The Spider-Man storyline "Flowers For Rhino" (guess what it was named after): dimwitted Spidey villain Rhino goes through a brain procedure to make him super-intelligent so he isn't treated like shit. While the procedure works, he finds that his intelligence just keeps growing (at one point he rewrites Hamlet due to finding the writing style "sloppy", and later manages to discover Spidey's secret identity through a mathematical equation), until he grows too smart to properly form relationships with people, loses interest due to Measuring the Marigolds (at one point, his love interest calls him a monster, and to his horror, all he can think of is the definition and etymology of the word), and growing boredom and nihilism, as there's nothing he can no longer figure out. The "Algernon" of the story, an ape that went through the same procedure eventually committed suicide out of boredom. Before he meets the same fate, Rhino orders the surgeons to not only reverse the procedure but make him stupider than he was before "just to be on the safe side". The doctors comply, he goes back to his old life and he couldn't be happier.
Bonus: Because of his invulnerability, they had to perform the surgery with an industrial strength oil drill.
Double Bonus: He refused anesthesia for the operation.
The newspaper comic Tank McNamara did a riff on this trope. Tank gets zapped by one of Dr. Tzapp's experimental machines, and it cures his fumblemouth. Before long, Tank starts fancying himself an incisive critic, and the show's ratings plummet because nobody wants to listen to that. Eventually one of the other characters re-zaps him and he turns into his lovable, fumblemouthed self again.
Another newspaper comic, Heart of the City, has done this a couple of times, usually with Dean. One arc had him becoming a popular jerk, and a more recent one has him becoming "mature." In most cases, Heart tries to snap him out of it.
A storyline in The Muppet Show Comic Book featured Animal taking pills to become calmer. Unfortunately, his drumming ability suffered (because All Drummers Are Animals), and the Electric Mayhem had to replace him until he stopped taking the tablets. This may be based on the Real Life story of jazz drummer "Witty Ticcy Ray" (see below).
Very common story concept in The Beano, especially in the strip The Bash St. Kids. The anniversary comic for that strip basically had this trope happen to the entire class.
An early storyline in Archie Comics' Sonic the Hedgehog featured Tails eating a fruit that made him into a supergenius. It also made him a stuck up jerk, and he tried to take on Robotnik by himself with his super intelligence. Unfortunately, by the time he reached Robotnik, the fruit's effects wore off and Tails was back to his normal intelligence...meaning the others had to come save him.
The mutant Prodigy of the X-Men can copy the knowledge or skills of anyone nearby but a mental block keeps him from remembering any of the knowledge after they leave. When he asks Emma Frost to remove the mental block, his exponential intellect makes him an uber-successful world leader who solves a lot of the world's problems through immoral means like carving up his best friend to cure major diseases. He believes himself a benevolent dictator and decides to nuke any country that doesn't go along with him, and his former comrades have to engage in a suicide strike on the White House to stop him. David then wakes up from Emma's telepathic hallucination and realizes he needs to keep a lid until he can handle the knowledge on his own.
Sabertooth once took one of Wolverine's claws to the brain, which resulted in him becoming peaceful and relaxed. It took a while, but eventually his Healing Factor repaired the damage, and he became an even worse psychopath with an increased psychic resistance: Prior to said claw-to-the-temple, Sabertooth could be (at least temporarily) pacified with certain psychic abilities, especially those of Psylocke, which put him in a state he called "the glow". Very Zen Buddhist. Shortly after he healed from Wolverine's attack, he was playing merry hell with the insides of the X-Mansion (having been a prisoner at the time) and Psylocke used her attack as a last resort... To no effect. Sabertooth explained how that psychic trick didn't work any more with a Slasher Smile that was spine-chilling even for HIM.
Hank McCoy, a.k.a. the Beast, has suffered from this syndrome at least twice in various continuities. His original mutant power was superhuman strength and dexterity and unusually large hands and feet, and it was established early on that he also happened to have genius-level intellect, leading to a career in biochemistry - a Genius Bruiser. He has occasionally suffered from traumas, or performed medical experiments on himself, that made him lose intelligence, turning him into Dumb Muscle. He often has time to see this coming and regret the loss (until something comes along and makes him better). In one continuity, being Dumb Muscle was the status quo for him and he was temporarily enhanced, playing this trope completely straight.
One issue of a Polish comic book series "Tytus, Romek i A'Tomek" dealt with the misguided education of Tytus (who happens to be a talking, civilized chimp). In order to make him less Book Dumb and more adjusted, professor T. Alent first mindwipes him back to kindergarten, then proceeds to educate Tytus using his crazy inventions, to the point of force-feeding the ape's brain with information. Over the next weeks Tytus gains professor-grade education, receives several academic awards and finally starts burning out. In the end, he breaks into T. Alent's lab, resets his brain again, this time to college level (in his own words, "just a bit above Romek") and resumes his former life.
