Like a lot of psychoactive substances, caffeine evolved as a pesticide in plants. Those plants tend to also evolve a lot of other compounds that modulate the ef

Like a lot of psychoactive substances, caffeine evolved as a pesticide in plants. Those plants tend to also evolve a lot of other compounds that modulate the effect of the pesticide. (I would guess there's probably some probabilistic/natural selection reasons for why this tends to happen.) That's why cannabis plants contain way more psychoactive molecules than just THC, for example, and why the experience of taking pure THC generally feels different from consuming cannabis. Monoamine oxidase (MAO) is an enzyme that helps break down certain neurotransmitters (monoanimes, such as dopamine, serotonin, and norepinephrine). Monoamine oxidase inhibitors (MAOI) inhibit the activity of MAO, which can lead to less breakdown of those neurotransmitters, and so a higher neurotransmitter concentration. This can have a synergistic and potentiating (or, if you're an insect, an additionally poisonous) effect for certain substances like caffeine. A certain amount of caffeine consumed along with MAOIs found in the coffee plant (e.g. from drinking coffee) could lead to more dopamine and norepinephrine concentration than the same amount of caffeine alone, for example. This is also why it can be very dangerous to combine MAOIs with certain other substances. For example, combining it with tryptophan can lead to potentially fatal serotonin syndrome. Coffee plants also contain much more than just caffeine and MAOIs. For example, theobromine, which is also found in chocolate (and which is responsible for harming or killing dogs if they consume chocolate). I think this is the case for most psychoactive plants that people consume. You're typically getting a complex cocktail of many different molecules which all may have mutually modulating effects. This is why different coffee and cannabis strains can potentially cause somewhat different subjective experiences; they have different ratios of all the different compounds.