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    Combining Dopaminergic Stimulants and SSRI's 
    #1
    First a couple of axiomatic statements:

    Common stimulants such as methylphenidate and Amphetamine exert their effects predominately by increasing extracellular dopamine levels in the brain, albeit through different methods.

    In 2011, Hugo Lövheim proposed a model of emotion in which all basic emotions can be modeled as functions of three pre-eminent monoamines: Serotonin, dopamine and Norepinephrine. Pictured below.



    Joy, or euphoria is then a result of increased dopaminergic and serotonergic activity.

    In support of this Cocaine, perhaps the paragon of all euphoric stimulants is in fact a triple re-uptake inhibitor rather then simply working through DA and/or NE.

    SSRI's are well known to increase the extracellular levels of serotonin in the brain.



    So then should co-administration of the aforementioned dopaminergic stimulants and an SSRI not give a more euphoric effect then the stimulant alone? Is this an oversimplification of the processes going on or have i started from one or more false axioms? And yes caution should be taken given the risk of serotonin poisoning, any dose of an ssri should be small in this scenario to help mitigate this risk.

    I'd appreciate any thoughts and comments and of course the moderators' tolerance of my uncertainty whether this query should be classified advanced or basic.
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    #2
    Bluelighter Ho-Chi-Minh's Avatar
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    Its over-simplification, but tbph you'll find reductive theories throughout psychopharmacology - there isn't a lot of hard science out there on it.

    Its a nice cube

    You wouldn't risk "serotonin poisoning" unless you're taking a loooot of amphetamine or meth

    Its probably best suited for OD. I don't think ADD is a bad place for it but they tend to not answer questions over there which 95% of the drug-taking population finds useful. Some of them are elitist pigs too (Hammilton, pretty much (luckily he's not on often)).
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    #3
    Quote Originally Posted by Ho-Chi-Minh View Post
    Its over-simplification,
    Is it perhaps then that the effects of SSRI's are seen predominately in an area of the brain which is not strongly associated with motivation? Is there some other confounding factor i have overlooked?

    but tbph you'll find reductive theories throughout psychopharmacology - there isn't a lot of hard science out there on it.
    Believe me when i say i know this to be true. Honestly though it shouldn't be too much longer before we just unravel a brain entirely and determine the purpose of various interrelations mathematically. We've had the electron microscope for nearly a century now and with the LHC continuing to produce data i can't imagine a neutrino microscope is far off which should finally allow us to observe (approximately) the atomic level since it would pretty much catch-22 out of heisenberg's famous uncertainty principle.

    We really do live in an exciting time, the the proverbial blank edges of the map are filling in and the age of psychological speculation is fast drawing to a close.
    Imagine what will be possible in a world where a theory of everything has fully united all of science and we have the human brain mapped to the last picometer.
    Imagine a theory of emotion in terms of Maxwell's three laws of thermodynamics!
    Imagine that serendipitous drug discovery will fall as a relic of the past to systemic drug synthesis founded in an intimate knowledge of every protein's shape, function and composition. Compounds mathematically calibrated for effects so precise that they could be individually tailored to a single person's needs. Mental illnesses that are physical rather then psychosomatic would cease to exist, and even psychosomatic ones could be mitigated beyond notice with therapy so profoundly understanding as to transcend description.

    We could solve the local problem (read: every problem that actually concerns us in terms of there's not enough energy to go around) within the next three generations; suffering of all kinds could be banished from the lives of those who so wish. Unlimited life-spans, unlimited energy, unlimited progress; constrained only by the pauli-exclusion principle (things take up space) and causality (Something can Cause something else) we could have anything and everything and a near eternity to solve the global problem. (Read: Usable energy is a finite, decreasing number, while the expansion of space is accelerating and removing objects from causal connection with each other, or more simply the ultimate eventuality of the universe seems to be a universe made only of useless energy in regions that physically can not interact. So whether we starve or tear apart at the sub-atomic level first, the global problem is really gonna suck at least 10^100 years from now.) Beyond that there is only apotheosis, perfection, infinity, the shedding of our mortal coils and depending on who you ask there's lotsa trumpets, fields of reeds, Alphas, omegas, epsilon's, clouds, fires, Everything, nothing, cherry-pie, angels, totality, no cherry-pie, peace, tranquility, and god-willing no transcendental-divine problem in which were' running out of real numbers to use or multiplication breaks or something. Then again maybe the problems are kinda fun and self-actualizing? I guess we'll cross that bridge when we get to it! Ordem e Progresso my friends. /end speed rant /Gratitude for indulging me

    TL: DR
    Tomorrows science is today's fiction and yesterday's magic. Also i latently brag about knowing physics terms to a predominately chem/bio audience, make subtle self-avowedly clever jokes of an incredibly technical nature, want a mass-energy conversion engine really bad, reference an obscure national motto digress, regress, progress, digress again, egress, express, profess, obsess, impress, and finally confess that this last bit wasn't clever at all and that i've wholly misunderstood the purpose of a TL: DR.

