Caffeine’s mechanisms of action are not completely understood, but the proposed mechanisms likely act in unison.[1][2][3]
Caffeine’s primary action is in the central nervous system, where it prevents adenosine from binding to its receptor.[4][1][3] This affects the secretion of several neurotransmitters — norepinephrine, dopamine, acetylcholine, serotonin, GABA, etc. — involved in alertness, mood, motivation, memory, and pain perception.[1][5] For example, adenosine released during exercise decreases the secretion of dopamine, a neurotransmitter that increases mood and motivation.[2][6] So, when taken before or during exercise, caffeine allows dopamine secretion to continue, potentially maintaining mood and motivation to work hard.[6] This, coupled with lower pain perception caused by the lack of adenosine signaling, may partly explain caffeine’s sports-performance-enhancing effects.
Caffeine also plays a role in cellular calcium transport, which regulates neurotransmitter secretion in neurons and contractile force in muscle cells.[1][3] Caffeine can have a direct effect on calcium transport in muscle cells and may, therefore, have a direct effect on muscle contractile force,[2][7][8][9][10][11] providing an additional explanation for its performance-enhancing effects.
Caffeine can also inhibit a group of enzymes called cyclic nucleotide phosphodiesterases (PDEs), preventing the breakdown of cyclic adenosine monophosphate (cAMP).[1][3] This is important because cAMP stimulates the release of neurotransmitters like dopamine, epinephrine, and norepinephrine, which regulate aspects of cognitive function, including alertness, mood, motivation, and memory.[1][3] However, this mechanism requires more research and may only occur in the presence of high concentrations of caffeine, i.e., following high caffeine doses.