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A Nicotine Fit is when a person is being driven by an addiction and craving for nicotine but does not have the nicotine available. This causes many types of withdrawal symptoms such as strong intense cravings for nicotine, tingling in the hands and feet, sweating, nausea, abdominal cramping, diarrhea, constipation, gas, headaches, coughing, sore throat, insomnia, restlessness, difficulty concentrating, anxiety, irritability, frustration, anger, depression and increased hunger. The level and depth of these symptoms vary from person to person, for instance, some people's irritability reaches the level of being out of control, angry and dangerous to self and others.https://www.healthline.com/health/smoking/nicotine-withdrawal#symptoms
https://www.webmd.com/smoking-cessation/understanding-nicotine-withdrawal-symptoms
https://www.mayoclinic.org/diseases-conditions/nicotine-dependence/symptoms-causes/syc-20351584
Nicotine mimics acetylcholine, the main neurotransmitter important for attention, memory, and cognitive processing. A neurotransmitter helps relay, pass on and hand off messages (transfer information that helps other cellular components, thus larger body components know what to do, how to react, respond, adjust, understand. This is the same as messenger rna and transfer rna). We've all seen what happens when one part of a relay team doesn't function properly. Acetylcholine imbalance is implicated as being at least a contributing cause of Dementia Syndrome and other Mental Illnesses.
Nicotine binds to acetylcholine receptors* in the brain which causes the release of dopamine, another chemical messenger. Dopamine plays an important role in inducing pleasure and reducing stress. Dopamine is also found throughout the body and plays a role in motor control [likely related to tardive dyskinesia and other movement disorders]. Dopamine also plays important roles in motivation, reward, cognitive function, maternal, and reproductive behaviors.
Dopamine manufacture occurs following the same sequence as norepinephrine. In fact, Dopamine is a precursor in the manufacture of Norepinephrine.
Dopamine is manufactured throughout the body wherever there are nerves and neurons, not just in the spinal cord and central brain. Thus dopamine is crucial to proper body functioning. A malfunction anywhere in the dopamine pathway may lead to neurodegenerative diseases such as Parkinson's[a symptom is motor dysfunction], Schizophrenia, Huntington's, Attention Deficit and Hyperactivity Disorder and Addiction. https://www.ncbi.nlm.nih.gov/books/NBK535451/ and https://pubmed.ncbi.nlm.nih.gov/30446950/
*Note: Acetylcholine receptors are foolishly called nicotinic receptors. Truth is they are acetylcholine receptors and also nicotine acceptors. They will accept nicotine when acetylcholine is not present.
Per https://pubmed.ncbi.nlm.nih.gov/19794359/, Cigarette smoking decreases the concentration of many drugs, including clozapine (Clozaril) and olanzapine (Zyprexa). Schizophrenic patients who smoke may require higher dosages of antipsychotics.
The body's cellular desire for nicotine's nervous system stimulating effects can be reduced by providing or helping the body increase the following: water and other nutrition especially rest, fresh air, sunlight, choline, iron, B-complex vitamins and probiotics.
https://pubchem.ncbi.nlm.nih.gov/compound/nicotine
https://www.ncbi.nlm.nih.gov/books/NBK500031/
Norepinephrine
Norepinephrine is a naturally occurring catecholamine hormone that functions as a neurotransmitter in the sympathetic nervous system. Norepinephrine directly stimulates adrenal receptors. Stimulation of various adrenal receptors causes vasoconstriction of the radial smooth muscle of the iris, arteries, arterioles, veins, urinary bladder, the sphincter of the gastrointestinal tract, an increase in myocardial contractility, heart rate, automaticity, atrioventricular (AV) conduction, and dilatation of bronchiolar and vascular smooth muscles.https://pubchem.ncbi.nlm.nih.gov/compound/norepinephrine
Catecholamine is derived from tyrosine. https://pubchem.ncbi.nlm.nih.gov/compound/catecholamine
Tyrosine can be eaten in dairy products, meats, fish, eggs, nuts, beans, oats, and wheat. The body uses tyrosine to make chemical messengers that are involved in conditions affecting the brain, such as mental alertness. https://www.webmd.com/vitamins/ai/ingredientmono-1037/tyrosineTyrosine amino acid is a precursor for the synthesis of catecholamine epinephrine , thyroid thyroxine, and melanin.
