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If nicotine is supposedly "not highly addictive," what heretofore obscure, hideous compounds are lurking in cigarettes that accounts for their legendary addicti

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.

jey 13y ago
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.
tarikjn 13y ago
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.).
- sliverstorm 13y ago
  you don't get as much addicted to the nicotine itself as the habit you have formed while taking nicotine Supported by the fact that some smokers use straws and carrots to help quit.
gwern 13y ago
> The hand-wavy "other compounds" that the article mentions and then doesn't describe? Anyone know what those would be? Excuse me? I went to considerable pains to give the primary source citations & jailbreak the PDFs.
- maxander 13y ago
  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.
  - gwern 13y ago
    > 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".
    - maxander 13y ago
      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?
      - gwern 13y ago
        > 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.
smosher 13y ago
I've never heard someone talk about MAOIs in isolation before. You do realize the point of these is to affect other drugs right?
- dllthomas 13y ago
  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. http://en.wikipedia.org/wiki/Monoamine_oxidase_inhibitor http://en.wikipedia.org/wiki/Monoamine_oxidase_inhibitor "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." Though there is admittedly a "citation needed".
  - smosher 13y ago
    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.
    - dllthomas 13y ago
      Sure; reasonable, just unclear.
- shabble 13y ago
  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.
mistercow 13y ago
It's not just MAOIs. It's the combination of nicotine and an MAOI that is so addictive (http://www.sciencedirect.com/science/article/pii/S0091305703002235 http://www.sciencedirect.com/science/article/pii/S0091305703...).

jey 13y ago

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.

tarikjn 13y ago

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.).

sliverstorm 13y ago
you don't get as much addicted to the nicotine itself as the habit you have formed while taking nicotine Supported by the fact that some smokers use straws and carrots to help quit.

gwern 13y ago

> The hand-wavy "other compounds" that the article mentions and then doesn't describe? Anyone know what those would be? Excuse me? I went to considerable pains to give the primary source citations & jailbreak the PDFs.

maxander 13y ago
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.
- gwern 13y ago
  > 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".
  - maxander 13y ago
    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?
    - gwern 13y ago
      > 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.

smosher 13y ago

I've never heard someone talk about MAOIs in isolation before. You do realize the point of these is to affect other drugs right?

dllthomas 13y ago
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. http://en.wikipedia.org/wiki/Monoamine_oxidase_inhibitor http://en.wikipedia.org/wiki/Monoamine_oxidase_inhibitor "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." Though there is admittedly a "citation needed".
- smosher 13y ago
  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.
  - dllthomas 13y ago
    Sure; reasonable, just unclear.
shabble 13y ago
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.

mistercow 13y ago

It's not just MAOIs. It's the combination of nicotine and an MAOI that is so addictive (http://www.sciencedirect.com/science/article/pii/S0091305703002235 http://www.sciencedirect.com/science/article/pii/S0091305703...).