We open in medias res to the narration of Eddie Morra (Bradley Cooper). The camera arches up to see him standing on the ledge of his penthouse suite balcony. His place is unpacked with boxes strewn all around. His apartment also has a panic room and a steel vault door. Somebody is screaming on the other side trying to get in. We go down to the lobby. The unknown intruders have disabled all the security and killed the lobby guards. Eddie wonders how he with a "four digit I.Q." could miss things that led him to this. He edges closer off the ledge, thinking he should jump. A gunshot rings out and Eddie looks to the window of his neighbor who was killed by the intruders for complaining about the noise. Eddie thought he would be making a difference in the world, but now all he will do now is "make a difference on the sidewalk" he says.
We jump back a few months to see a much different Eddie. He has long straggly hair, unkempt clothes, and is not doing well. Eddie has a book deal but has yet to write a single word even with several days at the computer. His first installment of the book is due in five days, and he won't have it. To make matters worse, his girlfriend Lindy (Abbe Cornish) breaks up with him, because he is not going anywhere. Eddie tries to propose but Lindy counters that didn't go well the first time. Eddie tells us that is true; he married his college sweetheart Melissa (Anna Friel) and the marriage imploded within a few months. Lindy gives back her keys and tells Eddie she got the promotion she wanted, to which he says he is happy for her.
Eddie walks down the street, alone and depressed. By chance, he bumps into Vernon (Johnny Whitworth) his ex-brother in law. Vernon asks him to get a drink, and Eddie agrees. At the bar, Eddie asks if Vernon is still dealing. Vernon says he in the consulting business. Vernon asks about his novel, and Eddie admits he hasn't written anything. Vernon begins to tell him about a drug that will be out the next year and is already FDA approved. It will tap into the other parts of his brain and make him more focused. He gives Eddie a single tablet in a small baggie. Eddie tries to decline it, but Vernon tells him not to be ungrateful because that pill costs 800 dollars. Vernon tells Eddie to call him if he wants more.
Eddie walks backs to his apartment where outside the door, he takes the pill with a "what the hell" attitude. He goes up to his apartment to see Valarie (T.V. Carpio) the wife of his landlord there. He replies he knows he is behind on the rent and will have it Tuesday. Valarie begins to berate him as Eddie notices things around him changing, his synapses firing. The drug is taking effect and he notices everything including a book in the woman's bag. He asks why she is so mad at him, and notes that it is probably because she is studying for the law exam. Valarie is flustered asking how he knew that. Eddie says he saw the book; but she counters he only saw the corner of it. Eddie remembers years ago when he was in college seeing the same book, waiting for a coed to find a condom, so they could have sex. That part of him had always been there waiting for the drug to reawaken the memory.
Eddie tells her its the wrong book to be using, and suggests some better sources so she can scoop her fellow classmates. He is witty and charming and thus Valarie is putty is his hands. They go back to her place and have sex and finish the paper. Eddie goes back to his own apartment and realizes how great the drug is. Feeling focused, he goes to his computer and begins to write. The next morning the drug has worn off, and he knows he will need more. Lucky for him though, he wrote ninety pages before the drug wore off, which will buy him time with his publisher. Eddie asks her to read three pages, and if she doesn't like it, he'll give back the advance. He gets home and sees three messages from his publisher who is very impressed with him. He smiles.
He goes to Vernon, and Vernon looks like he has been beat up. Eddie asks what happened but Vernon tells him he doesn't want to know. Eddie learns the drug is being called NZT-48 and it isn't exactly legal. Nevertheless, Vernon can get him more. Vernon asks Eddie to pick up his suit and get them some breakfast. Eddie agrees, telling the audience he would be Vernon's errand boy forever if he can get more NZT. Eddie gets back to the apartment to find it trashed and Vernon dead from a gunshot to the head. Eddie is shocked and calls 911. As he waits, he realized Vernon was killed by someone he knew and because they wanted the drug. Eddie begins to look and then uses the connection of needing to buy breakfast to find the drugs hidden in the oven, along with a black book of names and a stack of cash.
Eddie is taken to the station and talks to a detective and explains that Vernon was in antiques. Melissa calls the station and Eddie talks to her. He tells her he's sorry and despite Eddie pressing for a meeting, Melissa tells him they cannot meet, and he is not invited to the funeral.
Eddie begins to walk home with his very large stash of NZT. He looks at his reflection and decides the first thing he needs to do is get a makeover. So he gets his hair cut, hits the gym and gets a bunch of tailored clothes. He finishes his novel in four days to the shock of his publisher. He learns the piano in three days and can pick up languages with only a passing knowledge of the words. His ability for conversation and deduction make him very popular with people and he makes new friends (even gets laid a few times). During this time, Eddie notes that the first side effect of NZT is that he has to keep moving forward or he feels restless physically and mentally.
