• N&PD Moderators: Skorpio | thegreenhand

Prolonged use of SSRI's and absence of *subjective* DA releaser "comedown".

N0 W4RN1NG

Bluelighter
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Jul 16, 2008
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Hi guys, long time no post. Today I thought of something I really couldn't find an answer to.

I used to get WICKED "comedowns" from DA releasers and reputake inhibitors alike.

I have been on escitalopram 10mg for around a decade, along with a benzo and mood stabilizer (both usually switched after a year). Since I am incapable of "rolling", I quite enjoy stimulant binges. Usually plain old d-amphetamine, although methamp, adderall, fluorophenmetrazine, and even the odd propylhexedrine (shame me elsewhere, I already know I'm an irredeemable, shameless hedonist) make their appearance now and again.

Tried what is (putatively) a DARI or SNDRI the other day, 4F-PHP. Felt ok. Nothing like MDPV or aPVP, but similar to 4F-PVP, which I was one of the few who enjoyed.

I am quite, QUITE familiar with pyrovalerones, I have honestly done almost a quarter K of the original MDPV all to myself (over years), but that 4F-PHP brought me back - to what a comedown really is. It seems in my (ab)use of DA releasers, I have had absolutely NO comedowns over the past ~decade. I very rarely use NDRIs, so things like (m)ethylphenidate never interested me after I had a first taste, and I went through a phase with cocaine in my younger days, but for a long time now I have only been using DA releasers (barring my 2 years of insane MDPV use, which was so crazy that my "comedowns" were frequently cut short with a little "hair of the dog", if you catch my drift) and notices no comedown from them. So, call me stupid, but I am just putting this together now.

So, is there any known link to (prolonged) SSRI use muting the after effects of extreme DA-efflux? Perhaps it is not SSRI related, but an effect of ion channel mediation? (My mood stabilizers are always lamotrigine and/or oxcarbazepine - in yearly rotation) I am not complaining by any means, but when I see some of my friends in agony after a day or two "hard at work" I'd like to know if maybe there's a preventative measure that could be employed.

GOD IN HEAVEN I GET SO WORDY

TLDR: I get no comedowns, at all, from even the most heroic doses of DA releasers. I used to in the distant past, but not since being on an SSRI and mood stabilizer. NDRIs still give me comedowns.

Surely there is a mechanism to be explored here?
 
My dearest of friends, try paroxetine and opipramol and tell me how you feel. Welcome back.
 
Maybe you are just living a better, more balanced lifestyle? When taken in reasonable doses and only once in a while, even strong DA/NE releasers like cocaine and methylphenidate can produce pleasurable experiences with a mild comedown.
 
:) Well paroxetine did not play nice with me. Better than sertraline, to be sure, but really (es)citalopram is the one for me. Been on it forever practically and it still works great. As to Opipramol, I am not fond of anything that messes with the D2 receptor. IMHO it's kind of a pharmacological "deal with the devil". D2 modulation can produce rapid amelioration of certain symptoms, but I truly do not trust that it is wise long-term. I am happy with lamotrigine/oxcarbazepine. I am not complaining about my current Rx. Merely wondering why some stimulants give me "comedowns" while those with different MOAs do not.

Re: Sekio
Well, my lifestyle has improved, that is for sure. But why then do NDRIs make me feel so awful hours later, while I can handle half a gram of d-amphetamine over a few hours and feel totally fine after it wears off?

And are cocaine and methylphenidate really DA *RELEASERS*? I was always under the impression that their primary MOA was reuptake inhibition...
 
Methylphenidate isn't a releaser but cocaine should be a triple releasing agent (TRA) as far as I'm concerned. The main route of action of opipramol isn't through D2, it's through sigma activation and cns thru dopa/adrenergic system.
 
Interesting. I thought both [alkyl]phenidates and cocaine alike were reuptake inhibitors, with methylphenidate being a NDRI and cocaine being a SNDRI. If that is true, it actually furthers my original question; I haven't done cocaine in so long, but I remember the comedowns being at least tolerable. *phenidates are like, "impending doom"-type feeling inducers.

As far as opipramol is concerned - you are correct in the sense that it's primary MOA is as a sigma agonist, although it still possesses appreciable affinity for D2, where it does, indeed, behave as an antagonist.

Thank you for correcting me, I actually really enjoyed doing some research on opipramol just now. I was not particularly familiar with it because, it is not available in the USA. Shame really, it seems rather efficacious, and in a way not really covered here.
 
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