Nicotine Is An Anti-Depressant And Reverses Learned Helplessness

[Drareg]

Didn't ask one, now who's the strawman?

In all seriousness, I think you guys agree on more than you disagree on here.

You kind of did to be fair, strawmans are for everyone!

It's just discussion, we won't get anywhere by going along to get along, forum will be redundant.

 

[Dopamine]

Nicotine - Gwern.net
Some more very interesting information on nicotine

 

[Drareg]

I

It's best used chronically though ie everyday... just like caffeine. Caffeine has addictive potential and causes withdrawals also... Many of the benefits of nicotine come from chronic use and chronic adaptation. The negative effects- prolactin/ffa/stress raises/angiogenesis do not generally occur with chronic use (unless already under high stress) but can occur with acute use especially when administered with low blood sugar... caffeine is the same way. Haidut posted a study showing adaptations to caffeine take place within 4 days, nicotine is the same- I found I adapted within 1-2 days. Adaptations begin after the 1st administration... The body already has become desensitized to prolactin after first administration and subsequent doses for 24h show progressively lowered prolactin. I can find the study if you want it. This is why chronic nicotine users have much lower prolactin levels...


They don't do what nicotine does... you are blantantly ignoring the positive benefits of nicotine while getting hung up on HDAC inhibition.

You did not address my statement:


Countless beneficial effects... and nicotine is declared worthless in your eyes just because it is a HDAC inhibitor and has a short half life? The main metabolite of nicotine (cotinine) has a half life of 16-19 hours anyway making your short half-life point mute.

Ray talks about addiction. How we become addicted to substances because they make up for a deficit in our physiology. I posted studies showing pregnenolone and progesterone administration lessen withdrawals to opiates and benzos and studies showing nicotine self administration decreases during pregnancy (due to higher physiological progesterone). So addictive potential is dependent on capacity to fill a need or make up for a deficit. Once this void is decreased with healthy thyroid and nutrition- the void should lessen and need for the drug will decrease. This makes sense as you see the people most heavily addicted to smoking are schizophrenics, depressives, anxiety suffers etc... those suffering from high serotonin and low dopamine... those who benefit most from nicotine's serotonin lowering and dopamine boosting effects. Nicotine is perceived as a tool to make up for their physiological disfunction and it is used/abused as such.

I think anything in this light can be seen as addictive so long as it is perceived as helpful or necessary to our condition. Food can be seen as addictive. We need to get this fix continuously and we suffer when we don't. Food (just like nicotine) satisfies a particular need, if we eliminate the need then we eliminate the addiction. It is foolish to eliminate an addiction without simultaneously fixing the underlying need that it was patching over- this leads to withdrawals.


Your guess is incorrect:

"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)."

Now smokers have been shown to have higher basal cortisol levels- keyword "smokers." tobacco contains MAO inhibitors which raise cortisol levels independent from nicotine. Also there are many other components in cigarettes that have been shown to raise cortisol independent from nicotine (like carbon monoxide).

Smoking, cortisol and nicotine. - PubMed - NCBI
"These results suggest that the nicotine supplied through patches was not sufficient to block the cortisol reduction following smoking cessation."

In this study when smokers quit smoking- basal cortisol levels decreased. Administering nicotine did not stop the cortisol decrease suggesting that something else in the cigarettes is raising cortisol...

You can offset acute stress effects from stimulants anyways with salt, sugar, GABA agonists, B6, B3 etc...

Your bring up the same points you did in the past that were put to you.

The things you mentioned do in many cases do what nicotine does.

The continine point was put to you before also, their is research on it showing it to have zero effect in humans, some research shows it has mild effect at best,it's not comparable to nicotine based on current research, I'm sure it would be in e cigarettes by now if it was.

Your all over the place with your understanding,conclusions and analogy of Peat and addiction.
Your all over the place with comparing nicotine to food, I put this point to you in another thread.

Your showing studies on cortisol not adrenalin. Show me where it lowers adrenalin response.

If prolactin is a major issue some Prolactin lowering drugs have a longer half life than nicotine.

 

[Drareg]

Nicotine - Gwern.net
Some more very interesting information on nicotine

It like an article by a religious fanatic apologist for Lord nicotine. Mania fuelled ramblings.
His nootropic section finds his methods out. Fish oils and the like. Fish oil fuelled ranting.

Nicely organised with content does not equal understanding/comprehension.

Terms like ,"not significantly addictive" ,"significant reinforcing properties".

 

[Parsifal]

I've tried nicotine for a few days (like 5 or 6). There has been an adaptation, because at first it raised stress hormones a bit (theanine took care of it), but it also improved a lot my motivation and attention/productivity (ADHD) without making me jittery, nothing did it like that since Peating and trying a lot of supplement, so I decided to take it for several days. Didn't really notice that it was very strong on my anhedonia but maybe I did not try it long enough. I noticed that it took care of my psoriasis/dandruff (which always flares up after masturbation making the skin on my fingers and dandruff form hard flakes) which means it lowered my prolactin.

What I've noticed is that it is highly anti-oestrogenic, I could breathe so well, I always have a bit of water retention in my lungs and stomach (and maybe everywhere in the body) but had none at all with nicotine, my breathing was so effortless, I could hold my breath for very long...

But the downside was that if was vasoconstrictive. I have weak blood vessels since an endotoxin poisoning thanks to antibiotics for lyme 4 years ago (see the study I posted on it in the study section), and had always a little chest pain while taking the nicotine, and started waking up with racing heart , not feeling stressed but like the heart had to work harder, and also my vision was always a bit blury (vasoconstriction) even though it also improved other aspects of my vision (I could see a lot more details and in perspective/depth).

So I will say no to it because of the vasoconstrictive effects , even if I hope I will find something as good for me in the future without negative effects...

 

[tyw]

I've tried nicotine for a few days (like 5 or 6).

What was the dose and delivery method you used?

The usual protocol is 1-4mg a day to start with, through gum (the only safe method IMO), and ideally in the morning.

Regarding delivery methods:
- Smoking obviously has it's many risks , plus nicotine absorption is very fast, and drops off very fast
- Chewing tobacco is full of random things (like heavy metals), and doses vary by batch (not easy to control)
- Patches may be too slow-acting to see effects, and usually come in doses which are pretty high (5+mg).
- Liquid nicotine easy to overdose, and is also very fast acting
- Gum usually comes in 1-4mg doses, and dosing speed can be controlled by how fast you chew, hence this is the preferred method.​

I agree that there is a huge variability in blood flow changes to nicotine. Some people get low blood pressure, others high blood pressure, etc ... I don't actually think the causes are fully known, but this is a side effect which can be pretty detrimental, and backing off nicotine if this happens is a good strategy.

Fatty acid oxidation on nicotine rises, but uncoupling rate also rises. The balance of risk/reward? No clue, and it likely depends on the individual's ability to metabolise nicotine.

Speaking of metabolism, yes, nicotine is processed in the liver. If liver is stressed, nicotine may not be handled well. (eg: One of my other friends, who claims to have a cytochrome p450 defect, doesn't handle nicotine well)

Siednote: nicotine's effects have likely nothing to do with nicotinamide (niacinamide). Nicotine activates the Nicotinic acetylcholine receptors, which have "higher level effects" from there, while niacinamide is transported directly into the cell and mitochondria to re-establish NAD+ pool -- http://www.cell.com/trends/endocrinology-metabolism/pdf/S1043-2760(12)00106-3.pdf​

As for benefits -- very good dopamine boosting and likely serotonin lowering effects on nicotine.

Nicotine + Caffeine likely very synergistic for metabolism.

Final personal sidenote: after experimenting with the compound for about 2 years now, and going as high as 80mg a day doses , I definitely keep it in the arsenal of "things to use when stressed".

Interestingly, I never had withdrawal symptoms ... meaning that I could do that 80mg day one day, and then back off to nothing for 3 days with no negative implications, and nowadays, it's basically "whenever I want I can have some" without any addictive consequences. This is always nicotine gum BTW.

I would speculate that "addictive behaviour" has more to do with dopamine / serotonin cycling, rather than nicotine being "inherently addictive", but this is just speculation. Your mileage will vary, and I will stick to conservative 1-4mg per day doses if you ever decide to experiment with nicotine.

Again, 1-4mg is really all you need to see good effects, and I keep it for use when needed.

...

 

[Dopamine]

The continine point was put to you before also, their is research on it showing it to have zero effect in humans, some research shows it has mild effect at best,it's not comparable to nicotine based on current research, I'm sure it would be in e cigarettes by now if it was.

I have only seen 1 study on isolated cotinine in humans and yes they observed no significant effects. This is not a natural context for cotinine as nicotine metabolizes into numerous compounds along with cotinine. Maybe cotinine is not bio-available to humans without the presence of the other compounds... there have been little if any studies into how nicotine's various metabolites interact. DMT in plants for example has no real physiological effect in humans unless consumed with an MAOI. Cotinine has shown major promise in animal studies and needs more testing in human studies and within a more natural context. This is a good point to bring up though.

Also cotinine is in e-cigarettes... nicotine breaks down into cotinine.

Your showing studies on cortisol not adrenalin. Show me where it lowers adrenalin response.

I can't find any studies showing it lowers adrenaline. Also adrenaline is synthesized from dopamine so I don't know if increasing dopamine levels would make one susceptible to higher adrenaline... I am however no more concerned about nicotine raising adrenaline than I am about caffeine raising adrenaline- I find caffeine gives me a stronger stress response but it is probably dose dependent. There are many substances that could be taken alongside nicotine to lower adrenaline.

If prolactin is a major issue some Prolactin lowering drugs have a longer half life than nicotine.

I would rather take something with a generalized/systemic action than a specific action... all the major substances that Peat recommends- aspirin, caffeine, thyroid etc all have generalized actions. I think nicotine is safer than most pharma drugs.

 

[Dopamine]

@Parsifal

Have you tried taurine to counteract the vasoconstriction? That sounds more like high blood pressure problems than vasoconstriction by the way (though I think the 2 tend to go together). Taurine also regulates blood pressure. Taurine also increases dopamine, lowers adrenaline, and prevents oxidative damage so it would probaly stack well with nicotine. Add a few mg b6 to lower stress response, some b3 or aspirin to lower FFA, and maybe some theanine and/or lysine to add to the anti-depressive effect. This would be a great combo I think.

Phenibut should also lower vasoconstriction as it is a calcium channel blocker. Magnesium should work similarly.

[Gravidaprotective action of phenibut in experimental pre-eclampsia]. - PubMed - NCBI
"Daily oral administration ofphenibut (25 mg/kg) in female rats with EP during pregnancy prevents the increase in blood pressure and the severity of proteinuria and edemation. Phenibut improves the vasodilator and antithrombotic endothelial functions, increases uterine blood flow, improves microcirculation, limits LPO, and increases the activity of antioxidant enzymes."

Mechanisms responsible for vasodilation upon magnesium infusion in vivo: clinical evidence. - PubMed - NCBI

Taurine regulation of blood pressure and vasoactivity. - PubMed - NCBI
"A single injection of taurine significantly lowered the systolic, diastolic, and mean arterial blood pressure in freely moving Long-Evans control rats. We further confirm the vasoactive properties of taurine using isolated aortic ring preparations. Mechanical responses of circular aortic rings to pharmacological agents were measured by an isometric force transducer and amplifier. We found that bath application of taurine to the aortic rings caused vasodilation which was blocked by picrotoxin. "

Taurine Supplementation Lowers Blood Pressure and Improves Vascular Function in Prehypertension: Randomized, Double-Blind, Placebo-Controlled Study. - PubMed - NCBI
"...Taurine supplementation significantly decreased the clinic and 24-hour ambulatory BPs, especially in those with high-normal BP. Mean clinic systolic BP reduction for taurine/placebo was 7.2/2.6 mm Hg, and diastolic BP was 4.7/1.3 mm Hg. Mean ambulatory systolic BP reduction for taurine/placebo was 3.8/0.3 mm Hg, and diastolic BP was 3.5/0.6 mm Hg. In addition, taurine supplementation significantly improved endothelium-dependent and endothelium-independent vasodilation and increased plasma H2S and taurine concentrations. Furthermore, changes in BP were negatively correlated with both the plasma H2S and taurine levels in taurine-treated prehypertensive individuals. To further elucidate the hypotensive mechanism, experimental studies were performed both in vivo and in vitro. The results showed that taurine treatment upregulated the expression of hydrogen sulfide-synthesizing enzymes and reduced agonist-induced vascular reactivity through the inhibition of transient receptor potential channel subtype 3-mediated calcium influx in human and mouse mesenteric arteries. In conclusion, the antihypertensive effect of chronic taurine supplementation shows promise in the treatment of prehypertension through improvement of vascular function."

Effects of increased adrenomedullary activity and taurine in young patients with borderline hypertension. - PubMed - NCBI
"Systolic blood pressure in the 10 patients who were treated with taurine decreased by 9.0 +/- 2.9 mm Hg (mean +/- SE; p less than .05 by paired t test), compared with a 2.7 +/- 2.3 mm Hg decrease (NS) in the nine patients treated with placebo and diastolic blood pressure in the taurine-treated patients decreased by 4.1 +/- 1.7 mm Hg (p less than .05) compared with 1.2 +/- 3.0 mm Hg (NS) in the placebo-treated subjects. In the patients receiving taurine plasma epinephrine (E) decreased significantly, with a negligible decrease in plasma norepinephrine (NE)."

Taurine elevates dopamine levels in the rat nucleus accumbens; antagonism by strychnine. - PubMed - NCBI

Effects of taurine, homotaurine and GABA on hypothalamic and striatal dopamine metabolism. - PubMed - NCBI

 

[Drareg]

I've tried nicotine for a few days (like 5 or 6). There has been an adaptation, because at first it raised stress hormones a bit (theanine took care of it), but it also improved a lot my motivation and attention/productivity (ADHD) without making me jittery, nothing did it like that since Peating and trying a lot of supplement, so I decided to take it for several days. Didn't really notice that it was very strong on my anhedonia but maybe I did not try it long enough. I noticed that it took care of my psoriasis/dandruff (which always flares up after masturbation making the skin on my fingers and dandruff form hard flakes) which means it lowered my prolactin.

What I've noticed is that it is highly anti-oestrogenic, I could breathe so well, I always have a bit of water retention in my lungs and stomach (and maybe everywhere in the body) but had none at all with nicotine, my breathing was so effortless, I could hold my breath for very long...

But the downside was that if was vasoconstrictive. I have weak blood vessels since an endotoxin poisoning thanks to antibiotics for lyme 4 years ago (see the study I posted on it in the study section), and had always a little chest pain while taking the nicotine, and started waking up with racing heart , not feeling stressed but like the heart had to work harder, and also my vision was always a bit blury (vasoconstriction) even though it also improved other aspects of my vision (I could see a lot more details and in perspective/depth).

So I will say no to it because of the vasoconstrictive effects , even if I hope I will find something as good for me in the future without negative effects...

Sound like you got an adrenalin response in the end from nicotine.

Have you tried small amounts of vitamin E for prolactin by chance?

 

[Drareg]

I have only seen 1 study on isolated cotinine in humans and yes they observed no significant effects. This is not a natural context for cotinine as nicotine metabolizes into numerous compounds along with cotinine. Maybe cotinine is not bio-available to humans without the presence of the other compounds... there have been little if any studies into how nicotine's various metabolites interact. DMT in plants for example has no real physiological effect in humans unless consumed with an MAOI. Cotinine has shown major promise in animal studies and needs more testing in human studies and within a more natural context. This is a good point to bring up though.

Also cotinine is in e-cigarettes... nicotine breaks down into cotinine.


I can't find any studies showing it lowers adrenaline. Also adrenaline is synthesized from dopamine so I don't know if increasing dopamine levels would make one susceptible to higher adrenaline... I am however no more concerned about nicotine raising adrenaline than I am about caffeine raising adrenaline- I find caffeine gives me a stronger stress response but it is probably dose dependent. There are many substances that could be taken alongside nicotine to lower adrenaline.


I would rather take something with a generalized/systemic action than a specific action... all the major substances that Peat recommends- aspirin, caffeine, thyroid etc all have generalized actions. I think nicotine is safer than most pharma drugs.

It would be more profitable from a marketing point of view to use cotinine if it had the same effects, it side steps public perceptions of nicotine. They are all over this I'm sure.

The adrenalin response is a point to note, caffeine seems to be kept at bay by calories, I'm not sure about nicotine so adrenalin response being stopped by calories.

 

[Simonsays]

I really miss my "fags" (thats English for cigarettes). Mentally and physically went right down when i gave them up . The nicotine and the caffeine definitely making up for the lack of thyroid methinks!!

Its also linked to the oral stage (Freudian), i loved the sensation of actually smoking,, (ex thumb sucker , pencil chewer)

My sharp as a razor 90 year old father refuses to stop ( 76 years now), the idiot!!

 

[Dopamine]

It would be more profitable from a marketing point of view to use cotinine if it had the same effects, it side steps public perceptions of nicotine. They are all over this I'm sure.

The adrenalin response is a point to note, caffeine seems to be kept at bay by calories, I'm not sure about nicotine so adrenalin response being stopped by calories.

I don't think cotinine is addictive in isolation so it wouldn't be very marketable but i'm not sure

Statements like this one from Ray have me confused:

"While it's true that the thyroid hormone increases sensitivity to adrenaline, its most noticeable effect is in improving the ability to relax, including the ability to sleep soundly and restfully. And it happens that increasing norepinephrine (the brain's locally produced form of adrenaline) helps to prevent seizures (Giorgi, et al., 2004)."

Thyroid hormone potentiates the effects of catecholamines
Nicotine increases catecholamines

I don't know if there is a big difference here? Both should increase adrenaline activity...
Without thyroid hormone adrenaline would have only a weak effect because thyroid hormone increases the number of epinephrine receptors of the cell

Someone needs to email Ray and get a more detailed explanation of his views on nicotine, whether chronic use elevates adrenaline and FFA, why it's different from caffeine, and whether it has any place in a healthy lifestyle. Also I would be interested in whether GABA agonists, sucrose, or anything else could eliminate this response.

 

[Parsifal]

What was the dose and delivery method you used?

The usual protocol is 1-4mg a day to start with, through gum (the only safe method IMO), and ideally in the morning.

Regarding delivery methods:
- Smoking obviously has it's many risks , plus nicotine absorption is very fast, and drops off very fast
- Chewing tobacco is full of random things (like heavy metals), and doses vary by batch (not easy to control)
- Patches may be too slow-acting to see effects, and usually come in doses which are pretty high (5+mg).
- Liquid nicotine easy to overdose, and is also very fast acting
- Gum usually comes in 1-4mg doses, and dosing speed can be controlled by how fast you chew, hence this is the preferred method.​

I agree that there is a huge variability in blood flow changes to nicotine. Some people get low blood pressure, others high blood pressure, etc ... I don't actually think the causes are fully known, but this is a side effect which can be pretty detrimental, and backing off nicotine if this happens is a good strategy.

Fatty acid oxidation on nicotine rises, but uncoupling rate also rises. The balance of risk/reward? No clue, and it likely depends on the individual's ability to metabolise nicotine.

Speaking of metabolism, yes, nicotine is processed in the liver. If liver is stressed, nicotine may not be handled well. (eg: One of my other friends, who claims to have a cytochrome p450 defect, doesn't handle nicotine well)

Siednote: nicotine's effects have likely nothing to do with nicotinamide (niacinamide). Nicotine activates the Nicotinic acetylcholine receptors, which have "higher level effects" from there, while niacinamide is transported directly into the cell and mitochondria to re-establish NAD+ pool -- http://www.cell.com/trends/endocrinology-metabolism/pdf/S1043-2760(12)00106-3.pdf​

As for benefits -- very good dopamine boosting and likely serotonin lowering effects on nicotine.

Nicotine + Caffeine likely very synergistic for metabolism.

Final personal sidenote: after experimenting with the compound for about 2 years now, and going as high as 80mg a day doses , I definitely keep it in the arsenal of "things to use when stressed".

Interestingly, I never had withdrawal symptoms ... meaning that I could do that 80mg day one day, and then back off to nothing for 3 days with no negative implications, and nowadays, it's basically "whenever I want I can have some" without any addictive consequences. This is always nicotine gum BTW.

I would speculate that "addictive behaviour" has more to do with dopamine / serotonin cycling, rather than nicotine being "inherently addictive", but this is just speculation. Your mileage will vary, and I will stick to conservative 1-4mg per day doses if you ever decide to experiment with nicotine.

Again, 1-4mg is really all you need to see good effects, and I keep it for use when needed.

...

I've used doses up to 8 or 10mg/day, liquid nicotine with e-cigs (I don't think it would have had a so good effect for lungs in gums?). I think that it also made me a bit teeth sensitive.

The rest of your message is interesting, thanks! I've tried some aspirin and niaciamide with it to lower FFA but still had the chest pain. As I've said, I had a lot of damage done to my vascular system so maybe it will be good for you but not for me?
The problem is that the effects are not very long so you want more quickly and you may increase FFA too much everytime? Do you feel that gums are longer? I've tried gums some times ago (nicorette in France) but it also had aspartam in it which is excitotoxic, it made me jittery, but I was also low carb and fasting a lot. It also increased my stomach acid and bile (burning stools) a lot and it increases serotonin a lot (bile acid) and can make me feel jittery.

I've also read that nicotine is very vasoconstrictive and can make the brain higly hypoxic the higher you smoke it, would explain while I had blury vision.
Quote from: Hydergine: Ergot-derived smart drugs | Brain enhancing products

Smoking cigarettes (Nicotine constricts blood vessels and decreases oxygen supply to the brain. It is estimated that those who smoke more than 20 cigarettes a day lose at least 7% of the normal blood flow to the brain).

@Parsifal

Have you tried taurine to counteract the vasoconstriction? That sounds more like high blood pressure problems than vasoconstriction by the way (though I think the 2 tend to go together). Taurine also regulates blood pressure. Taurine also increases dopamine, lowers adrenaline, and prevents oxidative damage so it would probaly stack well with nicotine. Add a few mg b6 to lower stress response, some b3 or aspirin to lower FFA, and maybe some theanine and/or lysine to add to the anti-depressive effect. This would be a great combo I think.

Phenibut should also lower vasoconstriction as it is a calcium channel blocker. Magnesium should work similarly.

[Gravidaprotective action of phenibut in experimental pre-eclampsia]. - PubMed - NCBI
"Daily oral administration ofphenibut (25 mg/kg) in female rats with EP during pregnancy prevents the increase in blood pressure and the severity of proteinuria and edemation. Phenibut improves the vasodilator and antithrombotic endothelial functions, increases uterine blood flow, improves microcirculation, limits LPO, and increases the activity of antioxidant enzymes."

Mechanisms responsible for vasodilation upon magnesium infusion in vivo: clinical evidence. - PubMed - NCBI

Taurine regulation of blood pressure and vasoactivity. - PubMed - NCBI
"A single injection of taurine significantly lowered the systolic, diastolic, and mean arterial blood pressure in freely moving Long-Evans control rats. We further confirm the vasoactive properties of taurine using isolated aortic ring preparations. Mechanical responses of circular aortic rings to pharmacological agents were measured by an isometric force transducer and amplifier. We found that bath application of taurine to the aortic rings caused vasodilation which was blocked by picrotoxin. "

Taurine Supplementation Lowers Blood Pressure and Improves Vascular Function in Prehypertension: Randomized, Double-Blind, Placebo-Controlled Study. - PubMed - NCBI
"...Taurine supplementation significantly decreased the clinic and 24-hour ambulatory BPs, especially in those with high-normal BP. Mean clinic systolic BP reduction for taurine/placebo was 7.2/2.6 mm Hg, and diastolic BP was 4.7/1.3 mm Hg. Mean ambulatory systolic BP reduction for taurine/placebo was 3.8/0.3 mm Hg, and diastolic BP was 3.5/0.6 mm Hg. In addition, taurine supplementation significantly improved endothelium-dependent and endothelium-independent vasodilation and increased plasma H2S and taurine concentrations. Furthermore, changes in BP were negatively correlated with both the plasma H2S and taurine levels in taurine-treated prehypertensive individuals. To further elucidate the hypotensive mechanism, experimental studies were performed both in vivo and in vitro. The results showed that taurine treatment upregulated the expression of hydrogen sulfide-synthesizing enzymes and reduced agonist-induced vascular reactivity through the inhibition of transient receptor potential channel subtype 3-mediated calcium influx in human and mouse mesenteric arteries. In conclusion, the antihypertensive effect of chronic taurine supplementation shows promise in the treatment of prehypertension through improvement of vascular function."

