91 replies to this topic

[Imagination]

Nicotine only provides focus to those who are already addicted, the only reason this is so, is because it takes your mind off the cigarettes and makes you feel normal again.

It's quite like banging your head against the wall just to stop and say wow, I feel great now compared to banging my head against the wall.

Good luck trying to quit.

[medicineman]

no,, that is impossible.... with any living thing, repeated stimuli has the same effect in every living organism, and that is desensitization. You are inquiring about receptor 'washing'.

Your post reminded me of a nice trick bodybuilders and ephedrine users did to make their stimulants work over and over again... They took zaditen, or generically known as ketotifen, and that made their stimulants more effective at same or lower dosages. I thought to myself, impossible.... I argued and argued, but I got told over and over, by different bodybuilders and athletes that it works. I tried it,, and viola,,, like a miracle, I take ephedrine for 5 days, take zaditen that night, and on the 6th day, ephedrine worked as good as the previous days if not better... So I looked more in depth at G protein Receptors to figure out where I went wrong. I don't know the in depth mechanics of it,,, but noradrenaline and adrenaline receptors undergo some form of refractory period, where their stimulation will yield lower or no results, thanks to something with the name of arrestin, and adrenergic activity is directed via Cyclic AMP.... my guess is ketotifen probably modulated or inhibited arrestin or modulated cyclic AMP, to a degree (speculation on my part), but it couldn't inhibit or modulate too much, because somehow your body finds a way around. (any input or addition here, or a correction would be welcome)

I am not hundred percent sure, but acetylcholines effects on memory are mediated not by its muscarinic G-Protein activity, but via its ionotrophic activity in the nicotinic receptors i think....the muscarinic activity is autonomic, as in it regulates your parasympathetic nervous system and keeps your sympathetic system in check... and to my knowledge, the ionotrophic channels are not regulated by any arrestin like protein or cyclic AMP,, but by ions.... it is too detailed to get into,, but basically these ions depolarize and hyperpolarize membrane potential, thus culminating in a large complex cascade of reactions and channels interacting to exert their effect... so, the next question is,,, can you 'wash' your ionotrophic channels??? No..... not that I know of... you can't alter your plasma calcium or sodium (or any ion) without disasterous results....

i hope this information is of some help.... it might seem a bit too technical, but it could be alot worse. plus,, if you aren't taking the time to know what you are putting in your body (which would be a shame), than ignore my post completely......

Edited by medicineman, 01 December 2008 - 11:05 PM.

[Heliotrope]

The "C' word , Cancer, sounds the most Scary about Nicotine Patch to me, as we've no cure for cancer, that's something that can cost your life, like smoking cigarettes may cause lung cancer.

So btw, where do you put on your patches huh? do you slap it on the same body part every time, like your upper arm , chest or what? Or do you rotate to a diff area each time? There's certainly systemic absorption , but in the same spot, wouldn't the skin be rubbed raw and all the chemical get localized in 1 region, BOOM , cancer in the chest, in lung , tumors on the arm etc??

[lynx]

no,, that is impossible.... with any living thing, repeated stimuli has the same effect in every living organism, and that is desensitization. You are inquiring about receptor 'washing'.

Wrong, nicotine does not cause receptor down regulation or translocation.

[medicineman]

Downregulation of nicotinic receptor function after chronic nicotine infusion
MJ Marks, SR Grady and AC Collins

Institute for Behavioral Genetics, University of Colorado, Boulder.

Chronic nicotine treatment generally results in tolerance to several actions of nicotine and a paradoxical increase in brain nicotinic receptor numbers. Receptor upregulation, it has been argued, arises as a consequence of functional desensitization. In the studies reported here, mice were chronically infused with saline (control) or one of five doses of nicotine (0.25-4.0 mg/kg/hr) for 10 days. This treatment resulted in a dose-dependent tolerance to nicotine-induced decreases in body temperature as well as decreases in locomotor and rearing activities in a Y-maze. The anticipated increase in [3H]nicotine binding was also observed. To assess functional status of the nicotinic receptors, nicotine-stimulated release of [3H]dopamine from striatal synaptosomes and 86Rb+ efflux from cortical and midbrain synaptosomes were also measured. Chronic nicotine infusion resulted in an infusion dose-dependent decrease in [3H]dopamine release from striatum and 86Rb+ efflux from midbrain; cortical 86Rb+ efflux was not affected by chronic nicotine treatment. Dose-response analyses of the release and efflux assays demonstrated that chronic nicotine infusion evoked decreases in the maximal effects of nicotine on the functional assays; potency was not altered by chronic drug treatment. These results are consistent with the hypothesis that behavioral tolerance to nicotine is a consequence of down-regulation of brain nicotinic receptor function.


