Bluelight

Thread: Trying to understand MDPV comedown and anxiety

Results 1 to 23 of 23
  1. Collapse Details
    Trying to understand MDPV comedown and anxiety 
    #1
    Hi,

    I've been searching the forums for a while now and couldn't find an answer to my question.

    As the title says, I'm trying to understand what happens in my brain during MDPV comedown (the biggest problem for me being extreme anxiety).

    I think I do understand the comedown and anxiety after a night out on Methylone (bk-MDMA): After ingestion, the drug provokes release of dopamine, serotonine and noradrenaline. After a few hours, most of the serotonine is used up and the synaptical serotonine levels drop to an amount smaller than before ingesting the drug. For whatever reason, dopamine and noradrenaline aren't used up as fast. Therefore, DA and NA levels are still increased. As DA and NA tend to induce anxiety whereas serotonine does the opposite, the increasing ratios of DA to serotonine and NA to serotonine make me feel anxious.

    Now I'll try to apply this theory to MDPV: Being an NDRI, MDPV increases the levels of NA and DA without any effect on serotonine. Therefore, I should feel anxious as soon as the drug crosses the BBB. But this is not true in reality. Even though MDPV is supposed to increase DA/5ht and NA/5ht ratios right away, it first gives me a mental high with raised self-confidence and reduced anxiety. Then after a while, these feelings fade away and I'm left with ongoing but "cold" stimulation and skyrocketing levels of anxiety. Redosing can bring back some of the positive feelings and slightly reduce anxiety, but even enormous amounts can't prevent the comedown.

    To make a long story short, my theory of high DA/5ht and NA/5ht ratios leading to increased anxiety must be flawed. In fact, the increase of DA and NA levels initially seems to reduce anxiety. Even though, adding MDAI (an SSRA) is said to solve the anxiety problem, a fact that assists my initial theory. So what's the thing I'm missing here?
    Reply With Quote
     

  2. Collapse Details
     
    #2
    Moderator
    Psychedelic Drugs
    Neuroscience and Pharmacology Discussion
    atara's Avatar
    Join Date
    Apr 2010
    Location
    not intended to diagnose, treat, cure, or prevent any disease
    Posts
    1,896
    Quote Originally Posted by BlueCrest View Post
    To make a long story short, my theory of high DA/5ht and NA/5ht ratios leading to increased anxiety must be flawed. In fact, the increase of DA and NA levels initially seems to reduce anxiety. Even though, adding MDAI (an SSRA) is said to solve the anxiety problem, a fact that assists my initial theory. So what's the thing I'm missing here?
    Dopamine and noradrenaline metabolize partially to adrenaline, which is more related to anxiety than either dopamine or noradrenaline. It should come as no surprise that adrenaline promotes anxiety, I hope!

    You have more than three neurotransmitters, and it's a good idea to pay attention to adrenergic, opioid, oxytocic, melatonergic, and cholinergic effects as well as our beloved catechols and serotonin.
    Reply With Quote
     

  3. Collapse Details
     
    #3
    MDAI definetly doesnt solve the issue. Well said atara thats my understanding as well. pregabalin seems to be very efficent for the comedown. It decreases noradrenaline and glutamate levels alot. id say more efficent than diazepam for mdpv caused anxiety
    Reply With Quote
     

  4. Collapse Details
     
    #4
    Quote Originally Posted by atara View Post
    Dopamine and noradrenaline metabolize partially to adrenaline, which is more related to anxiety than either dopamine or noradrenaline. It should come as no surprise that adrenaline promotes anxiety, I hope!
    In fact, this is somewhat surprising to me. I thought that adrenaline doesn't play an important role in the brain (as a neurotransmitter), instead acting mostly as a hormone on the body (e.g. increasing heart rate, inducing vasoconstriction). Obviously, what I've read about brain chemistry is not remotely enough. Though, the metabolization of DA/NE to adrenaline and the anxiety caused by the latter seem not sufficient to explain the MDPV comedown/anxiety. While it does help me understand why the anxiety comes up some time after DA and NE levels peak, it doesn't explain why redosing reduces the anxiety to the extent that even on some sort of "MDPV binge", the anxiety can be kept under control by continuous redosing (I'm pretty much talking about my personal experience now, with "binge" meaning some 10-12 hours of ongoing consumption rather than several days.). At least as long as I stick to the idea that DA and NE themselves don't reduce anxiety.

