Frank Zappa was a well-known teetotaler for such a supposedly “far out” rock star. Although he chain-smoked cigarettes like they were food and pounded coffee, the head Mother frowned on drug use and actively discouraged it in his sidemen to the point of allegedly even firing future Little Feat leader Lowell George (who was on Weasels Ripped My Flesh) just for smoking pot—that per Pamela Des Barres—or it might have been for composing a pro-pot song that he wanted the Mothers to play. As George himself revealed to a Rochester, New York audience onstage in 1975 right before playing “Willin’”:

“I was in a group called the Mothers of Invention, but I got fired for writing a song about dope. How ‘bout that shit?”

Perhaps he should have taken his mentor’s advice. Later Zappa was alleged also to have fired Ike Willis for enjoying the high life.

Zappa was so anti-drug that he did something few other rock stars (especially ones with as weird a reputation as he had) would have done (at least convincingly) at the time: He recorded several improvised anti speed PSA radio spots for the Do It Now Foundation. In one of them he claims that using speed will turn you “into your mother and father.” He also tells the listener not to “use smack or downers.”

In the first one, Zappa addresses someone who will be familiar to all Mothers fans and wonders what’s gotten into her…
 

 
Later Zappa would record several PSAs admonishing kids to floss their teeth and one urging people to register to vote.
 
Zappa addresses drug use on Canadian television in 1971:

 
Bonus: The Mothers of Invention (with Lowell George, not Frank Zappa, playing lead guitar) lay down some “Underground Freak-out Music” in 1969: