BrahminBoss
Boatsman from river of Styx triple 6
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Nicotine is the main active compound in tobacco and thus the main active compound in tobacco cigars and cigarettes. Many studies have painted a picture of the negative health effects brought on by smoking. It is important however to differentiate between smoking tobacco and consumption of nicotine isolated from tobacco. With the advent of E-Cigarettes, nicotine gum, and nicotine patches- The isolated effects of nicotine are being studied and show many potential benefits. I posit nicotine as being similar in effect to caffeine- a drug which is well known on the forum for its pro-metabolic effects. Nicotine however must be seen in its own light for its unique and potentially useful effects.
Nicotine Effects on Resting Metabolic Rate (RMR)
Acute effects of nicotine on resting metabolic rate in cigarette smokers. - PubMed - NCBI
Increased 24-hour energy expenditure in cigarette smokers. - PubMed - NCBI
The 1st study shows an increase in daily energy expenditure of around 6%. The 2nd study shows an increase in daily energy expenditure of around 10% which correlates to an extra energy expenditure of around 200kcal per day. This would equal weight loss of around 10kg/22lbs per year if caloric intake does not increase and remains consistent. Nicotine has been demonstrated in numerous studies to raise basal metabolic rate and body temperature. Nicotines ability to raise metabolic rate and increase thermogenesis is similar to caffeine.
Effects of caffeine ingestion on NE kinetics, fat oxidation, and energy expenditure in younger and older men | Endocrinology and Metabolism
In this study- caffeine boosts energy expenditure by an average of 10%. This is similar to the effects demonstrated by the nicotine studies.
The effects of nicotine and caffeine are dose- dependent but likely harbor similar potential for raising metabolic rate and energy expenditure. Both Caffeine and Nicotine consumption are associated with lower incidence of obesity and leaner body mass due to their actions of increasing energy expenditure.
Nicotine Effects on Pituitary Hormones
“On the level of the whole organism, stress causes overactivity of the pituitary, and removal of the pituitary extends life, and retards the hardening of the extracellular connective material
(Everitt, et al., 1983).”
“Several of his [Everett] experiments strongly pointed to the prolactin-growth hormone family as the aging factors. Removal of the pituitary caused retardation of aging similar to food restriction.”
(Ray Peat PHD)
“The “little mouse,” and the experiments of Denckla and Everitt, show that a simple growth hormone deficiency or lack of pituitary function can double the life span: Intervention in the many other self-stimulating excitatory pathways can produce additional retardation of the aging process, acting at many levels, from from the extracellular matrix to the brain.” (Ray Peat PHD)
Smoking may alter physiological systems involved in the stress response. Smokers show attenuated (Lowered) cortisol and systolic blood pressure response to acute stressors when compared to nonsmokers. The extent to which absent cortisol response is due to an enhanced negative feedback caused by the higher basal cortisol concentrations or to attenuated sensitivity to stress-related physiological activation is not yet clear. Potential central mechanisms involved in the altered stress response include a reduction in the number or affinity of receptors mediating effects of nicotine in different central nervous system structures that integrate the neuroendocrine stress response (al'Absi et al., 2003). Chronic nicotine consumption may also lead to lower responses of other stress hormones (ACTH, prolactin, growth hormone) to a variety of stimuli (Kirschbaum et al., 1994).
-Thyroid Stimulating Hormone (TSH) Is released to stimulate the thyroid to produce more hormones. Having low TSH is generally an indicator of good health and means that thyroid hormone is being used efficiently by the body.
-Growth hormone (GH) Teams up with estrogen and nitric oxide to produce edema. Growth hormone also increases the release of free fatty acids into the blood stream.
-Prolactin (PRL) Stimulated by TRH and Estrogen and suppressed by dopamine and progesterone. Increases with stress and age and likely contributes to osteroperosis.
-TRH-Follicle-Stimulating Hormone (FSH) Increases aromatase and estrogen. "The activity of aromatase increases with aging, and under the influence of prolactin, cortisol, prostaglandin, and the pituitary hormones, FSH (follicle stimulating hormone) and growth hormone. It is inhibited by progesterone, thyroid, aspirin, and high altitude." (Ray Peat PHD)
-Luteinizing Hormone (LH) "Estrogen's stress-mimicking action probably tends to increase the secretion of LH, in ways that can be corrected by supplementing progesterone and thyroid." (Ray Peat PHD)
-Adrenocorticotropic Hormone (ACTH) Stimulates stress hormone and androgen production.
Studies seem to show mixed results in that acute exposure to cigarettes and/or nicotine may increase or decrease certain pituitary hormones. Overall however chronic nicotine intake is associated with reductions in the pituitary hormones suggesting that nicotine induces adaptive mechanisms that support the body. These same adaptations are seen in caffeine studies in that acute intake can increase stress and pituitary hormones however chronic users adapt and show reduced amounts. Most of the benefits of nicotine seem to come from chronic use and many of these adaptations take place in around 3 days.
Nicotine Lowers TSH, LH, FSH, and GH:
Acute effects of nicotine on serum glucose insulin growth hormone and cortisol in healthy smokers. - PubMed - NCBI
"A secondary finding observed in the overall study group (primarily in females) was that nicotine caused a 29% median decrease in serum growth hormone (P =.02)."
Involvement of cholinergic nicotine-like receptors as modulators of amine turnover in various types of hypothalamic dopamine and noradrenaline nerv... - PubMed - NCBI
"Nicotine significantly reduced serum prolactin and TSH levels, and after H 44/68 it also reduced LH and FSH serum level"
Haidut Posted a Study Showing That Caffeine Also Lowers TSH and Growth Hormone:
Effects of caffeine on anterior pituitary and thyroid function in the rat. - PubMed - NCBI
"Caffeine lowered serum TSH and GH in a dose-dependent manner with ED50 values of 30 and approximately 50 mg/kg, respectively."
Chronic Nicotine Significantly Lowers Prolactin
Acute nicotine administration stimulates prolactin release (Wilkins et al., 1982; Rasmussen, 1995). However, serum prolactin levels are significantly lower in both male and female chronic smokers who smoke more than 10 cigarettes per day (Andersen et al., 1984). This apparent discrepancy could be explained by a similar mechanism to that with ACTH (Fuxe et al., 1989).
Nicotine acts directly on pituitary GH3 cells to inhibit prolactin promoter activity. - PubMed - NCBI
"Nicotine was also observed to yield a concentration-dependent inhibition of the stimulation by thyrotrophin-releasing hormone (TRH) of PRL promoter activity, implying that nicotine can also interfere with hormonal regulation of the PRL gene."
Chronic nicotine treatment increases dopamine levels and reduces dopamine utilization in substantia nigra and in surviving forebrain dopamine nerve... - PubMed - NCBI
"Chronic nicotine treatment under the present conditions did not significantly alter serum levels of corticosterone and reduced prolactin serum levels in sham-operated rats."
