Bobby and Dean have locked Sam up in Bobby's demon-proof panic room. Sam begs Dean to release him, but Dean tells him he has to dry out from his addiction to demon blood and that Sam has been lying to him about it. Sam insists that he needs the blood and the power it gives to defeat Lilith, but Dean tells him that he and Bobby will kill Lilith and Sam will stay there.
Sam starts to hallucination from going cold turkey and the demon Alastair appears to him. Alastair tortures him without mercy while Bobby and Dean are forced to listen to Sam's screams. Bobby receives a call from fellow hunter Rufus about something important.
Next, a younger version of Sam appears to him. Young Sam wonders how Sam could addict them to blood, and blames Sam for letting Jessica die. He insists that Jessica wouldn’t have wanted Sam to drink demon blood, then warns his adult self that there's a demon inside him... as Young Sam's eyes turn yellow.
Rufus tells Bobby that a number of Seals have been broken recently. Dean admits he has no idea where the angels are and Bobby suggests that they free Sam so he can help them. When Dean refuses, Bobby wonders if they're protecting him too much.
In the panic room, Mary Winchester appears and tells him that he's doing the right thing. She insists that Sam should use his gift against the demons who gave it to him, and that Dean will never understand. Mary tells him to let nothing get in is way and disappears.
Out in Bobby's junkyard, Dean yells for Castiel until the angel comes. Castiel refuses to discuss anything other than Sam, and warns that while Sam could kill Lilith, he'd become a monster from drinking enough demon blood to do so. Castiel warns that to stop Sam, Dean will have to accept his role as God's chosen warrior and defeat Lilith himself. Dean reluctantly agrees. After he swears obedience, Castiel tells him to wait for the angels' call.
In the panic room, Sam hallucinates black veins appearing all over his body. Bobby and Dean are discussing Dean's new status and have to agree Dean had no choice. They're interrupted when they hear Sam screaming: the demon blood is literally throwing him around the room in convulsions. They manage to restrain him and cuff him to the bed.
When Sam recovers, he hallucinates Dean asking him why he started drinking demon blood. Dean says there was no point in Sam doing it for revenge, and that God picked Dean, not Sam, to kill Lilith. Upstairs, Bobby worries that forcing Sam to go cold turkey isn't doing any good and they'll kill him. Dean insists they continue, figuring that Sam should die human if need be. He refuses to let Sam become a monster.
"Dean" accuses Sam of being a monster, and having always been a monster. He insists that Sam is nothing to him and then disappears. The handcuffs open on their own and then the door swings open. Sam cautiously leaves... while Castiel lurks in the shadows. Once Sam is gone, Castiel gestures and closes the door behind him.
As Sam slips through out of the house, Castiel goes to a pier and waits for Anna. She wonders what he means to do by releasing Sam, and Castiel insists that he's following orders. Anna warns that Sam will die but Castiel tells her she shouldn't have come. Two angels appear and take Anna away in a burst of light.
Bobby intercepts Sam in the junkyard and points a shotgun at him. However, Sam realizes that Bobby wont' shoot him, gets close enough to yank the shotgun away, and then knocks Bobby out and steals a car.
Later, Bobby wakes up and he and Dean examine the panic room. The demon traps are broken and they figure Ruby somehow managed to engineer Sam's escape. Dean goes to find Sam.
Sam rents a honeymoon suite and calls Ruby so she can meet him. She says that she's been tracking down Lilith, and Sam explains he rented the honeymoon suite because it's not the typical hotel room he gets. He then throws Ruby on the bed, uses her own knife to cut open a vein on her arm, and starts drinking her blood.
Bobby calls Dean and informs him the stolen car has turned up, abandoned. They check the police report and find two other missing cars. Dean goes with the flashy car that Sam wouldn't normally take.
After Sam is done feeding, Ruby comments that he's becoming hungrier, and the extra blood will let him defeat Lilith. However, she warns there are only two or three seals left and the angels aren't trying to stop Lilith anymore. However, the last Seal can only be opened by the first human that Lucifer corrupted and transformed into a demon: Lilith. If they kill Lilith, then Lucifer can't escape. She tells Sam that she's managed to track down Lilith's personal "chef.
Two nurses are checking on babies in a maternity ward. As they look at the babies, one of them reverts her eyes to solid-black.
Ruby knows how to find Lilith's demon but admits they need to find more blood for Sam than ruby can give. Sam is concerned about his relationship with Dean and hopes he can fix things once Lilith is dead.
Bobby checks the police reports and gets a sighting on the second car Sam stole, and that it's in Cold Springs. The weather report shows there are numerous aberrations indicating demons. He calls Dean with the news, and warns him that their goal is to save Sam, not get angry with him.
Dean tracks down Sam and watches as his brother leaves. He then goes into the honeymoon suite and attacks ruby with the demon-killing knife. He prepares to kill her but Sam returns and stops him. Sam tells Ruby to leave and refuses to kill her despite Dean's insistence. He asks Dean to come with them to kill Lilith, but Dean refuses to take Ruby along.
Sam begs Dean to trust him, warning that Dean isn't strong enough to do it on his own. Dean just looks on him, and then says he's finally become a monster. Sam attacks him and the two struggle. Sam finally beats his brother and then starts to strangle him. He manages to stop just in time, and then tells Dean that he never really knew him. As Sam goes to the door, Dean warns him that if he leaves, then they're through. Sam just looks at him for a moment and then turns his back and leaves.
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