    Quote Originally Posted by atara View Post
    You have more than three neurotransmitters, and it's a good idea to pay attention to adrenergic, opioid, oxytocic, melatonergic, and cholinergic effects as well as our beloved catechols and serotonin.
    I do know of course that there are more than three neurotransmitters and I also know that more of them are involved in anxiety. E.g. GABA greatly reducing anxiety which is why benzos, GBL and ethanol help. But the only thing I know about MDPV is that it raises DA and NE levels in the synapse by inhibition of their respective reuptake transporters. I don't know how this might affect other processes in the brain (or anywhere else in the body) that play a role in mediating anxiety. That's actually what I meant with "what's the thing I'm missing here?".
    Reply With Quote
     

  5. Collapse Details
     
    #5
    Quote Originally Posted by kken View Post
    MDAI definetly doesnt solve the issue. Well said atara thats my understanding as well. pregabalin seems to be very efficent for the comedown. It decreases noradrenaline and glutamate levels alot. id say more efficent than diazepam for mdpv caused anxiety
    What exactly do you mean by "the issue"? The anxiety or the comedown in general? I heard of MDAI bringing the MDPV experience closer to MDMA (makes sense in my simple 3-neurotransmitter-model of stimulants, entactogens and antidepressants). Personally, I haven't experienced MDMA yet but I know bk-MDMA and with that substance, anxiety only hits me mildly after a 2-3 hours plateau-like experience (or even later when I redose 1/3 to 1/2 of the initial amount), whereas MDPV makes my anxiety levels explode less than an hour after the onset unless I redose like 1-1.5 times the initial dose every 30-45 minutes and even if I manage to do so, the anxiety is still above baseline whereas it feels below baseline on bk-MDMA. On a night out, this makes the difference for me between a really valuable stimulant and entactogen and a complete disaster involving escaping parties due to panic attacks. I was hoping that MDAI being a non-stimulating, "pure" entactogen* would be the ideal solution to the specific problem of increased social anxiety on MDPV (a pretty prototypical "pure" stimulant, lacking any serotinergic activity afaik), bringing the whole experience closer to bk-MDMA or even MDMA (I would be satisfied with the former, not even knowing the latter) but without any serotinergic neurotoxicity. I never thought it would prevent the general comedown associated with any known stimulant or stimulant-entactogen.

    *As far as I know, MDMA-style entactogenic activity is generally attributed to massive serotonin release. Oxytocin might play a role and is released by MDMA as well, but do we know if MDAI doesn't have the same effect? Therefore, from all we know, MDAI should very well mimic the isolated entactogenic effects of MDMA while of course lacking the stimulating components that are also part of what MDMA users call the "unique magic". In fact, the "unique magic" might never be experienced without any neurotoxicity involved as MDAI seems safe only with NDRIs not with more potent NDRAs. But then, the lacking part of the "unique magic" would probably be on the stimulating side rather than on the pro-social one. And this sounds like something I - being a somewhat shy guy - can easily sacrifice for being able to "roll" more often with less fading of the effects due to the (hypothetical) lack of serotinergic neurotoxicity.

    As for the pregabalin, this pretty much supports my original idea of the "stimulating" neurotransmitters NE and DA increasing anxiety (glutamate being an excitatory neurotransmitter fits in the "stimulation" category nicely) whereas the "sedating" neurotransmitter serotonin and the inhibitory neurotransmitter GABA decrease anxiety. But this seems like too much simplification and I don't understand how this would explain my MDPV experience. Especially during the mentioned binge-like consume pattern when every additional MDPV administration clearly reduced anxiety almost the same way a medium (i.e. not enough for noticeable sedation) dose of GBL has done in similar situations before.

