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ATTN: Malice.
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2016-07-11 at 3:38 AM UTCI have an enquiry that might warrant combining our autismal powers, this should be fun, also your pharmacology power level is comparable to mine. Ok so here's the deal, let's take me as a case study. In my experience some stimulants or more specifically those that exert their influence primarily due to re uptake inhibiting effects, tend to be more anxiogenetic than those that exert their influence by merit of being a catecholamine releaser or(due to the pharmacodynamics involved) having both these traits. That is to say they're releasers/re-uptake inhibitors at the same time, like amphetamine. Now i suspected at first that this was due to the non-selectivity of the substances involved. For instance i thought that methylphenidate(Your post in TRT made me think of this so good jerb) might bind more to beta adrenergic receptors than amphetamine which would explain the disparity in relative effects. However and here is where it gets interesting, a second theory of mine has to do with the long term effects of phosphorylation of the receptor sites amphetamine binds to.
So let's take a quick look at amphetamines pharmacodynamics in so far as it's binding profile is concerned. So in contrast to RI stims, where action is primarily concentrated in VMAT 1 and 2 amphetamine also binds to the trace amine associated receptor or TAAR for short. If you'll humor me, this article goes a little in depth about the receptor sub family involved. The reason i mention this is because they talk about the genes involved with this receptor as well which leads me to believe extended down regulation of TAAR might lead to reduced gene expression making the brain respond less to dopaminergic effects while being of no consequence to (nor)adrenergic effects? Possibly evidenced by the fact only dopamine and phenylethylamine like substances have a specific effect on this receptor. http://www.guidetopharmacology.org/G...d?objectId=364
Now my question to you has to do with the plausibility of my hypothesis and if you may have read some literature to support or refute my thoughts. I think my hypothesis may have some merit but i would be more than happy to be proven wrong of course, because muh science.
Some evidence to support my theory would seem to be that in the case of my gf, who has been prescribed methylphenidate in the past. The same effects i observed became apparent in her after she was exposed to a few recreational doses of amphetamine over a 6 week period.
Looking forward to your expert opinion,
Sincerely Sophie. -
2016-07-11 at 6:44 AM UTCHmm...I was actually doing some reading through r/DrugNerds recently about methylphenidate and came across a discussion on the relative prevalence of side effects. People were pretty split, and IIRC a p-doc chimed in that in his experience with hundreds it was clearly amphetamine, which wouldn't surprise me.
Have you considered binding affinities? IIRC MPH is far more selective for dopamine in particular, while amphetamine has a more widespread effect. The key factor would likely be serotonin, and fortunately due to fluorinated amphetamines (4-FA, 2-FA and 2-FMA) and other designer drugs in the stimulant class serotonin, by far the least well understood monoamine, seems to have repeatedly been described as smoothing/balancing it out, making drugs more pro-social/empathogenic.So let's take a quick look at amphetamines pharmacodynamics in so far as it's binding profile is concerned. So in contrast to RI stims, where action is primarily concentrated in VMAT 1 and 2 amphetamine also binds to the trace amine associated receptor or TAAR for short. If you'll humor me, this article goes a little in depth about the receptor sub family involved. The reason i mention this is because they talk about the genes involved with this receptor as well which leads me to believe extended down regulation of TAAR might lead to reduced gene expression making the brain respond less to dopaminergic effects while being of no consequence to (nor)adrenergic effects? Possibly evidenced by the fact only dopamine and phenylethylamine like substances have a specific effect on this receptor. http://www.guidetopharmacology.org/G...d?objectId=364
Wait, what? Wouldn't that imply the opposite? Or did I misunderstand you, or you make a typo.
Regardless, and this has been a recurrent theme, due to genetic/neurological variation and how widely response can differ speculating isn't of much use, unless you attempt to find a method to ameliorate for this divergence and are certain enough of it.
Example, the similarity MPH can have with cocaine, and how both that and amphetamine can be remarkably axiolytic and prosocial for many people.
If she's experiencing symptoms, it would be best to have her switched to dextro-amphetamine, if it's available. Even if not, the isomer separation, along with amph being so cheap, should make this a feasible option.
