted in the
literature and verified by the University of
Minnesota Medical School the
neurotransmitter molecules serotonin, dopamine,
norepinephrine, and epinephrine exist in two
states. The endogenous state (the state
where the patient is taking no 5-HTP aka
5HTP or 5 HTP,
tyrosine aka L-tyrosine, and L-dopa aka
dopa. The second is the competitive inhibition state (the
state when the patient is taking the 5-HTP
aka 5HTP or 5 HTP, tyrosine aka L-tyrosine, and L-dopa
aka dopa). As
reported by NeuroResearch and verified by
the University of Minnesota Medical School
urinary serotonin and dopamine neurotransmitter testing in the
endogenous state (prior to starting 5-HTP
aka 5HTP or 5 HTP, tyrosine aka L-tyrosine, and L-dopa
aka dopa) has no correlation
with urinary neurotransmitter testing
performed once in the competitive inhibition
state (taking 5-HTP aka 5HTP or 5 HTP, tyrosine
aka L-tyrosine, and
L-dopa aka dopa). |
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With regards to
recommending baseline urinary serotonin and
dopamine neurotransmitter testing prior to
treatment there appears to be two distinctly
different types of lab involved here. The
first is the labs
directed by hospital based board certified
pathologists who holds forth the recommendation
that baseline testing is of no value. While
the labs recommending baseline urinary
neurotransmitter testing has no licensed
medical doctor in charge of day to day
operations, no license to practice medicine,
no hospital affiliation, no clinic, no
patients of their own, and no experience in
treating patients in clinics. |
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We have been
doing twelve AMA category I continuing
medical education conferences a year since
2000. At virtually every one of these
conferences we hear from physicians who have
tried the protocols of labs holding out
baseline urinary serotonin and dopamine neurotransmitter testing is
needed prior to treatment. The results
reported to us are all the same. Almost none
of the patients treated this way get better. |
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Several
independent physicians took the initiative
to do split sample urinary serotonin and
dopamine neurotransmitter testing ,submitting
samples to DBS Labs directed by Tom Uncini,
MD hospital based pathologist and a lab
recommending baseline testing. In all cases
there was no correlation between the two lab
reports returned on the same urinary
serotonin and dopamine neurotransmitter sample. In
looking at the situation, we trust the
lab of the hospital based pathologist. |
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THE PROPER
RELATIVE
PERSPECTIVE ON
NEUROTRANSMITTER
LEVELS |
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Low levels of
neurotransmitter |
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do not
cause disease
such as depression, ADHD, etc. |
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Neurotransmitter
levels that are
not high enough
to keep the
electrical flow
of compromised
neuron bundles
functioning
properly cause
disease
such as depression, ADHD, etc. |
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There is
a
tendency
when
providing
a
patient
with
reuptake
inhibitor
depression
or ADHD drugs
that
increase
synaptic
levels
of
neurotransmitter
molecules
to
believe
that low
levels
of
neurotransmitter
molecules
cause
disease
such as depression, ADHD, etc.,
if the
patient
gets
better. |
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In
studying
the
urinary
serotonin
and
dopamine
neurotransmitter labs
of
thousands
of
patients,
the
problem
becomes
defining,
“What
does the
lab show
in low
levels
of
serotonin
and
dopamine
neurotransmitters?” |
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To
achieve
resolution
of
disease
such as
depression,
ADHD,
etc.
symptoms
and to
obtain
the
neurotransmitter phase 3
therapeutic
response
of
urinary
serotonin
and
dopamine neurotransmitter
molecules,
it is
apparent
that the
level of
serotonin
and
dopamine neurotransmitter
molecules
needed
to get
symptoms
of
depression,
ADHD,
etc. under
control varies
on a
huge
scale
from
patient-to-patient.
There is
no
correlation
between
the
serotonin
and
dopamine neurotransmitter
levels
directly
measured
in the
system
and the
resolution
of
disease
such as
depression,
ADHD,
etc.
symptoms
in
patients.
5-HTP
aka 5HTP
or 5 HTP
and
L-dopa
aka dopa
are
freely
synthesized
into
serotonin
and
dopamine neurotransmitter
molecules
without
regulation.
