• Log in with Facebook Log in with Twitter Log In with Google      Sign In    
  • Create Account
LongeCity .                       Advocacy & Research for Unlimited Lifespans

Photo
* * * * * 3 votes

Nicotine and Vasoconstriction


  • Please log in to reply
75 replies to this topic

#31 haha

  • Registered User
  • 91 posts
  • 10

Posted 26 April 2010 - 11:25 AM

I would doubt theres a better drug on a risk/reward trade off basis, The billions of people who smoke global are in part a testament to this, as they do suffer great harm from the smoking effect,but yet they still do it. I remmeber seeing striking studies against the onset of parkinsons and dementia corrected for earlier fatality in smokers. The benefits of enhanced REM are significant and are involved with associative learning, for this reason I leave my patch(20mg) on at night, I feel this has freed me to think for myself to a greater degree in quite a short time period(2months). Some of those studies show acute cognitive improvement that I would doubt could be achieved by anything but amphetamine(with all its perils).Just opinion and people will respond differently

#32 chrono

  • Topic Starter
  • Member, Moderator
  • 2,440 posts
  • 794
  • Location:New England

Posted 27 April 2010 - 11:55 AM

A case can be made for a good risk/benefit of long-term transdermal nicotine. Though issues such as vasoconstriction and free radical generation make this very debatable. But with so many other cognitive enhancers available, which don't have the issues of safety brought up here, I hardly think it's a compelling choice for constant use.

If you have to qualify the positive effects of smoking with "corrected for earlier fatality," it's going to be pretty hard to balance out that ratio. Let alone with the many other well-studied downsides of smoke inhalation. The fact that billions of people do it isn't a testament to its long-term benefits, it's a result of addiction and poor health priorities.

sponsored ad

  • Advert
Click HERE to rent this advertising spot for BRAIN HEALTH to support LongeCity (this will replace the google ad above).

#33 Anthony_Loera

  • Lifetime Member
  • 3,121 posts
  • 699
  • Location:Miami Florida

Posted 27 April 2010 - 12:40 PM

ok so now what to believe? That study showed obvious cognitive benefit while other studies show it can lead to dementia's? Or is that just from smoking...ugh...

The meta-analysis only looked at the short-term effects of nicotine in non-smokers. Whether nicotine is bad for the brain long-term is a different question.


but so many articles subtly saying it could or is good long term, from what I read. So I think nicotine in moderate doses maybe very beneficial and is why they are creating receptor specific nicotine drugs for cognitive gains and even neuroprotection. However I could be wrong, and long term could equate with cognitive problems/decline.

Either way, I take the nicotine gum, now in moderate to low doses as an after effect response of a severe addiction to cigarettes for 4 years whilst very depressed and psychotic.



This article suggests that enymes in people can metobilze nicotine into aminoketone, which is a precursor to NNK carcinogen:
http://www.thefreeli...ogen-a067328680

This article bugs the heck out of me, because I know folks that take nicotine (not cigarettes)... and it may be appear to be an issue for them later.

A
  • like x 1

#34 chrono

  • Topic Starter
  • Member, Moderator
  • 2,440 posts
  • 794
  • Location:New England

Posted 27 April 2010 - 02:47 PM

Nice one Anthony, I haven't seen this before. Really changes my thinking on why it was OK to use this in the first place.

2'-Hydroxylation of nicotine by cytochrome P450 2A6 and human liver microsomes: formation of a lung carcinogen precursor. [full text]

Smokers or people undergoing nicotine replacement therapy excrete approximately 10% of the nicotine dose as 4-oxo-4-(3-pyridyl)butanoic acid (keto acid) and 4-hydroxy-4-(3-pyridyl)butanoic acid (hydroxy acid). Previously, these acids were thought to arise by secondary metabolism of the major nicotine metabolite cotinine, but our data did not support this mechanism. Therefore, we hypothesized that nicotine is metabolized by 2'-hydroxylation, which would ultimately yield keto acid and hydroxy acid as urinary metabolites. This pathway had not been established previously in mammalian systems and is potentially significant because the product of nicotine 2'-hydroxylation, 4-(methylamino)-1-(3-pyridyl)-1-butanone (aminoketone), can be converted to the potent tobacco-specific lung carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Incubation of nicotine with cytochrome P450 2A6 and cofactors did indeed produce aminoketone, which was identified as its N-benzoyl derivative by GC-MS. The rate was 11% of that of cotinine production. Incubation of human liver microsomes with nicotine gave keto acid by using aminoketone as an intermediate; keto acid was not formed from cotinine. In 10 human liver samples, rates of formation of keto acid were 5.7% of those of cotinine and production of these metabolites correlated. These results provide definitive evidence for mammalian 2'-hydroxylation of nicotine and elucidate a pathway by which endogenous formation of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone could occur in humans.

PMID: 11050152 [PubMed - indexed for MEDLINE]

This abstract could have been worded a little better for such a significant finding. Basically, aminoketone is produced from nicotine by human P450 2A6 (not found in rats). Aminoketone can be very easily nitrosated into NKK (a carcinogen). No NKK has been found in urine samples of transdermal nicotine users. They propose that it could be produced locally in tissues such as the liver, but that it occurs most easily at pH 3-4 (i.e. non-physiological, except for the stomach). They emphasize that risk probably increases with constant use.

Edited by chrono, 29 September 2010 - 12:54 PM.
fixed quote tag


#35 bacopa

  • Validating
  • 2,223 posts
  • 159
  • Location:Boston

Posted 27 April 2010 - 03:00 PM

ok so now what to believe? That study showed obvious cognitive benefit while other studies show it can lead to dementia's? Or is that just from smoking...ugh...

The meta-analysis only looked at the short-term effects of nicotine in non-smokers. Whether nicotine is bad for the brain long-term is a different question.


but so many articles subtly saying it could or is good long term, from what I read. So I think nicotine in moderate doses maybe very beneficial and is why they are creating receptor specific nicotine drugs for cognitive gains and even neuroprotection. However I could be wrong, and long term could equate with cognitive problems/decline.

Either way, I take the nicotine gum, now in moderate to low doses as an after effect response of a severe addiction to cigarettes for 4 years whilst very depressed and psychotic.



This article suggests that enymes in people can metobilze nicotine into aminoketone, which is a precursor to NNK carcinogen:
http://www.thefreeli...ogen-a067328680

This article bugs the heck out of me, because I know folks that take nicotine (not cigarettes)... and it may be appear to be an issue for them later.

A

can you tell me what issues occur for them later please?

#36 chrono

  • Topic Starter
  • Member, Moderator
  • 2,440 posts
  • 794
  • Location:New England

Posted 27 April 2010 - 03:52 PM

can you tell me what issues occur for them later please?

In the context, I'm pretty sure he's talking about the generation of carcinogenic agents in the body leading to cancer.

#37 Anthony_Loera

  • Lifetime Member
  • 3,121 posts
  • 699
  • Location:Miami Florida

Posted 27 April 2010 - 06:25 PM

I apologize dfowler,
As Chrono correctly clarified: I did mean the generation of carcinogen agents from the metabolism of nicotine, leading to cancer.

Thanks Chrono

Edited by Anthony_Loera, 27 April 2010 - 06:27 PM.


#38 Guacamolium

  • Registered User
  • 747 posts
  • 31
  • Location:Tahoe

Posted 27 April 2010 - 06:29 PM

As long as you're taking your Krill/fish/or seal oil, vasoconstriction shouldn't be a problem.

#39 chrono

  • Topic Starter
  • Member, Moderator
  • 2,440 posts
  • 794
  • Location:New England

Posted 27 April 2010 - 06:56 PM

Hmm, well this brings me back to part of my original question: are there any other ways to tell if vasoconstriction is going on, besides measuring your BP? I sometimes got cold hands, but maybe only the first few times I tried it and it was still winter. Haven't noticed it much lately. Will it have a noticeable effect on heart rate, response to exertion, etc?

#40 Guacamolium

  • Registered User
  • 747 posts
  • 31
  • Location:Tahoe

Posted 27 April 2010 - 07:44 PM

Hmm, well this brings me back to part of my original question: are there any other ways to tell if vasoconstriction is going on, besides measuring your BP? I sometimes got cold hands, but maybe only the first few times I tried it and it was still winter. Haven't noticed it much lately. Will it have a noticeable effect on heart rate, response to exertion, etc?


You simply look at the size of your veins on your wrists. Small, sunken veins = vasoconstriction. Larger than usual and protruding = vasodilation. As far as your capillaries go, there's no way to tell other than numbness or cold fingers/toes/feet/hands. Also for me, since I have type 1.5 skin, there is subtle color change in my hands.

I consume so much capsaicin and garlic on a daily basis that it usually isn't a problem for me. Seriously, I'm a pepper freak. I have to have peppers on whatever I eat every day. Also, I don't know if you supplement with protein, but pea protein has a very high ratio of arginine in it compared to other proteins. Arginine turns into nitric oxide in the body which causes global vasodilation.

#41 bacopa

  • Validating
  • 2,223 posts
  • 159
  • Location:Boston

Posted 28 April 2010 - 01:47 AM

I apologize dfowler,
As Chrono correctly clarified: I did mean the generation of carcinogen agents from the metabolism of nicotine, leading to cancer.

Thanks Chrono

no apology needed, as a nicotine gum chewer myself do I have to worry about metabolizing carcinogens through some metabolic interactions?