    To explain this in more detail, the reduced anxiety in both cases manifested in less jittering, less unintentional gestures of awkwardness and a generally clearer state of mind because of less interruption by "bad thoughts". This similarity in effects makes me curious wether there's a link between the two substances though I can only find a really minor one. As GABA-ergic activity and an NDRI don't go together at all afaik, there's only the GHB-receptor left and that one is in fact said to increase levels of dopamine which is said to induce a clearer state of mind in AD(H)D people. Though, the idea of dopamine decreasing anxiety seems somewhat strange to me. Plus I'm just wildly speculating without beeing too much into neuropharmacology so please correct me if I'm talking utter nonsense.
    Reply With Quote
     

  6. Collapse Details
     
    #6
    Moderator
    Psychedelic Drugs
    Neuroscience and Pharmacology Discussion
    atara's Avatar
    Join Date
    Apr 2010
    Location
    not intended to diagnose, treat, cure, or prevent any disease
    Posts
    1,896
    Quote Originally Posted by BlueCrest View Post
    In fact, this is somewhat surprising to me. I thought that adrenaline doesn't play an important role in the brain (as a neurotransmitter), instead acting mostly as a hormone on the body (e.g. increasing heart rate, inducing vasoconstriction). Obviously, what I've read about brain chemistry is not remotely enough.
    Not chemistry, psychology. The brain exists to measure the state of the body and tell it what to do, not to be entertained by our little endeavors with arylaminopropanes. So, if you have a higher heart rate, are sweaty, and have constricted blood vessels, your mind will conclude that you are, in fact, quite anxious; this effect was originally the James-Lange theory of emotion, viz. that our emotional state is largely driven by changes in the body. It's now considered to be more complex than that, but JL theory is still quite relevant -- and it shouldn't be too hard to imagine that if you find yourself sweating and your heart pounding, you will be anxious.

    Though, the metabolization of DA/NE to adrenaline and the anxiety caused by the latter seem not sufficient to explain the MDPV comedown/anxiety. While it does help me understand why the anxiety comes up some time after DA and NE levels peak, it doesn't explain why redosing reduces the anxiety to the extent that even on some sort of "MDPV binge", the anxiety can be kept under control by continuous redosing (I'm pretty much talking about my personal experience now, with "binge" meaning some 10-12 hours of ongoing consumption rather than several days.). At least as long as I stick to the idea that DA and NE themselves don't reduce anxiety.
    For certain.

    I'll wager a guess, though, that for adrenaline to produce its trademark changes in the body, it has to leave the brain. As long as MDPV is keeping your dopamine in the synapses, the adrenergic bodily response won't occur.

    This is of course not an encouragement of redosing MDPV, because that causes other issues.


    I do know of course that there are more than three neurotransmitters and I also know that more of them are involved in anxiety. E.g. GABA greatly reducing anxiety which is why benzos, GBL and ethanol help. But the only thing I know about MDPV is that it raises DA and NE levels in the synapse by inhibition of their respective reuptake transporters. I don't know how this might affect other processes in the brain (or anywhere else in the body) that play a role in mediating anxiety. That's actually what I meant with "what's the thing I'm missing here?".
    I didn't want to be pedantic, and if I came off as such I apologize. I of course missed glycine, phenethylamine, anandamide, and a host of others. Though it seems doubtful that your MDPV anxiety is caused by another effect of MDPV itself, because I've noticed anxiety coming off of some other stimulants (many of which I no longer use).