Volume 266, Issue 3, pp. 1268-1276, 09/01/1993
Copyright © 1993 by American Society for Pharmacology and Experimental Therapeutics


Nicotinic receptor inactivation after acute and repeated in vivo nicotine exposures in rats





References and further reading may be available for this article. To view references and further reading you must purchase this article.

Robert E. Vann^{a, ,} , John R. James<a href="http://&quot;http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6SYR-4JPR879-8&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=2569d2ae74e1f18d393223fd1f228f02#aff2&quot;" target="_blank">^b, John A. Rosecrans^a and Susan E. Robinson^a

</a>^aDepartment of Pharmacology and Toxicology, Virginia Commonwealth University, PO Box 980613, Richmond, VA 23298, USA

<a name="aff2">^bDepartment of Pharmaceutics, Virginia Commonwealth University, PO Box 980613, Richmond, VA 23298, USA


Accepted 19 February 2006. Available online 13 April 2006.
<h3 class="h3">Abstract</h3>Nicotine tolerance is often accompanied by an upregulation of brain area nicotinic acetylcholine receptors (nAChRs) in both animal and human subjects. This upregulation has been hypothesized to result from repeated or prolonged exposures of these receptors to nicotine. To explore this further, this study examined the level of nAChR desensitization following acute and repeated nicotine administration in the male Lewis rat. Nicotine-stimulated ⁸⁶Rb⁺ efflux was measured in synaptosomes prepared from the frontal cortex, hippocampus, striatum, and thalamus. Analysis of receptor functionality was achieved by calculating area-under-the-curve (AUC) for nicotine-induced fractional ⁸⁶Rb⁺ efflux. Nicotine-stimulated ⁸⁶Rb⁺ efflux from all brain regions was significantly less in rats that received an acute injection of 0.4 mg/kg nicotine (s.c.) 15 min prior to dissection compared to control rats. This decrease in nAChR functional status was also observed in rats treated with 1 day or 14 days of twice-daily nicotine administration. These results are consistent with the concept that acute exposure to nicotine induces rapid desensitization of nAChRs. In addition, following repeated exposure to nicotine, nAChRs did not become tolerant to the loss in receptor function that occurs after an initial nicotine administration. Overall, these data suggest that neuronal adaptations underlying nicotine tolerance may begin upon initial exposure then persist following repeated exposures.





Maybe Im missing something,, can you please explain?As I said, any input and corrections would be welcome. With explanations... I would be delighted to be corrected, that means I learn something new... But I apologise, I can't just believe any comment you throw with no explanation.. I will check back for any information you might have. I might have misread the above studies as well, but it seems they both point to some sort of mechanism of desensitization of nAchR's after nicotine administration. Thank you

Edited by medicineman, 02 December 2008 - 06:50 PM.

[Galantamine]

You'll always have the law of mass action, but I don't think galantamine would necessarily be a competitive inhibitor. Instead, galantamine would exert an additive effect by combining two nAchR ligands.

Combining the two would be an interesting experiment.

[edward]

You'll always have the law of mass action, but I don't think galantamine would necessarily be a competitive inhibitor. Instead, galantamine would exert an additive effect by combining two nAchR ligands.

Combining the two would be an interesting experiment.

I take both and it is a very good combo only galantamine is annoyingly expensive, it shouldnt be but it is.

Edited by edward, 03 December 2008 - 12:20 AM.

[Cuil]

Well, I decided to try the nicotine patch. I actually have a heavy smoking habit though. Not to mention I really enjoy combining syrian rue with chocolate for a stimulant effect. I tried half a patch yesterday and today but I still smoked a few cigarettes here and there. Tomorrow, I may go with a full patch. Considering that I am halting a pack a day habit of organic american spirits, I think that my tolerance is on par with a full patch.

[thefreeaccount]

There's nothing wrong with putting 2 x 21 mg patches on at once, and this has been tested this quite thoroughly in smoking quitters - although they showed unusually that it had no greater or even less effectiveness than a 21mg patch when it came to people actually giving up smoking. Although it is a high dose, it's a 24 hour timed release.

