Histamine Receptors H1,H2,H3 and Neurotransmitter / Hormone Release

Histamine H(1) Receptor Activation 

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ACTIONS when Activated

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• Potentiate and Activate GABA release (1) - is Ca2+ dependent.
• Inhibit or Stimulate Noradrenaline Activity, enhances norepinephrine and glutamate especially when H(3)'s are blocked. (2) (3) (4)
• Inhibit Potassium-evoked serotonin release. (5)
• Increases phospholipase C and PKC (Protein Kinase C)-induced NT release. (6)
• Increases tyrosine hydroxylase (and thus production of dopamine from tyrosine). (7)
• Increases cortisol, ACTH, beta-endorphin and Prolactin release. (8) (9) (10)
• Increases neuronal nNOS, iNOS and eNOS (nitric oxide synthases, increases N.O) (11)
• Nitric Oxide is partly increased by histamine through Ca2+, although other channels may be involved as well.
• Upregulation of Alpha-Adrenergic Receptors and Activity (12)
• Amplifies NMDA-induced depolarization. (13)
• Induces Calcium Channel induced cAMP (cyclic adenosine monophosphate) and Cytosolic Ca2+ concentrations. (14) (15)
• Increases and Amplifies Glutamate Release (16)
• Increases Acetylcholine Release (17)
• Increases GnRH (Gonadotropin-Releasing-Hormone) and thus stimulates production of sex hormones (18).
• Inhibits growth hormone release. (19)
• Stimulates Oxytocin Release. (20) (21)

THINGS THAT AFFECT NEGATIVELY HISTAMINE (H1) Receptor Expression and Histamine Release

• Beta-Adrenergic Agonists (such as albuterol, clenbuterol and higenamine will decrease H(1) receptor mRNA with time. (!)
• Sensitive to some antipsychotics and may downregulate in response to high potency blockade, however there are some studies indicate it can elicit supersensitivity and become immune to blockade.

Short- and long-term effects of antipsychotic drug treatment on weight gain and H1 receptor expression.

• High Levels of Adrenaline or use of adrenergic analogs aside from beta-agonists. Alpha-2-Receptor activation inhibits histamine release. (!) (!) (!) (!) (!) (!)

•  High Copper levels (also increases histamine breakdown through Diamine Oxidase. (!)
• Serotonin 5-HT1A (presumably post-synaptic) activation. (!) (!)
• Corticotropin-Releasing Hormone and Cortisol decrease histamine synthase enzymes (!)

• Use of Green Tea; catechin supplements and naringenin may decrease histamine synthesis and correspondingly, H(1) receptor mRNA. (!)
• Low Estrogen Levels. (!)

WHAT UPREGULATES H(1) Receptors Expression and Histamine Activity

• Protein Kinase C activation (such as with alpha-1-agonists or 5-HT2A agonism seen with LSD) (!) 
• H(3)R blockade by betahistine, thioperamide, Clobenpropit etc (!) (!)
• Alpha-2-Blockade and Low Serotonin Levels. (!) (!) (!)
• Estradiol (Estrogen) (!) (!) (!)
• Complex; but NMDA-blockade enhances histamine release, yet indirect upregulation of aromatase activity by NMDA may then lead to histamine release. (!) (!)
• 5-HT1A blockade.(!)
• High Protein Diet (!) (!) (!)
• Muscarinic Receptor Activation and anything that decreases Cyclic AMP (beta blockers etc) (!) (!)
• Some central nicotinic receptors and thus nicotine use (affects HDC) (!) (!)
• Dopamine D(2) Agonists (parkinson's drugs; requip and pramipexole mainly)