Involvement of D1 dopamine receptors in the nicotine-induced neuro-endocrine effects and depletion of diencephalic catecholamine stores in the male... - PubMed - NCBI
"Nicotine treatment and to a minor degree also acute intermittent exposure to cigarette smoke produced a reduction in serum prolactin, LH and TSH but not in serum FSH, vasopressin and testosterone levels."
Effects of chronic nicotine treatment and withdrawal on hypothalamic proopiomelanocortin gene expression and neuroendocrine regulation. - PubMed - NCBI
"Chronic daily nicotine administration induced significant changes in serum corticosterone, serum prolactin, MBH TH mRNA, and MBH POMC mRNA concentrations that tended to persist through day 3 of withdrawal; serum prolactin and MBH POMC mRNA concentrations were suppressed whereas serum corticosterone and MBH TH mRNA concentrations were stimulated."
-Estrogen raises prolactin[1] therefore chronic aromatase/estrogen inhibition by nicotine should lower prolactin.
-Thyrotropin-releasing hormone (TRH) has a stimulatory effect on prolactin release. Nicotine lowers TRH.
[1]Role of estrogen in the dopaminergic control of prolactin secretion. - PubMed - NCBI
"Treatment of ovariectomized rats with estradiol benzoate (25 microgram/kg, sc) daily for 5 days resulted in a marked elevation of the serum PRL concentration."
Effects of maternal nicotine exposure on thyroid hormone metabolism and function in adult rat progeny. - PubMed - NCBI
"Levels of both TRH and TSH were lower in offspring exposed to Nicotine..."
Chronic Nicotine Use has Neutral Effect on ACTH Levels
In contrast to the acute effect of smoking on ACTH levels, the latter are not altered in chronic smokers (del Arbol et al., 2000). This is probably due to desensitization of the central nicotinic cholinergic receptors involved (Fuxe et al., 1989).
Several of the symptoms of tobacco abstinence are characteristic of the stress response; the latter is associated with increases in plasma levels of ACTH (Selye, 1976). If tobacco withdrawal is a stressful event, nicotine abstinence would be expected to lead to increases in the plasma levels of ACTH. However, ACTH levels did not significantly increase during nicotine abstinence over ad libitum smoking levels (Pickworth et al., 1996).
Neuropsychopharmacology - Chronic Nicotine Self-Administration Augments Hypothalamic-Pituitary-Adrenal Responses to Mild Acute Stress
"On day 1 of acquisition of nicotine self administration, plasma levels of both adrenocorticotropin (ACTH) and corticosterone were significantly increased 15–30 min after the first dose of nicotine. These hormonal changes were no longer significant on day 3, when adrenocorticotropin levels were <60 pg/ml and corticosterone levels were <110 ng/ml during the hour after the first dose of nicotine."
Nicotine Effects on Estrogen, Aromatase, and Testosterone
Again it is important to differentiate between cigarettes and isolated nicotine. Polycyclic aromatic Hydrocarbons are present in cigarette smoke which increase estrogenic activity. These are the same estrogenic compounds found in many plastics. Cigarette smoke also increases carbon monoxide in the body which is estrogenic. Nicotine and its metabolite cotinine however are strong anti-estrogens and aromatase inhibitors.
Nicotine Inhibits Aromatase (The Enzyme Which Converts Testosterone to Estrogen)
Nicotine Blocks Brain Estrogen Synthase (Aromatase): In Vivo Positron Emission Tomography Studies in Female Baboons
"The size of the effect (more than 50% of the maximal inhibition obtained with a blocking dose of vorozole) suggests that nicotine is capable of inhibiting the activity of aromatase in the primate brain."
JCI - Nicotine, cotinine, and anabasine inhibit aromatase in human trophoblast in vitro.
"In choriocarcinoma cell cultures, nicotine, cotinine (a major metabolite of nicotine), and anabasine (a minor component of cigarette tobacco) all inhibited androstenedione conversion to estrogen in a dose-dependent fashion. Removal of nicotine, cotinine, and anabasine from the culture medium resulted in the complete reversal of the inhibition of aromatase."
Potential Contribution of Aromatase Inhibition to the Effects of Nicotine and Related Compounds on the Brain
"Thus, we have shown that nicotine doses producing plasma levels comparable with those found in smokers are capable of a significant but partial (∼50%) inhibition of aromatase."
Nicotine Also Directly Lowers Estrogen and Helps Clear it From the Liver
Smoking, estradiol metabolism and hormone replacement therapy. - PubMed - NCBI
"However, it has been proven that, depending on the type, duration and intensity of nicotine consumption, smoking can reduce or completely cancel the efficacy of orally administered estrogens."
"The reduction or loss of therapeutic efficacy is mainly caused by dose-dependent elevated hepatic clearance, partially in conjunction with lower estrogen levels, and has been demonstrated only with oral estrogen applications."
Nicotine raises DHT by decreasing conversion of DHT to alpha-androstanediol (estrogenic)
Nicotine and cotinine effects on 3 alpha hydroxysteroid dehydrogenase in canine prostate. - PubMed - NCBI
"The results suggest that nicotine and cotinine are competitive inhibitors of the HSD, an important enzyme involved in the metabolism of DHT and produce an accumulation of DHT."
Progesterone and Chronic Caffeine Consumption Also Raise DHT:
http://www.karger.com/Article/Pdf/12299
"At 6–8 h after administration of Progesterone, serum T and DHT levels were consistently increased without any alterations in the serum LH and FSH levels. "
Chronic caffeine intake increases androgenic stimuli, epithelial cell proliferation and hyperplasia in rat ventral prostate
"Our results show that caffeine intake increased the concentrations of T and DHT, organ weight, epithelial cell proliferation and AR tissue expression in the ventral prostatic lobe."
Nicotine and Testosterone
Hormones.gr
Evaluation of the effects of cigarette smoking on testosterone levels in adult men. - PubMed - NCBI
http://www.biomed.cas.cz/physiolres/pdf/62/62_67.pdf
Effect of cigarette smoking on levels of bioavailable testosterone in healthy men | Clinical Science
There are conflicting opinions as to whether or not nicotine raises testosterone. This is probaly due to the fact that many studies on nicotine and testosterone levels use cigarettes which have both estrogenic and anti-estrogenic compounds. Most studies demonstrate that smokers have at least normal if not higher levels of testosterone than non-smokers. Nicotine will most certainly lower estrogen and many symptoms of low testosterone are really caused by high estrogen. Therefore nicotine can have a positive effect on people experiencing symptoms of low testosterone.
Nicotine, Progesterone, DHEA, and Memory
Hormones, Nicotine and Cocaine: Clinical Studies
"Progesterone treatment decreases nicotine self-administration under a progressive-ratio schedule"
Effects of pregnancy on nicotine self-administration and nicotine pharmacokinetics in rats. - PubMed - NCBI
"NSA (Nicotine Self Administration) decreased over the course of pregnancy with NSA significantly lower in the third trimester compared to nonpregnant controls."
Progesterone effects on subjective and physiological responses to intravenous nicotine in male and female smokers. - PubMed - NCBI
"Progesterone also suppressed smoking urges by nicotine as assessed by the Brief Questionnaire on Smoking Urges"
When progesterone is high (such as in pregnancy)- nicotine use and cravings decrease. This suggests that nicotine may compensate for low progesterone or may directly increase progesterone.