Effects of increased adrenomedullary activity and taurine in young patients with borderline hypertension. - PubMed - NCBI
"Systolic blood pressure in the 10 patients who were treated with taurine decreased by 9.0 +/- 2.9 mm Hg (mean +/- SE; p less than .05 by paired t test), compared with a 2.7 +/- 2.3 mm Hg decrease (NS) in the nine patients treated with placebo and diastolic blood pressure in the taurine-treated patients decreased by 4.1 +/- 1.7 mm Hg (p less than .05) compared with 1.2 +/- 3.0 mm Hg (NS) in the placebo-treated subjects. In the patients receiving taurine plasma epinephrine (E) decreased significantly, with a negligible decrease in plasma norepinephrine (NE)."

Taurine elevates dopamine levels in the rat nucleus accumbens; antagonism by strychnine. - PubMed - NCBI

Effects of taurine, homotaurine and GABA on hypothalamic and striatal dopamine metabolism. - PubMed - NCBI

Thanks! I was taking taurine with it and a bit of epsom salt.
Lately, I've noticed that my body doesn't really tolerate taurine so I've stopped it, it increased my anhedonia... I think that I've read that it can increase prolactin and LH elsewhere on the forum, not sure if it was that or methylene blue.
I will maybe try to toy another time with nicotine with some of your advices guys, but I want to try micro-doses of psychedelics or hydergine before that.

Sound like you got an adrenalin response in the end from nicotine.

Have you tried small amounts of vitamin E for prolactin by chance?

I think that it might be because of acetylcholine, not adrenalin (coffee even when it makes me very jittery or increase blood pressure doesn't cause this blury vision or pain in the heart area).
I'm taking vitamin E and have tried higher doses but never experienced something really strong from it, at least it was not noticable as nicotine.

 

[tyw]

I've used doses up to 8 or 10mg/day, liquid nicotine with e-cigs (I don't think it would have had a so good effect for lungs in gums?). I think that it also made me a bit teeth sensitive.

The rest of your message is interesting, thanks! I've tried some aspirin and niaciamide with it to lower FFA but still had the chest pain. As I've said, I had a lot of damage done to my vascular system so maybe it will be good for you but not for me?
The problem is that the effects are not very long so you want more quickly and you may increase FFA too much everytime? Do you feel that gums are longer? I've tried gums some times ago (nicorette in France) but it also had aspartam in it which is excitotoxic, it made me jittery, but I was also low carb and fasting a lot. It also increased my stomach acid and bile (burning stools) a lot and it increases serotonin a lot (bile acid) and can make me feel jittery.

I've also read that nicotine is very vasoconstrictive and can make the brain higly hypoxic the higher you smoke it, would explain while I had blury vision.
Quote from: Hydergine: Ergot-derived smart drugs | Brain enhancing products
.

Yes, those are legitimate risks.

A lot of the nicotine gum today has artificial sweeteners in it. The gum I get here in Australia, Nicorette (uncoated) classic, is basically just a small amount of sorbitol (0.18g per 4mg dose). That can be an issue in high doses to the gut, but it is purely a gut issue, and not a potentially systemic problem like aspartame.

I still prefer gum a lot more to any other delivery method -- http://pharmrev.aspetjournals.org/content/57/1/79.full

See figure 2, comparing various methodologies of intake. Smoke gives a huge spike and quick drop off, whereas chewing 4mg of nicotine gum leaves a more sustained release (if chewed according to instructions).

The same applies to e-cigs. I do not support Ginko's chain smoking habit

Also, in huge doses, you get increased sucrose permeability to brain ( 4.5mg / kg / day dose, which for me is 4.5 * 70 = 315mg a day ). -- Nicotine increases in vivo blood-brain barrier permeability and alters cerebral microvascular tight junction protein distribution. - PubMed - NCBI

I don't find this a realistic dose, but "over-sensitivity" of neurons may be a side effect of Nicotine.

Sidenote: I also do not trust studies like this "Nicotine Binds to Complex 1 and inhibits it's action" study -- In vitro effects of nicotine on mitochondrial respiration and superoxide anion generation. - PubMed - NCBI . Like I noted above, nicotine does not enter the cell, and thus cannot bind to Complex 1 (unless something is really really wrong, in which case you have more problems that nicotine overdose to worry about).​

And yes, adrenaline is downstream from dopamine, so it is plausible that nicotine can increase that as well. I do not know the significance, but some symptoms like increased heart rate may suggest that this is significant.

Taurine itself is something that is heavily involved in methylation. Technically it can be used as a "calming agent" (in terms of preventing over-excitation), but also assumes normal methylation function. There are lots of information on the web about MTHFR defects (especially Dr Amy Yasko), about how this ties in. If there is a methylation defect somewhere (regardless if it is genetic or not), nicotine should be used with caution.


....

 

[Drareg]

I don't think cotinine is addictive in isolation so it wouldn't be very marketable but i'm not sure

Statements like this one from Ray have me confused:

"While it's true that the thyroid hormone increases sensitivity to adrenaline, its most noticeable effect is in improving the ability to relax, including the ability to sleep soundly and restfully. And it happens that increasing norepinephrine (the brain's locally produced form of adrenaline) helps to prevent seizures (Giorgi, et al., 2004)."