                            HISTAMINE H(2) Receptor Activation
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                              Actions when Activated
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• Increases glycine activity as well as Ca2+ stimulated influx of glutamate release. (!)
• Stimulates hypothalamic norepinephrine (noradrenaline) levels. (!)
• Increases Acetylcholine (striatal) when stimulated on Cholinergic/GABAergic neurons. (!) (!) (!)
• H(2) Receptors are found co-localized with norepinephrinergic nerve terminals, as well as dopamine expressing neurons and GABAergic terminals. Each area will yield a different result, thus it is difficult to say in ratio what H(2) receptor activation would, given unique circumstances and brain development. (!) (!)
• Potently increases cAMP levels (cyclic AMP) - is even more potent than Beta-Adrenergic Activation in this regard. (!) (!)  
• Increases Gonadotropins; Testosterone,Estradiol by this same mechanism.
• Increases T4 Converstion from TSH, increases metabolism (just as forskolin would). (!) (!)
• Increases GABA release. (!) (!)
• Increases Oxytocin release. (!) (!)
• Broadly excites glutamatergic neurotransmisson (!)

                                                                   Relation to Behavior

Histamine H(2) blockade causes fear like responses and unwarranted fear behavior. It also may induce paranoia and hallucnations in vulnerable subjects. Thus, taking stomach acid pills that can cross the BBB may result in negative psychological manifestations and negative behavioral phenotypes. In addition, H2 activated-dependent cAMP produces an antipsychotic effect and may alleviate psychosis.

On the flip side, super high histamine may induce adrenal fatigue and low adrenaline levels, leading to a fearless state of mind but corresponding fatigue as well. High Histamine individuals tend to have high libido and fast sexual responsiveness as well. 

  Blockade of histamine H2 receptors of the periaqueductal gray and inferior colliculus induces fear-like behaviors.

 Abnormal Brain Histamine

Central nervous system reactions to histamine-2 receptor blockers.

Histapenia (Low Histamine) and Mental Disorders

Histamine Actions in the Central Nervous System






HISTAMINE H(3) RECEPTORS 
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ACTIONS WHEN ACTIVATED
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• Inhibit Dopamine D(1) receptor activated cAMP levels. (!)
• Inhibit histamine release and production. (!)
• Inhibits dopamine production. (!)
• Downregulates/Decreases Dopamine D2 Receptors. (!)
• Depresses synaptic transmission and CNS function. (!)
• Inhibits norepinephrine release. (!)
• Inhibits Dopamine D(1) stimulated GABA release. (!)
• Inhibits Serotonin Release. (!)
• Inhibits Glutamate Release. (!)
• Inhibits Dopamine Synthesis (Production) (!)
• Inhibits Acetylcholine Activity and Release. (!) (!)
• Increases MAPK signaling. (!) (!)
• Increases Growth Hormone. (!)

*GENERAL / OTHER SOURCES & MAIN REFERENCES*

The histamine H3 receptor as a novel therapeutic target for cognitive and sleep disorders.

Molecular Pharmacological Aspects of Histamine Receptors

                      Histamine Receptors in Human Prefrontal Cortex

                      Histamine Actions in the Central Nervous System (CNS)

                            HISTAMINE AND EMOTIONAL MEMORY


 Decreased Histamine Release / Histamine Deficient Mice causes Anxiety-like behavior by actions in Amygdala.



      AMYGDALA KINDLING IN H(1) Receptor Deficient Mice

              Histamine H1 receptors and Amygdaloid Kindling / Seizures.


Histamine in the Central Nervous System : It's role in Circadian Rhythmicity

Cardiac Histamine Receptors : Histamine Effects on Heart

                                            Histamine receptors influence blood-spinal cord barrier permeability, edema formation, and spinal cord blood flow following trauma to the rat spinal cord.


   Histamine H(1) Receptors and Depression::Decreased histamine H1 receptor binding in the brain of depressed patients.

Neuroimaging of histamine H1-receptor occupancy in human brain by positron emission tomography (PET): a comparative study of ebastine, a second-generation antihistamine, and (+)-chlorpheniramine, a classical antihistamine.

GSK189254, a novel H3 receptor antagonist that binds to histamine H3 receptors in Alzheimer's disease brain and improves cognitive performance in preclinical models.

