If nicotine is supposedly "not highly addictive," what heretofore obscure, hideous compounds are lurking in cigarettes that accounts for their legendary addictiveness?
MAOIs? True, they give withdrawal symptoms. But despite being a widely used pharmaceutical, to my knowledge no MAOI-only drug has seen anything resembling the abuse patterns of tobacco.
The hand-wavy "other compounds" that the article mentions and then doesn't describe? Anyone know what those would be?
So, sure- maybe nicotine isn't very addictive, yet it makes an otherwise non-addictive drug dreadfully addictive. Or perhaps the scientific truth of the matter, whatever it is, is simply complicated enough that someone who really wants one particular thing to be true can twist a bit of evidence around to support his case. Either way- stick to coffee.
Its possible I've missed something? I don't have time to read all the papers you cite, but from titles/abstracts they all appear to be talking about the effects of MAOIs. If there are separate substances in play I've somehow managed to read your article and completely miss any mention of them.
> Its possible I've missed something? I don't have time to read all the papers you cite, but from titles/abstracts they all appear to be talking about the effects of MAOIs.
Well, yes, what exactly else would you expect papers to be about when someone claims that nicotine+MAOIs is different from just nicotine...? Presumably the papers are going to have titles like "Monoamine Oxidase Inhibition Dramatically Increases the Motivation to Self-Administer Nicotine in Rats".
Perhaps I wasn't very clear; in your article, you contrast the apparent non-addictiveness of pure nicotine with, to quote directly, "the addictiveness coming from MAOIs & other compounds present in tobacco." And it is precisely the latter part of the phrase "MAOIs & other compounds" that I was asking about when I said "other compounds."
The implication seemed to be that there were other things beyond MAOIs in tobacco that were (or helped nicotine to be) addictive; is that not the case?
> The implication seemed to be that there were other things beyond MAOIs in tobacco that were (or helped nicotine to be) addictive; is that not the case?
Well, I don't know that it's not the case. There's a lot of stuff in tobacco, it wouldn't surprise me if there were other chemicals besides MAOIs with relevant psychoactive effects. But from the snippet you quote, I see why you might be reading that as a stronger claim than I intended. I'll amend that to '& possibly other compounds' so it's clearer.
I believe what is described is that nicotine is a potent agent for habit-forming, so you don't get as much addicted to the nicotine itself as the habit you have formed while taking nicotine, ie. smoking. The article describe utilizing this process to one's advantage by taking safe forms of nicotine while forming desired habits or (i.e working, learning etc.).
I believe they can be used in isolation, because by suppressing/slowing the oxidative metabolism of synaptic neurotransmitters, they can be used to compensate for low baseline levels by extending their active lifespan.
The main reason they're not used is that better & more selective releasing agent/reuptake inhibitors exist, and MAOIs have potentially fatal interactions with a huge variety of different substances (including some cheeses, if memory serves)
We're definitely in agreement that MAOIs have a strong effect on the (heightened) levels of synaptic neurotransmitters (released by some nicotinic upstream signalling), giving a synergistic effect.
Right. I suppose I took it for granted that brains are big ol' drug factories and assumed everyone was on the same page. The point is the MAOI isn't a used as neurotransmitter, but to affect the metabolism of monoamine transmitters—now matter how they got there.
I've mostly heard of them in the context of treatment for depression (in a lower-division biopsych course, not personal experience). My understanding was that they'd be taken on their own, and the Wiki article doesn't obviously disagree.
"Monoamine oxidase inhibitors (MAOIs) are chemicals which inhibit the activity of the monoamine oxidase enzyme family. They have a long history of use as medications prescribed for the treatment of depression. They are particularly effective in treating atypical depression."
That's my understanding as well, but the salient point is MAOIs work indirectly by increasing the effectiveness of some neurotransmitters—including dopamine, which nicotine increases the level of.
MAOIs are the last resort anti-depressants. There are two left on the US and they are extremely highly-regarded in effectiveness. They're more effective than the typical SSRIs of today but they are sadly not as prescribed today due to over-blown fears of interactions. It's a case of newer not always being better.
They work by preventing the breakdown of dopamine, serotonin, etc. therefore increasing levels in your brain.
In fact the gold standard for anti-anxiety is an MAOI, Nardil, which has additional inhibition leading to increased levels of GABA (the target of alcohol/benzodiazepines.)
In fact two medications in my daily mix with Nardil are on that list and it's such a pain dealing with ignorant pharmacists that see a warning on my their screen and refuse to call my doctor to confirm their combined safety, even though he's been practicing for 50 years (really.)
I urge you to read the various reports from real users confirming the safety even with the supposedly not safe to mix.
The problem is that most of the recommendations in the list were added before precise measuring of tyramine levels in foods was developed and list is one big CYA. To make matters worse is that nobody has made a significant effort to do real testing to define safe levels so most users are left to responsible trial and error.
I.E. read this about pepperoni, debunking the conventional "wisdom":
> BACKGROUND: Continuous refinement of the monoamine oxidase inhibitor (MAOI) diet has resulted in much reduced and simplified recommendations that attempt to balance safety and practicality. In the spirit of evidence-based practice, dietary restrictions should be based on carefully documented case reports and valid tyramine analyses. Residual concerns have focused on combination foods such as pizza and a variety of soy products. We determined the tyramine content of pizzas and a variety of soy products in order to refine dietary recommendations for use with MAOIs. METHOD: High-pressure liquid chromatography analysis of tyramine content was performed on a variety of pizzas, soy sauces, and other soybean products. A tyramine level of 6 mg or less was considered safe. RESULTS: No significant tyramine levels were found in any of the pizzas, including those with double pepperoni and double cheese. Marked variability was found in soy products, including clinically significant tyramine levels in tofu when stored for a week and high tyramine content in one of the soy sauces. CONCLUSION: Pizzas from large chain commercial outlets are safe for consumption with MAOIs. However, caution must be exercised if ordering pizzas from smaller outlets or gourmet pizzas known to contain aged cheeses. All soybean products should be avoided, especially soy sauce and tofu. Individualized counseling and continuous surveillance of compliance are still essential.
>
Bonus:
Tranylcypromine enhancement of nicotine self-administration.
Good question. I had assumed that he was referring to a synergistic effect of MAOIs and Nicotine causing increased addictive potential, but I really have no idea whether monoamine oxidase is involved in the metabolization of nicotine.
MAOIs? True, they give withdrawal symptoms. But despite being a widely used pharmaceutical, to my knowledge no MAOI-only drug has seen anything resembling the abuse patterns of tobacco.
The hand-wavy "other compounds" that the article mentions and then doesn't describe? Anyone know what those would be?
So, sure- maybe nicotine isn't very addictive, yet it makes an otherwise non-addictive drug dreadfully addictive. Or perhaps the scientific truth of the matter, whatever it is, is simply complicated enough that someone who really wants one particular thing to be true can twist a bit of evidence around to support his case. Either way- stick to coffee.