#42 MoodyBlue

  • Registered User
  • 144 posts
  • 13
  • Location:San Francisco, CA

Posted 28 April 2010 - 02:40 AM

The definition of nicotine is that it is a highly toxic alkoloid which is valued as an insecticide. Those are the facts. I don't beleive there is as yet any evidence that it causes cancer directly (that doesn't mean it does not contribute in some direct way--it just isn't known). I did read an article in a reputable science magazine almost 6 yrs. ago which published a study which proved that it does contribute to cancer indirectly. The way that it does, it claimed, was by inhibiting the action of a protein our body makes to communicate to early development cancerous cells that they should go into apoptosis.

I think Picamilon is the best vasodilator.

#43 chrono

  • Topic Starter
  • Member, Moderator
  • 2,440 posts
  • 794
  • Location:New England

Posted 28 April 2010 - 04:34 AM

no apology needed, as a nicotine gum chewer myself do I have to worry about metabolizing carcinogens through some metabolic interactions?

I think it's hard to say with certainty. What that research study demonstrated was that all the building blocks for NKK (aka NNK) are there. It was not shown to actually occur; studies in rats (9067560) and humans (9973205) from a few years before failed to detect NKK in urine, but in the study Anthony posted they posit that it could be generated in tissue.

The enzyme which metabolizes nicotine (and is necessary for its conversion into the NKK precursor aminoketone), P450 2A6 (CYP2A6), is specific to the liver. When chewed as a gum, a large part of the dose is swallowed before it can be absorbed by mouth tissues (11294371). Thus a higher portion of the dose undergoes metabolism by this enzyme, resulting in more aminoketone: "Disproportionately higher metabolite-to-nicotine ratios while chewing gum compared with smoking suggested that some nicotine was swallowed and underwent first-pass metabolism" (3829583). Oral bioavailability of nicotine is between 20-45%, meaning a lot of it gets metabolized. Transdermal nicotine is absorbed directly through the skin, and does not undergo first-pass metabolism. If I were you, I would think about switching over.

I haven't done enough research on cancer to know how much of a potential problem this is. How effectively is NKK eliminated? Does it need to reach a "critical mass" concentration over a certain period of time before it can form malignant cells or tumors? If no NKK was found in urine, large amounts of it probably aren't being produced.

For myself, I'm going to start using nicotine very rarely. Will probably eliminate it from use entirely as I'm able to afford different occasional-use nootropics which don't have a demonstrable carcinogenic pathway. But I'm very risk-averse to this kind of thing; you'll have to make your own mind up based on the spectrum of possibility to probability.

A great review of nicotine metabolism and pk: Metabolism and Disposition Kinetics of Nicotine

Edited by chrono, 28 April 2010 - 04:37 AM.


#44 haha

  • Registered User
  • 91 posts
  • 10

Posted 28 April 2010 - 04:47 AM

It definitly sounds that transdermal is superior to chewing gum, also as a x smoker i dont like the gum because by choosing to use nicotine at specific times it still leaves me habitated rather than just dependent, which im not anyway. Its a pitty we dont have much info on the intenisty of the carcingoencicty of nicotine, may things cause unfavourable gene expression. And not knowing if its NNK is formed in the body sucks, does anyone know about nitro,ation biopathways etc? I havent heard of nitros in signal transduction but maybe they exisit as protien breakdown pathways, dont know do some research later

#45 chrono

  • Topic Starter
  • Member, Moderator
  • 2,440 posts
  • 794
  • Location:New England

Posted 28 April 2010 - 04:58 AM

does anyone know about nitro,ation biopathways etc? I havent heard of nitros in signal transduction but maybe they exisit as protien breakdown pathways, dont know do some research later

Here's the crucial paragraph from the paper anthony posted:

Aminoketone is easily nitrosated, with an intrinsic rate constant similar to that of other secondary amines such as pyrrolidine (22, 28). Because the pH maximum for nitrosation of secondary amines, such as aminoketone, is typically 3–4, this reaction would occur most readily in the stomach (29). However, nitrosation also occurs at neutral pH under a variety of conditions (29). Iminium ions such as Δ1′(2′) iminium ion, which is in equilibrium with aminoketone, are nitrosated at neutral pH (30). Nitric oxide and peroxynitrite react with secondary amines—via N2O3, N2O4 and other intermediates—to produce nitrosamines at neutral pH (31–33). Nitric oxide and peroxynitrite are formed endogenously under conditions of chronic inflammation or infection, leading to endogenous nitrosamine formation (33–36), and substantial amounts of nitrogen oxides are present in cigarette smoke, resulting in endogenous nitrosamine formation in smokers (29, 34, 35, 37). Although we did not find evidence for endogenous production of NNK in exsmokers using nicotine replacement theory, that conclusion was based on analysis of urinary NNK metabolites (38). Local formation of NNK in certain tissues would not be detectable by analysis of urinary metabolites. We also did not detect increased levels of NNK metabolites in the urine of rats treated with nicotine and nitrite; however, rats lack a hepatic enzyme related to P450 2A6 and therefore may not produce significant amounts of aminoketone from nicotine (39, 40). These considerations lead to the realistic possibility that NNK could be formed endogenously in people who use tobacco products, resulting in exposure to this carcinogen above and beyond the amounts already present in these products. It is also possible that NNK could be formed endogenously during nicotine replacement therapy, particularly under conditions of long-term therapy.


