What does nicotine actually do? Need help for research proposal...

[ebola?]

Also, isn't Bupropion (a Dopamine-Norepinephrine antagonist of sorts) prescribed for smoking cessation?

Buproprion is also a selective nicotinic antagonist. They sure as hell don't prescribe ritalin for smoking cessation, and with good reason.

ebola

 

[endotropic]

It seems like a big part of nicotine addiction involves activation of mu opioid receptors. Mu opioid knockout mice show less withdrawal symtpoms following nicotine cessation and find nicotine less rewarding in a conditioned place preference test.

So theoretically this means that naloxone or some other Mu opioid antagonist taken in conjunction with nicotine should uncouple nicotine from its rewarding effects, and on nicotine cessation withdrawal symptoms should be less (although its also possible that Mu opioid antagonism would precipitate withdrawal symptoms, but I’m not sure if any of this has ever been examined in humans).

Source: http://www.jneurosci.org/content/22/24/10935.long

 

[kaskelot]

Coffee actually contains MAO-A and B inhibitors too. I imagine that it causes dopamine levels to crash on the comedown which would probably increase evening cravings. I should add that I was vaporising my nicotine in an electronic cigarette, which causes it to hit the bloodstream at the same rate as smoking does.

Alright, that's pretty cool. Didn't know that about coffee and had some quite interesting read up due to your post pointing it out.

 

[FnX]

I feel like something crucial has been overlooked in this thread, pure nicotine (patches, chewing gum, e-cigarettes) and cigarettes are quite different things. There's a pretty big arsenal of additives and byproducts from combustion in tobacco smoke, not to mention the tobacco industry and it's attempts to create more addictive cigarettes by chemically manipulating the tobacco.

http://www.ncbi.nlm.nih.gov/pubmed/16728749 - Brand differences of free-base nicotine delivery in cigarette smoke: the view of the tobacco industry documents.

There's definately something in the smoke. I use a vaporizer for cannabis and have occasionally used it with tobacco as well. Breaking down a regular cigarette and vaporizing it with the volcano produces very, very different effects than smoking said cigarette would. There is no immediate rush for example, I do not find vaporizing the exact same kind of tobacco as reinforcing or addicting as smoking it. I'd argue it's the rapid rise of nicotine concentration in the brain that makes smoking cigarettes so addictive.

http://jpet.aspetjournals.org/content/288/1/188 - Subjective and Physiological Effects of Intravenous Nicotine and Cocaine in Cigarette Smoking Cocaine Abusers

Interestingly "Nicotine showed a more rapid onset of subjective effects than cocaine." and "Although the highest nicotine dose produced greater effects than the highest cocaine dose on most subjective measures, the highest cocaine dose produced somewhat greater ratings of drug liking."

To me would indicate that nicotine can reach the brain faster and in higher concentrations than cocaine when administsred IV, although the qualitative effects of cocaine are usually more preferred. Smoking tobacco for the first time is a pretty intense experience and blacking-out after a bong hit with too much tobacco is not that much of an uncommon sight.

As for the opioid receptor connection, there's certainly something going on with opioids and nicotine. Especially buprenoprhine (which has extremely high binding affinity at the mu- and kappa opioid receptors) has a pretty big synergistic/potentiating effect with nicotine, smoking while having buprenorphine in your system seems to produce sudden and heavy opiate like nausea and drowsiness in many people from my experience.

Somehow I feel like I'm drifting off-topic... I propose research for medical applications of nicotine, such as transdermal nicotine patches in the treatment of ADHD. I believe there is enough evidence out there that it can be used to treat ADHD patients effectively, such as this isolated case http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2446482/ along with more generalized studies http://www.springerlink.com/content/1q9n6yq6m0t3epp3/ - there should be plenty more too.

The problem is, atleast I am not aware of studies which try to find out how exactly should an adhd patient be treated with nicotine so that the treatment would be most effective. Difference between medicine and poison is in the dose, or something.

 

[KAYLA2010]

Hey guys,
I'm writing a research proposal involving smoking cessation and writing my section on nicotine vs, other stems. I'm not a scientist but believe I may be able to get some money to fund some small scale highly speculative research in the area of smoking cessation. I've been reading the literature the past few weeks but thought I'd start a thread on this awesome board to get some additional commentary going.

From what I can tell, though nicotine has widespread actions in the brain and peripherally, nicotine is not in itself all that reinforcing or hedonic. It seems that it takes significant effort to get animals to self administer, and giving nicotine patches to ex smokers, then withdrawing them. Does not cause readdiction to cigarettes. And of course we don't see teenagers hanging outside Walgreens begging adults to buy them Nicolette's. But nicotine does stimulate vta dopaminergic neurons and light up the nacc like other more addictive drugs of abuse. So what gives?

What I have read seems to say that what nicotine does is enhance the reinforcing value of other stimuli, help to give it rewarding valence. So things like the ritual of smoking, the airway sensations of nicotine (which seem to be important), the smell, the psychosocial reward, now these things have been made far more reinforcing via nicotines actions in the nacc. Is this an accurate understanding? How then do the maoi constituents of smoke play into this?

