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Stimulation of nicotinic repectors via non-nicotine substances....

Whitespy420

Whitespy420

Bluelighter
Joined
Sep 8, 2006
Messages
98
Location
NE Florida
Alright, here's the background for my question:
Its unarguable that there are certain mental and emotional advantages to smoking/chewing/using tobacco... however the effect on the overall health is enough in question that it doesn't seem to be the best method of stimulating the brain.
I have tried the RX meds for quitting (mind you I'm actually over a year free of smoking, however I recognize that there is a higher functionality to be had with the intake of nicotine) IE wellbutrin, strattera (which although they don't RX for smoking cessation, its widely touted as a "side effect"). The problem with these is, and I don't know why I react like this, is that they cause extreme depression, anxiety, and irritability, most likely (as according to several doctors and my own understand of the situation) due to the enormous amount of noradrenaline they release/block the reuptake of.
I recall reading about a nicotine receptor active drug in development possibly as a parkinson's med, although when I went back to where I had found the information it was gone (possibly failed?)

Ok, now the point of the post: Seeing as how I'd rather not go back to smoking nicotine, nor would I recommend it as a method of ingesting, even though I believe the outcome can be most rewarding and increase productivity and overall mood, can anyone think of anything else that specifically works on stimulation of the nicotinic receptors (and therefore releasing DA and NE from the same sources that tobacco does, rather than "trying to make up for it")?

Sorry if this is too basic for advanced forum, but I had a feeling it was too advanced for basic forum.
 
If I'm not mistaken, Galantamine, a substance generally sold as a nootropic, has some action on nicotinic receptors.

Some of the drugs prescribed for demential/parkinsons/alzhiemers are nicotinic agonists.

Keep in mind that all of the above are prone to producing nausea in some people...

L-Huperzine A is an Acetylchollinesterase inhibitor (non-toxic at reasonable doses - and in fact classed as nootropic), so that might help. From my experience, it is one of the most useful OTC substances for both mood and cognitive enhancement, and a friend has found it helpful when she quit smoking.

As an aside, later I found out that L-Huperzine A also has some NMDA-antagonist properties, heh.
 
You mention Rx meds for smoking cession but only list the dopaminergic-noradrenergic. Glantamine a positive allosteric modulator(sensitizer) at the Alpha4Beta2 subtype nicotinic receptor, which is the same subtype that the presciption stop-smoking med Chantix(US) Varenicline is a partial agonist at. Have you tried either or both together?

Alternately for harm reduction there is mecamylamine...a drug you would probably hate alone as it's a non-specific nicotine receptor antagonist. However when given with nicotine it seems to function much like ultra low dose naltrexone for the opioid tolerant- reducing development & expression of tolerance to nicotine. With the right dose you might be able to reduce the amount you smoke, chew etc, or get more mileage out of a nicotine replacement vehicle- inhaler, gum, patch.

Mecamylamine co admin with nicotine & tolerance reduction
http://www.springerlink.com/content/m65vbpe2ejeleaev/

As a last stop and I recommend this in light of the fact of smoking being the #1 preventable cause of death you can obtain nicotine suplfate & apply it to blotter paper. Standardize to say 2mg per 1cm*3 or whatever suits your fancy. Because of the way nicotine tastes it is essentially impossible to overdose. I quit smoking in this manner years ago. The only caveat is not to increase your dose because you can get into the stimulant effects which can be even more addictive than low dose.
 
Crimethink said:
As a last stop and I recommend this in light of the fact of smoking being the #1 preventable cause of death you can obtain nicotine suplfate & apply it to blotter paper. Standardize to say 2mg per 1cm*3 or whatever suits your fancy. Because of the way nicotine tastes it is essentially impossible to overdose. I quit smoking in this manner years ago. The only caveat is not to increase your dose because you can get into the stimulant effects which can be even more addictive than low dose.
Click to expand...
WTF!?!?

Nicotine blotter? This is anything BUT "harm reduction" since someone working with pure nicotine can very, very easily kill themselves.

You are aware of the existence of Nicotine patches, gum, and inhalers, right?
 
Well, cessation isn't my goal, as I've been a nonsmoker for a year+, my thought is if theres another drug that mimics the actions of nicotine (and I mean closely as possible, I understand that there are plenty of dopamine agonists that sort of resemble some of the action of nicotine, but something that is closer or more true to the nicotine action) without the risks associated with nicotine... I guess it wouldn't because the side effects are probably part of the whole action that also causes the elevated mood and attention level... Actually, I wonder how safe nicotine patches are in comparison to other methods. I guess I'll just have to let this one go.
 
