Dean beats Sam at Rock-Paper-Scissors for the first and only time (as of 03/2017). While he technically won in episode 6.17 "My Heart Will Go On," they were in an alternate reality, making this the only occurrence in this universe.
There is a mention of Jessica Simpson. In the late 90s, Jensen Ackles and Jessica Simpson dated.
When Dean says, "Drop a house on her", as a way to slow down a witch, he is referring to the classic scene from The Wonderful Wizard of Oz where the wicked witch of the East was killed by Dorothy's house falling on her.
This episode bears similarities between the 1981 horror film My Bloody Valentine in which the victims' hearts are ripped out on Valentine's Day. Jensen Ackles starred in the 2009 remake.
At the beginning of the episode as Staci is flipping through the TV channels three Adult Swim shows are shown in this order: Your Pretty Face is Going to Hell, Neon Joe: Werewolf Hunter, and Rick and Morty.