                                   HISTAMINE : Biology 307: Immunology


                                      
A detailed autoradiographic mapping of histamine H3 receptors in rat brain areas.

Signal transduction by histamine in the cerebellum and its modulation by N-methyltransferase.

Cerebellar histamine-H1 receptor distribution: an autoradiographic study of Purkinje cell degeneration, staggerer, weaver and reeler mutant mouse strains. (!)

Brain Histamine in Alzheimer's Disease



Imaging histamine H1 receptors in the living human brain with carbon-11-pyrilamine.


Basic Neurochemistry: Principles of Molecular, Cellular, and Medical Neurobiology

The Pharmacology of Sleep

Histamine H3 Receptors and Sleep-Wake Regulation

Histamine H1 Receptors in the Brain and Spinal Cord of the Cat


Histamine Impairs Midbrain Dopaminergic Development in vivo by activating Histamine type 1 receptors

Natural Serotonin Receptor Blockers / Antagonists

This article has been Published with the valuable input of the_apollo at longecity, thanks again.
:: http://www.longecity.org/forum/topic/72744-need-to-find-5ht1b-antagonist-drugherbal-to-treat-ocd-behavior/  ::

This article will explain specifically serotonin receptor blockers, as opposed to just serotonin reducers (by means of level of as opposed to receptor function). These remedies are all natural and can be bought OTC - Over the Counter.

I'm going to go into the lesser known ones first.

The first one is a natural 5-HT6 antagonist (producing pro-cognitive/nootropic effects). It also can rapidly deplete overall serotonin levels by antagonizing potassium-induced serotonin release.

The product is known as "Magnolia Bark Extract" - it should be noted however that it's effects are not purely serotonin antagonism - it also acts as a Benzodiazepine receptor potentiator/agonist.

http://www.ncbi.nlm.nih.gov/pubmed/19505549

Interactions of Magnolia and Ziziphus extracts with selected central nervous system receptors.

Koetter U1, Barrett M, Lacher S, Abdelrahman A, Dolnick D

 ETHNOPHARMACOLOGICAL RELEVANCE: Magnolia officinalis Rehder and Wilson [Magnoliaceae] bark and Ziziphus spinosa (Buhge) Hu ex. Chen. [Fam. Rhamnaceae] seed have a history of use in traditional Asian medicine for mild anxiety, nervousness and sleep-related problems.

AIM OF THE STUDY:To identify pharmacological targets, extracts of Magnolia officinalis (ME), Ziziphus spinosa (ZE), and a proprietary fixed combination (MZE) were tested for affinity with central nervous system receptors associated with relaxation and sleep.

METHODS:In vitro radioligand binding and cellular functional assays were conducted on: adenosine A(1), dopamine (transporter, D(1), D(2S), D(3), D(4.4) and D(5)), serotonin (transporter, 5-HT(1A), 5-HT(1B), 5-HT(4e), 5-HT(6) and 5-HT(7)) and the GABA benzodiazepine receptor. RESULTS: Interactions were demonstrated with the adenosine A(1) receptor, dopamine transporter and dopamine D(5) receptor (antagonist activity), serotonin receptors (5-HT(1B) and 5-HT(6) antagonist activity) and the GABA benzodiazepine receptor at a concentration of 100 microg/ml or lower. ME had an affinity with adenosine A(1) (K(i) of 9.2+/-1.1 microg/ml) and potentiated the GABA activated chloride current at the benzodiazepine subunits of the GABA receptor (maximum effect at 50 microg/ml). ME had a modest antagonist action with 5-HT(6) and ZE with the 5-HT(1B) receptor. CONCLUSION: The interactions in the receptor binding models are consistent with the traditional anxiolytic and sleep-inducing activities of Magnolia officinalis bark and Ziziphus spinosa seed.