Indeed This Study Shows That Nicotine Increases Neuro-Steroid Levels of Pregnenolone, Progesterone, and Allopregnanolone:
Neurosteroids in nicotine and morphine dependence. - PubMed - NCBI
"Acute intraperitoneal administration of nicotine (0.3-2 mg kg-1) or morphine (5-30 mg kg-1) induced dose- and time-dependent increases in the cerebrocortical and plasma concentrations of pregnenolone, progesterone, and allopregnanolone."
Caffeine Does the Same Thing
Caffeine-induced increases in the brain and plasma concentrations of neuroactive steroids in the rat. - PubMed - NCBI
A single intraperitoneal injection of caffeine induced dose- and time-dependent increases in the concentrations of pregnenolone, progesterone, and 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone) in the cerebral cortex.
Drug Withdrawal Caused by Reduced Neuro-Steroids?
Neurosteroid coadministration prevents development of tolerance and augments recovery from benzodiazepine withdrawal anxiety and hyperactivity in m... - PubMed - NCBI
Chronic neurosteroid treatment prevents the development of morphine tolerance and attenuates abstinence behavior in mice. - PubMed - NCBI
The neuro-steroids progesterone and pregnenolone seem to eliminate tolerance and withdrawal symptoms from long term drug use. I think it is likely that nicotine/caffeine withdrawals come from the bodies adjustment to reduced neuro-steroids on cessation of the drug.
Nicotine Increases DHEA
Effects of Low and High Nicotine Cigarette Smoking on Mood States and the HPA Axis in Men
"After high nicotine cigarette smoking began, plasma ACTH levels increased significantly above baseline within 12 min and reached peak levels of 21.88 ± 5.34 pmol/L within 20 min. ACTH increases were significantly correlated with increases in plasma nicotine (r=0.85; P<0.0001), DHEA (r=0.66; P=0.002), and epinephrine (r=0.86; P<0.0001). Cortisol and DHEA increased significantly within 20 min (P<0.05) and reached peak levels of 424 ± 48 nmol/L and 21.13 ± 2.55 ng/ml within 60 and 30 min, respectively."
Ray States the Benefits of Progesterone as Follows:
"Experiments have shown that progesterone relieves anxiety, improves memory, protects brain cells, and even prevents epileptic seizures. It promotes respiration, and has been used to correct emphysema. In the circulatory system, it prevents bulging veins by increasing the tone of blood vessels, and improves the efficiency of the heart. It reverses many of the signs of aging in the skin, and promotes healthy bone growth. It can relieve many types of arthritis, and helps a variety of immunological problems."
Progesterone Summaries - Progesterone Deceptions - Progesterone Supplementation - Dosage of Progesterone
-Nicotine and Caffeine Use Both Elicit Many of These Effects, probaly through increasing neurosteroids.
Nicotine Increases Short Term and Working Memory Similar to Progesterone
Repeated nicotine exposure in rats: effects on memory function, cholinergic markers and nerve growth factor. - PubMed - NCBI
"In the present study, male Wistar rats exposed a relatively low dosage of nicotine (0.35 mg/kg every 12 h) for 14 days demonstrated improved memory performance (assessed in two separate water maze testing methods) when compared with controls. Autoradiographic experiments indicated that nicotine increased [3H]-epibatidine, [125I]-alpha-bungarotoxin and [3H]-AFDX384, but not [3H]-pirenzepine binding sites in several learning- and memory-related brain areas."
Cotinine reduces amyloid-β aggregation and improves memory in Alzheimer's disease mice. - PubMed - NCBI
"Cotinine (Nicotine metabolite) reduced Aβ deposition, improved working and reference memories, and inhibited Aβ oligomerization in the brains of transgenic (Tg) 6799 AD mice."
Cotinine reduces depressive-like behavior, working memory deficits, and synaptic loss associated with chronic stress in mice. - PubMed - NCBI
"Cotinine-treated mice displayed better performance than vehicle-treated cohorts on the working memory task, the radial arm water maze test. In addition, with or without chronic stress exposure, cotinine-treated mice engaged in fewer depressive-like behaviors as assessed using the tail suspension and Porsolt's forced swim tests."
"Taken together, our results show for the first time that cotinine reduces the negative effects of stress on mood, memory, and the synapse."
Nicotinic systems and cognitive function - Springer
Nicotine Increases Bone Growth (Possibly Through Decreasing Prolactin)
Nicotine Increases Osteoblast Activity of Induced Bone Marrow Stromal Cells in a Dose-Dependent Manner: An in vitro Cell Culture Experiment
Our study demonstrated a statistically significant effect of nicotine dose on osteoblast activity in vitro.
Low level nicotine: a novel approach to reduce osteoporosis incidence. - PubMed - NCBI
Studies also indicated that the prime criminal for osteoporosis is smoking not nicotine. Moreover, low level nicotine has preventive efforts on osteoporosis by stimulating osteoblasts proliferation and differentiation. We present a hypothesis that low level nicotine may be a novel approach to reduce osteoporosis incidence.
Nicotine Potentially Anti-Epileptic.
Nicotine as an antiepileptic agent in ADNFLE: an N-of-one study. - PubMed - NCBI
"In an open study, nicotine patches reduced seizures..."
-Nicotine is also structurally similar to nicotinic acid (Niacin) which has demonstrated anti-epileptic effects.
Nicotine, Caffeine, and Progesterone Are Neuro-Protective Against Parkinsons
Current evidence for neuroprotective effects of nicotine and caffeine against Parkinson's disease. - PubMed - NCBI
Association of coffee and caffeine intake with the risk of Parkinson disease. - PubMed - NCBI
Progesterone prevents depression-like behavior in a model of Parkinson's disease induced by 6-hydroxydopamine in male rats. - PubMed - NCBI
Nicotine, Caffeine, and Progesterone are Carbonic Anhydrase Inhibitors Thus Increasing Levels of CO2 in the Body and Making Breathing Easier.
Effects of nicotine and vitamin E on carbonic anhydrase activity in some rat tissues in vivo and in vitro. - PubMed - NCBI
Carbonic anhydrase I and II inhibition with natural products: caffeine and piperine. - PubMed - NCBI
An association between plasma progesterone and erythrocyte carbonic anhydrase I concentration in women. - PubMed - NCBI
Smoking Slows Arthritis
Cigarette smoking and radiographic progression in rheumatoid arthritis
"heavy smokers (>1 pack‐day) progressed significantly less than non‐smokers or moderate smokers (p<0.001)."
Nicotine Effects on Cortisol
-Again we will differentiate between cigarettes and isolated nicotine. Cigarettes Contain MAO-A inhibitors which increases epinephrine and norepinephrine. Increases of these stimulatory Neurotransmitters will eventually lead to increases in cortisol and ACTH. Carbon Monoxide exposure from cigarette smoke also increases cortisol and ACTH.
