The effect of that first encounter proved to be hugely influential, a “road-to-Damascus experience” as he told the Paris Review:

"It knocked you off your horse, taking LSD. I remember going to work that Monday, after taking LSD on Saturday, and it just seemed like a cardboard reality. It didn’t seem real to me anymore. Seemed completely fake, only a paper-moon kind of world. My coworkers, they were like, Crumb, what’s the matter with you, what happened to you? Because I was just staring at everything like I had never seen it before. And then it changed the whole direction of my artwork. […] I got flung back into this cruder forties style, that suddenly became very powerful to me. It was a kind of grotesque interpretation of this forties thing, Popeye kind of stuff. I started drawing like that again. It was bizarre to people who had known my work before. Even [Mad Magazine Editor Harvey] Kurtzman said, What the hell are you doing? You’re regressing!" - R. Crumb

Article: R. Crumb Describes How He Dropped LSD in the 60s & Instantly Discovered His Artistic Style