   WHERE TO BUY NATURAL 5-HT6 Antagonist : Magnolia Bark Extract 

 
_______________________________________________________________________RECEPTOR BLOCKER #2________________________________________________________________________The next one is natural 5-HT2A antagonist  - which can aid in depression and may also lower cortisol and prolactin levels - consistent with effects of 5-HT2A blockade.It's known as NANTENINE - from the herb known as "Heavenly Bamboo" or "Sacred Bamboo".Other Names : Nandina (Nandina Domestica)
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2677726/

 Analogs of (±)-nantenine were synthesized and evaluated for antagonist activity at human 5-HT2Areceptors in a calcium mobilization assay. This work has resulted in the identification of the most potent 5-HT2Aantagonist known based on an aporphine. Our results also suggest that the C1 position may be a key site for increasing 5-HT2A antagonist activity in this compound series. In addition, the structural rigidity of the aporphine core appears to be required for nantenine to function as a 5-HT2A antagonist.

I have not found a valid product yet with solely Nadina but I will update this page when I find it.You can buy the seeds below.

_____________________________________________________________RECEPTOR BLOCKER #3______________________________________________________________The third natural serotonin receptor blocker is known as Wild Jujube Extract.It contains chemicals that antagonize 5-HT1B receptors, this will produce effects on behavior and may alleviate depressive disorders.

 ETHNOPHARMACOLOGICAL RELEVANCE: Magnolia officinalis Rehder and Wilson [Magnoliaceae] bark and Ziziphus spinosa (Buhge) Hu ex. Chen. [Fam. Rhamnaceae] seed have a history of use in traditional Asian medicine for mild anxiety, nervousness and sleep-related problems.

AIM OF THE STUDY:To identify pharmacological targets, extracts of Magnolia officinalis (ME), Ziziphus spinosa (ZE), and a proprietary fixed combination (MZE) were tested for affinity with central nervous system receptors associated with relaxation and sleep.

METHODS:In vitro radioligand binding and cellular functional assays were conducted on: adenosine A(1), dopamine (transporter, D(1), D(2S), D(3), D(4.4) and D(5)), serotonin (transporter, 5-HT(1A), 5-HT(1B), 5-HT(4e), 5-HT(6) and 5-HT(7)) and the GABA benzodiazepine receptor. RESULTS: Interactions were demonstrated with the adenosine A(1) receptor, dopamine transporter and dopamine D(5) receptor (antagonist activity), serotonin receptors (5-HT(1B) and 5-HT(6) antagonist activity) and the GABA benzodiazepine receptor at a concentration of 100 microg/ml or lower. ME had an affinity with adenosine A(1) (K(i) of 9.2+/-1.1 microg/ml) and potentiated the GABA activated chloride current at the benzodiazepine subunits of the GABA receptor (maximum effect at 50 microg/ml). ME had a modest antagonist action with 5-HT(6) and ZE with the 5-HT(1B) receptor.

CONCLUSION:The interactions in the receptor binding models are consistent with the traditional anxiolytic and sleep-inducing activities of Magnolia officinalis bark and Ziziphus spinosa seed.

_____________________________________________________RECEPTOR BLOCKER #4______________________________________________________Yohimbine HCL
ACTS as a competitive antagonist at multiple serotonin receptor subtypes - with the highest affinity being for 5-HT1B and 5-HT1D receptors - produces potent anti-depressant and aphrodisiac effects by this mechanism among others.

WHERE TO BUY YOHIMBINE HCL
~ DIFFERENT PRODUCTS BELOW ~ 

How to Tell if you are Low Histamine or High Histamine

~CLICK HERE For A Version of this Article that is Easier to Read~

                :::: Some humorous artwork for ya, but it gets the "picture" across ::::

 It also lays an important example of the differences in personality between a low histamine (histapenic) and high histamine individual ("Histadelic")

So how do you really tell if you are a histapenic or histadelic?
 For the purpose of bringing more information on the histamine imbalance topic, I will outline all of this.