-Many studies show similar effects of acute nicotine and caffeine on increasing cortisol and ACTH. Chronic use of nicotine and caffeine however are adaptive and improve stress biomarkers as evidenced by reduced pituitary activity and increased thyroid activity.
Stress-like adrenocorticotropin responses to caffeine in young healthy men. - PubMed - NCBI
The effects of oral caffeine (3.3 mg/kg, equivalent to 2-3 cups of coffee) on plasma adrenocorticotropin (ACTH) and cortisol (CORT) were tested in 47 healthy young men at rest in a double-blind, placebo-controlled, crossover study. Following caffeine, ACTH was significantly elevated at all times from 30 min to 180 min, and CORT was elevated from 60 min to 120 min
http://www.ncbi.nlm.nih.gov/pubmed/2550038
Plasma ACTH and cortisol levels after oral administration of nicotine (chewing gum containing nicotine 2 mg) in short and long time (10 and 45 min) were studied in smokers and non smokers. Non smokers after short time administration showed significant rise in ACTH and cortisol. No modifications were seen in the other groups of subjects. [1]
[1]*Note that only the non-smokers experienced a stress response to acute nicotine and the smokers showed no changes. This is similar to how acute caffeine in infrequent drinkers creates a stress response but chronic users experience the opposite effect- lowered stress and stress adaptation.
http://www.ncbi.nlm.nih.gov/pubmed/21733336
"Chronic caffeine intake decreases circulating catecholamines and prevents diet-induced insulin resistance and hypertension in rats."
Nicotine Effects on Dopamine and Serotonin
Nicotine activates the sympathoadrenal system and increases the synthesis and release of noradrenaline and adrenaline into circulation, and also alters the bioavailability of dopamine (Pomerleau, 1992). Single and repeated injections of nicotine in rats increase the expression of tyrosine hydroxylase, a rate-limiting enzyme in the catecholamine biosynthetic pathway (Hiremagalur & Sabban, 1995).
-Increased expression of tyrosine hydroxylase suggests more tyrosine is being converted into dopamine in the body.
Nicotine Increases Expression of Tyrosine Hydroxylase- Increasing Dopamine
http://www.ncbi.nlm.nih.gov/pubmed/12538809
"Chronic nicotine treatment elicited long-lasting, dose-dependent increases in the levels of adrenal TH mRNA, TH protein, and TH activity. In contrast, a single injection of nicotine elicited only a small increase in adrenal TH mRNA levels, which was transient and did not result in the induction of TH enzyme. Chronic nicotine administration also elicited a sustained increase in adrenal TH gene transcription rate, which persisted for up to 7 days after the final nicotine injection. This sustained transcriptional response correlated with a modest sustained increase in adrenal TH AP1 binding, but not in the levels of Fra-2 or other fos or jun proteins. These results demonstrate that repeated nicotine injections administered chronically over 1 to 2 weeks lead to sustained stimulation of the TH gene and consequent induction of TH gene expression in rat adrenal medulla."
http://link.springer.com/chapter/10.1007/978-3-0348-7457-1_45
"...implying that as little as a single dose of nicotine is as effective as chronic nicotine administration in increasing tyrosine hydroxylase activity in noradrenergic neurones."
Nicotine Decreases Expression of Tryptophan Hydroxylase- Decreasing Serotonin
http://www.ncbi.nlm.nih.gov/pubmed/12165397
"Based on the results, it can be suggested that the pathogenesis of alcohol- and nicotine-induced neuropsychological disorders involves alcohol- and nicotine-induced suppression of 5-HT synthesis and TPH expression in raphe..."
Nicotine Decreases rate of Tryptophan Uptake Into Brain and Decreases Rate of Serotonin Production in Brain
http://www.ncbi.nlm.nih.gov/pubmed/7140821
"Both the acute and chronic (40 days) administration of nicotine (0.4 mg/kg s.c.) caused a decrease in the rate of formation of 5-HT by hippocampal synaptosomes (P less than 0.05) while 24 h withdrawal of the drug from chronically treated rats resulted in a partial recovery of this effect. Chronic nicotine treatment also reduced the rate of L-tryptophan uptake by hippocampal synaptosomes (P less than 0.01) an effect which appeared to be the result of a reduction in the number of L-tryptophan carrier molecules in the synaptosomal membrane."
Chronic Nicotine Exposure Acts Like an SSRE Drug by Enhancing Uptake of Serotonin
http://www.ncbi.nlm.nih.gov/pubmed/14515338
"A significant increase in [(3)H]5-HT uptake was observed in synaptosomes prepared from both regions. To rule out the possibility that the increases were due to the last injection given, in a separate set of experiments a single injection of nicotine was administered the evening before sacrifice. No change in uptake occurred in either region, suggesting that the increases in uptake caused by nicotine was an effect of chronic exposure and not to an acute treatment."
http://www.ncbi.nlm.nih.gov/pubmed/16463401
Nicotine at 4 microM increased [(3)H]5-HT uptake by 75%.
Nicotine, Caffeine, and Creativity
It is amazing see how many creative writers, philosophers, psychologists, actors, and artists are prolific smokers and caffeine drinkers. Many of these people swear by their" vices" claiming that it helps them work and is a source of their creative muse. Stephen King claims it takes him longer to finish a book after quitting smoking and Kurt Vonnegut claimed that smoking sped up his creative process. Sigmund Freud (Father of modern psychology) smoked 20 cigars a day and refused to quit smoking despite countless professional recommendations to do so. Philosopher Voltaire drank 40-50 cups of coffee per day. One must wonder if their is an association between creative genius and the changes in brain physiology brought on by nicotine and caffeine addiction- increased dopamine, metabolism, and neuro-steroids.
“Be careful when you cast out your demons that you don’t throw away the best of yourself.”
-Nietzsche
Final Thoughts
Please bear in mind that I am not advocating for the use of tobacco or cigarettes. I do think nicotine has many potential benefits and is worth experimentation and further research. Nicotine patches are probaly the safest option for obtaining nicotine however e-cigarettes and vaporisers are likely the most convenient, practical, and cheap option for long term use.
Ray has expressed concern that nicotine may increase acetylcholine levels in the body. It is hard to find firm evidence as to how nicotine effects acetylcholine levels. Choline uptake into the brain remains neutral or actually decreases in response to nicotine.
http://www.ncbi.nlm.nih.gov/pubmed/16758358
"No significant changes in choline uptake after acute or chronic nicotine exposure were observed in whole brain or cortex. Of considerable interest was a significant decrease in regional brain choline uptake measured in the hippocampus after chronic nicotine exposure (28 d). Our data suggest that the increased ACh transmission observed after nicotine exposure does not correlate with increased blood-to-brain transfer of choline. "
Another thing to note is that exposure to Acetylcholinesterase inhibitors (drugs that increase acetylcholine) generally decrease nicotinic acetylcholine receptors in the brain. The brain decreases its receptors to reduce sensitivity and protect from overload.
http://www.ncbi.nlm.nih.gov/pubmed/1575351
"Chronic elevations of ACh observed with organophosphorus poisoning or chronic use of reversible cholinesterase inhibitors results in down-regulation of AChRs."
