Factors regulating cytochrome P450 (CYP450) enzymes in the brain. Brain bioavailability of systemically administered drugs is P450 dependent. Drug response is not only linked to brain P450 enzymes, but also indirectly influenced by factors that independently or synergistically affect CYP enzymatic activity: (i) endogenous factors or regulators (e.g., hormones, neurotransmitters, biological clock, or cerebral blood flow); (ii) exogenous factors (e.g., xenobiotics, dietary constituents, substances of abuse, or pesticides); (iii) demographics (e.g., genetics, age, gender, ethnicity or race); and (iv) disease-specific factors (e.g., cancer, epilepsy, psychiatric diseases, neurodegenerative disease, or stroke).