One Justice League of America arc has a hyper-dimensional force separate the league and their secret identities into different beings, allowing the heroes to be full-time heroes and the civilian-modes to have normal lives. Two of them were not happy about this. Plastic Man's normal self Eel O'Brian, who doesn't like the idea that he can't be Plastic Man again. When talking about this to Martian Manhunter's civilian identity John Jones, he even mentions Flowers for Algernon. Bruce Wayne and Batman didn't fare too well either. The anger that made Bruce into Batman stayed with Bruce. Batman lost all motivation to be a crime fighter and Bruce lost control because he no longer had an outlet for his anger.
This trope is the major plot point of a 1990 movie starring Robin Williams, Awakenings, which has some basis on real life and describes the treatment of catatonic patients with a then-new drug called L-Dopa.
Disney's The Computer Wore Tennis Shoes (1969). A computer student has the knowledge and abilities of a computer downloaded into his brain, leading to multiple problems and opportunities. By the end of the movie he's lost everything he gained and is normal again.
Rookie of the Year. A kid gains a Major League caliber pitching arm from an accident. Another accident sees him lose that ability in his last game and have to bluff his way through the final inning.
The Lawnmower Man. A modern adaptation of the Flowers for Algernon story: a retarded gardener, Jobe Smith, is raised to super-human intelligence with the use of medication and virtual reality with unintended consequences. Incidentally, it has SFA to do with the Stephen King story of the same title. It's hinted that Jobe would have inevitably gone crazy from the medication he was given initially, as it was a milder version of the one that Dr. Angelo had made for the government. When they switched the drugs, it simply sped up the process.
Limitless features a drug that enhances your intelligence, but only temporarily. Long term usage causes addiction, and mixing with alcohol and/or taking too much makes you lose complete control of yourself. If you stop after becoming addicted, your body becames incredibly frail, most people die from it. The protagonist's ex ended up looking like a meth addict. At the end, the protagonist figures out a way to wean himself off the drug while keeping the effects. Or maybe he was lying about the weaning himself off it part, it's left ambiguous.
In Ernest Goes to School, our hero's usual mutton-headedness was cured with the help of a Subatomic Brain-Accelerator invented by a couple of rather overqualified high school teachers. True to form, Smart Ernest was a complete jerk, and his friends were happy when the effect wore off just in time for him to take his exit exams the old-fashioned way.
In The Bourne Legacy, "Outcome" operatives are given intelligence-boosting pillsnote Called "Blues," as opposed to "Greens" which enhance their physical strength. Aaron Cross reveals that he used to be 12 IQ points below the Army recruitment minimumnote The Army doesn't actually use IQ to measure recruits, but that would make him developmentally impaired, which made his fear of losing the boost very serious. You can see the Blue meds start to wear off before Marta starts viraling him off (IE: making the alterations permanent).
One of the alternate trope names, "The Algernon Gordon Effect", was an in-universe thesis describing this trope. Charlie's own research while he's super intelligent predicts what is going to happen.
Invokedand then defied in Understand by Ted Chiang: a man has been through an accident that destroyed a lot of his brain cells and gets an experimental treatment that works too well, giving him Super Intelligencenote to the point that he needs to create a whole new language just to conceptualize his thoughts. The trope comes into play when the protagonist — in case he meets another "enhanced" person that opposes him — devises a technique that reverts enhanced minds to normal. When he tries it, however, the adversary shrugs it off.
In Animorphs, Tobias overstays his morph as a hawk and ends up stuck that way for a considerably long time. Later, a Sufficiently Advanced Alien known as the Ellimist restores his morphing power and allows him to morph into his own human form, with the same rules as earlier. Though he could return to human form permanently, he chooses not to, both because he wants to stay in the war and because he actually prefers his hawk form. This is actually a inversion of the trope though since Tobias wants to stay in his altered form, not his original one.
In John DeChancie's Living With Aliens, the main character starts out as a below-average teenage boy who befriends a pair of eccentric, stoner, renegade aliens. They offer him "smart pills", which greatly boost his intelligence into high genius levels. Since the story is written in first person, the effects of the intelligence drugs change the prose as the story goes along. Eventually, the pills wear off slightly, but enough of the effect lasts that he's able to maintain membership in Mensa.
In the My Teacher Is an Alien book series, unintelligent bully Duncan Dougal has his brain fried into a more intelligent state in the second book, and later becomes horrified when learning that he may lose this intelligence.
Although Duncan was never actually stupid, he merely bullied because he grew up in an abusive household. Becoming a genius gave him some perspective, and even though he will return to normal intelligence, it's implied that Duncan will be much wiser as a result of seeing his potential.
Detritus becomes temporarily hyper-intelligent after being locked in a meat locker, but it is explained that the optimum temperature for his silicon-based brain is also close to fatal for trolls. After he is rescued, his supercomputer-level intelligence largely goes away, but he receives a cooling helmet to make him smarter for the rest of the series.
A different Xanth novel further reveals that ogres aren't particularly stupid at all-their Hulk Speak, low IQ, and lack of conventional manners are entirely based on the prejudices of others. If one lets go of the notion that ogres are stupid slobs who act like they were raised in someone else's stolen barn, one gains the capacity to see them behaving just like anyone else (which means that Xanthian prejudice is strong shit). One ogre gets the Flowers for Algernon treatment at least three times over the course of the book as the viewpoint character repeatedly forgets that ogres aren't as stupid as he's always been taught.
Also subverted in the Isaac Asimov story "Lest We Remember". The protagonist, a middle-manager at a pharmaceutical company, receives an experimental treatment which gives him perfect memory; after it becomes inconvenient to his bosses, they try to administer an antidote. He resists and bangs his head in the scuffle, and then manages to convince them—incorrectly—that he's lost his perfect memory as a result of the head injury.
In the second book of the Chronicles of Prydain, the main characters encounter The Wise Prince Adaon. Adaon has heightened senses, psychic dreams, is a Warrior Poet with keen insight into people, etc. When Adaon dies, he gives Taran (the teenage main character) a brooch of his, and Taran begins to experience some of the heightened senses and psychic dreams and visions, making him feel for the first time something like the hero he has always wanted to be. He does have to give it up though, and for a good reason: it's the only thing a trio of super powerful witches will trade for the Artifact of Doom that they are on a quest to destroy.
In the Stephen King short story The End of the Whole Mess, a young genius discovers how to rid everyone in the world of their violent impulses. He and his brother complete the task in a few years, but they were unaware of a terrible side effect: early onset Alzheimer's. The story is narrated by the brother as the effects catch up to him.
Averted in Star Trek: Deep Space Nine's Season 7 episode "Chrysalis". Doctor Bashir meets a genetically altered person whose intelligence is actually extremely high, but is completely withdrawn into herself, able to express herself normally. Complications set in that threaten to revert her to her normal state or worse, but Bashir manages to fix the problem. The first draft of the episode's script played it straight, though.
Played straight in the Star Trek: The Next Generation episode "The Nth Degree". Reginald Barclay is zapped by an alien probe that raises his IQ to 1200+. After becoming superhumanly good at everything (including putting the moves on Councilor Troi), he reprograms the Enterprise to take the crew to the homeworld of the aliens who built the probe (this was the aliens' intent all along) — and then his intellect drops back down to normal. (Well, almost down to normal, anyway.)
The Adventures of Superboy: in one storyline, Bizarro is 'cured' of his condition. He eventually needs to be 'uncured' to save Superboy.
NewsRadio, "Flowers for Matthew": Matthew drinks what he thinks is a intelligence-boosting drink and becomes smart through the placebo effect. Paradoxically, his intelligence eventually drives him to understand that the drink has no actual chemical effect, at which point the placebo stops working on him and he rapidly returns to his original state.
In an earlier episode Lisa thinks she's getting dumber, and Dave actually refers to her as Algernon.
The Six Million Dollar Man — Jaime Sommers' first appearance in the show gave her bionics, then apparently ended with her death because her body rejected them. (Of course, she was revived and re-empowered when the network discovered she'd make a good spinoff, but that was outside of the realm of the original episode's plot.)
Chandler: We can't live there after living here! Didn't you ever read Flowers For Algernon?!
Monk, "Mr. Monk Takes His Medicine" — Adrian Monk begins taking medication to combat his Obsessive Compulsive Disorder. It works; however, he not only loses his amazing detecting abilities, but in a twist, he also turns into an insufferable egotistical jerk who talks like a '50s hipster and wants to be referred to as "The Monk." Naturally, by the end of the episode, everyone is begging him to stop taking the medicine.
Angel — Charles Gunn undergoes a magical procedure to give him encyclopedic legal knowledge, but after half a season it begins to degrade. This is referred to in the episode as 'acute "Flowers for Algernon" syndrome.' In this case, he is able to regain the knowledge through some shady dealings, but comes to regret it.
Red Dwarf: Rimmer gets a "mind patch" to raise his intelligence to genius-level so he can pass the entrance exam for a ship of super-genius holograms. Naturally, his brain rejects it. (But he passes anyway, when his opponent forfeits.)
Rimmer also gains his self-confidence and self-respect back (externalised as dashing swordsmen) in the episode "Terrorform", but loses them again almost at once on finding out what his comrades really think of him.
Rimmer assumes his dashing alter-ego Ace (what a guy!) on a number of occasions, but things are soon back to normal.
Until the last time they cross paths. Then Status Quo Is God is played by bringing back pre-character-development Rimmer.
In Scrubs, psychiatrist Molly Clock talks to The Todd, the innuendo-spouting stereotypical jock surgeon, and manages to turn him into a normal, nice man. When asked about it, she responds, "Yeah, but I only talked to him for a few hours. Without continuing therapy, he'll probably be back to normal in a week," lampshading the eventual Snap Back he'd fall victim to.
In the 2000 The Invisible Man series, the protagonist's partner, Hobbes, is accidentally injected with an intelligence-boosting retrovirus. Unfortunately, the effects ultimately lead to mental overload and catatonia; by the time this is discovered Hobbes doesn't care, but his partner does, and manages to emotionally blackmail him into creating an antidote.
In Doctor Who, Donna Noble's incredible journey and transformation from "The Runaway Bride" to the end of series 4, culminating in the human-Time Lord metacrisis and her becoming DoctorDonna. Then the Doctor has to wipe every single memory of these adventures to save her. Unlike most of these entries, this actually is presented as a tragedy.
Subverted in the final Third Doctor serial, Planet of the Spiders, where a minor, mentally retarded character gains normalised intelligence through handling a Metebelis Crystal, and gets to stay that way at the end of the story.
Andromeda: In Season 1, in the episode "Harper 2.0", the Andromeda rescues a dying Perseid librarian who is carrying a huge archive of knowledge within his own brain. At the point of death, the Perseid seizes Harper and dumps the archive into his brain, giving him access to a huge store of knowledge. This leaves him with the twin problems of an overheating brain and a ruthless bounty hunter who'd like to separate him from it. He solves the former problem by downloading the archive for storage in a sun after the bounty hunter experiences a touch of You Have Failed Me at the hands of the Big Bad.
This happens several times on House, where apparently anything that makes Dr. House happy, more considerate, or not constantly in pain also steals his keen observation and intellect.
Most examples involving House himself are implied to actually be subversions: Wilson and Cuddy are usually quick to point out that he is looking for an excuse to go back to the way he was because he is scared that this trope will happen. A completely straight example, however, is when he is treating a little girl and indulges the parents' request for a pointless test that will prove she doesn't have a disease he already eliminated. The test does more harm than anticipated.
In one Seinfeld episode George is prevented from having sex for a fixed period of time; the result is that this frees an enormous previously-unused part of his mind (the part that had been obsessed with sex) and his progressively growing intelligence enables him to solve Rubik's Cubes, read scientific journals and learn Portuguese by simply reading through a translation dictionary. Of course, he ends up back where he started (presumably because he had sex with the Portuguese waitress, reversing the effect).
Inverted with disturbing implications in the third season episode of Fringe, "The Plateau". At the end of the episode instead of reverting to normal or subpar intelligence, the subject has instead continued to exponentially rise to the point where his thoughts are incomprehensible to ordinary humans and only a machine can begin to understand what he thinks.
Subverted in the "Flowers for Charlie" episode of It's Always Sunny in Philadelphia. Charlie is the subject of an experiment where he takes intelligence pills which appear to make him much smarter (he learns Mandarin in two days and starts speaking English more formally) but cause headaches and other pains as side effects. The end of the episode reveals that the pills were actually placebos and Charlie didn't get any smarter, he just became EXTREMELY arrogant and the side effects were all in his head.
Next To Normal subverts this twice, in that neither the medication nor the ECT worked, as they were supposed to, in the first place.
In the Let's Play of Fallout 2 Trogg overdoses on Mentats, and becomes a near-genius from a barely sentient troglodyte. He realizes what he was doing and sets out to atone. When the effects wear off, though, he reverts to his old self, not understanding why he did things he did. In fact, he even becomes dumber than he originally was for a while (as a side effect of the Mentat withdrawal).
Funnily enough, there is autistic weapons upgrader in New Reno Arms basement who is a reference to and named after Flowers for Algernon. Trogg accidentally kills him.
In Kanon, Makoto suffers from this. It turns out that Makoto was actually a fox, and she picked up the name because when Yuichi was younger, he took care of the injured fox, and told it that Makoto Sawatari was the name of a girl he liked at the time, then had to abandon her when she got better and he had to leave the town he was visiting during summer vacation. When Yuichi comes back to live in the town 7 years later, he runs into her fox form again, and she makes a wish that allows her to turn into a human girl. Unfortunately, the wish has 2 catches to it. The first is that it'll cause her to lose her memory, and the second one is that it'll eventually take her life away. As Yuichi gradually opens up to her, she begins to forget ever being a human and gradually gets sicker. Her strong feelings for him allow her a small Hope Spot, but eventually she dies, or rather, fades away.
Fighter of 8-Bit Theater becomes temporarily intelligent after Black Mage's millionth of so attempt to assassinate him. Black Mage, figuring out that Fighter's new intelligence won't last, decides to save some time and stab his brain back into stupidity. Which happens a second before Fighter can communicate the solution he devised to the team's current problem.
Also happens twice (albeit very briefly) to Black Mage, in both the Marsh Cave and the Castle of Ordeals. On the first occasion, he was thinking about his polar opposite, White Mage, and realized that perhaps he should change his murderous, spiteful way of life and become a better person. This goes down the drain the second his thoughts are interrupted by anger at another of Fighter's stupid statements.
In the Castle, each member of the team got faced with the manifestation of their worst sin. The whole Castle is a place for the chosen warriors to defeat their own bad side and become the pure and good heroes they are supposed to be. The problem is, Black Mage loves being evil. So much, in fact, that where all other sins look like monsters, his are represented by himself, because nothing else exists to adequately represent how evil he is. He kills the clone and achieves purity... but is revealed to have set up a magic spell beforehand that would channel all the residual evil energy back into himself, thus keeping him as he was.
