Edward "Eddie" Morra (Bradley Cooper) is a writer who lives in New York City. He has recently been dumped by his girlfriend Lindy (Abbie Cornish) in addition to failing to meet the deadline to turn in his new book, which he hasn't started yet. One day, Eddie comes across Vernon Gant (Johnny Whitworth), the brother of his ex-wife, Melissa Gant (Anna Friel). Vernon is a drug dealer, and he offers Eddie a sample of a new nootropic drug, NZT-48, claiming it has the ability for humans to access 100% of the brain's power, as opposed to the normal 20%. Eddie accepts, and, much to his surprise, the drug does indeed work, allowing him to finish his book that excites his agent.
Eddie asks for more of the drug, but when Vernon asks him to go pick up his dry cleaning, he returns to find Vernon murdered and his apartment ripped apart. Eddie calls the police and deduces that Vernon was probably killed by someone who wanted his stash. He finds the NZT and a wad of cash, and uses them to turn his life around. He focuses on trading stocks, borrowing capital from a Russian mafia thug, Gennady (Andrew Howard).