Nicotine has the reverse effect of these acetylcholinergic drugs and greatly increases the density of receptors suggesting nicotine may behave differently from other cholinergics.
Nicotine Effects on Resting Metabolic Rate (RMR)
Acute effects of nicotine on resting metabolic rate in cigarette smokers. - PubMed - NCBI
Increased 24-hour energy expenditure in cigarette smokers. - PubMed - NCBI
The 1st study shows an increase in daily energy expenditure of around 6%. The 2nd study shows an increase in daily energy expenditure of around 10% which correlates to an extra energy expenditure of around 200kcal per day. This would equal weight loss of around 10kg/22lbs per year if caloric intake does not increase and remains consistent. Nicotine has been demonstrated in numerous studies to raise basal metabolic rate and body temperature. Nicotines ability to raise metabolic rate and increase thermogenesis is similar to caffeine.
Effects of caffeine ingestion on NE kinetics, fat oxidation, and energy expenditure in younger and older men | Endocrinology and Metabolism
In this study- caffeine boosts energy expenditure by an average of 10%. This is similar to the effects demonstrated by the nicotine studies.
The effects of nicotine and caffeine are dose- dependent but likely harbor similar potential for raising metabolic rate and energy expenditure. Both Caffeine and Nicotine consumption are associated with lower incidence of obesity and leaner body mass due to their actions of increasing energy expenditure.
Nicotine Effects on Pituitary Hormones
“On the level of the whole organism, stress causes overactivity of the pituitary, and removal of the pituitary extends life, and retards the hardening of the extracellular connective material
(Everitt, et al., 1983).”
“Several of his [Everett] experiments strongly pointed to the prolactin-growth hormone family as the aging factors. Removal of the pituitary caused retardation of aging similar to food restriction.”
(Ray Peat PHD)
“The “little mouse,” and the experiments of Denckla and Everitt, show that a simple growth hormone deficiency or lack of pituitary function can double the life span: Intervention in the many other self-stimulating excitatory pathways can produce additional retardation of the aging process, acting at many levels, from from the extracellular matrix to the brain.” (Ray Peat PHD)
Smoking may alter physiological systems involved in the stress response. Smokers show attenuated (Lowered) cortisol and systolic blood pressure response to acute stressors when compared to nonsmokers. The extent to which absent cortisol response is due to an enhanced negative feedback caused by the higher basal cortisol concentrations or to attenuated sensitivity to stress-related physiological activation is not yet clear. Potential central mechanisms involved in the altered stress response include a reduction in the number or affinity of receptors mediating effects of nicotine in different central nervous system structures that integrate the neuroendocrine stress response (al'Absi et al., 2003). Chronic nicotine consumption may also lead to lower responses of other stress hormones (ACTH, prolactin, growth hormone) to a variety of stimuli (Kirschbaum et al., 1994).
-Thyroid Stimulating Hormone (TSH) Is released to stimulate the thyroid to produce more hormones. Having low TSH is generally an indicator of good health and means that thyroid hormone is being used efficiently by the body.
-Growth hormone (GH) Teams up with estrogen and nitric oxide to produce edema. Growth hormone also increases the release of free fatty acids into the blood stream.
-Prolactin (PRL) Stimulated by TRH and Estrogen and suppressed by dopamine and progesterone. Increases with stress and age and likely contributes to osteroperosis.
-TRH-Follicle-Stimulating Hormone (FSH) Increases aromatase and estrogen. "The activity of aromatase increases with aging, and under the influence of prolactin, cortisol, prostaglandin, and the pituitary hormones, FSH (follicle stimulating hormone) and growth hormone. It is inhibited by progesterone, thyroid, aspirin, and high altitude." (Ray Peat PHD)
-Luteinizing Hormone (LH) "Estrogen's stress-mimicking action probably tends to increase the secretion of LH, in ways that can be corrected by supplementing progesterone and thyroid." (Ray Peat PHD)
-Adrenocorticotropic Hormone (ACTH) Stimulates stress hormone and androgen production.
Studies seem to show mixed results in that acute exposure to cigarettes and/or nicotine may increase or decrease certain pituitary hormones. Overall however chronic nicotine intake is associated with reductions in the pituitary hormones suggesting that nicotine induces adaptive mechanisms that support the body. These same adaptations are seen in caffeine studies in that acute intake can increase stress and pituitary hormones however chronic users adapt and show reduced amounts. Most of the benefits of nicotine seem to come from chronic use and many of these adaptations take place in around 3 days.
Nicotine Lowers TSH, LH, FSH, and GH:
Acute effects of nicotine on serum glucose insulin growth hormone and cortisol in healthy smokers. - PubMed - NCBI
"A secondary finding observed in the overall study group (primarily in females) was that nicotine caused a 29% median decrease in serum growth hormone (P =.02)."
Involvement of cholinergic nicotine-like receptors as modulators of amine turnover in various types of hypothalamic dopamine and noradrenaline nerv... - PubMed - NCBI
"Nicotine significantly reduced serum prolactin and TSH levels, and after H 44/68 it also reduced LH and FSH serum level"
Haidut Posted a Study Showing That Caffeine Also Lowers TSH and Growth Hormone:
Effects of caffeine on anterior pituitary and thyroid function in the rat. - PubMed - NCBI
"Caffeine lowered serum TSH and GH in a dose-dependent manner with ED50 values of 30 and approximately 50 mg/kg, respectively."
Chronic Nicotine Significantly Lowers Prolactin
Acute nicotine administration stimulates prolactin release (Wilkins et al., 1982; Rasmussen, 1995). However, serum prolactin levels are significantly lower in both male and female chronic smokers who smoke more than 10 cigarettes per day (Andersen et al., 1984). This apparent discrepancy could be explained by a similar mechanism to that with ACTH (Fuxe et al., 1989).
Nicotine acts directly on pituitary GH3 cells to inhibit prolactin promoter activity. - PubMed - NCBI
"Nicotine was also observed to yield a concentration-dependent inhibition of the stimulation by thyrotrophin-releasing hormone (TRH) of PRL promoter activity, implying that nicotine can also interfere with hormonal regulation of the PRL gene."
Chronic nicotine treatment increases dopamine levels and reduces dopamine utilization in substantia nigra and in surviving forebrain dopamine nerve... - PubMed - NCBI
"Chronic nicotine treatment under the present conditions did not significantly alter serum levels of corticosterone and reduced prolactin serum levels in sham-operated rats."
Involvement of D1 dopamine receptors in the nicotine-induced neuro-endocrine effects and depletion of diencephalic catecholamine stores in the male... - PubMed - NCBI
"Nicotine treatment and to a minor degree also acute intermittent exposure to cigarette smoke produced a reduction in serum prolactin, LH and TSH but not in serum FSH, vasopressin and testosterone levels."