One quarter of a 21mg nicotine patch made me feel vaguely ill; half a patch gave me extreme vertigo/nausea and rapid, irregular heartbeat. Since I had never smoked a cigarette, my tolerance for the drug was much lower than typical users of the patch.

[nito]

i have something called "snus" which is tobaco you put under your upper lip. It's mainly used in sweden and norway. Since they contain nicotine, will they enhance memory do you think?

[gerhard]

Hi Nito,

I'm a regular user of snus and, provided that you enjoy the taste, I think it makes an excellent - and MUCH CHEAPER - alternative to nicotine patches. However, in my experience snus has a tendency to "sneak up" on you - it takes a while really to get started, likely due to the time it takes for the tobacco to become saturated with saliva, and then, just as you might start forgetting to mind it, it will suddenly surge into your system. Best to start with the varieties that are mild in nicotine content!

[nito]

Hey Gerhard

Thanks for ya reply. I am just starting this thing out. How addictive is it, i mean is it like cigarettes? Because it took me a long time to get off those, and i don't really wanna be addicted again. I'm just experimenting right now.

[gerhard]

I can't say. I smoke cigars, pipes, use snus and snuff, even smoke e-cigarettes - and I just don't get addicted, I forget about them all for months at a time. Try asking on a snus forum? Good luck.

[Phreak]

Hmmm, so just out of curiosity: would a Nicotine patch - say, a 21mg one - help out a smoker in terms of concentration/motivation/focus/stimulation etc..? I mean, I know that for about 20-40 minutes after smoking a cigarette it can potentially help with all of the above, due to it's cholinergic and stimulant effects (citation needed for this; it's just from memory, but I remember reading an explanation or a study here on this site)...

But does that mean that, with the patch, these effects can be sustained throughout the day? Or would it just "satisfy" a smoker's physical reactions/cravings?

[NeuroByte]

Phreak, i'm a smoker and adding a patch to smoking is not that great, it felt like i smoked a LOT more than i normally do, gave me a head ache. i've checked on wikipedia and it says that the effects of nicotine are dose dependent, a little acts like a stimulant, a lot acts like a depressant. wikipedia - nicotine

the patch that Bqwithadd is using (21mg) is for people that smoke ten or more a day(half a pack), this is why he got better results with the 1/4 patch. personaly i have found that on it's own nicotine doesn't do much, but when mixed with other drugs it can work much better, The best combo i've found is nicotine, caffeine, Zoloft, and provigil. but thats me.

[doctordog]

does anyone know whether nicotine induces any long-term changes in the brain that might help w/ anhedonia and mild depression? in other words, would it be worth going on a 'course' of nicotine (lozenges/patch/etc.), or, outside of potentially inducing a positive-feedback behavioural cycle, is it only useful as long as you stay on it?

[NeuroByte]

dr. Dog the way nicotine works by binding to receptors in the brain. The only long term change in the human brain is the number of receptor sites. This increase in receptor sites is what causes addiction, as someone quits smoking these receptor slowly decrease in number. So although there may be some long-term effects, they would not be significant.

[doctordog]

dr. Dog the way nicotine works by binding to receptors in the brain. The only long term change in the human brain is the number of receptor sites. This increase in receptor sites is what causes addiction, as someone quits smoking these receptor slowly decrease in number. So although there may be some long-term effects, they would not be significant.

ah okay, i think i remember something saying something about nicotine growing more ACh receptor sites, which is why i was curious. thanks

[helmingstay]

no,, that is impossible.... with any living thing, repeated stimuli has the same effect in every living organism, and that is desensitization. You are inquiring about receptor 'washing'.

Firstly, Medicineman, thanks for posting references. Out here on the edge, access to accurate, relevant data is often scarce, making it all the more important.

After reading this full thread, i have a number of thoughts. I'll try to limit these to core points, with a little bit of background: I have a history of mild-to-moderate bipolarity, OCD, and social anxiety. As a long-term student, I've been able to structure my life to minimize stress, achieve a high level of mental stimulation, and receive emotional support from a small number of good friends.

Over the past ~4 years, I smoked on-and-off with long stretches of each. I've smoked american spirits (which i mention it both because i can't stand anything else, and a seemingly common experience). I notice significant calming and focus improvements, along with some short-term recall benefits when i'm smoking. However, I feel profound physical negative effects after 6-9 months of smoking and i stop with significant effort for 6-9 months, restart slowly, and ramp back up to 1/2 to 2/3 pack a day of blues (~2 mg/cig).

