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Nicotine and SSRIs... (link)

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blase deviant

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http://www.nature.com/bjp/journal/v139/n6/full/0705359a.html

I'm on Lexapro, and switching to Celexa, and when I picked up smoking again, I noticed a cigarette would affect me more strongly than it used to for some reason...

Any connection, or not?

I guess they dislike linking... redirects to main page, so here's a summary of the abstract (at least they're nice enough not to make you subscribe to view journals for $4000000/month like everyplace else)...

1. Epidemiological and clinical observations suggest the involvement of nicotinic acetylcholine receptors (nAChRs) in depressive illness. Nonetheless, there is no clearcut evidence that nicotine and/or nAChR antagonists produce an antidepressant effect.
2. In the tail-suspension test (C57/Bl male mice), nicotine (0.8−1.2 mg kg-1 s.c. or i.p.) given 15−60 min before the measurement exerted no effect on immobility.
3. Given 30 min before the measurement, citalopram (2 mg kg-1) produced a slight decrease in immobility; coadministration of nicotine (0.8 mg kg-1, 15 but not 40 min before the test) to citalopram-treated mice resulted in a robust decrease in immobility. Imipramine (4 mg kg-1) did not affect immobility, but given in combination with 0.8 mg kg-1 of nicotine (15 but not 40 min before the test), a decrease in immobility was observed. Nicotine (0.8 and 1.2 mg kg-1) also produced an enhancement in the anti-immobility effect of imipramine (20 mg kg-1).
4. We further investigated if nAChR antagonists would influence the antidepressant-like effects of imipramine and citalopram. Unexpectedly, mecamylamine (1−2.5 mg kg-1) and dihydro-beta-erythroidine (2 mg kg-1) potentiated the antidepressant-like effect of imipramine (4−20 mg kg-1). Mecamylamine (2.5 mg kg-1) but not dihydro-beta-erythroidine also increased the antidepressant-like effect produced by 2 mg kg-1 of citalopram.
5. The interaction between nAChR antagonists and antidepressants appeared synergistic.
6. Neither nAChR ligands, antidepressants nor combinations of the two, affected locomotor activity.
7. The present results demonstrate an unexpected interaction between nAChR ligands and imipramine and citalopram in the tail-suspension test.
Click to expand...
 
Another fucking stupid study on antidepressants... why is it that nearly all experimental scientists forget that antidepressants need to be given for weeks for them to work?

Anyway, this study shows the nicotine potentiates SSRIs, not the other way around, so it doesn't explain your feelings.
 
True, good point.

I have noticed a bit more lethargy since I picked up smoking again. I dunno if it has anything to do with this or the MAO-B inhibition. But tobacco doesn't even inhibit MAO-B fully, and there's still MAO-A.

Perhaps I'm just not used to smoking and there's no correlation...

I assume then that when they say citalopram-treated mice, they didn't feed them citalopram for 4-6 weeks ahead of time?

Also, would doses of citalopram like they were given have no immediate effect? I mean, the anti-depressant effect takes 4-6 weeks to work, but don't the 5HT/DA/NA blocking effects begin immediately? Or not.
 
I have read twice that citalopram blocks nACh Receptors, so maybe that is whys smoking is different on this SSRI

never read anything about lexapro - it is the l isomer of citalopram yeah ?
 
Lexapro is the s isomer, that's why the call it es-citalopram... that's such a lame construct, but it's getting common.

But yeah, I've read that citalopram has some nAChR antagonist abilitiy [1]. But it's such a stupid method they used... damn neurochemists.... and they had electrophysiology... it was almost a useful study
 
I have noticed a bit more lethargy since I picked up smoking again.
Click to expand...
Well carbon monoxide will do that. Also you have nicotine competing for Ach receptors. Up-regulation counteracts this...but I'm not sure if the up-regulation is uniform throughout the body.

I have noticed that if I smoke a cigarette after not smoking for a while (like two weeks), the effects are more acute.

Specifically, I feel a sudden weakness in any weight-bearing muscles about 5-10 seconds after I inhale. Not a terrible weakness, but noticeable.

I think this is because after quitting nicotine, the body reverses the up-regulation and Ach receptor counts return to their normal (lower) numbers.

Then when you put the nicotine back in...there are less AcH receptors to go around and nicotine takes a good handful of them.

Is this right or am I way off base?
 
I think you mean downregulation, as nicotine is an agonist at Ach receptors (or a particular subset thereof, rather).

ebola
 
Actually, i just checked up on this...and its more complicated:

In experimental animals, chronic exposure to nicotine, using regimens which cause desensitisation of the catecholamine responses to nicotine, often causes an increase in the density of the nicotine receptors which bind nicotine with high affinity.177 This increased density seems to reflect a decreased turnover of the receptor complex.197,198 The psychopharmacological significance of this effect remains unclear, although it appears to be associated with repeated or prolonged exposure to concentrations of nicotine which cause desensitisation of the receptors. It seems unlikely, however, that the increased receptor density accounts for the sensitisation to nicotine discussed above because upregulation of the receptors is not observed with dosing regimens which elicit the sensitised dopamine responses.199 The increase in receptor density may nevertheless be significant to the mechanisms underlying nicotine addiction since they are also observed in brain tissue taken from humans who have been habitual smokers.200
Click to expand...

Hmm....I can *almost* understand this
 
For some reason when I started taking Celexa, I really didn't have the urge to smoke anymore and eventually quit after 5 years without a problem...

I don't know if there is a link between the two or if the reason I was smoking had to do with depression (hell if I know). Just wondering because I really wasn't expecting much from the Celexa, but it turns out it is a hell of a drug.
 
Screw it, I got a bad cold and quit smoking anyway (i wasn't a real 'smoker' per se, just 6-7 cigs per day).

Also, has anyone here ever smoked tobacco out of a hookah before? Comparing a hookah to even the best cigarette is like comparing food to poison...
 
many ssris have been shown to suppress the CYP2D6 (going from memory here)...enzyme...this enzyme is responisble for metabolising caffeine and nicotine....

less of the enzyme increases the active ingredients in the system....

you might want to lower your dosage of nicotine....
 
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