Well, it depends on the target audience. If your target audience is 'the people who replied to this thread' then it looks like stoner jokes are a no-go. If your audience is larger than this or a different environment than this website - that could be different.
Comedy is a difficult thing to write - because everyone has a different brand of humour and not everyone is going to 'get it.' It's REALLY important when writing comedy stuff to know the audience that you want to speak to.
Let's say, hypothetically, you wanted to write a game filled with in-jokes from this forum - everyone loves it! Reception is so good you decide to take it commercial on Steam. No one on Steam gets any of the jokes and the game does poorly. Now let's say you make a game filled with 'stoner comedy' and release it to the people in this thread. None of us get (or appreciate) the jokes, and we don't have much to say for the game. You could turn around and present that game to a different group of people who have more interaction with 'stoner comedy' and they could tell you it's the funniest thing they've seen all their lives.
Personally, when making a game that is hinged on comedy, I recommend playing the comedy at a few different angles. No one person has to get
every joke in a game. Let's say you have a game that relies on both 'stoner comedy' and, idk, jokes about elephants. Now you've opened the gates to people who are going to say, "The stuff about the elephants was really funny, dude!" and "All them elephants were strange, but the stoner guy was hilarious!" and "STONER ELEPHANTS!? That's my jam!" Obviously, group three was your intended audience - but you were able to scoop up two other audiences at the same time.
The majority of people in this thread didn't come across as saying, "Yo, don't do that." The general consensuses seemed to be "It wouldn't upset me, but it's not my brand of comedy." So if you want to tell a story about a stoner alien, don't stop just because we here said we might not get it. Somewhere, you have an audience that is going to match your brand of humour. (I mean, unless you suck at telling jokes, but then that's not the stoner alien's fault.

)
EITHER WAY - if you are going to include drug abuse or allusions to it (be it for serious world building or comedy), put a warning somewhere in your game thread or at the start of the game. As for some people, drugs have had negative impacts on their lives.