It's arguable that BM ever became pure, or even went back to normal. If anything absorbing the manifestation of his evil side made him even more evil. Somehow.
Ctrl+Alt+Del: Ethan becomes normal after being electrocuted and falling out of a power-line trying to get the Internet back. His friend Lucas and wife Lilah are so used to his wacky antics that they start to compensate by acting crazy themselves (Zeke the robot is unaffected), which has the unusual consequence of actually having consequences — Ethan has Lilah cosplay as video game characters during sex and it's normal; Lucas asks his girlfriend to paint her boobs like Kirby and Jigglypuff and she dumps him (again); Ethan stays up for days playing video games and he's fine; Lilah stays up for days and she's a wreck who wants to cut off her eyelids. Ethan becomes so afraid for his loved ones that he electrocutes himself six times trying to get back to "normal" and when he remembers he also hit his head he... goes to a doctor, who tells him that he got a brain injury that will slowly go back to "normal"; as for his friends they don't remember anything from their seven weeks (real time) in crazy town.
In The Order of the Stick, Belkar is normally a psychotic mass murderer, but in one strip, Varsuvius uses a spell to increase his Wisdom, at which point he realizes the error of his ways and vows nonviolence. This lasts for all of about 15 seconds before the spell is dismissed.
In the latest story arc of Flaky Pastry, Nitrine gets a conscience. She got better, though.
Aqua Teen Hunger Force, "Dumber Days" reveals that Meatwad's brain was actually a cat toy with a little bell in it. Carl manages to procure a brain (later revealed to be Steve's, assistant to Doctor Weird) for Meatwad, which Frylock doesn't use the actual brain shoves into Meatwad's body. Meatwad begins to take up reading, goes to the library, and becomes smart, going to the library and reading books from the Hardy Boys to Heisenberg's Uncertainty Principle, while his meat body begins to grow to tremendous size (which he attributes to thermal expansion). When Frylock finds that Meatwad is squandering his super intelligence on $5 car rides (in which a now psychic Meatwad can make the car spin around and flip in the air with his mind), Frylock removes Meatwad's brain, showing that it was just his old brainwith some glitter and macaroni glued to it. Meatwad gradually shrinks back down to his old, dumb self (and Carl's car smashes into the ground, the child safe.)
Beverly Hills Teens, "Rad to Worse": Chester uses one of his inventions to make Radley more intelligent so he can finish his homework. However, this also makes him a condescending jerk. The gang attacks him with a wave machine to revive his love of surfing and turn him back to normal.
In "The Cyber House Rules" Leela gets a second eye surgically installed. She goes back to one, after seeing that the person she's been dating (and who gave her the operation) treats a kid with three ears differently from other kids. In this case, it had been established earlier in the episode that having one eye wasn't really a problem since it didn't stop Leela from being successful and accomplished...it just made her look odd (and the second eye was merely cosmetic, she still had no depth perception). Going back down to one eye was actually Character Development for her to accept that fact.
In "Parasites Lost" Fry accidentally ingests parasitic worms that make him super-strong and super-intelligent. He gets rid of the worms because he wants Leela to love him for who he really is. This also turned into Character Development because Fry finally was smart enough to realize that he had feelings for Leela and spent the rest of the series trying to better himself normally.
Subverted in "Mars University" where Farnsworth creates an intelligence hat for his experimental monkey, Gunther. Gunther decides he's unhappy being smart, and throws the hat away. Then he realizes he doesn't like not being sapient either. When the hat becomes damaged, he decides he likes it that way as it bestows a moderate amount of intelligence.
Done with much emotion in the last episode of the original FOX run, "The Devil's Hands Are Idle Playthings" where Fry enters into a deal with the robot devil in exchange for hands that are good enough to play the holophoner. Hedonism Bot hires Fry to write an opera. In the end, Fry gives the devil back his hands to save Leela from marrying the robot devil.
In "Overclockwise", Cubert overclocks Bender for reasons that make sense in context. He winds up becoming even more powerful when everything follows suit.
Mort from The Penguins of Madagascar once had his foot fetish cured, only to get it back (which was actually necessary to save King Julien).
Inverted when the penguins lowered their intelligence to Mort's level so they could be too stupid to feel pain. They returned to their smart old selves (well, maybe a bit of an overstatement for Rico) later in the episode.
Rugrats, "Smell of Success": A copy of Flowers for Algernon, except with Chuckie having his severe allergies temporarily cured gaining his sense of smell, only for the cure to wear off. Came complete with Chuckie befriending the white lab mouse as homage.
"HOMЯ". Dumb Homer had a crayon lodged in his nose since childhood, and when it was removed he became intelligent Homer. He eventually had the crayon re-inserted after discovering that a man with a 105 IQ is too intelligent to be happy in today's world (which isn't much comfort to Lisa).
"Brother's Little Helper". Bart takes a behavior drug called Focusyn to control his "ADD". Sure enough Bart becomes focused but he becomes paranoid about Major League Baseball spying on the town using satellites (he's right). After stealing a tank he's convinced to stop taking the Focusyn and onto "good old Ritalin".