Low histamine people are generally very lax people, who are tired / sleep all day or most of the day and then are up all night. Low histamine is characterized by persistent paranoia (even of family members and formerly or current good friends/aquaintances) - and is also characterized by a generally indifferent, depressed or dysphoric mood. Low Histamine people are generally HIGH IN COPPER.

This means high copper will show in blood work but also manifest in symptoms of adrenal fatigue, nervous system disorders, and alcohol dependence / addiction. 

People with high copper and low histamine seem to have a propensity to drug addiction, violent crimes and are prone to confrontation. 

This is with or Without hormone imbalances being taken into consideration.


Low Histamine High Copper individuals feel very little pain signals, if any. Some have been documented putting their finger through open flames without being bothered by it, or breaking light bulbs in their hand as a show of force, seeing as they would be unbothered by or not notice the pain signals. Thus Pain Asymbolia runs particularly strong in low histamine individuals.

Low histamine people have an absence of seasonal allergies, but may have dramatic food allergies and drug sensitivities.

If you are a depressed individual who has considered or has taken SSRI's, and you also have low histamine - you have probably experienced exaggerated side-effects...

Low histamine, High Copper individuals are prone to high blood pressure and spontaneous hypertensivity.


With low histamine, it is very likely that you will feel (at least once in a while) that people are watching you.

IN BLOODWORK, the following things are notable in LOW HISTAMINE individuals. So what to look for in blood work relating to low histamine???
** = Hormones

• Elevated Norepinephrine levels (NORADRENALINE)
• Elevated Serotonin / 5-H1AA Metabolites 
• Elevated Dopamine Levels   (poor usage though)
• Low Glutamate, Acetylcholine and GABA.
• Low serum / basil histamine.
• Elevated beta-endorphin, serum opioid concentration.
• Elevated Prolactin Levels**
• Elevated Cortisol**
• Elevated or depressed estradiol (estrogen)**
• High DHT in males but low - moderate serum testosterone**
• Increased SHBG**
• Low or High Epinephrine (Adrenaline), usually high. Histamine opposes adrenaline.

In addition.....levels of cholesterol may be elevated and there may be platelet aggregation or blood clotting disorders, especially in older low histamine folk.

Also with low histamine the following physical signs may be apparent.

-Pear shaped body (body fat accumulation near abdominal, hips and chest)

-^^ GYNECOMASTIA ^^ as well.

-Balding in men, unusual body* hair growth / heavy body* hair growth in both men and women

-Acne *(due to related estrogen imbalance, high copper and ZINC deficiency noted in histapenics)

-Veins hiding, or very hard to find veins when doing bloodwork.

-Lack of diuresis and STRONG thirst.

-CAVITIES, and DRY MOUTH....

-Lack of energy, General fatigue, Daytime Sleepiness, Narcolepsy.

-Lack of Normal Nerve Function, Erectile Dysfunction, Sexual Dysfunction.

-Low Pain Respondency / Feeling
-Lack of seasonal allergies, pet allergies.
-No symptoms and / or never seems to gets sick. Cold fails to produce a rhinitis/congestion.
-Frequent headaches and / or migraine...or a complete absense of headaches.
-Tan very easily (Copper stimulates Mealnin and A-MSH)


The following PSYCHOLOGICAL SIGNS are also Probable with Low Histamine

-Poor Spatial Memory, Problems remembering basic tasks.
-Hyperactivity in Children, and Mood Swings / BiPolar episodes in Adults.
-Depression, Suicidal Ideations but lack of energy to carry it out.
-Generalized Anxiety, Obsessions but not Compulsions..or Altered Compulsions (mainly mental, in head obsessions as opposed to things like hand washing).
-Cravings for Alcohol and / or Stimulants.
-Low Appetite, Low Sex Drive and General Lack of Motivation / Zest for Life.
-Trouble forming relationships / friendships with people, lack of communication skills or no desire for communication and / or interaction with society.
-Intense Paranoia, even of close relatives.
-Panic Disorders; Claustrophobia, Agoraphobia.
-Other Phobias.
-Loss of creativity, or an extra zest for Art that wasn't there before..but no motivation to do anything with it or lacks focus to APPLY it to real-life scenarios.
-Grandiose sense of self, delusions of Grandeur, Fantasizing about Unlimited Power and Success.
-Aggressive, Unpredictable and Acts on Fear. Emotinally unstable, but at times apathetic. (lack of emotions).