With the last of Vernon's money, Eddie moves into working the stock market, doubling his money four days in a row. But he does not like how slow his returns are so he goes into the underworld for a loan. He meets up with Gennady (Andrew Howard) a Russian mobster for a 100K loan. Gennady doesn't want to do business but Eddie convinces him. Gennady warns what will happen if Eddie screws him.
Eddie abandons his writing to take up finance full time. He begins to make several big gambles on the trading floor that pay off to the point he makes 2 million in ten days. Kevin Doyle (Darren Goldstein) notices this and is very impressed, offering Eddie a job. By this point Eddie has doubled his dosage of NZT, to make the effects work better.
Eddie is happy with his new life but feels paranoid, thinking people are following him; one in particular, a Man in a Tan Coat (Tomas Arana). Nevertheless, he pushes forward, using his new success to reconnect with Lindy and restart their relationship.
Eddie's success with the market allows him to get a meeting with reclusive and powerful businessman Carl Van Loon (Robert De Niro). Doyle warns Eddie he has to be on point or they will lose their shot. Eddie stays on point and shocks Carl by deducing he is about to do a major merger with another businessman Hank Atwood. Carl asks Eddie to do some work for a meeting in two days to figure out how to do the merger best. Eddie gets out of Carl's car and starts walking.
It is here that Eddie sees more of the side effects of the drug. He walks dozens of blocks without realizing it....only to find himself in a bar at night. He then wakes up in a party, working the crowd. He then finds himself in a high-end hotel with a hot blonde woman who he has sex with (with the man in a tan coat not far behind). When the final jump occurs he is on a bridge walkway not knowing how he got there. He has lost 18 hours of time.
Eddie sleeps it off and wakes up hours before his meeting. He tries to look at the merger documents, but without NZT to guide him, it is gibberish to him. He tries to call Doyle and back out of the meeting but Doyle tells he has to go. Eddie goes but cannot give more info about Atwood other than he came out of nowhere like him. Carl is talking about the merger but Eddie is looking at the television to see the woman he was with was murdered. Putting the pieces together, he excuses himself and vomits in the street. He goes home, fearful that he killed a person.
Eddie gets a call from Melissa and he picks up because she mentions NZT. He asks her to meet him at a diner then hears a weird clicking noise on the phone. Eddie starts to think his phone is tapped. He goes to the park and begins to call everyone in Vernon's book. 3 are dead, and many are hospitalized, all from the drug. Eddie calls another number only for the phone to ring right next to him. It is the Man in a Tan Coat, the man who is stalking him. Eddie runs off and the man gives chase. Eddie causes a car accident to stall him and gets into a cab to escape.
Melissa meets Eddie at a dinner. She looks horrible looking, as if she aged twenty years instead of ten. She tells Eddie she didn't want him to see her like this. Eddie asks her what she knows about the drug, and Melissa tells him she took it. That is why she was so successful at first in business and everything. But even she realized that using a drug like that would cause her to burn out so she stopped which made her mental functions worse. She didn't die like other people did but she lost some of her mental abilities due to NZT. She tells Eddie to moderate his dose and slowly taper off while he still can.
Eddie goes back to his apartment to find Gennady there. Eddie hasn't paid him yet and Gennady is there to collect. He begins to beat Eddie up and when Eddie reaches for his NZT, Gennady takes it instead. Eddie goes to the bank and gets Gennady his money. Gennady says the drug is good. It is clear he wants more.
Since Eddie hadn't had a dose that day, he is crashing out and can't make it home, so goes to Lindy. With no choice he tells her everything. She is shocked but he says he can make it better. He needs the pills though. They are at her apartment. She gets them only to realize someone is following her in her taxi. It is The Man in a Tan Coat. She jumps out and the man gives chase. She sees two strong men and pleas for help. The men try to spook the man but he kills them both with a large blade. Lindy is on the phone with Eddie and tells her to take a pill so she can escape. She does and races to an ice rink where the man is chasing her. She grabs a child and whirls her to cut the man with the skate then disappears.
Lindy gives Eddie a pill and he recovers. Since they cannot go home, they check into a hotel. The next morning Lindy makes it clear she can not have any part of what he is doing, but Eddie says he has a plan to get a nest egg then cut the drug cold turkey. Lindy wishes him the best and leaves.
Eddie begins to moderate his use, and with precautions experiences no more blackouts. He starts to build the merger for Carl and will profit about 40 million by its completion. In the meantime, realizing he will run out soon, finds a chemist to make him more of the drug in exchange for 2 million dollars.