Edited by chrono, 29 September 2010 - 12:54 PM.
fixed quote tag


#46 Guacamolium

  • Registered User
  • 747 posts
  • 31
  • Location:Tahoe

Posted 28 April 2010 - 05:02 AM

One can still opt for an array of antioxidants, like idebenone, grapeseed extract, vitamin E, C, A to combat the unknown that NNK may produce. Not sure of its polarity without looking it up or figuring it out through its dielectric constant. I have tons of work to do, so determining something like that unfortunately falls to the near-bottom of that list - unless its polarity is already written in an accessible place.

#47 chrono

  • Topic Starter
  • Member, Moderator
  • 2,440 posts
  • 794
  • Location:New England

Posted 28 April 2010 - 05:06 AM

One can still opt for an array of antioxidants, like idebenone, grapeseed extract, vitamin E, C, A to combat the unknown that NNK may produce.

It would be interesting to know if there are any preventative measures. But NKK is a known carcinogen...I don't know if any of those supplements could reasonably be relied upon as an effective countermeasure to that.

#48 Guacamolium

  • Registered User
  • 747 posts
  • 31
  • Location:Tahoe

Posted 28 April 2010 - 05:20 AM

One can still opt for an array of antioxidants, like idebenone, grapeseed extract, vitamin E, C, A to combat the unknown that NNK may produce.

It would be interesting to know if there are any preventative measures. But NKK is a known carcinogen...I don't know if any of those supplements could reasonably be relied upon as an effective countermeasure to that.


I'd need to look into NNK further, but I'm officially in sleep-dep mode and need to retire, my apologies.

#49 aLurker

  • Registered User
  • 715 posts
  • 403
  • Location:Scandinavia

Posted 02 September 2010 - 02:25 PM

Good ideas in this thread, I like the suggestion about pomegranate.

Well, I looked at the wiki list of treatments for Raynaud's phenomenon. That list should give some kind of indication of what might be good to counteract the harmful effects of vasoconstriction. A few interesting ones are sildenafil (and perhaps taldalafil too then), fish oil and Piracetam. The last one is especially intriguing since it is a favorite for many here at the forums, myself included. I assume most of us here take fish oil too.

Vasoconstriction is probably the most undesirable adverse effect of transdermal nicotine use. I find this agent quite useful for its dopaminergic qualities, and would like a better idea of the consequences of its use.


I know chrono uses Piracetam at least occasionally and I assume he takes fish oil too. Chrono were you on Piracetam and fish oil and still had noticeable problems with nicotine or didn't your regimen include these items or did you abandon nicotine due to caution?

Anyone with Nicotine+Piracetam experience? Does Piracetam (or fish oil or pomegranate) help with the vasoconstriction at all?

Edited by aLurker, 02 September 2010 - 02:43 PM.

  • like x 1

#50 chrono

  • Topic Starter
  • Member, Moderator
  • 2,440 posts
  • 794
  • Location:New England

Posted 02 September 2010 - 07:24 PM

I know chrono uses Piracetam at least occasionally and I assume he takes fish oil too. Chrono were you on Piracetam and fish oil and still had noticeable problems with nicotine or didn't your regimen include these items or did you abandon nicotine due to caution?

That's an interesting link you've proposed with Raynaud's; it seems that nicotine is one of the largest behavioral factors which worsen the symptoms, so its treatments might potentially ameliorate nicotine's vasoconstriction, perhaps by other means than direct vasodilation (from somethingtoxic's comments above, stacking these opposing mechanisms may be undesirable).

I was definitely taking 2x800-1200mg piracetam last winter, though it was somewhat sporadic, and when using nicotine I may have been more likely to forgo my dose. I think I started fish oil a few months after my nicotine experiments.

Just to clarify, the effects I described (mainly cold hands) were pretty slight. In and of themselves, they wouldn't have been sufficiently annoying to prompt my cessation. My concern was that they might be indicative of vasoactivity that I should be worried about. However, I did stop due to questions about the cancer risk; there really isn't much 'evidence' of this beyond that paper we discussed, but when cancer is involved, even tenuous evidence can be compelling.