Pyrazolam powder is also becoming much more readily available, and cheap, and would make an excellent adjunct to counteract anxiety. -
2016-07-11 at 7:53 AM UTC
Hmm…I was actually doing some reading through r/DrugNerds recently about methylphenidate and came across a discussion on the relative prevalence of side effects. People were pretty split, and IIRC a p-doc chimed in that in his experience with hundreds it was clearly amphetamine, which wouldn't surprise me.
Have you considered binding affinities? IIRC MPH is far more selective for dopamine in particular, while amphetamine has a more widespread effect. The key factor would likely be serotonin, and fortunately due to fluorinated amphetamines (4-FA, 2-FA and 2-FMA) and other designer drugs in the stimulant class serotonin, by far the least well understood monoamine, seems to have repeatedly been described as smoothing/balancing it out, making drugs more pro-social/empathogenic.
That's an excellent point. The halogenated amphetamines rarely cause excessive stimulation in my case. However this wouldn't explain why at first MPH did not seem excessively stimulating/adrenergic to my gf. But after she took recreational doses of amphetamine a couple times the effects of the MPH felt more adrenergic to her at the same dose.Wait, what? Wouldn't that imply the opposite? Or did I misunderstand you, or you make a typo.
What i meant was, if dopaminergic effects are reduced due to downregulation at TAAR, the adrenergic effects of stimulants in general would seem comparatively more intense. My reasoning being that the endogenous ligand for TAAR is dopamine and it's precursors.Regardless, and this has been a recurrent theme, due to genetic/neurological variation and how widely response can differ speculating isn't of much use, unless you attempt to find a method to ameliorate for this divergence and are certain enough of it.
Example, the similarity MPH can have with cocaine, and how both that and amphetamine can be remarkably axiolytic and prosocial for many people.
If she's experiencing symptoms, it would be best to have her switched to dextro-amphetamine, if it's available. Even if not, the isomer separation, along with amph being so cheap, should make this a feasible option.
Pyrazolam powder is also becoming much more readily available, and cheap, and would make an excellent adjunct to counteract anxiety.
Yeah medically she is pretty much set i convinced her psychiatrist to prescribe 4x 1mg clonazepam a day due to the up tick in anxiety. -
2016-07-11 at 7:57 AM UTCDoes 2cb come up as a false positive for anything in a standard 5 panel test?
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2016-07-11 at 9:24 AM UTC
Does 2cb come up as a false positive for anything in a standard 5 panel test?
Nah, you'll be fine.
https://www.erowid.org/chemicals/2cb/2cb_testing.shtml -
2016-07-11 at 9:43 AM UTCOh, I forgot to mention this! I think I've posted it before, but unless you've religiously followed my rantings in TRT threads throughout the years there are a lot of valuable things that no one will remember. Did you ever hear about this paper that was published?
Cocaine and methylphenidate may not be reuptake inhibitors after all, but inverse agonists!
https://www.reddit.com/r/DrugNerds/comments/2eswkq/dopamine_reuptake_transporter_dat_inverse_agonism
If you read/skim through the paper you'll quickly find convincing evidence that there would have to be something very strange/different about them if they were, finish and comprehend it (It's a pretty easy read.) and you'll find they have a pretty convincing argument.
This is revolutionary in terms of understanding their mechanism of action! It's incredible that it took so long for someone to write this. -
2016-07-12 at 2:43 AM UTC
Oh, I forgot to mention this! I think I've posted it before, but unless you've religiously followed my rantings in TRT threads throughout the years there are a lot of valuable things that no one will remember. Did you ever hear about this paper that was published?
Cocaine and methylphenidate may not be reuptake inhibitors after all, but inverse agonists!
https://www.reddit.com/r/DrugNerds/comments/2eswkq/dopamine_reuptake_transporter_dat_inverse_agonism
If you read/skim through the paper you'll quickly find convincing evidence that there would have to be something very strange/different about them if they were, finish and comprehend it (It's a pretty easy read.) and you'll find they have a pretty convincing argument.
This is revolutionary in terms of understanding their mechanism of action! It's incredible that it took so long for someone to write this.
That's really interesting. Thanks for mentioning that. I'll be sure to look into it.