Realizing how vulnerable he is, Eddie buys a new apartment a secure penthouse (the one from the beginning of the film). He gets two large security guards to watch him at all times. In the middle of a meeting, the detective who interviewed him about Vernon confronts him, telling him he is a suspect in the murder of the woman from the hotel. Eddie gets the best lawyer in New York, Morris Brandt (Ned Eisenberg), to defend him.
Gennady is asking for more of NZT and Eddie gives him a few tablets to buy time. Eventually, Gennady asks for more and more until Eddie tells him to screw himself.
On the day Carl and Hank Atwood are to sign the papers, Atwood doesn't show up. His wife does, and explains that Hank is in the hospital and not well. They plan to do the merger but cannot at this time. Mrs. Atwood leaves with her driver, who is revealed to be The Man in the Tan Coat. Eddie now knows who is after the drug so badly and why Atwood was such a rising star in the financial world like him.
Eddie and Brandt go to a police line up and Eddie is cleared of the murder because the witness couldn't identify him. He goes to the bathroom later and sees his stash of NZT which he keeps on him at all times is gone. He wonders who stole it.
He sees Carl and sees the merger was leaked to the press. Mrs. Atwood denies any merger taking place. Her lawyer is Brandt which makes him realize who stole the drugs. Eddie gets a package with the severed hands of his bodyguards. He has a good idea who killed them (Gennady).
Eddie goes home to his penthouse only for Gennady try to get in. We are now back at the beginning. Eddie decides he doesn't want to die, he wants to live. So he needs one pill in order to find out how to escape. He thinks there might be one in the tin he originally kept them. He rips through boxes as Gennady breaks the steel door down. Eddie gets the pill just as Gennady busts through, causing Eddie to drop the pill down a crack in the floor.
Gennady explains he melts the pills down into liquid form so he can inject them directly into the bloodstream. He takes his last dose and tells Eddie his men are going to find the drugs or they will kill Eddie. Eddie grabs a knife when Gennady has his back turned. Gennady says he plans to cut out Eddie's intestines and see how long they are. When he gets close, Eddie stabs him dead while Gennady's men are cracking a safe they think holds the drugs. Not having a dose to take, Eddie drinks Gennady's blood which has the drug in order to think quickly.
One of Gennady's men discovers the body of his boss while Eddie pretends to be dead. Eddie uses the syringe needle to blind him (the goon already had one bad eye). The other thug comes in and begins shooting but Eddie evades them both, eventually tricking the blind goon to shoot his buddy. Eddie then kills the blind goon by shoving him through a glass window.
Atwood dies at the hospital. Eddie goes to see The Man in the Tan Coat (who most likely who killed the woman in the hotel, not Eddie) telling him that Brandt is responsible for Atwood's death, since he had the drugs that could have saved him but he kept them for himself. With Atwood dead, the man has no reason to kill Eddie. So they come to an understanding. They hold Brandt hostage (it's implied the man kills him afterwards) while Eddie recovers the drugs.
12 MONTHS LATER
We now cut to a campaign office. Eddie Morra is now a prospective Senator. His book is about to be published as well. It is clear that he has plenty of support and a shoo in to win the race and one day possibly the presidency. One of his aides says he has a representative from Ivan Kemp, a pharmaceutical company waiting to speaking to him. Eddie resists but since they are his biggest contributors, he relents. It turns out Carl Van Loon is there to see him. He now owns the company.
Carl tells Eddie that he knows what is going on since Ivan Kemp made NZT. Carl has shut down all other labs including Eddie's so he has no hope of getting more. So Carl proposes a deal; his company will give him an unlimited supply. In return Eddie will push forward certain agendas Carl wants (more or less making Eddie a puppet). Carl says they should go to lunch.
When they get to the car, Eddie tells him to leave. Carl makes it clear that Eddie cannot win but Eddie smiles. Eddie asks Carl if he thinks Eddie wasn't smart enough to reverse engineer the drug by now and take out the kinks, making himself a permanent dose, so to speak in order to leave his productivity optimal without taking the drug anymore. Eddie says he is clean of NZT, but has all the abilities of it. To prove it, he shows that a van is about to crash into a taxi, which it does.
Eddie says he doesn't need the drug. He is clear minded now and Carl is no use to him. Carl won't own Eddie. Eddie would own HIM. Carl leaves, saying they should talk later, but Eddie shoots him down. He's won.
Eddie goes to his scheduled lunch. It was with Lindy who he has reconciled with. When the waiter comes, Eddie speaks to him in his own language (like he did at another dinner with Lindy before) which makes Lindy look at him funny. Eddie just shrugs and says "What?"
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