I would still consider using it occasionally, maybe once every couple of months. But I have a few dopamine precursors that allow me many of the same effects, and without this risk attached, so I try to save it for "special occasions" when I might want all the mental enhancement that I can get.

#51 Pike

  • Registered User
  • 517 posts
  • 6

Posted 02 September 2010 - 11:44 PM

i was under the impression that nicotine had no direct carcinogenic activity, but it was the other chemicals in tobacco and tobacco smoke that did. oh well.

however, in terms of your original concern about vasoconstriction:

i sincerely doubt you were getting cold hands as a result of vasoconstriction from nicotine. the amount you said you used, 4mg a day for 10 days, is extremely small. 4mg of nicotine is the equivalent of about 2 cigarettes, and you were spacing 2 cigarettes worth of nicotine out over a 24 hour administration. that's literally one-sixth of a milligram per hour; 0.16mg (in 10 days, you had the amount of nicotine in about one entire pack of cigarettes). you might get 1/6mg from about 2 or 3 puffs of a cigarette. and sure 1/6mg of nicotine might be enough to give a non-smoker a buzz of sorts, but that's because you'd be receiving it instantly.

just for arguments sake, let's assume it takes 1 full minute to puff and receive the 1/6mg nicotine from a cigarette. in one minute, you received 1/6mg of nicotine, which would probably cross that threshold to have an effect and give someone a "buzz." in contrast, let's take your administration method of 1/6mg per hour. calculated down, that is literally 1/360mg of nicotine in a minute; 0.0027mg. to space a few puffs' worth of nicotine over an entire hour probably wouldn't even affect a non-smoker. that amount hardly seems like it would be having any kind of effect at all, let alone be enough to cause serious vasoconstriction.




as for an alternative to patches and gum:
you could look into nicotine lozenges. the problem with gum is that despite the gum having as much nicotine as a cigarette, the amount of time it takes to receive that same amount of nicotine is a lot longer than it would take to actually smoke a cigarette; and they taste like ass. nicotine lozenges dissolve a lot faster and come in a nice minty flavor.

if you're serious about continuing your use of nicotine and plan to for quite some time, you could opt for an electric cigarette. same nicotine, zero carcinogens.

#52 aLurker

  • Registered User
  • 715 posts
  • 403
  • Location:Scandinavia

Posted 03 September 2010 - 10:56 AM

Out of the issues Pike brings up, there is one thing that strikes me as something that needs to be discussed: Does transdermal nicotine generally act as a vasoconstrictor for most people?

Common wisedom and the wikipedia article on nicotine currently says the following:
[quote]Peripheral circulation in arteries going to the extremities is also highly susceptible to the vasoconstrictor effects of nicotine and the increased risk of clots and clogging.[citation needed][/quote]
But an unsourced statement doesn't bring us any closer to the truth, what do scientific studies actually show?

Smoking definitely decreases blood flow to extremities yet nicotine only doesn't seem as clear cut:
[quote]Infrared Imaging to Measure Temperature Changes of the Extremities caused by Cigarette Smoke and Nicotine Gums
Infrared (IR) image sequences and physiological data (heart rate, blood pressure, blood oxygenation) were acquired in a well-controlled environment adhering to stringent experimental protocols from several test persons who chewed nicotine gums or smoked cigarettes. Task-optimized digital image processing techniques (registration, segmentation, morphological operations) were implemented in a MATLABtrade-based graphical user interface developed for automatic analysis of the acquired infrared images and automatic generation of finger and palm temperature time plots. We found significant temperature decreases due to vasoconstriction mainly in smokers, and temperature increases due to vasodilation mainly in non-smokers. However, the effects of nicotine on vasomotor control, skin vascularization and temperature via the sympathetic nervous system are difficult to assess and also depend on a subject's baseline temperature[/quote]
The conclusion here is kind of unclear regarding nicotine and I couldn't seem to access the full paper :/

Another relevant study:
[quote]
Short-term effects of transdermal nicotine on acute tissue plasminogen activator release in vivo in man

