Pharmacodynamics of caffeine/stimulants

[Pimp Lazy]

Stimulants don't seem to effect me very much. Caffeine almost makes me sleepy. Cocaine seems to do little as well. Amphetamines and methylphenidate which were prescribed to me for ADHD didn't do much more than make my heart beat fast; although I did not feel hyper myself. I don't have a long history with any medicinal or recreational use of stimulants. I realize there is a whole host of possibilities: enzyme malfunction, receptor density, etc., but I'm hoping someone just happens to know what it is.

I've been diagnosed as ADHD, depressed, and then bipolar. My goal is to understand my physiology a little better and reconcile what I know about bipolar disorder with my experience. Shouldn't cocaine make me go crazy? Shouldn't LSD as well? The only drugs that affect me terribly are MDMA, mushrooms, and amphetamines, but amps only on the comedown.

I've done some searching, UsedTFSE, but I haven't be able to find anything.

Thanks in advance.

PAX,
PL

 

[Ham-milton]

This is sort of borderline ADD material, so I'll give it a shot.

I've also been diagnosed BP1, ADHD, and so I've been depressed as well.

It's not really true that stimulants are going to make you crazy. They may push you into a mania with heavy use, but I find that they're much less prone to that than SSRIs are.

Psychedelics like LSD are more likely to cause you problems if you're prone to psychosis. They're not a good idea for the mentally ill, but I managed to trip dozens of times and never had the slightest problem.

Personally, I think that the problems associated with them are overstated. Occasionally someone will just snap, but it's really uncommon.

 

[Pimp Lazy]

Thanks Ham... I guess I digressed a little, but I did manage to avoid a full rant which I wrote then erased .

I'm specifically curious about caffeine and why it has little to no effect. I know various theories of the physical basis of ADHD. I'm aware that caffeine has efficacious use in ADHD treatment, but it seems to do nothing for me. I'm curious what the cause of that might be. I guess the other stuff was more of addendum.

Thanks again.

PAX,
PL

 

[Ham-milton]

Caffeine has never, ever been shown to be effective in ADHD. Usually it has negative impact.

Stimulants that increase extracellular DA are effective. Even Modafinil, which does so only very slightly, is even much better than caffeine.

 

[Pimp Lazy]

http://pharmrev.aspetjournals.org/cgi/content/full/51/1/83#top

"A. Activation of Dopaminergic Transmission and Effects on Motor Behavior

The interaction between adenosine A2A and dopamine D2 receptors highlighted above could provide a mechanism for several actions of caffeine and some of its metabolites on dopaminergic activity. Thus, an inhibition of A2A receptors by caffeine would be expected to increase transmission via dopamine at D2 receptors (Ferré et al., 1992). There is indeed ample evidence that caffeine (and other adenosine receptor antagonists) can increase behaviors related to dopamine. The first demonstration of an adenosinedopamine interaction on behavior was the finding that several adenosine receptor antagonists, including caffeine, theophylline, and isobutyl-methylxanthine, could increase dopamine receptor-activated rotation behavior (Fredholm et al., 1976). This finding was preceded by the observation that theophylline could enhance such rotation behavior (Fuxe and Ungerstedt, 1974), but in that study the authors proposed that the mechanism was phosphodiesterase inhibition. In the later study (Fredholm et al., 1976) this possibility was discounted. This type of finding has since been repeatedly confirmed and elaborated (see Daly, 1993; Ferré et al., 1992; Ongini and Fredholm, 1996). Indeed, dopamine receptor antagonists can inhibit the stimulatory effects of caffeine on motor behavior (Fredholm et al., 1983; Herrera-Marschitz et al., 1988; Garrett and Holtzman, 1994b), and long-term treatment of rats with caffeine reduces the effects of both caffeine and dopamine receptor agonists (Garrett and Holtzman, 1994a)."

Interesting enough on its own, but it also seems some support as to why coffee is a hangover cure.

Read section E as well. Also hangover cure support as well as ADHD support just by your definition of allowing for an increase in extracellular dopamine. I'm sure you're aware that there is contention as to whether or not a lack of dopamine is the main culprit.

http://www.ncbi.nlm.nih.gov/pubmed/16856124

EDIT: I'm still curious if anyone knows a common reason for caffeine's blatant suckiness.

 

[Mr Blonde]

EDIT: I'm still curious if anyone knows a common reason for caffeine's blatant suckiness.

Maybe cause it doesn't bind to anything that useful

It increases levels of dopamine (and 5-HT?) and increases levels of epinephrine, all by being an adenosine antagonist. It's probably similar to how bupropion works; not all dopamine receptors mean sweet, sweet pleasure.

I like caffeine. I drink a lot of coffee and energy drinks, and that with smoking gets me revved up for work. It's a productive stimulant for me.