    TL: DR for TL: DR
    I'm bored, speeding and think I'm way more interesting and clever then i am.

    Its a nice cube
    I do so love cubes. They very rarely fail to delight.

    You wouldn't risk "serotonin poisoning" unless you're taking a loooot of amphetamine or meth
    1) Observe above speed rant as well as unnecessarily complex and pedantic diction and syntax throughout writing. 2) Consider also the prospective motivation for construing a post of this topic and the number of pointless digressions. 3) Draw own conclusions; or maybe even paint them if you're feeling creative.

    Disclaimer
    *Xeromatosis LLC does not endorse, recommend, or encourage excessive use of addictive and potentially harmful substances and discourages anyone from breaking local laws or chasing local, magical dragons. Always follow your doctor's instructions when taking medication.*

    Its probably best suited for OD. I don't think ADD is a bad place for it but they tend to not answer questions over there which 95% of the drug-taking population finds useful. Some of them are elitist pigs too (Hammilton, pretty much (luckily he's not on often)).
    The best way to deal with elitists is to let them think whatever they want about their relative self-worth, It's no skin of my back if someone derives self-confidence through arbitrarily demeaning users of an internet forum. Maybe i even made their day a little bit better by allowing them to profess their contempt for me!

    Retrospectively this post is largely conversational and off-topic yet amuses me far too much to edit down, so i reiterate:

    Is it perhaps then that the effects of SSRI's are seen predominately in an area of the brain which is not strongly associated with motivation? Is there some other confounding factor i have overlooked? Do the mechanisms of the two drugs actions fall in some way counterpoint to each other such as to not combine additively or multiplicatively? A brief explanation of the fatal flaw in this concept's logic or link to literature explaining the same would be greatly appreciated. Bonus points for relevant cube graphics and/or impressive looking hard data.
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    #4
    Bluelighter RobotRipping's Avatar
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    Quote Originally Posted by Xeromatosis View Post

    Joy, or euphoria is then a result of increased dopaminergic and serotonergic activity.

    In support of this Cocaine, perhaps the paragon of all euphoric stimulants is in fact a triple re-uptake inhibitor rather then simply working through DA and/or NE.

    SSRI's are well known to increase the extracellular levels of serotonin in the brain.



    So then should co-administration of the aforementioned dopaminergic stimulants and an SSRI not give a more euphoric effect then the stimulant alone? Is this an oversimplification of the processes going on or have i started from one or more false axioms? And yes caution should be taken given the risk of serotonin poisoning, any dose of an ssri should be small in this scenario to help mitigate this risk.

    I'd appreciate any thoughts and comments and of course the moderators' tolerance of my uncertainty whether this query should be classified advanced or basic.
    cocaine releases serotonin though doesn't it? I know it's a DNRI but not sure if it's a SRI.

    In practice - it doesn't seem to be the case that SSRIs in addition to a dopamine/NE releaser increase euphoria. TBH i've taken NE dominant drugs (ethcathinone), SE releasers, MDMA and such and DA/NE releaser as well as DNRI (EPH) DRI (d-EPH) and there's not a hell of a lot of difference between them. On SSRIs side effects seem to increase, perhaps i don't respond well to them.

    However, in contrast to amphetamine, methylphenidate had no effect on extracellular serotonin. These results do not support the hypothesis that a stimulant-induced increase in serotonin is necessary for the appearance of stereotyped behaviors.
    source: http://onlinelibrary.wiley.com/doi/1...8052032.x/full

    Amphetamines have effects on extracellular serotonin, what this study misses is that MPH fucking sucks recreationally and amphetamines are amazing. Since amphetamines have already been shown to increase extracellular serotonin, how would adding an SSRI really help? and is it really the case that extracellular serotonin is responsible for the drastic differences in euphoria between MPH and amphetamines. If so, that's probably why cocaine is so great. Still ethylphenidate is a DRNI like cocaine but does not interact with serotonin (AFAIK) yet still provides incredible euphoria.

    sorry hope that makes some sense, i'm a tiny bit spun as well and found this discussion interesting (especially the cube). I think there's a hell of a lot more going on in regards to euphoria than just three neurotransmitters though.

