To the amazement of all, including Bart himself, the drug appears to work, and he becomes focused, productive, and well-behaved, and begins tutoring a Navajo boy in his spare time; however, Lisa notes that he also seems to have lost his sense of fun. Homer and Marge decide to celebrate Bart's turnaround by going to see Showgirls, but when they return, Lisa tells them Bart's behaviour has taken a turn for the bizarre. They find him in his bedroom in the grip of intense paranoia, having hung coat hangers from his ceiling, wrapped himself in tin foil, and tied a metal trash can lid to his head; he tells them that Major League Baseball are spying on everyone in Springfield and collecting their personal information.
Homer and Marge take Bart back to the lab for observation, and are told that a change in his medication might alleviate his paranoia. An alarmed Bart refuses, downs a large dose of Focusyn, and flees the drug lab. He proceeds to sneak onto the Fort Fragg military base and steal a tank, which he drives to the playground of Springfield Elementary before his family catch up with him. But before he agrees to Marge's plea to get out of the tank, he fires a single round into the sky... and a satellite with the MLB logo falls to Earth, confirming Bart's accusations. Before the townsfolk can process this revelation, then-single-season home run record holder Mark McGwire shows up and distracts them with a home run demonstration while he hides the printout of their personal details. Their adventures over, Homer and Marge decide to take Bart off Focusyn and put him on Ritalin instead.
- Arson, Murder, and Jaywalking: Homer reads the side effects of Focusyn: Erratic behavior, paranoia, diarrhea. Marge says she doesn't think Bart has diarrhea, and Homer responds "but how do we know, HOW DO WE KNOW!!!"
- Accidental Hero: Bart's unrelated prank of flooding the gymnasium accidentally saved Flanders' life by dousing the flames when Flanders set himself on fire. This doesn't stop him from being punished for it, and isn't even acknowledged.
- As Himself: Mark McGwire, who arrives to provide a distraction with his home run showcasing while the MLB satellite's data is taken away... hidden (poorly, not that the townsfolk notice) under his cap.
- Bait-and-Switch: Bart tells Lisa, "Did you know most people use ten percent of their brains?" Instead of saying something like, "Thanks to these pills, I'm using more than that.", but instead he says, "I am now one of them."
- Borrowed Catchphrase: When Bart aims his tank at Springfield Elementary, Mrs. Krabapple, in an uninterested tone, utters Helen Lovejoy's "Think of the children."
- Bread, Eggs, Milk, Squick: While introducing the fire safety play, Principal Skinner says "Fire can be our servant, whether it's toasting s'mores, or raining down on Charlie.".
- Call-Back: Homer mentions that he was banned from a water park for ten years (which, at the time of this episode's premiere, would be incorrect), which could be a reference to when he got stuck on the H2-WHOA! ride at Mt. Splashmore on the episode "Brush With Greatness." If it's not, then it's a Noodle Incident.
- Clown Car: Bart runs over one, driven by Krusty and full of other clowns. One of them with a humongous butt gets stuck and the destruction pops his buttocks, and the clown's response is "I'm sure I'm alive, but why?"
- The Cuckoolander Was Right: Major League Baseball was indeed spying on people, but rather than explain why, Mark McGwire dazzles the crowd with some dingers.
- Deranged Animation: The poses when Homer tries Focusyn.◊
- Expy Coexistence: Combined with an (off-screen) Dark Parody: when Marge calls the police to try to find Bart, her description is drawn by Lou and is Dennis the Menace. Wiggum then says that it's the kid who "roughed up the Wilson widow".
- Focusyn seems to be a stand-in for Ritalin, until the end of the episode, when Marge says she's getting Bart off of Focusyn... and back on Ritalin.
- Everyone Has Standards: Skinner is horrified when Willy suggests killing Bart by dragging a hoe through his back and making it look like suicide.
- Firehouse Dalmatian: Milhouse meets the Springfield Volunteer Fire Department's Dalmatian at a fire safety event at the school. He asks Moe if the dog can do any tricks, but Moe says the dog's so inbred that he can barely stand up, and surely enough the dog collapses on the ground.
- Heh Heh, You Said "X": During the fire safety assembly, Bart gets a kick out of Principal Skinner saying the names of various firefighting implements.Bart: What's that stuff?
Skinner: This is retardant.
Bart: (snickers) It sure is! What's this thing?
Skinner: This is a hose-lengthener.
Bart: (snickers harder) You need one! What about this?
Skinner: Why don't you read the label? It's a king-size flamer!
Bart: (laughs hysterically)
- Iris Out: The episode ends with Bart singing a Popeye parody, then we iris out as two puffs of smoke come out of Bart's ears.
- Milkman Conspiracy: Bart seemingly goes crazy by the third act and starts to think that the MLB is spying on the city... which they are. With a Spy Satellite and memorabilia with a Spy Cam implanted in it somewhere. Though Mark McGwire dodges the question of why, the satellite recording mentions it's really aggressive market research.
- Of Course I Smoke: The straight-edged Ned tries to smoke a cigarette while performing in the fire safety play, though his coughing is actually the least of his problems as he inadvertently sets his pants ablaze.
- OOC Is Serious Business: Ms. Krabappel tries to have the class read a poem before Nelson interrupts about two dogs fighting outside. When she tells them to return to their seats, she's stunned to see that Bart was in his seat the whole time.
- Percussive Therapy: After Bart's stunt at the fire prevention fair, Skinner calls for a meeting with Homer and Marge, where we see him punching a pop-up clown before addressing them.
- Pop-Culture Pun Episode Title: The title references The Rolling Stones song "Mother's Little Helper", which is also about drug addiction.
- Hosey the Bear, which can be seen in the beginning of the episode, is a reference to the United States Forest Service's mascot Smokey Bear.
- After Bart has flooded the school gym, Skinner can be seen wiping mud off his eyes in an homage to Oliver Hardy.
- Homer and Marge go to see Showgirls.
- When Marge reports Bart's disappearance to the police (tow-headed, snub nose, often seen with a slingshot), Lou the police officer makes a drawing of Dennis the Menace.Chief Wiggum: Looks like the kid who roughed up the Wilson widow.
- As Bart rolls through the streets of Springfield in a tank, he sings the refrain of "Don't Stop" by Fleetwood Mac.
- "When I can't stop my fiddlin', I just takes me Ritalin, I'm poppin' and sailin', man!"
- Take That!: When Homer and Marge try to get Bart on board with the idea of taking (prescription) drugs, they name several of his "favourite stars" who take drugs, all of whom had made headlines for their substance abuse in the years leading up to this episode's air date.Bart: I don't wanna take drugs!
Homer: Sure you do! All your favourite stars have used drugs. Brett Butler, Tim Allen...
Marge: Tommy Lee...
Homer: Andy Dick...
Bart: He's just flamboyant!
Homer: Yeah, and I'm a size 4.
- Tank Goodness: The climax of the episode is Bart stealing a tank from the local army base and going on a rampage. At first it looks like he's going to blow the town up, but then he manages to shoot the MLB's Spy Satellite with the tank's main gun.
- When All You Have Is a Hammer...: The only thing the doctors that diagnosed Bart can think of after the Focusyn seemingly drives him nuts is to give him more drugs (which is standard procedure for weaning someone off, but Marge still calls them out on this for good reason. In response, and to calm her down, they inject her with Valium (Homer was supposed to get injected too, but the automated syringe was full of air).