Effects of chronic nicotine treatment and withdrawal on hypothalamic proopiomelanocortin gene expression and neuroendocrine regulation. - PubMed - NCBI
"Chronic daily nicotine administration induced significant changes in serum corticosterone, serum prolactin, MBH TH mRNA, and MBH POMC mRNA concentrations that tended to persist through day 3 of withdrawal; serum prolactin and MBH POMC mRNA concentrations were suppressed whereas serum corticosterone and MBH TH mRNA concentrations were stimulated."
-Estrogen raises prolactin[1] therefore chronic aromatase/estrogen inhibition by nicotine should lower prolactin.
-Thyrotropin-releasing hormone (TRH) has a stimulatory effect on prolactin release. Nicotine lowers TRH.
[1]Role of estrogen in the dopaminergic control of prolactin secretion. - PubMed - NCBI
"Treatment of ovariectomized rats with estradiol benzoate (25 microgram/kg, sc) daily for 5 days resulted in a marked elevation of the serum PRL concentration."
Effects of maternal nicotine exposure on thyroid hormone metabolism and function in adult rat progeny. - PubMed - NCBI
"Levels of both TRH and TSH were lower in offspring exposed to Nicotine..."
Chronic Nicotine Use has Neutral Effect on ACTH Levels
In contrast to the acute effect of smoking on ACTH levels, the latter are not altered in chronic smokers (del Arbol et al., 2000). This is probably due to desensitization of the central nicotinic cholinergic receptors involved (Fuxe et al., 1989).
Several of the symptoms of tobacco abstinence are characteristic of the stress response; the latter is associated with increases in plasma levels of ACTH (Selye, 1976). If tobacco withdrawal is a stressful event, nicotine abstinence would be expected to lead to increases in the plasma levels of ACTH. However, ACTH levels did not significantly increase during nicotine abstinence over ad libitum smoking levels (Pickworth et al., 1996).
Neuropsychopharmacology - Chronic Nicotine Self-Administration Augments Hypothalamic-Pituitary-Adrenal Responses to Mild Acute Stress
"On day 1 of acquisition of nicotine self administration, plasma levels of both adrenocorticotropin (ACTH) and corticosterone were significantly increased 15–30 min after the first dose of nicotine. These hormonal changes were no longer significant on day 3, when adrenocorticotropin levels were <60 pg/ml and corticosterone levels were <110 ng/ml during the hour after the first dose of nicotine."
Nicotine Effects on Estrogen, Aromatase, and Testosterone
Again it is important to differentiate between cigarettes and isolated nicotine. Polycyclic aromatic Hydrocarbons are present in cigarette smoke which increase estrogenic activity. These are the same estrogenic compounds found in many plastics. Cigarette smoke also increases carbon monoxide in the body which is estrogenic. Nicotine and its metabolite cotinine however are strong anti-estrogens and aromatase inhibitors.
Nicotine Inhibits Aromatase (The Enzyme Which Converts Testosterone to Estrogen)
Nicotine Blocks Brain Estrogen Synthase (Aromatase): In Vivo Positron Emission Tomography Studies in Female Baboons
"The size of the effect (more than 50% of the maximal inhibition obtained with a blocking dose of vorozole) suggests that nicotine is capable of inhibiting the activity of aromatase in the primate brain."
JCI - Nicotine, cotinine, and anabasine inhibit aromatase in human trophoblast in vitro.
"In choriocarcinoma cell cultures, nicotine, cotinine (a major metabolite of nicotine), and anabasine (a minor component of cigarette tobacco) all inhibited androstenedione conversion to estrogen in a dose-dependent fashion. Removal of nicotine, cotinine, and anabasine from the culture medium resulted in the complete reversal of the inhibition of aromatase."
Potential Contribution of Aromatase Inhibition to the Effects of Nicotine and Related Compounds on the Brain
"Thus, we have shown that nicotine doses producing plasma levels comparable with those found in smokers are capable of a significant but partial (∼50%) inhibition of aromatase."
Nicotine Also Directly Lowers Estrogen and Helps Clear it From the Liver
Smoking, estradiol metabolism and hormone replacement therapy. - PubMed - NCBI
"However, it has been proven that, depending on the type, duration and intensity of nicotine consumption, smoking can reduce or completely cancel the efficacy of orally administered estrogens."
"The reduction or loss of therapeutic efficacy is mainly caused by dose-dependent elevated hepatic clearance, partially in conjunction with lower estrogen levels, and has been demonstrated only with oral estrogen applications."
Nicotine raises DHT by decreasing conversion of DHT to alpha-androstanediol (estrogenic)
Nicotine and cotinine effects on 3 alpha hydroxysteroid dehydrogenase in canine prostate. - PubMed - NCBI
"The results suggest that nicotine and cotinine are competitive inhibitors of the HSD, an important enzyme involved in the metabolism of DHT and produce an accumulation of DHT."
Progesterone and Chronic Caffeine Consumption Also Raise DHT:
http://www.karger.com/Article/Pdf/12299
"At 6–8 h after administration of Progesterone, serum T and DHT levels were consistently increased without any alterations in the serum LH and FSH levels. "
Chronic caffeine intake increases androgenic stimuli, epithelial cell proliferation and hyperplasia in rat ventral prostate
"Our results show that caffeine intake increased the concentrations of T and DHT, organ weight, epithelial cell proliferation and AR tissue expression in the ventral prostatic lobe."
Nicotine and Testosterone
Hormones.gr
Evaluation of the effects of cigarette smoking on testosterone levels in adult men. - PubMed - NCBI
http://www.biomed.cas.cz/physiolres/pdf/62/62_67.pdf
Effect of cigarette smoking on levels of bioavailable testosterone in healthy men | Clinical Science
There are conflicting opinions as to whether or not nicotine raises testosterone. This is probaly due to the fact that many studies on nicotine and testosterone levels use cigarettes which have both estrogenic and anti-estrogenic compounds. Most studies demonstrate that smokers have at least normal if not higher levels of testosterone than non-smokers. Nicotine will most certainly lower estrogen and many symptoms of low testosterone are really caused by high estrogen. Therefore nicotine can have a positive effect on people experiencing symptoms of low testosterone.
Nicotine, Progesterone, DHEA, and Memory
Hormones, Nicotine and Cocaine: Clinical Studies
"Progesterone treatment decreases nicotine self-administration under a progressive-ratio schedule"
Effects of pregnancy on nicotine self-administration and nicotine pharmacokinetics in rats. - PubMed - NCBI
"NSA (Nicotine Self Administration) decreased over the course of pregnancy with NSA significantly lower in the third trimester compared to nonpregnant controls."
Progesterone effects on subjective and physiological responses to intravenous nicotine in male and female smokers. - PubMed - NCBI
"Progesterone also suppressed smoking urges by nicotine as assessed by the Brief Questionnaire on Smoking Urges"
When progesterone is high (such as in pregnancy)- nicotine use and cravings decrease. This suggests that nicotine may compensate for low progesterone or may directly increase progesterone.
