Day 1 of Winchester separation saw both brothers making bad decisions. Dean decided to take the mark of Cain, which could have unforeseen consequences down the road. Sam was so pushed by guilt that he pushed Cas to continue extracting grace from him when it nearly killed him. We know from the trailer that next week they'll be back together. I really think they need more time apart to learn to make decision that account for their own well being without being pushed into it by the other.
I'm predicting this mark is going to have some sort of effect on Dean. My guess is that it's going to make him more of a cold-hearted killer than before. The brothers have always been violent, but this will probably magnify that effect. In fact, it may even make him more violent towards people he wouldn't otherwise be violent towards, like Sam and Cas.
This story certainly has some implications for the mythology of the show. Sam and Dean are supposed to be direct descendants of Cain and Able. Cain said that Able was being tempted by Lucifer and that he made a deal with Lucifer to kill Able and send him to heaven. Cain would then serve Lucifer in Able's place. This has a certain parallel to how Sam was tempted to become Lucifer's vessel. The only question is whether the story will conclude in the same way, with Dean killing Sam in order to save him.
We learned in this episode that a bit of grace is left behind whenever an angel leaves its vessel. It'd be interesting to see if that grace had any potential side effects. Perhaps it makes it easier for the vessel to be found again. It might also establish some sort of bond between angel and vessel. Castiel said there wasn't enough grace left for them to use a spell to summon Gadriel. I wonder it there's just the teeniest bit of Lucifer's grace left in Sam. It wouldn't be very much, just enough to skew the effects of the spell.
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