    On another note, discussing neurotoxicity is silly without some attention to dosage levels:

    In animal neurotoxicity studies, there was no observable neurotoxicity of ibogaine at 25 mg/kg, but at 50 mg/kg, one-third of the rats had developed patches of neurodegeneration
    (A typical human dose of ibogaine ranges from 5-30 mg/kg and so analogously little if any neurotoxicity would be expected)

    Can one experience an MDMA-esque roll without significant long-term neurotoxicity? I'm going to give a tentative (and admittedly uninformed) 'yes', but attempting to prolong it, especially by redosing your DRI, will almost certainly exacerbate oxidative stress. IAP may be better in this regard than MDAI, if only because a cursory glance at the molecule makes me think it has less chance of generating reactive oxygen species, what with it lacking any phenolic ethers. Of course neurotoxicity is also observed with AET, so there's certainly more to the picture than the metabolism of phenols.
    Last edited by atara; 19-04-2010 at 10:21.
    Reply With Quote
     

  7. Collapse Details
     
    #7
    Quote Originally Posted by BlueCrest View Post
    To make a long story short, my theory of high DA/5ht and NA/5ht ratios leading to increased anxiety must be flawed. In fact, the increase of DA and NA levels initially seems to reduce anxiety. Even though, adding MDAI (an SSRA) is said to solve the anxiety problem, a fact that assists my initial theory. So what's the thing I'm missing here?
    I'm gonna throw neuroscience out the window and go all psychology on you. To simplify things grossly, dopamine = motivation to do work and expend energy. When your brain releases large amounts of dopamine it means you're really motivated about something which means it must be very important. My theory being your brain expects some sort of reward at the end of it (in the form of an endorphin release) to let it know you've achieved what you set out to do.

    Now if you take a stimulant, you trick your brain into thinking you're "super-psyched" about something in particular, but in reality you're not- you've just taken a drug.

    When your dopamine levels start to drop without any significant endorphin release (as the drug wears off) your brain thinks you've just failed at whatever you were so motivated about and as a result you feel low for a while.
    Reply With Quote
     

  8. Collapse Details
     
    #8
    Quote Originally Posted by atara View Post
    Not chemistry, psychology. The brain exists to measure the state of the body and tell it what to do, not to be entertained by our little endeavors with arylaminopropanes. So, if you have a higher heart rate, are sweaty, and have constricted blood vessels, your mind will conclude that you are, in fact, quite anxious; this effect was originally the James-Lange theory of emotion, viz. that our emotional state is largely driven by changes in the body. It's now considered to be more complex than that, but JL theory is still quite relevant -- and it shouldn't be too hard to imagine that if you find yourself sweating and your heart pounding, you will be anxious.
    Even though this sounds quite logic to me, psychological explanations just don't satisfy me the way modern neuroscientific explanations do. In the end, there seems to be a physical reason for whatever goes on in your brain. It might just be too complex to be understood yet.

    Quote Originally Posted by atara View Post
    I'll wager a guess, though, that for adrenaline to produce its trademark changes in the body, it has to leave the brain. As long as MDPV is keeping your dopamine in the synapses, the adrenergic bodily response won't occur.
    While some of the bodily stimulation definitely occurs before any anxiety appears, there might very well be a second stage in physical response caused by decreasing dopamine levels. I just haven't been looking out for that yet. Anyway, this is the type of explanation I'm looking for. High levels of dopamine preventing the anxiety caused by massive adrenergic acticity (or preventing the adrenergic activity itself) would explain pretty much every aspect of my MDPV experience. This includes the nasty redosing-providing-temporal-relief-thingy.

    Quote Originally Posted by atara View Post
    Though it seems doubtful that your MDPV anxiety is caused by another effect of MDPV itself, because I've noticed anxiety coming off of some other stimulants (many of which I no longer use).
    I agree with you. But then, what's the most state-of-the-art, generally accepted theory of anxiety caused by non-serotinergic stimulants? Someone must have done any research on this topic given the widespread use of MPH.