Abstract

Objective: Cigarette smoking impairs peripheral endothelium-dependent vasodilatation and acute tissue plasminogen activator (t-PA) release in man. The aim of the study was to determine if this endothelial dysfunction is, in part, mediated by the effects of nicotine. Methods: Blood flow and plasma fibrinolytic factors were measured in both forearms of eight healthy male non-smokers during unilateral brachial artery infusion of the endothelium-dependent vasodilator, substance P (2 to 8 pmol/min). Endothelium-independent vasodilatation was assessed using intra-arterial infusion of sodium nitroprusside (2 to 8 μg/min). Subjects attended after 7 days treatment with transdermal nicotine or placebo in a double blind randomised crossover design. Results: Plasma cotinine concentrations rose from 0.4±0.1 (placebo) to 125±25 ng/ml during nicotine administration (P<0.001). On both treatment days, substance P caused dose-dependent increases in blood flow and plasma t-PA antigen and activity concentrations (P<0.001 for all) but had no effect on plasma plasminogen activator inhibitor type 1 (PAI-1) concentrations. Compared with placebo, nicotine administration increased the substance-P-induced release of t-PA antigen and activity (P<0.05 for both) without an effect on endothelium-dependent or -independent vasodilatation. Conclusions: Short-term transdermal nicotine treatment does not affect endothelium-dependent vasomotion but does increase substance-P-induced t-PA release in vivo in man. This suggests that nicotine administration alters specific aspects of endothelial function and enhances the acute endogenous fibrinolytic capacity in vivo. The long-term effects of nicotine exposure, including the potential to cause depletion of endothelial t-PA stores, now needs to be assessed.
[/quote]

Excerpts from the study above:

[quote]Epidemiological studies of long-term nicotine treatment have not been conducted but relevant information can be inferred from studies of chewing tobacco or snuff users where there is systemic absorption of nicotine but not of other combustion products. These studies have found no evidence of an increased risk of myocardial infarction or sudden cardiac death [22,23]. Two prospective studies involving treatment of smokers with known cardiovascular disease using transdermal nicotine have also failed to find an association between nicotine use and the risk of acute cardiovascular events [24,25]. Indeed, one study of smokers [25] reported more adverse events with placebo than nicotine patches suggesting a protective role of nicotine. Moreover, an experimental study of smokers with known coronary artery disease demonstrated that nicotine supplementation caused a substantial reduction in exercise-induced reversible myocardial perfusion defects as assessed by quantitative SPECT scanning [26]. Although there are differences between epidemiological and experimental studies, these results suggest that nicotine in itself is not a direct cause of tobacco-related cardiovascular disease.[/quote]

[quote]Another finding of the present study is that nicotine administration was associated with an increase in basal forearm blood flow suggesting a vasodilator effect of nicotine on the peripheral vascular bed. The cardiovascular effects of systemic nicotine administration are complex and include actions of nicotine on the central and peripheral nervous systems. Of the studies that have examined the direct effect of nicotine on vascular reactivity, all have suggested a vasodilator action. Ex vivo studies indicate that nicotine induces a neurally and nitric oxide-mediated, endothelium-independent, vasodilatation [37,38]. This has been confirmed by an in vivo canine model [39] that demonstrated that the intracarotid injection of nicotine increased cerebral blood flow through the release of nitric oxide from vagal nerve terminals. Moreover, Fewings et al. [40] have reported that intra-arterial nicotine infusion increases forearm blood flow in man. Our findings suggest that short-term nicotine administration does not impair endothelium-dependent vasomotion but does cause systemic vasodilatation as indicated by an elevation in resting forearm blood flow and heart rate.

In conclusion, we have demonstrated, for the first time, that nicotine administration alters specific aspects of endothelial function and enhances the acute endogenous fibrinolytic capacity in vivo. Future studies are now needed to assess the effects of long-term nicotine exposure, including the potential to cause depletion of endothelial t-PA stores, particularly in recent ex-smokers.[/quote]

Citation needed indeed...

Reading this post I sound like someone trying to justify their nicotine habit but for the record I haven't had a nicotine habit ever and I just want to get all the facts before I try something potentially addictive. I'd really appreciate more information regarding this and whether it really is a problem or not. Feel free to chip in.
  • like x 1

#53 chrono

  • Topic Starter
  • Member, Moderator
  • 2,440 posts
  • 794
  • Location:New England

Posted 03 September 2010 - 03:47 PM

just for arguments sake, let's assume it takes 1 full minute to puff and receive the 1/6mg nicotine from a cigarette. in one minute, you received 1/6mg of nicotine, which would probably cross that threshold to have an effect and give someone a "buzz." in contrast, let's take your administration method of 1/6mg per hour. calculated down, that is literally 1/360mg of nicotine in a minute; 0.0027mg. to space a few puffs' worth of nicotine over an entire hour probably wouldn't even affect a non-smoker. that amount hardly seems like it would be having any kind of effect at all, let alone be enough to cause serious vasoconstriction.

While an interesting thought experiment, I don't think this really gets us anywhere. Without knowing how much vasoconstriction is caused by a certain dosage of inhaled nicotine, it's not really possible to extrapolate across to a delivery system with vastly different pk, and draw a conclusion about the resulting magnitude. I'm not really comfortable with the answer that a vaguely small amount of constriction isn't harmful (though it may well be true).

