Neuroscience Nicotine is an antidepressant - Yet it gives me anhedonia and depression. Why?

[ContemporaryCaveman]

Hey everyone,

Nicotine itself seems to be an antidepressant - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192315/ - mostly by desensitizing a4b2 nicotinic receptors - cholinergic agonists themselves are depressants

I'm facing an interesting puzzle. I have a very odd reaction to nicotine - smoking. Doesn't matter if it's vaping, normal cigarettes, heat not burn (iqos). And it doesn't matter the dose.
What I'm noticing is that smoking, almost instantly, makes me extremely depressed - I just feel dysphoric after, I lose all my motivation to interact with the world or do anything - and if I am outside and talking with someone, after smoking I don't even want to talk/don't even know what to talk about.

+I don't get a buzz anymore when smoking - I don't feel anything in fact. I do have cravings (weak ones) but once I smoke I feel nothing/feel bad instead
+When I first started smoking (I am 29 - first started smoking 1 year ago) - it gave me extreme anxiety in the first months
+When I smoke now, I instantly need to go to the bathroom
+I get something similar with weed - weed doesn't relax me, but only gives me anxiety.
+I also find it very easy to quit Nicotine. I may have some small cravings for a day or two but it's all extremely easy and tolerable, ad this happened even after I smoked for 3 months daily.

This is very, very weird. While the cholinergic theory of depression states that depression arises when the cholinergic signalling is stronger than adrenergic, and that cholinergic antagonists are antidepressants - nicotine being an agonist, it desensitizes those receptors and is basically a functional antagonist -I do believe that most people 'enjoy' smoking.

So, what gives? Do I have some polymorphism or certain nicotinic receptors? I'm not keen to smoke anymore, but for a long time I thought it's all in my "head" (well it is haha) and that I can't feel bad from nicotine.
But I tried many times - enough times to know there's a direct, casual relationship between smoking and me feeling depression.

Any ideas?

 

[Lil'LinaptkSix]

Not a scientist, doctor of anykind and basically a nobody.

My take?
Iron worker for over 40 years mostly in south florida.
Firing one up while waiting on steel to get to you seems to be a big thing.
Well, I noticed that my energy levels would drop right after a cig and although I knew what was causing the "drop" in my mentality and body I continue to this day to smoke. Crazy, innit?
Just a stab: The smoke/co2 whatever the hell in cigs cuts off oxygen supply to body/brain and there is the negative side effects that follow. Shit'll make me wanna puke in the heat, humidity, altitudes (sometimes) is no joke.
I find only the habit is the only "good" thing about it but just aint gonna stand around puffin on an unlit cig.

 

[Neuroprotection]

i’m no scientist, but I do think genetic polymorphisms of the nicotinic receptors might be involved. Have you tried nicotine in its pure form?

Strangely, I have the complete opposite reaction, I find nicotine extremely euphoric and energising. When I describe my reactions to nicotine to other people, they say this is abnormal and it shouldn’t feel that good. interestingly, my brother is more like you, nicotine makes him very ill, Nauseous and possibly temporarily depressed.
I don’t recommend drug use, but I assume there’s another substance which you find more enjoyable. however, smoking really isn’t worth it, especially if you don’t enjoy it.

 

[Dextro .45]

Nicotine is used as a “Nootropic” and general stimulant. In an oral tablet or chewing gun 2-4mg (average cigarette has 3mg ish of Nicotine entering the bloodstream very quickly entering the brain and releasing Dopamine & Acetylcholine (few other neurotransmitters in the CNS)

Nicotine is very unique in the sense that it have both stimulating AND relaxing/anxiolytic properties. Having a smoke often endures feeling of a pleasurable calmness.

Premium coffee/espresso with a square of premium Madagascar 70% Cocoa (Lindt Dark Chocolate/hint on vanilla) and then slowly smoking a king sized Belmont premium cigarette…..lol….I can actually feel my brain chemistry changing lol. Dopamine & endorphins it feels like……damn it’s pure sex for me.