system
Given the following post, respond as if you're commenting on Reddit:
human
What is the biochemical origin of caffeine dependence?

There's a joke that if you've been drinking coffee for a long time, when you wake up you'll need a coffee to get you back to the point where you were before you started regularly drinking coffee. But, if you stop for a week or two, your baseline goes back up. What happens to regular coffee drinkers to lower their baseline wakefullness, and is it chiefly neurological or psychological?
gpt
Caffeine is a nonselective adenosine receptor antagonist, acting at A1, A2a, A2b, and A3 receptors (it also binds to a few other receptors, but we’ll ignore those for simplicity’s sake). From knockout studies in mice, it appears A2a is critical for the stimulating effect of caffeine. In the brain, Adenosine levels fluctuate as the day passes with the highest levels at night. Higher levels of adenosine produce a drowsiness effect. When you consistently apply an antagonist to a cell, a common response is the cell will upregulate the particular receptor that is being antagonized. As such, consistent caffeine intake can result in an upregulation of adenosine receptors [1]. When you do not intake caffeine, you thus experience a heightened response, or a sensitization, to adenosine, and thus feel an increase in drowsiness.       
        
1. Cell Mol Neurobiol. 1993 Jun; 13(3): 247–261.