Indeed This Study Shows That Nicotine Increases Neuro-Steroid Levels of Pregnenolone, Progesterone, and Allopregnanolone:
Neurosteroids in nicotine and morphine dependence. - PubMed - NCBI
"Acute intraperitoneal administration of nicotine (0.3-2 mg kg-1) or morphine (5-30 mg kg-1) induced dose- and time-dependent increases in the cerebrocortical and plasma concentrations of pregnenolone, progesterone, and allopregnanolone."
Caffeine Does the Same Thing
Caffeine-induced increases in the brain and plasma concentrations of neuroactive steroids in the rat. - PubMed - NCBI
A single intraperitoneal injection of caffeine induced dose- and time-dependent increases in the concentrations of pregnenolone, progesterone, and 3alpha-hydroxy-5alpha-pregnan-20-one (allopregnanolone) in the cerebral cortex.
Drug Withdrawal Caused by Reduced Neuro-Steroids?
Neurosteroid coadministration prevents development of tolerance and augments recovery from benzodiazepine withdrawal anxiety and hyperactivity in m... - PubMed - NCBI
Chronic neurosteroid treatment prevents the development of morphine tolerance and attenuates abstinence behavior in mice. - PubMed - NCBI
The neuro-steroids progesterone and pregnenolone seem to eliminate tolerance and withdrawal symptoms from long term drug use. I think it is likely that nicotine/caffeine withdrawals come from the bodies adjustment to reduced neuro-steroids on cessation of the drug.
Nicotine Increases DHEA
Effects of Low and High Nicotine Cigarette Smoking on Mood States and the HPA Axis in Men
"After high nicotine cigarette smoking began, plasma ACTH levels increased significantly above baseline within 12 min and reached peak levels of 21.88 ± 5.34 pmol/L within 20 min. ACTH increases were significantly correlated with increases in plasma nicotine (r=0.85; P<0.0001), DHEA (r=0.66; P=0.002), and epinephrine (r=0.86; P<0.0001). Cortisol and DHEA increased significantly within 20 min (P<0.05) and reached peak levels of 424 ± 48 nmol/L and 21.13 ± 2.55 ng/ml within 60 and 30 min, respectively."
Ray States the Benefits of Progesterone as Follows:
"Experiments have shown that progesterone relieves anxiety, improves memory, protects brain cells, and even prevents epileptic seizures. It promotes respiration, and has been used to correct emphysema. In the circulatory system, it prevents bulging veins by increasing the tone of blood vessels, and improves the efficiency of the heart. It reverses many of the signs of aging in the skin, and promotes healthy bone growth. It can relieve many types of arthritis, and helps a variety of immunological problems."
Progesterone Summaries - Progesterone Deceptions - Progesterone Supplementation - Dosage of Progesterone
-Nicotine and Caffeine Use Both Elicit Many of These Effects, probaly through increasing neurosteroids.
Nicotine Increases Short Term and Working Memory Similar to Progesterone
Repeated nicotine exposure in rats: effects on memory function, cholinergic markers and nerve growth factor. - PubMed - NCBI
"In the present study, male Wistar rats exposed a relatively low dosage of nicotine (0.35 mg/kg every 12 h) for 14 days demonstrated improved memory performance (assessed in two separate water maze testing methods) when compared with controls. Autoradiographic experiments indicated that nicotine increased [3H]-epibatidine, [125I]-alpha-bungarotoxin and [3H]-AFDX384, but not [3H]-pirenzepine binding sites in several learning- and memory-related brain areas."
Cotinine reduces amyloid-β aggregation and improves memory in Alzheimer's disease mice. - PubMed - NCBI
"Cotinine (Nicotine metabolite) reduced Aβ deposition, improved working and reference memories, and inhibited Aβ oligomerization in the brains of transgenic (Tg) 6799 AD mice."
Cotinine reduces depressive-like behavior, working memory deficits, and synaptic loss associated with chronic stress in mice. - PubMed - NCBI
"Cotinine-treated mice displayed better performance than vehicle-treated cohorts on the working memory task, the radial arm water maze test. In addition, with or without chronic stress exposure, cotinine-treated mice engaged in fewer depressive-like behaviors as assessed using the tail suspension and Porsolt's forced swim tests."
"Taken together, our results show for the first time that cotinine reduces the negative effects of stress on mood, memory, and the synapse."
Nicotinic systems and cognitive function - Springer
Nicotine Increases Bone Growth (Possibly Through Decreasing Prolactin)
Nicotine Increases Osteoblast Activity of Induced Bone Marrow Stromal Cells in a Dose-Dependent Manner: An in vitro Cell Culture Experiment
Our study demonstrated a statistically significant effect of nicotine dose on osteoblast activity in vitro.
Low level nicotine: a novel approach to reduce osteoporosis incidence. - PubMed - NCBI
Studies also indicated that the prime criminal for osteoporosis is smoking not nicotine. Moreover, low level nicotine has preventive efforts on osteoporosis by stimulating osteoblasts proliferation and differentiation. We present a hypothesis that low level nicotine may be a novel approach to reduce osteoporosis incidence.
Nicotine Potentially Anti-Epileptic.
Nicotine as an antiepileptic agent in ADNFLE: an N-of-one study. - PubMed - NCBI
"In an open study, nicotine patches reduced seizures..."
-Nicotine is also structurally similar to nicotinic acid (Niacin) which has demonstrated anti-epileptic effects.
Nicotine, Caffeine, and Progesterone Are Neuro-Protective Against Parkinsons
Current evidence for neuroprotective effects of nicotine and caffeine against Parkinson's disease. - PubMed - NCBI
Association of coffee and caffeine intake with the risk of Parkinson disease. - PubMed - NCBI
Progesterone prevents depression-like behavior in a model of Parkinson's disease induced by 6-hydroxydopamine in male rats. - PubMed - NCBI
Nicotine, Caffeine, and Progesterone are Carbonic Anhydrase Inhibitors Thus Increasing Levels of CO2 in the Body and Making Breathing Easier.
Effects of nicotine and vitamin E on carbonic anhydrase activity in some rat tissues in vivo and in vitro. - PubMed - NCBI
Carbonic anhydrase I and II inhibition with natural products: caffeine and piperine. - PubMed - NCBI
An association between plasma progesterone and erythrocyte carbonic anhydrase I concentration in women. - PubMed - NCBI
Smoking Slows Arthritis
Cigarette smoking and radiographic progression in rheumatoid arthritis
"heavy smokers (>1 pack‐day) progressed significantly less than non‐smokers or moderate smokers (p<0.001)."
Nicotine Effects on Cortisol
-Again we will differentiate between cigarettes and isolated nicotine. Cigarettes Contain MAO-A inhibitors which increases epinephrine and norepinephrine. Increases of these stimulatory Neurotransmitters will eventually lead to increases in cortisol and ACTH. Carbon Monoxide exposure from cigarette smoke also increases cortisol and ACTH.
-Many studies show similar effects of acute nicotine and caffeine on increasing cortisol and ACTH. Chronic use of nicotine and caffeine however are adaptive and improve stress biomarkers as evidenced by reduced pituitary activity and increased thyroid activity.