    Quote Originally Posted by atara View Post
    Can one experience an MDMA-esque roll without significant long-term neurotoxicity? I'm going to give a tentative (and admittedly uninformed) 'yes', but attempting to prolong it, especially by redosing your DRI, will almost certainly exacerbate oxidative stress. IAP may be better in this regard than MDAI, if only because a cursory glance at the molecule makes me think it has less chance of generating reactive oxygen species, what with it lacking any phenolic ethers. Of course neurotoxicity is also observed with AET, so there's certainly more to the picture than the metabolism of phenols.
    An MDMA-esque roll seems possible without significant long-term neurotoxicity by combining an SSRA with an NDRI. But I'm sure this won't satisfy anyone looking for the "unique magic". The difference between an NDRI and an NDRA just seems too big.
    Reply With Quote
     

  9. Collapse Details
     
    #9
    Senior Moderator
    Neuroscience and Pharmacology Discussion
    Philosophy and Spirituality
    ebola?'s Avatar
    Join Date
    Sep 2001
    Location
    situated in space-time
    Posts
    20,338
    I think that we might be going about this question in the wrong way--the question isn't just, "Why is MDPV anxiogenic?" but really, "Why is MDPV more anxiogenic than comparable stimulants, in particular racemic methylphenidate?" Here, I don't have an answer. The known binding screens, IIRC, suggest it a DNRI, like Ritalin, but w/o a disproportionately strong effect on NE (I don't know who started the rumor that MDPV is highly selective for dopamine; it's not).

    This suggests to me that we missed something on the binding screen. Either the compound itself exerts a great of direct adrenergic agonism (this is often neglected on such screens), or one of the metabolites is more selective for NE and/or exerts greater direct adrenergic agonism.

    An MDMA-esque roll seems possible without significant long-term neurotoxicity by combining an SSRA with an NDRI. But I'm sure this won't satisfy anyone looking for the "unique magic". The difference between an NDRI and an NDRA just seems too big.
    Some people have had good luck combining DNRIs and SSRAs in search of ersatz MDMA. Unfortunately, I am not one of them (complete releaser-type brain). Unfortunately for others, MDPV is not the right DNRI (if anything, the 5ht release will simply temper some of the nastiness).

    ebola
    Reply With Quote
     

  10. Collapse Details
     
    #10
    Quote Originally Posted by vinylmesh View Post
    I'm gonna throw neuroscience out the window and go all psychology on you. To simplify things grossly, dopamine = motivation to do work and expend energy. When your brain releases large amounts of dopamine it means you're really motivated about something which means it must be very important. My theory being your brain expects some sort of reward at the end of it (in the form of an endorphin release) to let it know you've achieved what you set out to do.

    Now if you take a stimulant, you trick your brain into thinking you're "super-psyched" about something in particular, but in reality you're not- you've just taken a drug.

    When your dopamine levels start to drop without any significant endorphin release (as the drug wears off) your brain thinks you've just failed at whatever you were so motivated about and as a result you feel low for a while.
    Thanks for your answer! As was the case with other explanations though, it doesn't quite satisfy me. Up to the point of feeling low for a while, I might agree with you. But feeling low is not even close to describing the state of MDPV-induced anxiety. I feel low (i.e. dysphoric, mildly depressed, but pretty calm) waking up after a night out on bk-MDMA. My MDPV-anxiety, on the other hand, kicks in right after the initial rush fades away. Therefore, the first part of the anxiety-experience goes with full-blown mental stimulation. As long as I can control my anxiety (i.e. on low dose MDPV, at home, alone), this state works great as a work-/study-aid. On a night out, though, the anxiety quickly increases to insane levels resulting in what I'd call an acute anxiety disorder (not being able to talk to people any longer, escaping parties while at the same time knowing exactly how irrational my behaviour and anxiety are). After a long-lasting plateau then, the mental stimulation fades away. This is where the worst part of the experience begins: Another long-lasting plateau with ongoing anxiety and physical-only stimulation. After that goes away, I feel pretty normal again.
    Reply With Quote
     

  11. Collapse Details
     
    #11
    Quote Originally Posted by ebola? View Post
    I think that we might be going about this question in the wrong way--the question isn't just, "Why is MDPV anxiogenic?" but really, "Why is MDPV more anxiogenic than comparable stimulants, in particular racemic methylphenidate?" Here, I don't have an answer. The known binding screens, IIRC, suggest it a DNRI, like Ritalin, but w/o a disproportionately strong effect on NE (I don't know who started the rumor that MDPV is highly selective for dopamine; it's not).