   Now...Onto HIGH HISTAMINE (HISTADELIA).

High histamine levels are characterized by a very profound, and strongly enthusiastic sense of self and of one's objectives - but this is quickly sunk or short-lived. Histadelics lack consistency, or they may start out VERY motivated, and consistent...and are very persuasive people, but they tend to Compulsively lose interest in a current project in favor of some new found ideology or project down the road. 

Histadelic's are masters of capturing opportunities, and are constantly looking for them. High Histamine people (Histadelic's) also are extremely motivated, but once again, when they crash and burn they veer away from the current objective and lose interest in it.

Part of this has to do with the excessive histamine's effects on the Adrenal Glands...which lowers adrenaline output Significantly over time...during the motivational highs that a histadelic gets, adrenaline initially rises; but then their crash is even more profound - their sympathetic nervous system goes into invariable stages of darkness. 

***Histadelics are characterized by very high impulsivity rates, very high sex drive and libido - to the point of absolute obsession and constant pre-occupation with sexual acts / fantasies. This is because histadelics are frequently undermethylated, and low in calcium and Vitamin D - leading to both a serotonin-deficient state and the natural lack of Norepinephrine due to histamine's Vasodilating properties often leads to a state of persistent sexual arousal. Some histadelic's are so sexually compulsive, that they have been known (in severe cases) to take a break at a meal, or when in a meeting leave to go to the bathroom suddenly, to masturbate.***


High Histamine people are generally very intelligent, and very creative.
High Histamine people generally seek a partner that has as high or similar of a sex drive, depending on their view of morality and relative obligation to their partner. However, many high histamine people prefer "NSA" No-Strings-Attached relationships...or hookups.

As once was quoted "being loyal is often a big task for those who are addicted to the joys of sex".

Histadelic's have a very high metabolism, and very rarely (if ever) gain much weight, they also have a naturally lower appetite, and are able to go long periods of time both without drinking and / or eating - assuming they are fit and healthy otherwise (besides histamine level). Histamine triggers diuresis (loss of cutaneous and subcutaneous water) - but it also helps ration intracellular electrolytes when the body is low or dehydrated.

In the gym, male histadelic's *(and sometimes females)* are often called "Hard-Gainers" - they have trouble building significant amounts of mass but they stay very lean and "cut up".  When they do build mass, it is solid, veiny and grainy muscle. 
The muscle definition and vascularity of a male histadelic is very significant.

Histadelic's are very naturally motivated to stay in shape..

However, the inherent seasonal allergies, histamine-induced headaches and sometimes inflammation (especially nasal) may get to him / her and put the brakes on activity until it is resolved.

Histadelic's like to finish everything on time (particularly their time), and can't/won't rest until their objective is completed.  Histadelic's can be unscrupulous, and can easily become compulsive liars and master manipulators.


High Histamine individuals may not share the paranoid characteristics of a low histamine individual, but like low histamine individuals..they can be prone to delusions of grandeur and fantasizing about success and power, and particularly, the object (or person) of sexual interest.  However the difference between a histapenic (low histamine person) and histadelic (high histamine) is that histadelic's actually have the motivation to pursue what others would call insane goals, and often don't care what other people think too much or their objective means more than the opinions of others.

High Histamine people are very OCD and easily become hooked on video games, sexual fantasies and work-related compulsions.

High Histamine people have limbs and body hair that develop anatomically to function with their metabolism..

Some of the physical attributes of a histadelic (high histamine individual)
are.....

