Mobilization of intracellular calcium
At very high concentrations of about 1–2 mM, caffeine lowers the excitability threshold in muscle cells, leading to prolonged contraction. The introduction of such high doses of caffeine allows calcium to enter the muscle cell through the plasma membrane and sarcoplasmic reticulum more readily. Influx of calcium through the membranes in muscle cells requires at least 250 μM of caffeine. Normally, other toxic effects of caffeine begin to occur in concentrations over 200 μM, however average consumption averages lead to concentrations less than 100 μM. This means that calcium influx and mobilization are most likely not the cause of caffeines effect on the central nervous system, and are therefore not the cause of caffeine-induced anxiety disorder. Inhibition of phosphodiesterases
Methylxanthines such as caffeine inhibit the action of cyclic nucleotide phosphodiesterase, which normally acts to break down cAMP. Cyclic adenosine monophosphate, or cAMP, is a second messenger important in many cellular processes and is a critical factor in signal transduction. The inhibition of the phosphodiesterase would lead to a buildup of cAMP, increasing the activity of the second messenger throughout the cell. Though this mechanism is possible, it only occurs after levels of caffeine have reached a toxic level, and therefore it is unlikely to explain the mechanism of caffeine in the brain. Antagonism of adenosine receptors
There are four well-known adenosine receptors found in the body, A1, A2A, A2B, and A3.
These studies showed that in adolescent rodents exposed to caffeine, functioning of serotonin systems was affected, leading to increased anxiety; anxiety-related behaviors were higher than in adult rats exposed to the same amount of caffeine; and reward seeking behaviors as well as mood fluctuations were increased as the rodents matured. Long-term health effects
When consumed in moderation, caffeine can have many beneficial effects. However, over the course of several years, chronic caffeine consumption can produce various long-term health deficits in individuals. Among these, rodent studies have suggested caffeine intake may permanently alter the brains excitability. As previously stated, long-term effects are most often seen in adolescents who regularly consume excess amounts of caffeine. This can affect their neuroendocrine functions and increase the risk of anxiety-disorder development. Treatment
For individuals being treated with benzodiazepines such as alprazolam (Xanax) for anxiety disorders, even small amounts of caffeine may have negative effects on treatment. Caffeine is able to negate the effects of benzodiazepines which can lead to heightened levels of anxiety and even panic attacks. Studies have linked caffeine intake to increased rates of cytotoxicity and cell death by necrosis associated with benzodiazepine use. However, this phenomenon (thought to be mediated via TSPO) is also present with benzodiazepine use alone. The clinical significance of caffeine-benzodiazepine induced cytotoxicity in humans is unclear and has not been shown to be harmful. Although benzodiazepines are effective at managing acute caffeine-induced anxiety symptoms,  avoiding caffeine is generally recommended rather than increasing benzodiazepine intake.