Meemaw is seen smoking in most episodes
A recurring character, old woman smokes cigarettes non-stop, but she's always coughing and hacking and gross, so it actually shows smoking is bad for you.
George and Connie are seen drinking alcohol in most episodes.
Meemaw says that she used to buy marijuana in one episode.
Season 1, Episode 2: Two teenagers brief smoke a cigarettes in the restroom, but put away when Sheldon replies "I do applaud your rule-breaking bravado."
Sheldon making jokes about him drinking too much because he's depressed over his career. This is done for comic relief.
There is drinking at home and at bars and restaurants all the time. The father in the series has a beer in his hand while watching TV or eating dinner all the time. The grandmother drinks both out and at home. People drink to forget stressful situations, too, but no one becomes a violent drunk. They do pass out and have hanghovers, though. Smoking is shown much less often, but the mother sneaks a cigarette at times when she is stressed out.
In season 2, Veronica mentions that her sister went to jail because she filled a piniata full of weed. Nothing shown.
In season 1, George Jr is Chewing tobacco but tells Sheldon that it's chocolate. It shows him grabbing massive handfuls of tobacco out of a packet and shoving it in his mouth.
Meemaw was also shown drinking rosé wine in some episodes.
Although George drinks alcohol in most episodes, he's never seen intoxicated.
A lot of drinking, especially by George. Many mentions and scenes of smoking. Drugs only mentioned once or twice.