As an aside, I've noticed that a single application of atropines (using mandrake in my case, which contains a mix of several) induces a 1 to 2 day strong intolerance of nicotine. I'd categorize the atropines as anti-nootropics, useful for a few days break from over-thinking, breaking a manic cycle, etc. Dosing is difficult, seemingly best cued on saliva output rather than subjective experience (more info in pendell, see below). Overdose is widely reported as extremely unpleasant and dangerous. Their action is long and slow due to G-protein interactions ( they're antagonists, see http://en.wikipedia....holine_receptor ).

I'm interested in the use of the patch as a medium-to-long term substitute for tobacco, and glad to hear that no negative effects are reported from cutting patches (advised against or unreported elsewhere). A few more points:

Human tolerance to nicotine builds with exposure up to very high levels. 2*20 mg patches will cause extreme discomfort in most non-smokers, and many smokers. Nicotine in any form is addictive, and I strongly advise use of the lowest effective dose, with periodic breaks. As I understand, more rapid delivery leads to more rapid addiction, which would make smoking more addictive than transdermal. On the other hand, Pendell comments that oral addiction is more difficult to break, though i don't know his citations off-hand ( i can't recommend this book enough for the curious: http://www.amazon.co...t/dp/1562790692 ).

On a personal level, I *strongly* advise against the use of SNUS or any other tobacco for nootropis. It's a long, dangerous, expensive, and often ugly road. Successful use of nicotine patches should not imply that tobacco in any form is safe.

[Ben]

Tobacco of any kind causes cancer. Cancer is not nootropic.

[Rational Madman]

Tobacco of any kind causes cancer. Cancer is not nootropic.

Agreed, but as long as the thread starter limits himself to a small transdermally delivered dose of nicotine, he would not be significantly at risk (if at all) for developing cancer. Rather, I believe nicotine is only co-carcinogenic when combined with components of tobacco smoke (benzo(a)pyrene) and other ingredients of tobacco products (e.g. tar). But, you are quite right, the smoking of tobacco is not worth the nootropic benefits, and would indisputably confound any serious attempt at life-extension.

Edited by Rol82, 07 September 2009 - 04:17 AM.

[helmingstay]

Rather, I believe nicotine is only co-carcinogenic when combined with components of tobacco smoke (benzo(a)pyrene) and other ingredients of tobacco products (e.g. tar).

Right. There's an ongoing danger of confusing nicotine with tobacco. Tobacco, smoked or otherwise, delivers a large number and quantity of toxic and useless chemicals to the body. While long-term risk of nicotine *alone* is not well characterized (only recently available in pure form for common use), evidence to date suggests that it has a relatively good risk-to-benefit profile. Nicotine *alone* appears to have a low toxicity (ask your doctor!). On the plus side (in my experience), acquired tolerance of nicotine is much like coffee/tea - it still works well after acclimation, just not *as* well as during initial use. Along those lines, i'm curious to hear if anyone has experienced benefits from periodic abstinence/de-acclimation followed by use.

The chief downside to nicotine *alone* would appear to be it's strong addictive potential. With this in mind, I would also strongly advise against using it before the age of 21. Evidence indicates first age of long-term use correlates strongly with long-term addiction, with 21 as a threshold of hard-to-stop (pre-21 use) vs. less-hard-to-stop (post-21 use). Most of this research is on tobacco, so it's unclear if this holds for transdermal nicotine.

references available upon request

[helmingstay]

I wanted to give a brief update. After 3 months of patch usage, i'm still a big fan. I'm now using 1/5 of a 21mg patch per day. At this dose, i can skip a day or two (usually weekends, less thinking required, less stress) without painful withdrawal. Sometimes i forget to put on a strip altogether, which strikes me as a good thing. I have none of the desire to "increase my dose" that i experienced when smoking.

I do still consistently get benefits from patch application. I can read material for longer without getting tired or distracted, and i can focus (e.g. obsess) on a single project for much longer. I'm also less spacey and more to the point in interpersonal communication. Every now and again, I forget to take the strip off when i go to sleep, and high dream recall and increased incidence of lucid or near-lucid dreaming (i.e. in-dream volition) is increased.

Overall, I find the patch about as effective as caffeine, in a slightly different way. I find it slighly *less* addictive than caffeine - i can't go a day without tea. There's less of a "ritual" with the patch, and there's none of the sensory pleasure of coffee/tea/tobacco, which i feel makes it significantly *less* addictive.