    so is euphoria the result of increases in serotonin and dopamine together? or do we need to distinguish different kinds of euphoria/joy. The high from an opiate rush, vs a stim rush vs an mdma rush vs a psychedelic euphoria are all different, especially in mechanism of action. I don't think it's clear cut that increases in 2 neurotransmitters are solely responsible for euphoria. Especially since without NE release/RI, most drugs of that class suck for euphoria.

    i think amphetamines in particular release enough serotonin to provide adequate euphoria already; SSRI may actually mess with that somehow, like how an SSRI will blunt an MDMA high. Inhibiting reuptake would be possibly dangerous, at a low dose, in theory, i have no idea but in my experience, not a combo i like to mess with.
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    #5
    Bluelighter Ho-Chi-Minh's Avatar
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    Guys,

    1) One cannot feel toxicity
    2) I'm not going to sift through our post and pull out what matters
    3) if you want my advice, or that of others, I'd suggest consolidating your questions
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    #6
    Bluelighter RobotRipping's Avatar
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    ^basically, would adding an SSRI somehow interact with a dopaminergic stimulant like amphetamines to create greater euphoria? if so, why? If not, why?

    Is an increase in serotonin necessary to achieve the greatest amount of euphoria possible? Would increasing serotonin and dopamine levels either through reuptake inhibition or through SE,DA releasers create greater euphoria than a DA/NE releaser or reupate inhibitor by itself? How large of a role does serotonin play in euphoria?

    and really my question is, subjectively, is there a difference in the euphoria received from increased NE, DA and SE (by themselves) and when combined? Especially in regards to releasers vs Reuptake inhibitors or triple releasers like cocaine/methamp or whatever they are classified as.

    Example: Ethcathinone - mostly NE releaser, great euphoria, d-eph mostly DRI, shit euphoria, EPH - DNRI great euphoria, Cocaine DNRI with serotonin great euphoria, amphetamines - great euphoria, small effects on serotonin but mostly DA/NE and psychedelic euphoria, what makes these distinct/indistinguishable in terms of euphoria? and what about opiates, is it the DA release? cannabis? SE releasers are also euphoric as well and almost indistinguishable from DA/NE releasers but not quite.

    IMO there's not a huge difference in the euphoria created but what's really going on under the hood in regards to euphoria? (pharmacologically) Do different drugs lead to the same euphoria or are there appreciable differences in a 'euphoric state' produced by certain neurotransmitters being affected by different drugs?
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    #7
    Bluelighter Ho-Chi-Minh's Avatar
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    I read the bold

    It's anyone's guess; probably

    Yes, but you'll never get euphoric effects from just one NT - always going to be in combination
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    #8
    Bluelighter RobotRipping's Avatar
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    thanks for your patience in addressing my long winded speed post lol

    if amphetamines have an affect on extracellular serotonin, it's possible that is what separates amphetamines from say methylphenidate in terms of euphoria. So if increasing serotonin in the synapse via SSRI could increase extracellular serotonin, it seems plausible the combination of the two could cause greater euphoria. Which i think is what the OP is getting at.

    however the study i listed above doesn't seem to support that idea. They probably weren't looking for euphoria though, just typical behaviors found with users of methylphenidate and amphetamines. Subjectively there's a huge difference in effects though.

    Ethcathinone is a dominantly NE releaser, which i find odd because it packs a hell of a punch euphoria wise, however wikipedia suggests it may be broken down to cathinone in the body, which would add that dopamine needed for euphoria. Still the ratio of NE : DA would make it seem like a shitty drug but it's not.
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    #9
    Bluelighter Ho-Chi-Minh's Avatar
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    sure thing

    yeah but amphetamine doesn't increase serotonin that much unless you're taking really large doses

    ive take both an ssri and amp at once; the euphoria was cumulative but it was less productive than just amp
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    #10
    Bluelighter
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    From personal experience I think rather it's safe, I've taken many DA/NA releasing agents and all I've had was a come down. First time on MDAI while on an SSRI I did get a huge serotonin buzz, but after that nothing. Just a mild speed buzz. Which is why I stick to DA/NA drugs, the serotonin toxicity experiences I've had are haunting to say the least.
    I'd put the euphoria down to the unusually high release of DA/NA etc, causing great pleasure. A serotonin high is very different from a dopamine high, it's less caring. While dopamine is about moving to fast heavy music, sexy and in general talking about anything BUT the difference is you wouldn't really want to open up on just dopamine. Where as serotonin has that blinding effect.
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