• Large and Prominent Ears, Nose, and other facial features.
• Lack of or very little facial hair (due to very high metabolism)
• Either a pale, or flushed face.
• Some histadelic's are noted with very "fierce looking" eyes. Whereas others have teary / light hearted eyes. It is not known why there is such difference between some histadelics.
• Produce tears, nasal mucus and phlegm easily (almost too easily).
• Premature Ejaculation
• Very low body fat and pronounced and even enlarged veins. 
• Very strong muscle tone / definition.
• Pronounced cheekbones, and jaw (for men especially).
• Tall stature and long limbs, particularly arms.
• Chronic Itching, Hair Pulling and / or skin redness. 
• Persistent seasonal and / or pet allergies, that can be severe enough to trigger hospitalization.
• Bad side-effects from anti-depressants, including but not limited to stomach problems and worsening of suicidal / homicidal ideations.
• Persistent acid reflux and consequent diagnosis of GERD.
•  Sensitivity to light and sun.
• Tan very easily (also a low histamine, high copper trait) Impossible to differentiate.***
• Very high metabolism and frequently needing to turn down the thermostat, even when everyone else is cold or content - (can be caused by other things as well though) very high heat production that can be felt emanating from the skin. 
• Sweats a lot.

PSYCHOLOGICAL TRAITS/ATTRIBUTES INCLUDE.

• Very strong competitiveness.
• Very high libido / persistent sexual arousal. 
• Very strong motivation at first, but compulsively loses interest / becomes bored. 
• Very creative and intelligent.
• VERY Impulsive
• Aggressive, often Confrontational.
• Delusions of Grandeur; Visions of Unlimited Power, Success, Sexual Gratification with object / person of interest.
•  Obsessive-Compulsive; with Compulsions / Relative Objective Oriented Behavior predominating as one gets older.

•  Pre-Occupation with Sexual Fantasies, Video Games or Work-related activities.

•  Persistent anticipation anxiety, but lack or or very little social anxiety.
• Shy as a teenager, but the opposite as he / she gets older.
• Insomnia
• Very analytical (examines everything) and very aware. **
• Able to lie easily, and can become great at manipulating others. **

**  - Not exclusive to histadelia. May be other reasons / cultural / environmental factors.


 In addition, bloodwork would show the following abnormalties (high histamine).

• Low Serum Norepinphrine (metanephrine/VMT included)
• Low Serotonin, 5-HT1AA and other Serotonin Metabolites
• High Whole Blood and Serum Histamine Levels
• Low Dopamine (and HMA/HVA metabolites)
• Elevated Glutamate, and / or GABA
• Low or High Acetylcholine (depending on the person).
• Elevated or low beta-endorphin.
• Elevated or low prolactin (more commonly low PRL).
• Elevated Cortisol, or low Cortisol (due to adrenergic/serotonergic deficiency)
• High Serum Testosterone and LH/FSH (Gonadotropins)

**Can low histamine cause ACNE? **

**Copper and Acne**

***SOURCES***

Dr. Jeremey E. Kaslow - Under-Methylation - "Histadelia"

Emmerson Chiropractic - "HISTADELIA"

"Histadelia" - A Conversation - "A doctor writes"

Diagnose-Me - "Histadelia" (High Histamine)

Everything you need to Know About Histamine Intolerance

American Journal of Clinical Nutrition - Histamine and Histamine Intolerance 

Diagnose Me - "Histapenia" (Low Histamine)
Biology of Obsessive-Compulsive Disorder
Histamine : Biology 307 : IMMUNOLOGY
Histamine and Mouse Corpus Cavernosum Relaxation
Brain Histamine and Alzheimer's Disease
Imaging histamine H1 receptors in the living human brain with carbon-11-pyrilamine.

Basic Neurochemistry: Principles of Molecular, Cellular, and Medical Neurobiology

The Pharmacology of Sleep
Histamine H3 Receptors and Sleep-Wake Regulation
Histamine H1 Receptors in the Brain and Spinal Cord of the Cat
Histamine impairs MidBrain Dopaminergic Development IN VIVO by activating Histamine H1 Receptor.