Thyroid hormone potentiates the effects of catecholamines
Nicotine increases catecholamines

I don't know if there is a big difference here? Both should increase adrenaline activity...
Without thyroid hormone adrenaline would have only a weak effect because thyroid hormone increases the number of epinephrine receptors of the cell

Someone needs to email Ray and get a more detailed explanation of his views on nicotine, whether chronic use elevates adrenaline and FFA, why it's different from caffeine, and whether it has any place in a healthy lifestyle. Also I would be interested in whether GABA agonists, sucrose, or anything else could eliminate this response.

The adrenalin,norepinephrine,catecholamines are helpful for some, I think if you are already sensitive it's going to take more than sugar to stop the response.

It seems it's more appropriate for some people to work on gaba and stopping the adrenalin response when under stress, he does speak about this in some articles.
In a way this is a positive if all you have to do is stop the extreme response to get the body coherent again, it may be overthink in some people in relation to their problems.

I posted elsewhere that it seemed niacinamide,b6,zinc will act as cofactors in some circumstances for adrenalin,someone emailed Peat recently about water retention and he mentioned it could be too much adrenalin from coffee for example, I have noticed this with said supplements, very slight but it's there. They have differing effects on top of that obviously.

This is a problem I think, niacinamide can alleviate anxiety but it's a cofactor for adrenaline production therefore it has an underlying side effect for those sensitive to adrenalin, different people will love it because their issues may not be adrenalin.
Many of the substances recommended have adrenalin effects.

The Wikipedia page on adrenergic substance is a quick insight List of adrenergic drugs - Wikipedia, the free encyclopedia

 

[Parsifal]

Yes, those are legitimate risks.

A lot of the nicotine gum today has artificial sweeteners in it. The gum I get here in Australia, Nicorette (uncoated) classic, is basically just a small amount of sorbitol (0.18g per 4mg dose). That can be an issue in high doses to the gut, but it is purely a gut issue, and not a potentially systemic problem like aspartame.

I still prefer gum a lot more to any other delivery method -- http://pharmrev.aspetjournals.org/content/57/1/79.full

See figure 2, comparing various methodologies of intake. Smoke gives a huge spike and quick drop off, whereas chewing 4mg of nicotine gum leaves a more sustained release (if chewed according to instructions).

The same applies to e-cigs. I do not support Ginko's chain smoking habit

View attachment 2664


Also, in huge doses, you get increased sucrose permeability to brain ( 4.5mg / kg / day dose, which for me is 4.5 * 70 = 315mg a day ). -- Nicotine increases in vivo blood-brain barrier permeability and alters cerebral microvascular tight junction protein distribution. - PubMed - NCBI

I don't find this a realistic dose, but "over-sensitivity" of neurons may be a side effect of Nicotine.

Sidenote: I also do not trust studies like this "Nicotine Binds to Complex 1 and inhibits it's action" study -- In vitro effects of nicotine on mitochondrial respiration and superoxide anion generation. - PubMed - NCBI . Like I noted above, nicotine does not enter the cell, and thus cannot bind to Complex 1 (unless something is really really wrong, in which case you have more problems that nicotine overdose to worry about).​

And yes, adrenaline is downstream from dopamine, so it is plausible that nicotine can increase that as well. I do not know the significance, but some symptoms like increased heart rate may suggest that this is significant.

Taurine itself is something that is heavily involved in methylation. Technically it can be used as a "calming agent" (in terms of preventing over-excitation), but also assumes normal methylation function. There are lots of information on the web about MTHFR defects (especially Dr Amy Yasko), about how this ties in. If there is a methylation defect somewhere (regardless if it is genetic or not), nicotine should be used with caution.


....

Very interesting and instructive informations, thanks.
I will maybe try nicotine again someday with gums as it had a lot of positive effects, hopping that it will not mess with blood circulation and oxygenation of the brain, will follow your advices then.

Hehe, nice to see another Mushishi fan here! And you even have the paper version :) (I remember reading on your website that you loved manga, well a lot of manga fans have bad tastes though so that's nice ). I guess that I would chain smoke like Ginko if I was followed by strange creatures and that it is the only way to repel them .

The adrenalin,norepinephrine,catecholamines are helpful for some, I think if you are already sensitive it's going to take more than sugar to stop the response.

It seems it's more appropriate for some people to work on gaba and stopping the adrenalin response when under stress, he does speak about this in some articles.
In a way this is a positive if all you have to do is stop the extreme response to get the body coherent again, it may be overthink in some people in relation to their problems.

I posted elsewhere that it seemed niacinamide,b6,zinc will act as cofactors in some circumstances for adrenalin,someone emailed Peat recently about water retention and he mentioned it could be too much adrenalin from coffee for example, I have noticed this with said supplements, very slight but it's there. They have differing effects on top of that obviously.

This is a problem I think, niacinamide can alleviate anxiety but it's a cofactor for adrenaline production therefore it has an underlying side effect for those sensitive to adrenalin, different people will love it because their issues may not be adrenalin.
Many of the substances recommended have adrenalin effects.

The Wikipedia page on adrenergic substance is a quick insight List of adrenergic drugs - Wikipedia, the free encyclopedia

Interesting. I think that everything dopaminergic substances might also be adrenergic, and thyroid does also that in my experience... Then, I wonder if thyroid does increase the heart rate by itself or if it is because it increases adrenalin in the first place... People like Wim Hoff also increase their temperature by increasing adrenaline with hyperventilation...

 

[Dopamine]

Interesting. I think that everything dopaminergic substances might also be adrenergic, and thyroid does also that in my experience... Then, I wonder if thyroid does increase the heart rate by itself or if it is because it increases adrenalin in the first place... People like Wim Hoff also increase their temperature by increasing adrenaline with hyperventilation...

That's an interesting thought. I think adrenaline is only a problem when you run out of blood sugar. When you run out of sugar to burn- cortisol is released to start the process of gluconeogenesis (breakdown of proteins and fat for energy)... This is why nicotine should be taken after a meal and the dose can't be too strong. If nicotine is raising cortisol then this isn't good but I don't think it necessarily will. Chronically elevated cortisol results in chronically high circulating FFA which cause oxidative damage and insulin resistance.

 

[tyw]

Interesting. I think that everything dopaminergic substances might also be adrenergic, and thyroid does also that in my experience... Then, I wonder if thyroid does increase the heart rate by itself or if it is because it increases adrenalin in the first place... People like Wim Hoff also increase their temperature by increasing adrenaline with hyperventilation...

That's an interesting thought. I think adrenaline is only a problem when you run out of blood sugar. When you run out of sugar to burn- cortisol is released to start the process of gluconeogenesis (breakdown of proteins and fat for energy)... This is why nicotine should be taken after a meal and the dose can't be too strong. If nicotine is raising cortisol then this isn't good but I don't think it necessarily will. Chronically elevated cortisol results in chronically high circulating FFA which cause oxidative damage and insulin resistance.

@Dopaminergic096 is probably right. I'll just add the qualification that "run out of blood sugar" is highly dependent to the local tissue. We should ideally be speaking in terms of "critical tissue running out of glucose". eg: liver, kidney, brain, etc .... (the heart is a bit of an exception, since it seems to have a preference for fatty acids, and does really well on ketones).

One of my annoyances is that people make claims about one tissue that do not generalise to good systemic function. Example: people will say "Fasting increases NAD+". This is true ..... in skeletal muscle .... Go look at any study showing a Fasting => higher NAD+ link, and you will find it's either in Skeletal muscle or the Brain. Again, it makes sense from a survival perspective -- more energy to think and run around to survive (and acquire some food!! )

Once you get to studies that look at Fasting and other tissues like the Liver, you'll find NAD+ depletion. Again, makes total sense from a survival perspective, and horrible for long term health.

Sidenote: and no, fasting is not the same as CRON -- Caloric Restriction with Optimal Nutrition. Mild CRON (say at most 20% restriction) can actually be done in a way to ensure adequate energetics.

And guess what? If you look at studies looking at tissue Unsaturation Index (Ui) and Peroxidation Index (Pi), you'll find that CRONed animals are getting "PUFA Depleted", which may explain the increased metabolic rate with CRON.

Note: This is not an endorsement of CRON; it is just a discussion of plausible mechanics.​

Nicotine is probably very active in liver, brain, and heart (among other tissues), so ensuring good energetic substrate delivery to those tissues while using nicotine is probably a good idea.

Personally, my preferred time and dose for nicotine use is 4mg right after breakfast.

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[tyw]

Hehe, nice to see another Mushishi fan here! And you even have the paper version :) (I remember reading on your website that you loved manga, well a lot of manga fans have bad tastes though so that's nice ). I guess that I would chain smoke like Ginko if I was followed by strange creatures and that it is the only way to repel them .
.

(Complete Comic Book Sidenote)

I am picky about my literature .

Really have no affinity for superhero comics / films (they Duex Ex Machina all the things ). Hence I'll gravitate to all the Seinen ("for young adults") type manga / anime -- Mushishi is on that list, as would be others like Tokyo Ghoul, Vagabond, Psycho Pass, Ajin, etc ... Some Shounen ("for teens"), but usually just Gintama (and 'Full Metal Alchemist' was pretty damn good back in the day)

For western analogues, things like the darker Batman comics, and of course 'V for Vendetta', would probably qualify for my preferences. As Evey Hammond said:

My father was a writer. You would've liked him. He used to say that artists use lies to tell the truth, while politicians use them to cover the truth up.​

But while I like fiction, reality is far more interesting I'll take 'Storm of Steel' or 'The Forgotten Highlander' any day. And while I like literature, current-day Politics is a crazy source of entertainment and good philosophy

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[narouz]

Personally, my preferred time and dose for nicotine use is 4mg right after breakfast......

What does that make you feel like, tyw?