    This suggests to me that we missed something on the binding screen. Either the compound itself exerts a great of direct adrenergic agonism (this is often neglected on such screens), or one of the metabolites is more selective for NE and/or exerts greater direct adrenergic agonism.
    In fact, both questions are interesting for me. As to the question why non-serotinergic stimulants are anxiogenic in general: would it be correct to say the generally accepted answer is adrenergic action mediated by a combination of NE direct agonism, increased adrenaline levels (due to increased levels of DA and NE) and possibly additional substance-specific adrenergic activity? High dopamine levels in the synapse, on the other hand, seem to inhibit this process at some point, which is why redosing dopaminergic substance provides temporal relief from anxiety (not necesssarily a good idea, though).

    Then where are the highly selective NRIs and DRIs necessary to create stimulants individually adjusted to every user's needs? Raise dopaminergic activity for reduced anxiety (albeit never zero), raise noradrenergic activity for increased physical stimulation and reduced urge to redose?


    Talking about MDPV again, answering the question why MDPV is more "jittery" and anxiogenic than MPH despite similar ratios of NERT to DART affinity should also help us judging which SSRA and NDRI combo might come the closest to MDMA.
    Reply With Quote
     

  12. Collapse Details
     
    #12
    Senior Moderator
    Neuroscience and Pharmacology Discussion
    Philosophy and Spirituality
    ebola?'s Avatar
    Join Date
    Sep 2001
    Location
    situated in space-time
    Posts
    20,338
    I'm a bit skeptical that non-5ht-genic stimulants are anxiogenic in general. It seems to me that what matters most, and you mighta covered this earlier, is the ratio of DA:NE reuptake inhibition or release. Serotonin appears to exert a distinct, further moderating effect, in some ways anxiolytic via the subjective spin it puts on things, but also anxiolytic in some more direct neural way, moderating loops of compulsion via dopaminergic transmission.

    Is dopamine itself anxiogenic? I'm not quite sure. It accords some cardio-push and increases seeking behavior (compulsive actions), the latter according anxiety insofar as seeking activity faces barriers (in short, DA euphoria is some behavioral interplay of extreme desire AND elation, not really static gratification). It remains clear, though, that dopamine later metabolizes into NE and later adrenaline. I think that this explains much of the crash (as you suggest above): DA activity wanes but NE and direct adrenal activity endures.

    A couple wrinkles, though: I find your overall model compelling, except NE actually appears to play a pretty complicated and not yet understood role, not only according alertness, anxiety, and a large part of the body high but playing some key role in the euphoria too...stuff like ethcathinone is indeed fun (it couldn't just be the cathinone metabolite...), and one study found d-amp's euphoria to remain intact even when administered w/ a DA antagonist (in fact, not rating much worse than d-amp taken alone, when 'adjusted' for the dysphoria of said DA antagonist).

    Finally, re: mdpv, particularly combined with mdai: it's a tough analytical pivot, as its activity ain't THAT well-known. I mean, same with buphedrone as a potential pair for MDAI--people assume selectivity for DA, but it's not thoroughly demonstrated. Or, hell, those ring-substituted cathinones too.

    ebola
    (sorry for the verbosity--my 'set' became more 'on topic' in this thread than I'd like to admit )
    Reply With Quote
     

  13. Collapse Details
     
    #13
    Moderator
    Psychedelic Drugs
    MAPS Forums
    any major dude's Avatar
    Join Date
    Feb 2009
    Location
    Dirty South, U.S.A.
    Posts
    2,929
    Since as its being referred to here, the anxiety isn't present until the drug starts to wear off, I would venture a guess that the waning 5HT & DA activity consequent to the drug breaking down combined with the continuing CNS stimulation due to extra NE results in quite the unpleasant mood.
    Reply With Quote
     