"Pygmoelian." Moe gets plastic surgery on his face. The reversion to the status quo was lampshaded. Moe's face is crushed by a falling piece of a TV set, which restores him to his previous ugliness.
Moe: "Here's what I don't understand. When that set fell on my face, how did I get my old face back? Shouldn't I have gotten some third face that was different? It don't make no -* End credits abruptly start*
"Large Marge". Marge goes in for liposuction and awakens to find that the doctor has mistakenly given her breast implants.
"My Fair Laddy". Lisa got Willie to be a gentleman.
Perhaps the only character change that ever stuck is Barney's sobriety, and even that's been reset.
In the episode "Bubba's Big Brainstorm", Bubba Duck becomes intelligent, civilized, and utterly ruthless and incapable of compassion, something indicated to be directly connected to his new intelligence. He becomes dumb and barbaric again when his brute strength is needed to pound a monster threatening his friends.
In an earlier episode, Scrooge is racing against a villain to gain the magical Pearl of Wisdom, which grants infinite wisdom for a moment in the morning. Huey, Duey, and Louie are surprised that the islanders seem unconcerned about the prospect of having their pearl stolen by the villain or Scrooge. The reason soon becomes clear: Scrooge and the villain both get their wisdom moment simultaneously, and in that instant realize that stealing the pearl would be wrong and put it back where they found it. The chief chuckles and says the same thing happens all the time. (It helps that the Pearl only activates on the shore of the island.)
In the episode "Superdoo!" Doofus finds an energy crystal from outer space that gives him superabilities. Through his new powers he becomes the all time junior woodchuck merit badge earning champion, but others dislike him even more than old laughable, clumsy and slow Doofus. He throws away the crystal, gives back his merit badges and later saves the camp without any superpowers, winning respect of others. Everyone is happy to have the old Doofus back, including Doofus himself.
The Transformers: Grimlock, who by the third season had suffered Flanderization to the point where he could barely speak coherently, became super intelligent after getting hit with a Transformation Ray in the episode "Grimlock's New Brain". He quickly became the best Autobot you could have ever wanted, but was forced to build a new team of combining robots and transfer his intelligence into them to solve a dilemma.
Averted by the biography on some of his more recent toys like the Transformers Universe Grimlock which actually gave him an intelligence score of eight (out of ten) and claims "Me Grimlock" is just a speech impediment.
ALSO averted by his original toy's tech specs, which gave him an intelligence of 7 out of 10. The common excuse for "Me Grimlock" is a speech impediment, as above, usually explained away as damage from the Gladiator Pits on Cybertron prior to the Great War (only in the cartoon was he built on Earth), one he chooses NOT to get repaired so people will underestimate him.
In the episode "Changing Gears", Megatron steals a circuit card from the Autobot Gears in order to power his solar needle. The effect of removing the circuit card makes Gears all happy and good natured instead of grumpy. The other Autobots are unsuccessful at convincing him to keep the card out when he gets it back at the end of the episode.
The Weekenders, "Sense and Sensitivity": Lor starts the episode as a ball hog to the determent of her basketball team and keeping that selfishness even off the court so her friends resolve to make her less so. However they go too far and turn her into the worst form of Extreme Doormat leading to the legitimate fear she'll do something like make bad passes in a championship game ("she might just give the opponents the ball") so they resolve to turn her back but she does get some development from the event as she actually passes in the championship game.
Captain Simian and the Space Monkeys: in one episode, the group try to complete the interrupted dose from the intelligence booster for Gor; instead, they give him an unexpected mega-boost that causes his intelligence to start growing exponentially, but Gor eventually not only becomes too detached to access his anger-fueled Gormungus form, his super-brain makes him the prime target of Rhesus-2, forcing him to revert.
In an episode of Tiny Toon Adventures, Dizzy Devil is made intelligent and cultured, but finds that none of his friends (or his bevy of attractive girlfriends) like his snobbish new personality. He is eventually restored to normal and is happy.
Family Guy does this, but with looks instead of smarts. Peter gets liposuction and cosmetic surgery to become beautiful. He also becomes a jerk becomes a slightly different kind of jerk than normal. And, even though his family recognize that he has become a jerk, most of them are willing to put up with it because he is beautiful. At the end, he is restored to the status quo by accidentally falling into a vat of lard at a meat factory and eating the contents to avoid suffocation. The family is happier. Lois asks, "I guess you learned a valuable lesson?", to which Peter replies, "Nope."
They did it again when Joe regained the ability to walk, then ditched his friends and alienated his wife. The episode ends with his wife trying to shoot him in the spine and repeatedly missing, until he finally takes the gun from her and does it himself to make her stop.
Also done when Meg got a makeover, she ended up being a big-time pop diva but went back to being normal after Jimmy Fallon had sex with her as part of a Saturday Night Live cold opening.
Played with in the episode where Peter died due to a drunk driving accident. The Grim Reaper then showed him what his life would be like without any drinking. His family is happy, and he is far more intelligent and articulate, but Peter doesn't like the change because his tee-totaling self is "a pompous ass" who is no longer friends with Joe, Cleveland and Quagmire.