Tyrosine is synthesized from phenylalanine.
https://pubchem.ncbi.nlm.nih.gov/compound/tyrosine
Phenylalanine is an amino acid found in fruits, vegetables and meat (includes seafood and poultry), Phenylalanine plays a key role in the biosynthesis of other amino acids and is important in the structure and function of many proteins and enzymes. Phenylalanine is converted to tyrosine, used in the biosynthesis of dopamine and norepinephrine neurotransmitters. The D-form of phenylalanine acts as a painkiller (thus a natural aspirin and acetaminophen, ibuprofen)
https://pubchem.ncbi.nlm.nih.gov/compound/phenylalanine
Even though fruits and vegetables contain amino acids and amino acids are used by cells to form proteins, the USA government published the following: “Fresh fruits and vegetables are poor protein sources that do not contribute significantly to protein requirement.”
https://pubchem.ncbi.nlm.nih.gov/compound/phenylalanine
ACTH
Corticotropin-releasing hormone (CRH) is released from the hypothalamus in the brain, which stimulates the anterior pituitary gland in the brain to release adrenocorticotropic hormone (ACTH). ACTH regulates cortisol and androgen production. ACTH is then sent downstream towards the kidneys where there are ACTH receptors in the adrenal glands located on both kidneys. This stimulates adenylyl cyclase which leads to an increase in intracellular cAMP and activation of protein kinase A. https://www.ncbi.nlm.nih.gov/books/NBK500031/Mice lacking type I adenylyl cyclase have deficits in spatial memory as well as long-term potentiation, a cellular model of learning and memory.
Type V adenylyl cyclase is also expressed in heart and kidney, where it is associated with blood vessels; the anterior lobe of the pituitary; and the retina. All of these tissues share the common feature of being stimulated by dopamine. https://www.ncbi.nlm.nih.gov/books/NBK27958/
cAMP serves as a cellular second messenger for numerous outside the cell signals in the nervous system. The number of functional processes regulated by cAMP is very large.
First, cAMP mediates some short-term aspects of synaptic transmission and mediates some rapid actions of certain neurotransmitters.
Second, cAMP and other cellular messengers, play a central role in mediating other aspects of message transmission between nerves and neurons such as virtually all other effects of neurotransmitters on their target neurons, including regulating the metabolic state of neurons, modulating neurotransmitter synthesis, storage and release; receptor sensitivity, cytoskeletal organization and structure; neuron growth and specialization and regulating long-term actions of neurotransmitters that are mediated through alterations in neuron gene expression, [thus capable of causing allele switches to be flipped, thus flipping the scripts being carried out].
cAMP also plays a role in the activation of certain glutamate receptors. cAMP then mediates several other effects of glutamate on the neurons. By virtue of numerous interactions between cAMP and other intracellular messenger pathways, these pathways play the central role in coordinating a myriad neuronal processes and adjusting/adapting neuronal function to environmental cues, [short, medium and longterm.]
The most important mechanism by which cAMP exerts its myriad physiological effects is through the specific activation of cAMP-dependent protein kinase. cAMP-dependent protein kinase is now known to phosphorylate virtually every major class of neural protein; this accounts for the ability of cAMP to influence many aspects of neuron/nerve function. https://www.ncbi.nlm.nih.gov/books/NBK27915/
Corticotrophin-releasing hormone's (CRH) main role in the body is as the central driver of the stress hormone system, known as the hypothalamic–pituitary–adrenal axis. Corticotrophin-releasing hormone is given this name because it causes release of ACTH which travels in the bloodstream to the adrenal glands where it causes the secretion of the stress hormone cortisol,a glucocorticoid.
Corticotrophin-releasing hormone also acts on many other areas within the brain where it suppresses appetite, increases anxiety, and improves memory and selective attention. Together, these effects co-ordinate behaviour to develop and fine tune the body’s response to a stressful experience.
In smaller quantities, corticotrophin-releasing hormone is also made by certain white blood cells, where it stimulates swelling or tenderness known as inflammation, particularly of the gut.
How is corticotrophin-releasing hormone controlled?
Corticotrophin-releasing hormone secretion is stimulated by nervous activity within the brain. It follows a natural 24 hour rhythm in non-stressed circumstances, where it is highest at around 8 a.m. and lowest overnight. However, corticotrophin-releasing hormone can also be increased above the normal daily levels by a stressful experience, infection or even exercise. An increase in corticotrophin-releasing hormone leads to higher levels of the stress hormone cortisol which mobilizes energy resources [ATP] needed for dealing with the cause of the stress. High levels of stress hormones over a long period can have negative effects on the body. Because of this, cortisol blocks the continued release of corticotrophin-releasing hormone and switches off the hypothalamus–pituitary–adrenal axis, which is known as a negative feedback loop.
What happens if I have too much corticotrophin-releasing hormone?
Abnormally high corticotrophin-releasing hormone levels are connected with a variety of diseases. Because it stimulates anxiety and suppresses appetite, too much corticotrophin-releasing hormone is suspected of causing nervous problems such as clinical depression, anxiety, sleep disturbances and anorexia nervosa.
What happens if I have too little corticotrophin-releasing hormone?
[Some studies, but not enough, suggest] people with Alzheimer’s disease have particularly low corticotrophin-releasing hormone levels.
https://www.yourhormones.info/hormones/corticotrophin-releasing-hormone/
ACTH plays a role in glucose metabolism and immune function. Glucose metabolism leads to the production of acetylcholine.Dysfunctions associated with ACTH can be with the [Nervous system, hypothalamus, nutrition], pituitary, adrenals or ectopic secretion.
