Dean's relationship with food is a key tell to his brother. When Dean first turns down dinner and then doesn't choose anything from the motel vending machine, Sam knows that something is deeply wrong with his brother. Later in the episode, Sam buys his brother a burger as a way to begin mending things between them.
First appearance of Benny. The actor who played Benny, Ty Olson, also played "vegetarian vampires" Eli in season 2 episode 3, Bloodlust (2006).
Sam mentions that porn star Sasha Grey made a Soderbergh movie. That movie is The Girlfriend Experience (2009).
This is "Supernatural"'s 150th episode.
When Sam tells Dean about meeting Amelia, Dean says, "So what, you dropped your peanut butter in her chocolate?" He is referring to the 1970's slogan for Reese's Peanut Butter Cups.