In the SpongeBob SquarePants episode "Patrick Smartpants", Patrick becomes a super-genius, but decides to go back to being stupid after he realizes he's turning into an Insufferable Genius and alienating all his friends.
Once Patrick got a sense of smell (via nose), but immediately regretted it after he realizes that he'll have to deal with nasty odors as well as pleasant ones. Subverted that he doesn't actually try to get rid of the nose, but try to make everything smell better, much to the annoyance of his friends. By the end of the episode, Spongebob, Squidward, Sandy, and Mr. Krabs work together to make a stink ball so smelly it would destroy Patrick's nose, and it worked.
In "Not Normal", SpongeBob gets upset by Squidward calling him not normal, so with the help of an instructional video, he changes his ways, and he's no longer a zany cartoon character. However, he winds up creating ink and paper Krabby Patties, causing Mr. Krabs to suspend him from work for the time being. SpongeBob then finds out he is incompatible with Patrick's ideas for fun. Squidward's reception for SpongeBob's change in character was positive at first, but gets annoyed at the latter's criticisms regarding his lifestyle and appearance. SpongeBob ultimately decides being normal is no fun for him, and tries to revert to his original personality with Patrick's help. At the end of the episode, it seems as though his new personality is permanent, but a normal version of Squidward appears and scares SpongeBob back to his original zany self.
In "A Breath Of Fresh Squidward", an electric shock affects Squidward's normal brain pattern, making him as friendly and diligent as Spongebob. He soon reveals himself to have the same clingy, saccharine nature as Spongebob, and eventually also steals his thunder at work, with Spongebob soon revealing he can't take what he dishes out and becoming irritable and resentful towards Squidward's new personality. Eventually just as Spongebob comes to accept Squidward, both of them are hit with another electric shock, making the two as grumpy and unsociable as Squidward was before.
Chowder takes this to the next level. In one episode Mung Daal gives him Brain Grub, which makes him super smart. So smart, in fact, that he realizes that he's a cartoon character in a TV show. Thinking that being in the show will keep him as a "scatterbrain," he uses his newfound power to turn the show into an educational program. However the new show doesn't work out; cooking is now boring and the show's audience started crying. Realizing the damage he has done, Chowder yanks his new brain out of his nose and smashes it into bits, effectively deleting the show altogether. Of course things go back to normal in the next episode.
Inverted in American Dad!: It's revealed that one of Steve's exceptionally stupid friends is only stupid as a side effect of a medication he regularly takes. This medication intentionally kept him stupid because he's secretly a brilliant psychopath.
There was also the time Aviarius' power-sucking staff gave her Hego's powers, due to his attack getting interrupted.
In The Inexplicable Adventures of Bob!, Bob gains super powers briefly. A villain tries to steal them, and they ultimately get transferred to a potted geranium, which likes them very much and flies away.
Another episode inverted this trope when Jimmy made himself stupid because everyone got tired of his Insufferable Genius tendencies. However, a meteor threatens to destroy Retroville shortly and they needed Jimmy's smarts to save Retroville. (Which, ironically, happened because of his genius earlier in the episode, not that anyone knew that.)
In the Frisky Dingo episode "Flowers for Nearl," Xander Crews' retarded twin brother is turned into a mastermind through an injection of "brain chemical." When he is fatally shot (because the plot was getting to complicated,) he reverts to his old speech pattern for his last half-second of life.
In an episode of South Park, Mr. Garrison gets a rhinoplasty having David Hasselhoff's face. He becomes a male model and pursue women. Until women are chasing him and wants his old face back.
In an episode of Pinky and the Brain, The Brain makes Pinky smart with a machine so he would stop making the world domination plans fail. Pinky proceeds to appoint flaws in all of the upcoming plans, angering his friend. This causes Pinky to get sad at his intelligence, and Brain to make calculations proving the duo only works with one of the two being dumb. Brain then uses the machine to make himself a dimwit... and shortly later Pinky does the same.
Pinky: What are we going to do tomorrow night, Brain? Brain: The same thing we do every night, Pinky. Pinky: What's that? Brain: ...I have no idea. Pinky: Poit. Brain: Narf.
Played with in Daria, in the episode "Quinn the Brain", when Quinn gets an A on her English essay. Quinn's actual intelligence doesn't increase, but she gets treated like it has and after she manages to make being a "brain" a fad, she embraces an identity as an intellectual. Daria ends up reverting her back after both the Fashion Club and Quinn's trio of admirers beg her to bring the "old Quinn" back. This consists entirely of Daria dressing like Quinn, getting the guys to show up at their house as her "dates" and waiting three seconds for Quinn to revert to her old self.
In the Maryoku Yummy episode "Shika's Wish," Shika wishes that Maryoku would follow the rules for a change, and since they live in a magical land, the wish comes true, turning Maryoku into an absolute stickler for the rules. So much so, in fact, that she takes on Shika's role as Chief Officer of Rules and Regulations and begins making even more restrictive rules than he ever did. Finally, Shika wishes that he never made that wish in the first place, and everything goes back to normal.
