Smoking, the harmala alkaloids and other drugs

[dopamimetic]

Tobacco contains harmala alkaloids, probably not in a high concentration but enough to exhibit some effects (pure nicotine is much less addictive than tobacco). But serotonin syndrome doesn't seem to be a complication of smoking even while on high doses of SSRIs and probably many doctors won't even know about the MAOI properties of tobacco. Why? I would have thought that the quick onset through the lungs would make the MAOI even more dangerous.

 

[Product]

Tobacco contains harmala alkaloids, probably not in a high concentration but enough to exhibit some effects (pure nicotine is much less addictive than tobacco). But serotonin syndrome doesn't seem to be a complication of smoking even while on high doses of SSRIs and probably many doctors won't even know about the MAOI properties of tobacco. Why? I would have thought that the quick onset through the lungs would make the MAOI even more dangerous.

I am prescribed Zoloft, i think its an SSNI or SSRI. Are you talking about the effect of smoking ciggarettes and using your medicine prescribed from the doctor and its effects on your body? Sorry im new here im just curious because I started smoking Cigs/Vapes with nicotine since I had to quit marijuana for a job. Please reply and thanks ! ( and im sorry im not particularly smart on the subject of harmala alkaloids. may i please get a short explanation of it? if not its okay

 

[dopamimetic]

Yeah, I'm thinking about regular cigarettes / tobacco. Usually I'm a non-smoker because I don't get much effects from it and the dangers scare me ... but when dissociatives enter the game, things change a bit. Smoking while on a sub-threshold dosage of a NMDA antagonist is maybe the most euphoric clear-headed rush I know of. Sometimes I just had to smile without reason. Unfortunately it's very short lived and tolerance builds rapidly. But because of this, I've tried an e-cig and it didn't work, so I've been searching for what might cause the rush and the harmala alkaloids are probably the best candidates.

Curiously this doesn't work when I'm in a depressive episode. (Recently discovered that I'm probably bipolar II with rapid cycling ... just that I mostly get the downs and little ups without chemical aid.)

Harmalas are reversible MAO inhibitors that are also used to brew ayahuasca, to make things like DMT orally active (but in much higher concentration). They have some effects on their own, but I know too little about them. Might make a decent antidepressant, also think to remember that they have some neuroprotective properties.

 

[sekio]

There's two different forms of MAO and as far as I know harmala alkaloids are reversible inhibitors of only one of 'em (read: they have transient temporary effects).

On top of that I don't think you get enough harmala alkaloids to produce a persistent effect if you smoke a single cigarette.

 

[Weltmeister]

tobacco mainly inhibts MAO-B which is selective for catecholamines but only has minor effects on MAO-A which is selective for serotonin. If cigarettes had a major influence on MAO-A smokers who take MDMA would get serotonin syndrome and smoking wouldve been linked to MAO-A inhibition a long time ago.

More on MAOIs in tobacco smoke (its in german unfortunately):
http://www.diss.fu-berlin.de/diss/s...ivate_000000003628/1_01_einleitung.pdf?hosts=
http://www.diss.fu-berlin.de/diss/s...07_fazit_zusammenfassung_methodikanhang.pdf;j

 

[dopamimetic]

Okay that's interesting, thanks for the links too - have to read them later, if there's interest I could translate a summary.

Used to think that the harmalas would be more or less selective for MAO-A because this is the one that metabolizes tryptamines, and overall they seem to be relatively gentle in regards of diet, so they can't strongly inhibit both forms of MAO... but well I could have been wrong.

(With that antidepressant moclobemide, which is a reversible MAO-A inhibitor, one doesn't need to hold any diet, because there's still the MAO-B available to oxidize tyramine etc.. but it's pretty useless for many too- at least for me and those I know it was.)

 

[Weltmeister]

Different harmala alkaloids have different effects. None of them is 100% selective for either MAO-A or MAO-B but they all prefer one or the other. Tobacco smoke contains mostly norharmane (at least according to my link above) which prefers MAO-B but also contains harmane (which prefers MAO-A) in less but still significant quantity.

syrian rue or caapi on the other hand contains a mix of harmine and harmaline which prefer MAO-A but will affect MAO-B aswell if you ingest enough. They also contain small amounts of Tetrahydroharmine which is rumored to be a weak SSRI but doesnt have significant MAOI properties.

MAO Inhibition isnt their only action in the brain tho. They are also inverse agonists at bonzodiazepine receptors, antagonists at 5HT2A receptors and agonists at an unknown beta-carboline receptor. They have actions at other serotonin receptors, dopamine receptors and other enzymes besides MAO.

I really think of them as being pretty safe because they naturally occur in the human body but you can never be safe enough i guess.