Personally, I feel that i "get along" very well with nicotine, and that smoking is not an option for me anymore. The patch fills this role for me perfectly - it's cost-effective, and i've found its downsides to be relatively minor compared to the benefits i get from it. I also think that using the lowest effective dose is preferable - negative side-effects seem to increase quickly with increasing dose, whereas benefits actually wane. If it feels good shortly after application, then i know i've taken too much, and i often feel bad/tired/burned out or faintly nauteous later on...

hope this helps...

[chembrain]

Very interesting post about nicotine, I'll have to do a bit more research on the matter. Its always good to have people reviewing/testing ''supplements''.

[Dorho]

I use nicotine gum as a nootropic from time to time and have not developed addiction. I tried nicotine gum first when I was 22 years old.

I'll probably switch to patches at some point.

Edited by Dorho, 10 December 2009 - 07:20 PM.

[Johann]

Best thing about the patch as opposed to gum is the slow delivery system. And Nicoderm CQ is by far the superior brand of patches. I have tried the other name brand and generic and none
live up to Nicoderm CQ. I have actually cut down to about 1/8 of a patch.

The slow delivery system is good in regards to addiction. I believe that a fast delivery, such as w/ cigarettes, is risky because it will cause addiction.

I've actually quit the patch before, went 8 or 9 months without any nicotine and when I did quit the patch it was only for one single day that I had cravings.

[bobman]

Tobacco of any kind causes cancer. Cancer is not nootropic.

Agreed, but as long as the thread starter limits himself to a small transdermally delivered dose of nicotine, he would not be significantly at risk (if at all) for developing cancer. Rather, I believe nicotine is only co-carcinogenic when combined with components of tobacco smoke (benzo(a)pyrene) and other ingredients of tobacco products (e.g. tar). But, you are quite right, the smoking of tobacco is not worth the nootropic benefits, and would indisputably confound any serious attempt at life-extension.

What is a co-carcinogen? Does that mean if you leave nicotine out on a table it won't grow a tumor? FYI, carcinogen already implies "co"factor.

Yeah nicotine has good cognitive properties. It might kill you, but I'm sure than you'll be super smart on your way down.

But it is not a nootropic. It has dangerous side effects. It has a very low LD50. Look up the definition of "nootropic". And if you argue that its an esoteric definition, and I'm being pedantic, I'll go ahead and argue that you should call it by what it is. And as any long-term tobacco addict will tell you, once you quit, all of those cognitive gains not only go away, but you're sometimes left slower, stupider, and more irritable than you ever were before. But yeah, when you start using, for a time, until the irritability and nervousness set in, you'll feel great.

Edited by bobmann, 10 December 2009 - 11:27 PM.

[bobman]

Hi Nito,

I'm a regular user of snus and, provided that you enjoy the taste, I think it makes an excellent - and MUCH CHEAPER - alternative to nicotine patches. However, in my experience snus has a tendency to "sneak up" on you - it takes a while really to get started, likely due to the time it takes for the tobacco to become saturated with saliva, and then, just as you might start forgetting to mind it, it will suddenly surge into your system. Best to start with the varieties that are mild in nicotine content!

You know what else it has a tendency to do? Leave you without a face.

I don't think that imminst should allow Nicotine threads in the "nootropic" section. This substance in principle is not aligned with the Immortality Institute's agenda. It is a deadly substance, and I'm concerned that people will come across threads like this and decide to give Nicotine a try. This is not something anyone should mess with. The great chance is that you will get addicted, and at best struggle with recovery. At worst you will develop cancer, or develop cardiovascular problems.

If you enjoy tobacco, that's your prerogative. We're not against that. But panning it like it is a fun substance, or something that enhances cognition with marginal side effects reserved for those with addictive personalities is reckless, and it is bad bad advice. It is difficult to predict how you easily you get hooked. Most people I know didn't think they were addicts until they tried to quit, and realized how large a part it played in their daily routine.

I'm not picking on you personally, but dip is not something anyone should recommend. It is in no way excellent. And cheaper? Well, besides your medical bills, many people start with a 7 dollar tin every month, and move to about a tin every day or 2. It gets expensive quickly.

Edited by bobmann, 10 December 2009 - 11:39 PM.

[Johann]

You know what? We got enough little nannys on here without needing another. Some of us are going to use
nicotine in moderation. Deal with it.

[Johann]

ScienceDaily: Nicotine Creates Stronger Memories, Cues To Drug Use