Personally i thought those nicotine inhalers were great, and im not even a smoker!

Like a cigarette thats always lit, you can't burn yourself on it, and because it doesn't produce smoke its not bad for your lungs, doesn't make you stink of smoke, and you can "smoke" them anywhere, in bed, at the movies, on the aeroplane, in class at uni....dunno why more people don't know about them!
 
It's probably damn expensive. Here, one 2mg tablet is probably as expensive as a packet of cigarettes. Can you imagine?
 
Whitespy- have you tried Chantix (Varenicline) the nicotine partial agonist? Possibly with Galantamine to increase its efficacy?

If you use the patches or the inhalers you can consider mecamylamine to make them more effective & prevent tolerance buildup. (Mecamylamine increases binding of nicotine with or without tolerance) The stuff is readily available & fairly inexpensive, too.

Nicotine patches are safe except for the cardiovascular effects which aren't a problem in a healthy person when you aren't dumping in radicals & toxins from smoke. If you think its a problem consider the Mecamylamine so you can use less. With the exception of two negative effects I detail below nicotine is pretty safe relative to smoke or snuff.

Nicotine seems to have some long term advantages too. You probably know it reduces the risk of Parkinson's disease by blocking MAO-B which degrades dopamine to 6-Hydroxy-Dop. and liberates a hydroxide racical- which is sorta like micro quantities of sodium hydroxide- drain cleaner. Since this is happening is everyone's body all the time, slowly destroying your subsantia nigra or dopamine producing cells at a rate of anywhere from 4-12% per decade.
This progressive loss of dopamine cells is one reason why as people age their movements slow down, their emotions flatten a bit, they're less likely to try new things etc...A good deal of this looks preventable with nicotine or any MAO-B inhibitor. So MAO-B inhibition over decades may end up helping you maintain your capacity for pleasure, feel & think younger.


Nicotine has essentially 2 negative effects:

its primary metabolite nornicotine permanently reacts with or covalently binds to all sorts of different proteins in your body rendering them useless.
This effects does have one practical upshot though- among the proteins it reacts with *and neutralizes* are Beta-amyloid & hyperphosphorylated tau -- two neurotoxic proteins that cause Alzheimer's.

While Nicotine is beneficial for many parts of the brain it is selectively and potently neurotoxic to one part of the brain known as the fasciculus retroflexus. The FR is a pathway important in aspects of self control, addiction(Frontal lobe projects thru FR back to limbic sys. exacerbating loss of higher brain control of impulses) REM sleep(vital to learning), hippocampal function & goal directed behavior.
 
^^^
Thats about the best answer I could've hoped for, thank you for your input!

Yeah, basically I was considering going on the patch because retrospectively I was slightly higher functioning while smoking but I'm not gonna pick up cigarette smoking again.
 
Crimethink said:
While Nicotine is beneficial for many parts of the brain it is selectively and potently neurotoxic to one part of the brain known as the fasciculus retroflexus. The FR is a pathway important in aspects of self control, addiction(Frontal lobe projects thru FR back to limbic sys. exacerbating loss of higher brain control of impulses) REM sleep(vital to learning), hippocampal function & goal directed behavior.
Click to expand...

Thanks for the information. This sounds bad - conscious control of the more primitive brain areas is a very desirable skill IMO... I did a quick search on this; it seems like other dopaminergics are neurotoxic the FR, too. I have a few questions about this please (regarding FR damage by drugs in general, not just nicotine):

- How strong is the evidence for this? (Are there multiple independent studies, has it been observed in humans, ...)
- Has it been demonstrated at doses comparable to those used by humans?
- The study is about continuous dosing. What about use on single days?
- Is the damage reversible?
- Does it apply to opioids?


Edit: I found a paper that partially answers these questions (PDF link).

- They didn't find any degeneration with LSD or NMDA antagonists (including PCP). (Opioids are not mentioned either way).
- They did find degeneration at nicotine levels "approximating those of heavy smokers"
 
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Crimethink said:
Nicotine seems to have some long term advantages too. You probably know it reduces the risk of Parkinson's disease by blocking MAO-B which degrades dopamine to 6-Hydroxy-Dop. and liberates a hydroxide racical- which is sorta like micro quantities of sodium hydroxide- drain cleaner.
Click to expand...
Is this accurate? According to Wikipedia, this is not how MAO oxidizes monoamines:

Wikipedia said:
Monoamine oxidases catalyze the oxidative deamination of monoamines. Oxygen is used to remove an amine group from a molecule, resulting in the corresponding aldehyde and ammonia.
Click to expand...