The
dosing
of the
5-HTP aka 5HTP
or 5 HTP,
tyrosine
aka
L-tyrosine,
and
L-dopa
aka dopa
needed
to get
depression,
ADHD,
etc. symptoms
under
control
in
patients
varies
on a
huge
scale,
as does
the
serotonin
and
dopamine neurotransmitter
levels
induced
when
they are
administered.
This
gives
rise to
the
observation,
“What
does it
mean to
say low
levels
of
serotonin
and
dopamine neurotransmitter
molecules
cause
disease
such as
depression, ADHD, etc.?” |
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At the
lab
level,
we
believe
that the
term
“low” in
the
direct
measurement
of
serotonin
and
dopamine neurotransmitter
molecules
can not
be
defined
with
regards
to
disease
symptoms
in
depression,
ADHD,
etc.
Identical
levels
of
serotonin
and
dopamine
neurotransmitter
levels
measured
in one
patient
with no
symptoms
from
disease
such as
depression,
ADHD,
etc.
can lead
to
severe
disease
such as
depression,
ADHD,
etc.
in
another
patient.
It turns
out that
there is
no
predictability
between
the
direct
systemic
measure
of
serotonin
and
dopamine neurotransmitter
levels
and
symptoms. |
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The
proper
way to
look at
this is,
“When
disease
such as
depression,
ADHD,
etc.
symptoms
are
present,
the
serotonin
and
dopamine neurotransmitter
levels
are not
high
enough
to
prevent
the
symptoms.”
Serotonin
and
dopamine
neurotransmitter
levels
that may
be very
high for
normal
patients
may not
be high
enough
to
control
depression,
ADHD,
etc. symptoms.
Parkinsonism
is a
good
example,
but this
concept
applies
to every
other
serotonin
and
dopamine neurotransmitter
disease
such as
depression,
ADHD,
etc.
as well. |
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neurotransmitter |
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THE BUNDLE DAMAGE THEORY |
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The bundle damage theory
states: |
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Serotonin and dopamine neurotransmitter dysfunction
disease such as
depression, ADHD, etc. symptoms develop when the electrical
flow through the serotonin
and dopamine neuron
bundles that regulate
serotonin and dopamine function is compromised by
damage to the individual
serotonin and dopamine neurons or the neuron
components composing the
neuron bundle which conducts
electricity to regulate or
control function. In order
to optimally restore
serotonin and dopamine neuron
bundle regulatory function,
synaptic serotonin and
dopamine neurotransmitter
levels of the remaining
viable neurons must be
increased to levels higher
than is normally found in
the system, which restores
adequate electrical outflow
resulting in relief of
symptoms and optimal
regulatory function. |
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DISEASE
(DEPRESSION, ADHD, ETC.) ETIOLOGY PERSPECTIVE |
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5-HTP aka 5HTP
or 5 HTP,
tyrosine aka L-tyrosine, and L-dopa aka dopa do not “cure.” They simply allow the body to make
enough serotonin and dopamine neurotransmitter molecules to overcome the problems that
cause neurotransmitter diseases
such as depression, ADHD, etc. |
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So what is the cause of all these
diseases such as
depression, ADHD, etc.
associated with the master neurotransmitter
molecules
serotonin, dopamine, norepinephrine, and epinephrine?
Permanent damage to the serotonin and dopamine neuron bundles of the brain.
Damage the correct dopamine bundles and you get Parkinson
disease. Damage other serotonin and dopamine bundles and you get chronic
insomnia or depression or ADHD or some other neurotransmitter
associated disease. We have identified almost 100
diseases such
as depression, ADHD, etc.
that appear to be from permanent
serotonin and dopamine neuron bundle
damage, where proper use of
5-HTP aka 5HTP
or 5 HTP,
tyrosine aka L-tyrosine, and L-dopa aka dopa will compensate
for the serotonin and dopamine neuron bundle damage problem. |
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On to the real depths and heart of the
matter, “What is the cause of this serotonin and
dopamine neuron bundle damage?” |
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If you damage enough
serotonin and dopamine neurons in a
bundle of neurons conducting electricity through the
brain, functions controls by that serotonin or dopamine neuron bundle will not
be controlled properly. In the case of Parkinsonism,
when enough neurons of the dopamine bundles in the
substantia nigra die off from damage, the classic pill
roll tremor with cogwheel rigidity develop. |
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Taking these observations one step
further, if enough serotonin or dopamine neurons of a neuron bundle regulating
sleep die off from toxic or traumatic damage, the
patient is left with poor sleep patterns. If the
serotonin or dopamine neurons
of the neuron bundles controlling affect are damaged,
the patient can be left with chronic depression.