And you're correct that this is a small amount of nicotine compared to smoking cigarettes. But you can't simply divide total patch dosage by time, and compare it directly to cigarette administration. One cigarette contains something like .75-1.3mg nicotine [1] [2], and results in a plasma concentration of 15-30ng/mL with a Tmax (duration of maximum plasma conc.) of 5-8min [3]. But a 15mg/16h transdermal patch has a Cmax (max plasma level) of 11-14ng/mL with a Tmax of 6-9 hours (with a range of 3-12h for different brands). And this is only the Cmax; depending on the brand, useful levels are probably maintained for 12-24h [4]. Smoking 1 cigarette an hour would give you approximately the same amount of nicotine over the course of time, but it would be impossible to achieve the same steady Cmax/Tmax, probably because of the difference in elimination pk and the matrix administration properties of the patch.

In addition to the drastically longer plateau of plasma levels, the reason a small amount (like a 4mg patch slice) is effective is because the effects of nicotine that I'm looking for are non-linear. Sucking down an entire pack in an hour wouldn't improve my concentration 20x more than a single cigarette; in fact, a single cigarette is probably too much, though for a very short time. The nicotine 'buzz' is not the goal; that feeling can be pretty 'dopey', and (at least for me) interferes with cognition and motivation more than it helps. A 4mg patch affords me a slight dopaminergic boost (and probably some nAChR, but that's not something I can identify subjectively), while an 8mg slice is more buzzy, euphoric, confusing, and anti-motivational.

Reading this post I sound like someone trying to justify their nicotine habit but for the record I haven't had a nicotine habit ever and I just want to get all the facts before I try something potentially addictive. I'd really appreciate more information regarding this and whether it really is a problem or not. Feel free to chip in.

I don't know if I can offer any good advice for you. One of the reasons I was comfortable playing around with this is that I don't find nicotine addictive; I've smoked something like 1-2 packs a year for the past 10 years or so, without having to exercise any restraint. Just doesn't do anything for me, beyond making me look cool. That being said, I don't think most people find patches to be very addictive, unless you use it quite frequently. I would definitely cycle or use sporadically. Check out the other thread in the pinned index for a bunch of good descriptions of the effects, and factors to consider over time.

And I'm still pretty curious about the vasoconstriction issue. My physiology knowledge is so wack, I'm not even sure if a small amount (like pike suggests) used every day would be harmless, or if it still places some kind of stress on the cardiovascular system that might result in permanent damage.

Edited by chrono, 03 September 2010 - 03:50 PM.


#54 medievil

  • Registered User Irresponsible Drug Addict
  • 3,725 posts
  • 20
  • Location:Belguim

Posted 03 September 2010 - 04:07 PM

For those interested:

http://www.mindandmu...=1

This thread has a good overview of the up and downsides of nicotine use.
  • like x 1

#55 aLurker

  • Registered User
  • 715 posts
  • 403
  • Location:Scandinavia

Posted 03 September 2010 - 05:19 PM

For those interested:

http://www.mindandmu...=1

This thread has a good overview of the up and downsides of nicotine use.

Thanks medievil. Fascinating reading for sure. This was by far the scariest part of that thread and it definitely makes me question the use of nicotine. :/

The results of the present investigation provide the first empirical evidence that an intermediate dose of isolated nicotine significantly reduces erectile response in healthy, young, nonsmoking men.

Perhaps a steady stream from transdermal administration would be different but the acute effects of a nicotine spike from nicotine gum in the study above puts nicotine in a bad light here. Still way better than smoking though.

Edited by aLurker, 03 September 2010 - 06:03 PM.


#56 Pike

  • Registered User
  • 517 posts
  • 6

Posted 03 September 2010 - 07:56 PM

@chrono, i'm super aware of all the flaws in mock model i calculated out, but the point of the whole mock model was more to stress that the minute amount of nicotine you're probably getting could very possibly not even be crossing the threshold have virtually an physical effect on your body at all. actually, due to the tendency for patches to release a "burst" of nicotine upon initial application from their edges, then a slower stream, the levels of nicotine you'd have might be at much smaller levels, and that could all be variable simply depending on what shape you cut the patches in. i'm just incline to think that the amount received could be not enough to cross the threshold boundary and have a real physiological effect on your body.

i've used the patches before, too, and i will say that the nicotine effect of patches feels absolutely nothing like any other form of nicotine administration (being cigarettes, gum, and lozenges). there was a point at which i was smoking a pack's worth of cigarettes a day, and every one of them had a paradoxically stimulating/calming effect (probably the effects of the stimulant coupled with deep breathing), but putting on an equivalent patch that would have contained the same amount of nicotine (21mg) it was absolutely dreadful. it made me sick, and was tranquilizing in a very unpleasant way. personally, i think it could have something to do with the brain going through some moderate amount of plasticity at the presence of a constant stream of nicotine. just my thoughts on it.

that said, you do bring up some good points, and i did completely overlook that maybe you weren't looking for the conventional nicotine buzz.

still, something to think about could be that perhaps the cold hands/feet could be due to some outlying variable that has nothing to do with the nicotine.