So which is true?
 
i think the first one is true, but that's no problem either. you just brush some muriatic acid through the brain and it will neutralize the drain cleaner.

@ threadstarter:
have you heard of cytisine, a nicotinic agonist that has 2 advantages over nicotine. first, it has a linear eliminination rate with a half-life of about 3h and second it isn't metabolized to cotinine, which reputedly blocks the desirable dopaminergic effects of nicotine in the long term.

cytisine is found in laburnum, a tree that grows, depending at where you live, in many front gardens.
 
Nicotine produces selective degeneration in the medial habenula and fasciculus retroflexus.
Brain Res. 2001 Jul 6;906(1-2):127-34.
http://www.ncbi.nlm.nih.gov/entrez/...ve&db=PubMed&list_uids=11430869&dopt=Citation

Selective neurotoxic effects of nicotine on axons in fasciculus retroflexus further support evidence that this a weak link in brain across multiple drugs of abuse.
Neuropharmacology. 2000 Oct;39(13):2792-8.
http://www.ncbi.nlm.nih.gov/entrez/...ve&db=PubMed&list_uids=11044749&dopt=Citation

Appears to be a legit claim.
 
I have read more than once that smoking inhibits MAO-B in ways that cant soley be accounted for on the basis of nicotine, rather the complex mixture of fumes in tobacco smoke. Selegiline definately might be an idea though. I have refs too if you dont believe me.
 
Yeah smoking seems to reduce MAO-B more rather than inhibit it...I was apparently wrong on the academic points regarding which radicals were produced by MAO-B degredation of dopamine and by what mechanism.

While I was trying to give a graphic example of how nicotine or at least tobacco products can prevent dopaminergic toxicity I was apparently wrong on the academic points even though MAO-B degredation of dopamine does produce an H2O2 radical which can beget hydroxyl radicals.

One thing worth pointing out that might hint at the mechanism of this neurotoxicity is the fact that Cocaine in the FR is neurotoxic whereas in most other brain regions cocaine will protect from Amp neurotoxicity.

I would find it interesting academically to see if low levels of toxicity or stress show up in other brain regions where their associated recptor populations are close to being as high as they are in the FR. It is my understanding that nicotinic cholinergic receptors are most densely expressed in the one tract...I wonder if the same is true for the dopaminergic recptor density in the other tract.


I didn't mean to seem like I was being a mindless nicotine neurotox nut like a marijuana madness person. I still have a cigarrette every now and then and used to use nicotine on paper as a smart drug for while.

I don't really think long term smokers are compromised by intellectually by this in any way...the part of the brain affected is just a primitive bundle of nerve fibres, it's not quite like cortex. As I pointed out I think you may stand to gain a few things-- notice how older smokers sometimes have a bit more 'spark' to them than their non smoking counter-parts? I think this may go back to them having preserved a bit more of their nigral dopamine producing machinery.
 
I an necroing this old-ass thread since it is the only thread with a mention of smoking laburnum to administer cytisine. I have been interested in this ever since I looked up the poisonous tree on wikipedia and saw that it works on the nicotinic acetylcholine receptors. It even mentions color enhancement. I cant find out if I should smoke the flowers or leaves, though. Dosage is probably easy, as it should come on pretty much instantly, and thus I can just start out with a ridiculously small amount, increasing the dose until effects are noticed. I'm a bit annoyed that I can't find any reports anywhere of anyone smoking this and then describing it. I went out and got some flowers and leaves that I will try drying. I will then try smoking retardedly miniscule amounts of each to see how it feels.
 
I have tried also a non nicotine containing tobacco species called Nicotina Glauca, or tree tobacco.
Anabasine, is the primary psychoactive agent in it.

Info circulates online about how it can help tobacco addiction, and even read something about opiate addiction.

Doses are 5 leaves in a tea. Its a very tastey paralitic agent. Theres only 1 erowid report, however of some one smoking it.

Nicotinic acid the b vitamin as a staple, and huperzine as something to feel excitement.

http://en.wikipedia.org/wiki/Anabasine
**I'd guess I'd reccomend that as a cheap/free alternative.
EDIT: holy SHIT, they updated the page with a teratogenic finding in swine. **possibly not

I kind of wanted to post this here to see if anyone else had tried it.
 
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