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But what is causing this damage to the
system that leads to these chronic serotonin or dopamine neurotransmitter
diseases
such as depression, ADHD, etc.
in patients? |
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In reviewing the problem for several
years, we are left with a short list of two.
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First, we have seen post traumatic head
injury cause chronic problems that can be relieved by
5-HTP aka 5HTP
or 5 HTP,
tyrosine aka L-tyrosine, and L-dopa aka dopa therapy in some cases. But, we firmly believe
that the main source is toxins. |
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In general toxicity is highly specific.
It certainly has been proven in medicine that certain
chemical toxins can induce serotonin or dopamine neuron damage and death to
specific neuron bundles, such as the dopamine neurons of
the substantia nigra in Parkinsonism while leave other
dopamine neuron bundles in the brain intact. |
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At present, I firmly believe that cause
of serotonin and dopamine neurotransmitter dysfunction in over 90% of the cases
is due to neurotoxic serotonin and/or dopamine neuron
bundle damage, which is permanent. While
the damage to the serotonin and dopamine neuron bundles is permanent, the
symptoms can be reversed in all the serotonin and
dopamine neurotransmitter associated diseases
such as depression, ADHD, etc.
by raising the
serotonin and dopamine neurotransmitter levels through proper use of
5-HTP aka 5HTP
or 5 HTP,
tyrosine aka L-tyrosine, and L-dopa aka dopa (as occurs with
L-dopa aka dopa treatment in Parkinson
patients). If we could get rid of all toxins from the
environment, I have no doubt that over 85% of the
diseases
such as depression, ADHD, etc.
people suffer with would be gone in a
generation. |
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THE REAL CAUSE OF MASTER NEUROTRANSMITTER PROBLEMS |
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TRADITIONAL THINKING |
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“Low levels of
serotonin and dopamine neurotransmitter molecules cause disease.
Therefore, by providing drugs which
increase synaptic neurotransmitter
levels, symptoms of disease resolve.” |
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THE
REAL CAUSE OF THE PROBLEM |
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Low levels of
serotonin and dopamine neurotransmitter molecules in the system do not
cause disease symptoms
such as depression, ADHD, etc. It is the
serotonin and dopamine neuron
bundles, which are damaged to the point
that serotonin and dopamine neurotransmitter levels have to be
elevated above normal levels in order to
get symptoms under control that cause
disease
such as depression, ADHD, etc. symptoms. |
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Getting to this
assertion was not easy. From a clinical
standpoint, the following assertions
look the same and have the same needs
(i.e. “Serotonin and dopamine neurotransmitter levels need to
be elevated in order to get symptoms of
disease
such as depression, ADHD, etc.
under control):
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Low levels of
serotonin and dopamine neurotransmitter cause disease
such as depression, ADHD, etc..
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Serotonin and
dopamine neuron bundles are
damaged to the point that
serotonin and dopamine neurotransmitter levels have to be
elevated above normal levels in
order to get symptoms of disease
such as depression, ADHD,
etc. under control,
which is the real problem.
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Our work started
10 years ago, this year; at a time when
there was nobody out there working to
optimize the serotonin and dopamine
systems with
5-HTP aka 5HTP
or 5 HTP,
tyrosine aka L-tyrosine, and
L-dopa aka dopa. It is this
experience that has brought us to the
current realization; is the glass half
full or half empty? Who cares, the real
problem is serotonin and dopamine neurotransmitter levels are
too low to keep the system functioning
properly with disease such as
depression, ADHD, etc. and only by realizing that
damaged serotonin and dopamine neuron bundles are causing the
problem in most cases can the situation
be dealt with optimally. |
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IF NEURON BUNDLE
DAMAGE OF SEROTONIN AND DOPAMINE IS DRIVING THINGS WHERE DID IS COME FROM? |
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In examining things, the list
grows short: |
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Neurotoxic damage to
serotonin and dopamine neurons.
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Traumatic injury to serotonin
and dopamine neurons.
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Biologic damage to serotonin
and dopamine neurons.
