Stimulant Hypersensitivity

This may sound like an obvious enquiry, and to be honest, I don't think I've posted a question on drug discussion for 18 months so forgive me if this has been covered:

Joe Blow uses meth on the weekend, not in huge amounts, but say in the realm of 150mg per weekend (keeping in mind he uses high quality uncut substance, so 150mg is a fair bit). Normal methods of administration vary from oral, insuflation and vapourising.

Joe has a strong cup of coffee during the day at work and feels more stimulated than when he was having fun on the weekend. Although, a much more dirty high is experienced.

Is it possible to build a hypersensitivty to less powerful dopamine antagonists/agonists such as caffiene or even glucose after frequent methamphetamine use?

I can't drink coffee anymore either because of this.. it sucks! Have I become a placebo baby, or is there a good reason why I have a degree of comedown from doing coffee? Argh.

Placebo might be the word here, or there could be something that a more chemistry-skilled mind than mine needs to discuss, in which case, I am listening.

i would like to know the answer to this too. somebunny?

I for one would probably have thought the reverse to be far more true but on second thought this hypothesis does have some merit.

I have a phsychiatrist friend who is doing a lot research on brain chemistry in relation to recreation drug use. I'll see if he can shed some light on the issue.

I definately notice the effects of coffee more after a huge weekend. Especially the day after no sleep and a lot of speed. I enjoy this feeling, I had a latte yesterday morning that gave me tingles all over

I couldn't find anything on meth-then-caffeine sensitisation at medline, only studies that looked at it the other way around. It looks like caffeine can cause sensitisation to the "motor-stimulant" effects of both caffeine and amphetamine:
Subchronic caffeine exposure induces sensitization to caffeine and cross-sensitization to amphetamine ipsilateral turning behavior independent from dopamine release. and
Subchronic caffeine administration sensitizes rats to the motor-activating effects of dopamine D(1) and D(2) receptor agonists.

We know that meth causes behvioural sensitisation, see here for example: Increased plasma concentration and brain penetration of methamphetamine in behaviorally sensitized rats. And if caffeine causes sensitisation to meth, I wonder if the reverse is also true?

GHB is considered a dopamine agonist, correct?

So is it more likley repeated GHB (or any of the derivatives that are more commonly used) would cause the aforementioned effects?

<dusts off vault of knowledge> It's been awhile

GHB has a complex pharmacology, with it's natural role still to be fully deduced. I believe most if not all dopamine release is from the secondary action of GHB's modulating of GABA receptors, making GHB an indirect dopamine agonist. Simply - and its much much more complex than this model- GABA is a neuromodulator, itself controlled by the firing of ion channels (on/off pulse). When the Chloride ion channels are made to fire more efficiently or with a different wave envelope to that of the endogenous electrical pulse, other neurotransmitter levels, particularly dopamine, are directly affected. Alcohol and benzo's (again roughly speaking) do a similar thing.

I don't know whether caffeine would potentiate GHB related activity or any metabolites. It's quite reasonable that it could potentiate or redirect metabolism of DA via the DA--> Norepinephrine --> Epinephrine (adrenaline) pathway, or even alter glutamate decarboxylation to GABA. The papers superbabydoc has mentioned as well as others I've seen indicate caffeine has a major pharmacological influence on many sympathomimetic amines/metabolites as well reports that caffeine also potentiates metabolites of THC.

I find the metabolites from meth are more physically stimulating than the actual buzz from insufflation. Sure there is more euphoria with the initial high, but the residual effect the next day with an early morning coffee is a powerful stimulant combination IMO. Which makes me think more about Selegiline. It results in the same metabolites as meth/amphetamine, yet is neuroprotecting rather than neurotoxic. Any compound that could give the duration of up experienced after the initial buzz of meth, even without any noticeable euphoria certainly seems like the go IMO, pardon the pun