Stress-like adrenocorticotropin responses to caffeine in young healthy men. - PubMed - NCBI
The effects of oral caffeine (3.3 mg/kg, equivalent to 2-3 cups of coffee) on plasma adrenocorticotropin (ACTH) and cortisol (CORT) were tested in 47 healthy young men at rest in a double-blind, placebo-controlled, crossover study. Following caffeine, ACTH was significantly elevated at all times from 30 min to 180 min, and CORT was elevated from 60 min to 120 min
http://www.ncbi.nlm.nih.gov/pubmed/2550038
Plasma ACTH and cortisol levels after oral administration of nicotine (chewing gum containing nicotine 2 mg) in short and long time (10 and 45 min) were studied in smokers and non smokers. Non smokers after short time administration showed significant rise in ACTH and cortisol. No modifications were seen in the other groups of subjects. [1]
[1]*Note that only the non-smokers experienced a stress response to acute nicotine and the smokers showed no changes. This is similar to how acute caffeine in infrequent drinkers creates a stress response but chronic users experience the opposite effect- lowered stress and stress adaptation.
http://www.ncbi.nlm.nih.gov/pubmed/21733336
"Chronic caffeine intake decreases circulating catecholamines and prevents diet-induced insulin resistance and hypertension in rats."
Nicotine Effects on Dopamine and Serotonin
Nicotine activates the sympathoadrenal system and increases the synthesis and release of noradrenaline and adrenaline into circulation, and also alters the bioavailability of dopamine (Pomerleau, 1992). Single and repeated injections of nicotine in rats increase the expression of tyrosine hydroxylase, a rate-limiting enzyme in the catecholamine biosynthetic pathway (Hiremagalur & Sabban, 1995).
-Increased expression of tyrosine hydroxylase suggests more tyrosine is being converted into dopamine in the body.
Nicotine Increases Expression of Tyrosine Hydroxylase- Increasing Dopamine
http://www.ncbi.nlm.nih.gov/pubmed/12538809
"Chronic nicotine treatment elicited long-lasting, dose-dependent increases in the levels of adrenal TH mRNA, TH protein, and TH activity. In contrast, a single injection of nicotine elicited only a small increase in adrenal TH mRNA levels, which was transient and did not result in the induction of TH enzyme. Chronic nicotine administration also elicited a sustained increase in adrenal TH gene transcription rate, which persisted for up to 7 days after the final nicotine injection. This sustained transcriptional response correlated with a modest sustained increase in adrenal TH AP1 binding, but not in the levels of Fra-2 or other fos or jun proteins. These results demonstrate that repeated nicotine injections administered chronically over 1 to 2 weeks lead to sustained stimulation of the TH gene and consequent induction of TH gene expression in rat adrenal medulla."
http://link.springer.com/chapter/10.1007/978-3-0348-7457-1_45
"...implying that as little as a single dose of nicotine is as effective as chronic nicotine administration in increasing tyrosine hydroxylase activity in noradrenergic neurones."
Nicotine Decreases Expression of Tryptophan Hydroxylase- Decreasing Serotonin
http://www.ncbi.nlm.nih.gov/pubmed/12165397
"Based on the results, it can be suggested that the pathogenesis of alcohol- and nicotine-induced neuropsychological disorders involves alcohol- and nicotine-induced suppression of 5-HT synthesis and TPH expression in raphe..."
Nicotine Decreases rate of Tryptophan Uptake Into Brain and Decreases Rate of Serotonin Production in Brain
http://www.ncbi.nlm.nih.gov/pubmed/7140821
"Both the acute and chronic (40 days) administration of nicotine (0.4 mg/kg s.c.) caused a decrease in the rate of formation of 5-HT by hippocampal synaptosomes (P less than 0.05) while 24 h withdrawal of the drug from chronically treated rats resulted in a partial recovery of this effect. Chronic nicotine treatment also reduced the rate of L-tryptophan uptake by hippocampal synaptosomes (P less than 0.01) an effect which appeared to be the result of a reduction in the number of L-tryptophan carrier molecules in the synaptosomal membrane."
Chronic Nicotine Exposure Acts Like an SSRE Drug by Enhancing Uptake of Serotonin
http://www.ncbi.nlm.nih.gov/pubmed/14515338
"A significant increase in [(3)H]5-HT uptake was observed in synaptosomes prepared from both regions. To rule out the possibility that the increases were due to the last injection given, in a separate set of experiments a single injection of nicotine was administered the evening before sacrifice. No change in uptake occurred in either region, suggesting that the increases in uptake caused by nicotine was an effect of chronic exposure and not to an acute treatment."
http://www.ncbi.nlm.nih.gov/pubmed/16463401
Nicotine at 4 microM increased [(3)H]5-HT uptake by 75%.
Nicotine, Caffeine, and Creativity
It is amazing see how many creative writers, philosophers, psychologists, actors, and artists are prolific smokers and caffeine drinkers. Many of these people swear by their" vices" claiming that it helps them work and is a source of their creative muse. Stephen King claims it takes him longer to finish a book after quitting smoking and Kurt Vonnegut claimed that smoking sped up his creative process. Sigmund Freud (Father of modern psychology) smoked 20 cigars a day and refused to quit smoking despite countless professional recommendations to do so. Philosopher Voltaire drank 40-50 cups of coffee per day. One must wonder if their is an association between creative genius and the changes in brain physiology brought on by nicotine and caffeine addiction- increased dopamine, metabolism, and neuro-steroids.
“Be careful when you cast out your demons that you don’t throw away the best of yourself.”
-Nietzsche
Final Thoughts
Please bear in mind that I am not advocating for the use of tobacco or cigarettes. I do think nicotine has many potential benefits and is worth experimentation and further research. Nicotine patches are probaly the safest option for obtaining nicotine however e-cigarettes and vaporisers are likely the most convenient, practical, and cheap option for long term use.
Ray has expressed concern that nicotine may increase acetylcholine levels in the body. It is hard to find firm evidence as to how nicotine effects acetylcholine levels. Choline uptake into the brain remains neutral or actually decreases in response to nicotine.
http://www.ncbi.nlm.nih.gov/pubmed/16758358
"No significant changes in choline uptake after acute or chronic nicotine exposure were observed in whole brain or cortex. Of considerable interest was a significant decrease in regional brain choline uptake measured in the hippocampus after chronic nicotine exposure (28 d). Our data suggest that the increased ACh transmission observed after nicotine exposure does not correlate with increased blood-to-brain transfer of choline. "
Another thing to note is that exposure to Acetylcholinesterase inhibitors (drugs that increase acetylcholine) generally decrease nicotinic acetylcholine receptors in the brain. The brain decreases its receptors to reduce sensitivity and protect from overload.
http://www.ncbi.nlm.nih.gov/pubmed/1575351
"Chronic elevations of ACh observed with organophosphorus poisoning or chronic use of reversible cholinesterase inhibitors results in down-regulation of AChRs."
Nicotine has the reverse effect of these acetylcholinergic drugs and greatly increases the density of receptors suggesting nicotine may behave differently from other cholinergics.