I'm writing my section comparing nicotine to other stimulants like cocaine, amphetamines, and methylphenidate. Im a little confused though, as these substances light up the mesolimbic dopamine circuit even more strongly than nicotine, yet none of these serve as effective substitute or treatments for nicotine dependency. My understanding of addiction science is very weak, and I know the cellular effects are different which may be the reason, but I find it odd that amphetamines do not treat nicotine dependency, as they are even more rewarding would in some sense "swamp" the nacc with dopamine....how does this not serve as an effective substitute for nicotine reward? And it actually seems as though giving stimulants noncontingently dosent treat nicotine dependency, it actually makes people smoke more! What is going on here? It seems bupropion and nortrp are effective stimulating treatments for smoking and lower reward thresholds that are raised in withdrawal, but amphetamine is not an effective treatment, why?

Thank you so much for any insight here. I am continuing to read as much as I can but do not have access to non pubmedcentral papers and have only checked out a few books from ucsf library and they haven't answered these specific questions...also any good recent papers about smoking in general that are of importance, or anything else relating to nicotine dependency that might be useful for me to check out, I'd sure love some references.

Thanks so much, I will post my proposal on this board when I'm finished as I'd love some comments....

I just read an article on how nicotine is supposed to be the new gateway drug for cocaine. It says once you smoke your brain fires up pathways and makes the spot where coke can have a good time later.
Do nicotines the new gateway drug? LoL pretty cool findings.

 

[Limpet_Chicken]

I am a smoker, and a pretty heavy one. I'll chain-smoke cigars, give enough of them. Recently I went to my doctor for a 'stop smoking' meeting, and left with a script for a nicotine nasal spray, 500mcg/dose, although the pharmacy actually gave me the wrong product, a 1mg/dose oral spray. I got a hell of a nasty shock when I sprayed a dose up my nose on leaving the pharmacy...as the oral spray uses anhydrous EtOH as a solvent...oh gods did that ever burn!

This product gives a rapid rise in nicotine levels, and gives a buzz that smoking does not, or rather, gives little of. I agree that the oral fixation must play a large part, as I've found that even after what would be considered a large dose of nicotine base (6-7mg, delivered through the oral mucosa) I will often want a rollup immediately after.

So nicotine activates MOR? I'll see just what effects it has on opioid withdrawal, as I'm soon doomed to undergo WD from oxycodone, although I have had some success with using baclofen (40mg as desired, usually twice to thrice daily) in alleviating withdrawal. and have both the propionyl ester of dihydrocodeine and DHC itself to lessen the effects of WD, as well as nitrazepam, loprazolam, chlormethiazole and pregabalin. I shall see if administration of nicotine alleviates WD to any extent.

I have found that I CRAVE smokes while using opioids. If I for instance, am on 120mg oxy, crushed, soaked and plugged, I wll light up one after the other. And nicotine spray does not appear to substitute for tobacco.

IIRC, there are beta-carbolines such as harmine in tobacco smoke, and that nicotine itself, delivery method irrespective, is not all that addictive. Which may explain your lack of dependency from your experiment with e-fags. I intend, sometime to experiment by using a combination of pure harmine/harmaline along with the nicotine spray.

Off topic...sort of..

I find that nicotine, administered in a relatively high dose, induces vivid dreams, so much so that the other day, I thought to myself that it reminded me of a ket/MXE experience on waking up, for a few minutes. Just happened again, funnily enough. I'd taken a few sprays, and rolled a smoke, and found that I had to lie down on my bed, instead of typing this post. Didn't intend to fall asleep, but did nevertheless. Had the most vivid dreams I can ever recall having, even more so than taking valerian root/extract. I think I'll trial taking both for their oneirogenic effect.

One of the very few times I can recall, childhood aside, that I have slept at all for that matter, without adrenal suppression.

Note-I had taken various GABAergics throughout the day, several hundred milligrams of chlormethiazole, along with 2-3 repeated doses of baclofen, and both nitrazepam and loprazolam. GABAergics don't usually allow me to sleep though. The only way I get any sleep at all, usually, is by taking large doses of either tizanidine or clonidine, plugged.

 

[endotropic]

Limpet I'd be very interested to hear how the nicotine affects your withdrawal, so please post again if you do decide to try it! I don't have time to read through them at the moment, but you might find these articles interesting:

"Endogenous opioids and smoking: A review of progress and problems"
http://www.sciencedirect.com/science/article/pii/S0306453097000747

"Experimentally-induced spontaneous opiate withdrawal: relationship to cigarette craving and expired air carbon monoxide."
http://www.ncbi.nlm.nih.gov/pubmed/17661199

 

[Limpet_Chicken]

I'll likely read them afterwards...I can't really function that well without supressing NA release as it is from a baseline state; Doing so with the sympathetic storm resulting from opioid (semi)cessation is just not an option.