#57 aLurker

  • Registered User
  • 715 posts
  • 403
  • Location:Scandinavia

Posted 04 September 2010 - 05:40 AM

IMHO the focus here should be on the cognitively enhancing aspects of nicotine since this is a nootropics forum and a nicotine patch works just fine for that according to studies even if it lacks some of smoking's pleasant/addictive effects.

Any information on how transdermal nicotine affects factors such as blood flow?

#58 chrono

  • Topic Starter
  • Member, Moderator
  • 2,440 posts
  • 794
  • Location:New England

Posted 07 September 2010 - 03:26 PM

I ended up trying nicotine again for a few days this week, after our discussion here. Perhaps the best effect is a slight, but very definite, boost in motivation. The other dopaminergics I currently have—manganese, L-TYR, NALT, and L-DOPA—really don't have this effect on me. I have some severe and entrenched task avoidance and sticktoitiveness problems, so I'm pretty comfortable saying that nicotine imparts an increased tendency to make progress on otherwise-difficult/unpleasant tasks, which is beyond a placebo effect.

Since I really need a little help with this right now, and because I don't have enough cash to try any of the other potentially-beneficials on my list, I've decided to use it a little more frequently for the time being.

@aLurker: I thought I'd mention this, since I know this is one of your targets, as well. I'd be very curious to hear about your experiences, when you get around to it.

There's a lot of hits on pubmed about vasoconstriction. I'll see if there's anything useful for us when I have a little more time.

Edited by chrono, 07 September 2010 - 03:28 PM.


#59 aLurker

  • Registered User
  • 715 posts
  • 403
  • Location:Scandinavia

Posted 07 September 2010 - 06:41 PM

[quote name='chrono' timestamp='1283873184' post='428588']
I have some severe and entrenched task avoidance and sticktoitiveness problems, so I'm pretty comfortable saying that nicotine imparts an increased tendency to make progress on otherwise-difficult/unpleasant tasks, which is beyond a placebo effect.
[/quote]
You and me both, glad to hear something helps people like us and I'll probably give the nicotine route a shot within a week or so if I can't find anything else to try, perhaps I'll even combine nicotine with galantamine.

[quote name='chrono' timestamp='1283873184' post='428588']
@aLurker: I thought I'd mention this, since I know this is one of your targets, as well. I'd be very curious to hear about your experiences, when you get around to it.
[/quote]
I appreciate the heads up and I'll definitely post my experience when I get around to trying it.

[quote name='chrono' timestamp='1283873184' post='428588']
There's a lot of hits on pubmed about vasoconstriction. I'll see if there's anything useful for us when I have a little more time.
[/quote]
Great.

Here are a couple of nuggets about vasoconstriction to get us started:

[quote]Nicotine Effects on Skin: Are They Positive or Negative?

The adverse effects of tobacco on the skin are well known but the role of nicotine is more controversial. Nicotinic receptors are expressed in the skin, on keratinocytes, fibroblasts and blood vessels. Nicotine induces vasoconstriction associated with local hyperaemia. It inhibits inflammation through effects on central and peripheral nervous system and through direct effect on immune cells. It delays wound healing and accelerates skin aging. The role of nicotine on skin diseases remains unclear. Therapeutic effects of nicotine could be possible and this a new stimulating field of research.
[/quote]
That study states pretty clearly that nicotine induces vasoconstriction so it might have some juicy references within it.

This is pretty interesting too, from Taurine treatment protects against chronic nicotine-induced oxidative changes.
[quote]Taurine supplementation to nicotine-treated animals reversed the contractile dysfunction and restored the endogenous GSH levels and decreased high lipid peroxidation and MPO activities in both tissues. These data suggest that taurine supplementation effectively attenuates the oxidative damage because of chronic nicotine administration possibly by its antioxidant effects.[/quote]
Don't know if taurine has been mentioned before but if it helps rats perhaps it could help us.

The oxidative effects might also be alleviated with pycnogenol/pine bark, (although that might interfere with the increase in dopamine, I'm not sure).

sponsored ad

  • Advert
Click HERE to rent this advertising spot for BRAIN HEALTH to support LongeCity (this will replace the google ad above).

#60 aLurker

  • Registered User
  • 715 posts
  • 403
  • Location:Scandinavia

Posted 09 September 2010 - 08:42 AM

Red wine extract might also be beneficial here. I might look into it later, just wanted to write it down for future reference.




0 user(s) are reading this topic

0 members, 0 guests, 0 anonymous users