It was before Sam became Lucifer's prom dress. The Croatoan virus was a few months in, the world was fading off, and the Winchesters had managed to shack up a nice encampment with what remained of the hunters and some rescued fallen angels. Tensions were high, what with the Mark of Cain making Dean more and more angry by the day, and Sam constantly suggesting he surrender himself to try and set things right.
Cas had fallen long ago, but his grace had officially burnt out, and he was past hollow. He felt useless now. They had to teach him how to use a gun properly, and he had to run everywhere, and heal slowly like the rest of them. It didn't really take effect until he broke his arm on a retrieval mission- they went for food, trying to scavenge what they could. A Croat cornered him and when he tried to topple an aisle down on it, he got crushed with it. It was a non-displaced fracture, so it healed with time, but the pain was excruciating. Dean rounded up all the medicine he could find from behind the counters before helping the angel back.
In little time, Cas was addicted to the pills. His arm healed eventually, and when he joined them on their missions again, he started taking more and more pills from where they went. He was an addict, and Dean punched him hard enough to bruise when he found out. They couldn't afford that. They would run out of pills eventually, and Cas wouldn't be able to think straight hopped up all the time. They fought, and it became an every day occurrence for them. Cas would get high, they would wrestle, and they would just continually spiral down into tension and anger and frustrations.
Maybe half a year into the camp, Castiel would wake up to notes on his dresser. They were never signed, but they were all awful, and he always assumed they were from Dean. They called him useless and worthless, and made him feel like absolute garbage. The fourth note he got led to his first overdose.
Dean found him later, passed out on the floor of his cabin, and he gave him CPR until his eyes blurred with the first real emotions he had felt in a long time. He kept it up, maybe out of desperation, until he finally got a steady breath out of him. He held the fallen angel for a long time, keeping watch over him for a change. When he woke up, Dean yelled at him for it, and left him again. Cas thought it was a sick joke.
Cas took up any drugs he could get his hands on, but it wasn't until he started smoking pot that Dean found out about the notes. The angel was high off his ass, smiling genuinely, and he hadn't torn up the note like he had done the others. When Dean came in to check on him, he read it, and waited until Cas had come down enough to talk about it. Dean revealed he hadn't written them.
Cas found out in the winter. The message his brother had drawn in the ice on his window stayed. Lucifer. He told Dean, and they kept it a secret from Sam, so he wouldn't blame himself. Dean camped out in Cas' cabin for a few months, to keep watch. The last they heard from Lucifer was a note on the door-
"Goodbye, brother. My love to Sam."
It was signed with the pitchfork. Shortly after finding out, Sam went to Chicago. It was the last they heard from him.
Castiel, Lucifer (C) Supernatural