  14. Collapse Details
     
    #14
    Senior Moderator
    Neuroscience and Pharmacology Discussion
    Philosophy and Spirituality
    ebola?'s Avatar
    Join Date
    Sep 2001
    Location
    situated in space-time
    Posts
    20,338
    For me, anxiety accompanies the high when I pass into the level where any effect on mood could present itself. It's quite horrid (my above post was not quite mdpv-inspired ) and quite a useless state.

    ebola
    Reply With Quote
     

  15. Collapse Details
     
    #15
    Neuropharmacology is FAR more complex than:

    serotonin = love fun, noradrenaline = anxiety, dopamine = stimulating fun

    ..or whatever, you get the point.

    There are MANY different brain areas, there are MANY receptors, MANY transmitters, and even two pure dopamine re-uptake inhibitors are not going to act EXACTLY the same.

    Been seeing this more and more in posts like this recently recently, wondering if mephedrone is making a generation of want-to-be-neuropharmacologists!
    Reply With Quote
     

  16. Collapse Details
     
    #16
    Senior Moderator
    Neuroscience and Pharmacology Discussion
    Philosophy and Spirituality
    ebola?'s Avatar
    Join Date
    Sep 2001
    Location
    situated in space-time
    Posts
    20,338
    Bluelight is. And we all start somewhere.
    Yet your larger point stands in that circuits of patterned firing likely have far more to do with specific patterns of experience than global changes in neuromodulators (in the sense that sum monoamine transmission amounts to the latter). Isn't this entire thread beginning to get at this though?

    ebola
    Reply With Quote
     

  17. Collapse Details
     
    #17
    Just talking about DA/NE/5-HT concentration in the synapses is a simplification, of course. But it's a simplification that works quite well in practice, explaining most of the effects of many stimulants/stimulant-entactogens.

    And what we're talking about is more than just emotions, it's rather emotional disorders. E.g. being afraid (or overly enthusiastic) for no logical reasons and not being able to control these feelings. While complex patterns of neuronal firing may play the most important role with ordinary emotions, I'd guess neurotransmitter concentrations grow in importance for the emotional disorders we're talking about.


    Quote Originally Posted by ebola? View Post
    I'm a bit skeptical that non-5ht-genic stimulants are anxiogenic in general. It seems to me that what matters most, and you mighta covered this earlier, is the ratio of DA:NE reuptake inhibition or release. Serotonin appears to exert a distinct, further moderating effect, in some ways anxiolytic via the subjective spin it puts on things, but also anxiolytic in some more direct neural way, moderating loops of compulsion via dopaminergic transmission.

    Is dopamine itself anxiogenic? I'm not quite sure. It accords some cardio-push and increases seeking behavior (compulsive actions), the latter according anxiety insofar as seeking activity faces barriers (in short, DA euphoria is some behavioral interplay of extreme desire AND elation, not really static gratification). It remains clear, though, that dopamine later metabolizes into NE and later adrenaline. I think that this explains much of the crash (as you suggest above): DA activity wanes but NE and direct adrenal activity endures.

    A couple wrinkles, though: I find your overall model compelling, except NE actually appears to play a pretty complicated and not yet understood role, not only according alertness, anxiety, and a large part of the body high but playing some key role in the euphoria too...stuff like ethcathinone is indeed fun (it couldn't just be the cathinone metabolite...), and one study found d-amp's euphoria to remain intact even when administered w/ a DA antagonist (in fact, not rating much worse than d-amp taken alone, when 'adjusted' for the dysphoria of said DA antagonist).
    I think that even highly selective DA releasers/inhibitors are slightly anxiogenic. At least as soon as the mental high wears off while adrenergic activity continues. But the amount of anxiety should be easy to control and no problem for most people.