The pituitary and/or adrenals can be hypofunctioning or hyperfunctioning.
Ectopic secretion refers to the production of a hormone outside of its normal physiology mechanism. Benign or malignant tumors secrete hormones which are not controlled by the normal feedback loop. https://www.ncbi.nlm.nih.gov/books/NBK500031/
Back To Acetylcholine, The Main Neurotransmitter
Acetylcholine is synthesized in nerve terminals from acetyl coenzyme A (acetyl CoA, synthesized from glucose) and choline from food, in a reaction catalyzed by choline acetyltransferase (CAT or ChAT). The protein, vesicular acetylcholine transporter (VAChT), is responsible for transporting acetylcholine from cellular cytoplasm into the synaptic vesicles. The expressions of ChAT and VAChT are regulated by multiple elements. https://writerswhirlpool.blogspot.com/2020/06/treatments-dementia-syndrome-2-of-2-delving-deeper-unity-2150.htmlAcetyl-CoA or acetyl coenzyme A is a component of cellular respiration (energy conversion) that adds acetyl groups to biochemical reactions. Acetyl-CoA can be produced via the catabolism (breakdown) of carbohydrates (glucose) and lipids (fatty acids). Acetyl-CoA is a product of glycolysis (at high glucose levels) or beta-oxidation (at low glucose levels). The components of acetyl co-A are acetyl and coenzyme A.
Coenzyme A (Co-A) is produced from vitamin B5 (pantothenic acid or pantothenate). Some natural sources are cabbage, broccoli, whole grains, and potatoes.
Many types of intestinal bacteria manufacture pantothenate from certain amino acids. When pantothenate levels in the body are low, CoA and acetyl-CoA levels will also be low.
CoA production overlaps with other vitamin-producing pathways which can also affect the availability of both CoA and acetyl-CoA. [When nutrient levels are insufficient] competing vitamins are B9-folic acid and B1- thiamine.
One of the known substrates of Protein histidine phosphatase (PHP) is ATP-citrate lyase (ACL), which is responsible for providing acetyl-CoA for acetylcholine synthesis in neuronal tissues. PHP downregulates the activity of ACL. Overproduction or overexpression of PHP will decrease acetylcholine levels and induce apoptosis (cell death), thus PHP function, dysfunction, disorder must be investigated for any casual indicators. https://biologydictionary.net/acetyl-CoA/ (2020) and https://www.amboss.com/us/knowledge/Citric_acid_cycle and https://duckduckgo.com/?q=protein+histidine+phosphatase+acetyl&ia=web
Nicotine Interactions With Drugs and Medications
Per https://pubmed.ncbi.nlm.nih.gov/19794359/, “Smoking prevalence for schizophrenic patients is higher than for general population. More than 60% of schizophrenic patients are smokers. Smoking increases the release of dopamine and inhibits its degradation.
Smokers should ask their doctors about nicotine and interactions with prescription and over the counter medications. Smokers should also perform individual searches for nicotine and each medication being taken.Nicotine use increases the oral clearance of rivastigmine by 23%, thus nicotine causes more rapid removal of rivastigmine from the blood, thus a higher dose might be necessary for cigarette smokers https://www.drugs.com/drug-interactions/nicotine-with-rivastigmine-1716-0-2023-0.html?professional=1 and https://www.drugs.com/drug-interactions/nicotine-index.html
Unlike donepezil that selectively inhibits AChE, rivastigmine inhibits both BuChE and AChE.
Considering the clinical effects of donepezil, rivastigmine and galantamine, there is no evidence that any of these medications is superior in terms of efficacy. However, donepezil has been found to be better tolerated, with less gastrointestinal side effects than rivastigmine or galantamine https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3648782/ (2013) and https://www.ncbi.nlm.nih.gov/books/NBK554534/ (2021)
Additional References
Pharmacology of Nicotine: Addiction, Smoking-Induced Disease, and Therapeuticshttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2946180/
https://www.jt-science.com/nicotine
Adenyl Cyclase* https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1344045/pdf/annsurg00285-0081.pdfMotivating and Helping Smokers to Stop Smoking
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1494968/
Nortriptyline https://pubchem.ncbi.nlm.nih.gov/compound/nortriptyline
Nortriptyline is a tricyclic antidepressant agent used for short-term treatment of various forms of depression. Nortriptyline blocks the norepinephrine presynaptic receptors, thereby blocking the reuptake of this neurotransmitter, thus raising the concentration in the synaptic cleft in the central nervous system. Nortriptyline also binds to alpha-adrenergic, histaminergic and cholinergic receptors. Long-term treatment with nortriptyline produces a downregulation of adrenergic receptors due to the increased stimulation of these receptors.
Cholinergic Medications [ & Acetycholine] https://www.ncbi.nlm.nih.gov/books/NBK538163/
The role of acetylcholine in drug addiction https://www.researchgate.net/publication/275493318_The_role_of_acetylcholine_in_drug_addiction