The Key's to Re-Activating the Hypothalamus / Pituitary may be the Same as Those in Treating Narcolepsy

In many ways, a decreased hypothalamic output mirrors the etiology and manifestations of narcolepsy, and considering that both of these conditions are the result of decreased excitory output from glutamatergic/histaminergic neurons - ultimately which stimulate the HPAA - it would seem feasible then that the solution to both narcolepsy and a hypoactive pituitary / hypothalamus would be the same or similar.

This would also be consistent with the (( PAPER/STUDY  )) where decreased testosterone and other sex hormones in noted in narcolepsy. Particularly high prolactin levels were noted in multiple narcoleptics. 

Oh, but if only it were that easy. But it's not, well, at least not without considering other factors. 

Before you even can get into the central (and 2nd) messenger's, you have to look at the key hypothalamus inhibiting HORMONES. 

These are ....
-Estrogen (Estradiol)
-DHT (Dihydrotestosterone)
-Progesterone (to an extent)
-Prolactin

This means that if any of the above are out of whack, fixing histamine and glutamate may be of little help.


However, assuming one is not consuming excess amounts of soy and / or phytoestrogen's, and is not on birth control or contraceptives (for women).....then the estrogen part should not be an issue.

As far as DHT, well DHT is a composite and marker for how high your testosterone levels are, and is present in men in much higher amounts than women.

However, there are some conditions which cause an excess of DHT conversion (namely, SHBG deficiency), and this can then cause decreased testosterone levels as well, causing the metabolic benefits of testosterone to cease, and then with tons of DHT - you may be getting some CNS benefits, at the cost of your hair (possibly).

DHT is a great hormone to have in high amounts (for men), make no mistake, but it does NOT provide extra muscle mass to any measurable extent (other than keying in enzymes which testosterone works off of), therefore without testosterone, DHT has no metabolic benefits.


So in terms of overall health and metabolism, as well as hypothalamic function, taking a MILD DHT inhibitor might be a prudent course of action in a very Small number of men.

Estrogen antagonism or the use of an aromatase inhibitor can be useful in both men and women with low pituitary and sex hormone production.

And..as said above, prolactin control may be crucial, taking a dopaminergic or L-Dopa may represent a very powerful precedent in treating narcolepsy. 
Prolactin increases the conversion of Glutamate into GABA, which means excess prolactin can cause narcolepsy and other mental disturbances (being that glutamate is needed for vigilance).

When hormone function is all sorted out, if there is still a hypothalamic problem, now you can say the next two keys lie with Histamine and Glutamate.


D-Aspartic Acid supplements have been a groundbreaking revolution in terms of re-igniting leydig cell function and sex hormone production for example, DAA (D-Aspartic Acid) is a NMDA-agonist (it stimulates at high potency, NMDA-glutamate receptors).


Second, histamine is a novel amine, and an extremely potent glutamate augmenter (or facillitator in some cases), it is also the primary "wakefulness neurotransmitter".  

The question is, we know how to activate glutamate, how do we activate histamine?


Well...I've been over this before.


You need a few things.


1.) For histidine decarboxylase enzymes (P5P - the active form of Vitamin B6 is required)
2.) Folic Acid supplements help to increase histamine activity and retention,
3.) A high-protein diet and / or L-Histidine supplements will improve histamine levels.


In addition, NOT drinking green tea and avoiding Quercetin and Naringenin supplements will help stop the ceasefire on histamine networks.


A final note, you can also add something like PhytoSERMs 347X which will amplify the above and supercharge your hypothalamus.

***OTHER SOURCES***

http://www.ncbi.nlm.nih.gov/pubmed/17020130

http://narcolepsynetwork.org/2013/07/new-research-shows-possible-cause-of-narcolepsy/

Histamine and the Hypothalamus