| > Nicotine plus MAOIs (1970s anti-depressants) are addictive There's some confusion on this point. There is a paper that shows this, but mostly the mechanism people are referring to is MAO A and B reuptake seems to be inhibited while smoking, but not after just using nicotine, which makes smoking more addictive than just nicotine. I don't dispute this; the evidence seems clear. I think that not very many people were/are on MAOIs, therefore it doesn't explain smoking addiction, and people confuse this mechanism with antidepressants. Nicotine is more addictive when you smoke tobacco to get it, or if you're on MAOIs, but it's addictive all on its own. We'll use vaping as an example for this: A third of users vaped within 5 minutes of waking in this study [0]. Subjects in this study [1] vaped consistently despite not wanting to. Here are some cool statements they copped to: “I hide in the bathroom to vape in secret.” “I look forward to times that I can stay in and vape all night.” “I love vaping, though I wish I did not.” Here are some things that happened to them when they didn't vape: “I cannot relax without my vape/e-cigarette.” “My hands and arms start trembling if I have not vaped in a while.” This study [2] compares users of Juul vapes w/ non-Juul vapes (Juul vapes deliver more nicotine), finding that "JUUL users were 1.77 (95% CI: 1.36-2.31) times as likely to report symptoms of nicotine dependence and 1.43 (95% CI: 1.02-2.01) time as likely to report using e-cigarettes on 20-30 days, compared to 1-5 days, relative to non-JUUL users". > Nicotine itself is not addictive, it's habit-forming. Those are completely different neural pathways at work and completely different forms of interaction. Even if this is true (I can't find any basis for it), it's at best a distinction without a difference. Here's nicotine's pharmacology: --- Stimulation of central nAChRs by nicotine results in the release of a variety of neurotransmitters in the brain, most importantly dopamine. Nicotine causes the release of dopamine in the mesolimbic area, the corpus striatum, and the frontal cortex. Of particular importance are the dopaminergic neurons in the ventral tegmental area of the midbrain, and the release of dopamine in the shell of the nucleus accumbens, as this pathway appears to be critical in drug-induced reward (12, 13). Other neurotransmitters, including norepinephrine, acetylcholine, serotonin, γ-aminobutyric acid (GABA), glutamate, and endorphins, are released as well, mediating various behaviors of nicotine. --- > In addition, nicotine outside of cigarettes is a newer distinction to be made, most pre-2000s papers do not make that distinction. This is generally because there's consensus that nicotine is addictive and there's no need to do further research on it. They're not ruling out that there are chemicals besides nicotine that inhibit MAO A and B reuptake, thereby enhancing addiction to smoking (not nicotine), but there are no studies I've seen that demonstrate consistent vaping without nicotine dependency. It's also worth saying that in young adults, vaping tends to lead to smoking [4], which is super bad. [0]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668279/ [1]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330178/ [2]: https://pubmed.ncbi.nlm.nih.gov/34614433/ [3]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2946180/ [4]: https://pubmed.ncbi.nlm.nih.gov/34999270/ |