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The key here is “damage to serotonin and dopamine neurons,” which is
irreversible and permanent. This is why simply taking
5-HTP aka 5HTP
or 5 HTP,
tyrosine aka L-tyrosine, and L-dopa aka dopa for a while will not cure the problem and
symptoms of disease
such as depression, ADHD, etc. and
return when the
5-HTP aka 5HTP
or 5 HTP,
tyrosine aka L-tyrosine, and L-dopa aka dopa are
stopped. For the most part, these diseases
such as depression, ADHD, etc.
are life-long
illnesses that need life-long control of serotonin and
dopamine. The incidences of
toxins in the environment have increased dramatically in
the last 50 years; as have the incidences of these
diseases
such as depression, ADHD, etc. I firmly believe that this is no coincidence.
5-HTP aka 5HTP
or 5 HTP,
tyrosine aka L-tyrosine, and L-dopa aka dopa provide the tools to get
disease symptoms of depression, ADHD, etc. under
control and not just mask them with reuptake inhibitor
depression drugs that have side
effects |
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From the peer reviewed
literature, baseline testing of urinary neurotransmitter levels is of no
value. |
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Marty Hinz, MD
Depression in I. Kohlstadt (ed.) Food and Nutrients in Disease Management (CRC Press, 2009) |
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THE
ARTICLE REVIEWED HERE: |
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Urinary
Neurotransmitter Testing Myths and
Misconceptions |
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Basis for the different approaches, a product
foundation comparison. |
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The following is not true in this article which
was not peer reviewed: |
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THE
BLOOD BRAIN BARRIER |
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The most difficult
challenge we were up against was the
literature. There was very little and in
retrospect, a lot of what was written
was not true when applied to the
clinical setting. People were claiming
that serotonin, dopamine,
norepinephrine, and epinephrine crossed
the blood brain barrier. They stated
that serotonin and dopamine neurotransmitter molecules were simply
filtered by the kidneys and ended up in
the urine. This misinformation led to
claims that urinary serotonin and
dopamine neurotransmitter
testing was a good assay of central
nervous system status. In addition,
claims were made that 1 or 2 pills,
twice a day could control disease
symptoms
such as depression, ADHD,
etc. in patients.
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Science has pushed
forward and we know that
serotonin and dopamine
neurotransmitter molecules
do not cross the blood brain
barrier. This means that
peripheral administration of
the serotonin and dopamine
neurotransmitter molecules has no value in
treating serotonin and dopamine neurotransmitter related
central nervous system
disease
such as depression, ADHD, etc. This is most evident in the
Parkinson patient who has a dopamine
drip started in the hospital. If
dopamine crossed the blood brain
barrier, you would expect marked
improvement, but there is none. Radio
isotope tagging of
5-HTP aka 5HTP
or 5 HTP,
tyrosine aka L-tyrosine, and
L-dopa aka dopa and
neurotransmitter molecules has proven that
urinary serotonin and dopamine neurotransmitter molecules are not
serotonin and dopamine neurotransmitter molecules filtered by the
kidneys and excreted into the urine.
They are serotonin and dopamine neurotransmitter molecules that are
synthesized by the kidneys and very
little systemic serotonin and dopamine neurotransmitter
molecules end up
in the urine. We now know that the
approach of using 1 or 2 pills of
5-HTP aka 5HTP
or 5 HTP,
tyrosine aka L-tyrosine, and
L-dopa aka dopa precursor twice a day is
ineffective in group treatment. The
shear volume of
5-HTP aka 5HTP
or 5 HTP,
tyrosine aka L-tyrosine, and
L-dopa aka dopa precursors
needed for optimal group treatment could
not fit into one or two pills |
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THERE IS ONLY
ONE WAY |
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The master
neurotransmitter molecules (serotonin, dopamine,
norepinephrine, and epinephrine) do not cross the blood brain
barrier. The only way to
increase central nervous
system levels of the
serotonin and dopamine neurotransmitter molecules is by
providing
5-HTP aka 5HTP
or 5 HTP,
tyrosine aka L-tyrosine, and
L-dopa aka dopa precursors that
cross the blood brain barrier and
synthesized by specific areas of the
brain into serotonin and dopamine neurotransmitter molecules. |
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There are many clinical observations
that verify the fact that these
serotonin and dopamine neurotransmitter molecules do not cross the blood
brain barrier. For example, a Parkinson
patient presents in the emergency room
with shock and a dopamine drip is
started. No relief of the Parkinson
symptoms is seen since dopamine does not
cross the blood brain barrier. |
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THE
BALANCE BETWEEN SEROTONIN AND DOPAMINE 5-HTP
aka 5HTP or 5 HTP, tyrosine aka L-tyrosine
AND L-DOPA aka dopa |
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GABA |
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SO,
WHERE IS THE PATHWAY? |
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Serotonin and dopamine
precursors treat GABA associated
diseases better than GABA precursors. We
have known about this for a long time,
but all attempts to find the chemical
pathway involved have come up short.