    On the other hand, I agree with you that NE doesn't produce unwanted effects (anxiety, tachycardia, hypertonia, etc.) only. It should at least act somewhat energizing on your brain, just without any happiness or positive emotions involved. Therefore, the typical stimulant euphoria seems to require both DA and NE in just the right, individually different balance. Too much DA might feel somewhat boring/weary while too much NE makes you feel jittery, anxious and uncomfortable.
    Reply With Quote
     

  18. Collapse Details
     
    #18
    The first couple of times of methylone wer great took away my dep and severe anxiety. But after a while once it would start coming down, i would start getting severe anx/pan attacks. Clearly a situation where something borrowed must be repaid and when your in the red, you pay double interest. Just saying that stimulants are not a long term solution to dep/anxiety. Of, course it does'nt help in the least that i smoke during. But when i'm coming down and have a cigarette, i feel like some one tied battery cables to my testicles and turned on the juice, can you believe it? Smoking already aggravates my condition then smoking during stimulant and you feel ok, but when the devil comes for his dues, you tell yourself, why, why why. Glad to know i'm not the only one that has panic attacks after mi,mdpv, dimethocaine. Lesso learned : Don't use stim's when you have pan'anx diordertrange how it calms me down at first, especially methylone-at first i was completely cured. Ha!ha! I calmed down, depression lifted, like magic-after 50+meds in 2 years. What goes must come down. Had tms treatment-worked on dep/not anxiety. No more for me but that godd%$#% nicotine has me by the gonads and won't let go. Most addictive substance on earth. And with my pan/anx disorder it puts me in a bad place. Your whole body wants but cant! Oh well, i guess there are worse things that can happen. Thanks evrybody, needed to get a load off. Please! All feedback welcomed!a mllion thanks!
    Reply With Quote
     

  19. Collapse Details
     
    #19
    try lyrica (pregabalin) it really works for mdpv comedown. even at low doses
    Reply With Quote
     

  20. Collapse Details
     
    #20
    Bluelighter muie's Avatar
    Join Date
    Dec 2008
    Location
    Canada
    Posts
    658
    I have a problem with this too, plus i'm scripted clonazepam for anxiety for past 5-6 yrs at 4mg/day and 0.3mg clonidine.

    I take massive doses of that plus alcohol and they just mask it (clonidine, clonazepam, high grade weed, alcohol) instead of get rid of it....after at least 24hrs they do but only make the comedown more comfortable instead of treating it.

    I'm sure that amo barbital would definatley cure this problem, and maybe even soma but im not sure on soma (the amobarb i can't get here anyways).

    How would GBL compare to benzos (i've had pretty much all other benzos you can think of, temazepam and nitrazepam were my favorites)?
    Reply With Quote
     

  21. Collapse Details
     
    #21
    Bluelight Crew allium's Avatar
    Join Date
    Nov 2009
    Location
    Russia
    Posts
    1,060
    Quote Originally Posted by txern41 View Post
    The first couple of times of methylone wer great took away my dep and severe anxiety.
    My experience with bk-mdma was somewhat opposite to your. I did it few times(~5) in moderate dosages. And anxiety was the most pronounced side effect of this drug. For me, Methylone don't worth side effects it causes.

    This post could be offtopic, but I abused MDPV in the past - and got some anxiety problems. Could such anxiety be long-term effect of MDPV overusing?

    EDIT: Another question somewhat related to the topic. Can phenibut taked together with MDPV reduce anxiety of the latter?
    Reply With Quote
     

  22. Collapse Details
     
    #22
    good weed is great for the comedown.
    Reply With Quote
     

  23. Collapse Details
     
    #23
    Moderator
    Psychedelic Drugs
    MAPS Forums
    any major dude's Avatar
    Join Date
    Feb 2009
    Location
    Dirty South, U.S.A.
    Posts
    2,929
    This weekend i came across a couple articles that may have some implications for this discussion

    Here's one from Neuroskeptic about a study on tonic dopamine

    And another from Neuropsychopharmacology on stimulant use disorder and directed attention. I'd imagine MDPV comedown to be somewhat comparable to withdrawal
    Reply With Quote
     

Posting Permissions

  • You may not post new threads
  • You may not post replies
  • You may not post attachments
  • You may not edit your posts
  •