Biochemistry is not a closed book with
nothing more to learn; new chemical
pathways are being defined on a regular
basis. The best answer we currently have
is, “We can see the results, but can we
find the pathway?” I have no doubt the
following chemical pathway link exists.
It is just a matter of defining it. |
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THE MASTER SEROTONIN AND
DOPAMINE
NEUROTRANSMITTER LEVELS |
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To be classified as a
“master neurotransmitter,” a molecule
must be a neurotransmitter and
control/regulate other
neurotransmitter
molecules. Under this
definition, serotonin, dopamine,
norepinephrine, and epinephrine are true
“master neurotransmitter molecules.” |
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ANXIETY AND PANIC
ATTACKS |
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There
appears to be a controlling chemical pathway of GABA by
the master neurotransmitter molecules serotonin, dopamine,
norepinephrine and epinephrine - but we can’t find it.
If anyone reading this newsletter knows of such a
pathway or has any ideas, we would like hear them. |
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THE EVIDENCE |
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In
medicine, the prototype diseases associated with GABA
dysfunction are anxiety and panic attacks. Research has
shown that with properly prescribed serotonin and
dopamine
5-HTP aka 5HTP
or 5 HTP,
tyrosine aka L-tyrosine, and L-dopa aka dopa precursors, over 95% of patients
show complete resolution of anxiety and panic attacks -
a rate that is far greater than treatment with GABA
precursors. “So, what is happening here?” |
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CLINICAL
IMPLICATIONS |
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Even
though we have not directly identified the chemical
pathway that indicates how serotonin and the
catecholamines control GABA to relieve symptoms of
diseases associated with GABA dysfunction, the clinical
evidence is clear. Proper use of serotonin and dopamine
precursors relieve symptoms of diseases associated with
GABA dysfunction far better than any approach we have
seen using GABA precursors. There are numerous doors
that we have opened with our work, which have led to
more research. The area of GABA being controlled by
serotonin and the catecholamines appears to be another
open door. |
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| dopamine_8 |
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CORTISOL REGULATION BY SEROTONIN, DOPAMINE, AND
NOREPINEPHRINE NEUROTRANSMITTER LEVELS |
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| dopamine_9 |
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HORMONE REGULATION BY
SEROTONIN, DOPAMINE, AND NOREPINEPHRINE
NEUROTRANSMITTER LEVELS |
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dopamine_10 |
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MELATONIN REGULATES SLEEP |
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If you need a medical speaker
for AMA Category I CME call NeuroResearch Clinics, Inc.
|
|
NeuroResearch Clinics, Inc.
only deals with and provides information to licensed health care
professionals. |
| |
| NeuroResearch Clinics, Inc |
| 1150 88th Ave W |
| Duluth, MN 55808 |
| Ph. 877-626-2220 |
| E-Mail: Info@NeuroAssist.com |
| |
|
DISCLAIMER: NeuroResearch is a research company that provides
speakers to programs for AMA category I continuing medical education
(CME) for physicians, continuing education for psychologists
approved by the American Psychological Association, and licenses
intellectual property for use. The NeuroResearch formulas and theory
of medicine is designed for the use of combining
5-HTP aka 5HTP
or 5 HTP,
tyrosine aka L-tyrosine, and L-dopa aka dopa
precursors of the serotonin and catecholamine systems. The formulas
are intended to be used as nutritional supplements and not as a drug
to treat, mitigate, treat, cure, or prevent disease. This web site
is intended to be educational purposes only. Constantly we receive
e-mails from people who are not licensed health care providers. We
wish we could answer them, but the new telemedicine laws that were
recently legislated (and put in place) prohibit us from providing
advice directly to people with no medical license or providing
medical care over the Internet. |
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