The Tick: a chimpanzee (named Charlie) becomes superintelligent after having been blasted into space. He slowly reverts over the course of the episode, but still ends up Director of NASA in the end.
One episode of Lilo & Stitch: The Series had Lilo and Stitch encounter a wish-granting experiment they named "Wishy-Washy". After catching (or actually, wishing they captured it) they used it to make laid-back, surfer David the smartest man on earth after Lilo misinterprets Nani's preference for smart men. Although he is now intelligent enough to reach a few moments of being The Omniscient (when Gantu wishes to have possession of Wishy-Washy and disappears, David shows up and asks Lilo if he can help, since his intelligence allows him to know that something has been going on) he is unable to speak properly with Nani due to his Sesquipedalian Loquaciousness and is not at all happy with his intelligence. In the end Lilo uses up the experiment's last wish to put everything back to normal again, restoring his average mind.
Grounder is exposed to this in Adventures of Sonic the Hedgehog, after accidentally installing a chip that made him super intelligent during his repairs in "Grounder the Genius". His normal dumb-sounding voice takes on a much more intellectual tone, and becomes a much more threatening villain than Robotnik could ever have hoped to be.
Season two of Archer had a story arc where Sterling was diagnosed with cancer, and became a decent human being when faced with death. He snapped back as soon as he was cured, to everyone's chagrin, but his personality bounced back and forth as the disease went in and out of remission.
In an episode of Regular Show titled "More Smarter," Rigby's belated attempts to get a high school diploma are futile until he sees an online ad for a brain-enhancing tonic. He drinks a month's worth of doses and instantly becomes smarter. However, he mainly uses his intelligence to insult Mordecai. Once Mordecai discovers Rigby's secret, he does the same. They go back and forth until they become too smart to understand any of the "normal" people. The cure turns out to be Rigby's homemade beverage (containing cola, fruit punch concentrate, hot sauce, and sugary cereal, among others), which Mordecai was originally "not dumb enough" to drink.
In an ep of the 80's animated version of The Incredible Hulk, Banner takes a potion that cures him, but it only works once. He brings back the titular alter ego so that he can rescue Rick Jones from a plane that was hijacked.
In an episode of Dave the Barbarian, Dave's family gets tired of Dave's cowardice and makes him wear the Red Sweater of Courage, making him completely fearless. However, when Dave gets addicted to danger and engineers a team up between the show's three recurring main villains, he is unable to defeat them as his only solution to solving the problem is to just fight head on, which won't work. It's only after he loses the sweater that he's able to think of an idea to defeat the villains.
Fang also got an episode like this when Candy decided to make her more civilized, transforming her into an insufferably Proper Lady who refuses to fight. In the end, she is forced to revert when an army of giant insects invades and her bug squashing prowess as "The Great Destructor" is needed.
In one episode of Dinosaucers, one of the villains, Quackpot, is accidentally hit by an "Allegiance Reversal" Ray, and briefly becoming friends with the good guys; before the end of the episode, Quackpot witnesses the wear off of the effects on a previous test subject and warns Allo that he will soon become his enemy again.
My Little Pony: Friendship Is Magic has the episode "Putting Your Hoof Down". Fluttershy attends a seminar hosted by a minotaur named Iron Will so she can learn to be assertive, but Iron Will winds up teaching her anger. Inspired by his motivational phrases, Fluttershy starts handing out Disproportionate Retribution to everyone who wrongs her, then progresses to lashing out at completely imaginary slights. (The unfortunate implications of the standard Flowers For Algernon plot are briefly touched on: when her friends confront her and say they don't like New Fluttershy very much, she accuses them of wanting a weakling they can push around. Her friends reply that they don't want Old Fluttershy back, they want Nice Fluttershy back.) Eventually she has a My God, What Have I Done? moment and reverts to an even more extreme version of her prior Shrinking Violet self. Finally, she's confronted by a problem that can't be solved by hiding in her house, and she realizes that moderation is what's needed. She saves the day by being assertive without being a bully. This bit of character development sticks, and it becomes important in a few later episodes.
In an episode of Invader Zim, Zim reprograms GIR into duty-mode, in order to be more obedient. However, after hijacking a police car, Zim orders him to stay at the base out of fear of being exposed. Shortly afterwards GIR goes on a rampage, stealing information from the library, attacking people, and trying to kill Zim. It's only with the help of a police officer with a squid's brain shooting ink at GIR that Zim is able to stop him and restore his original personality.
Neurologist Dr. Oliver Sacks (The Man Who Mistook His Wife For A Hat) has one chapter on "Witty Ticcy Ray", a man with severe Tourette's Syndrome who takes Haldol during the week to control his tics, but forgoes his medication on weekends where his condition actually enhances his wild jazz drumming.
Also, his patients suffering from Sleeping Sickness for decades recovered after he gave them L-Dopa. He writes about them in his book Awakenings (later a movie starring Robin Williams). Unfortunately, as the patients developed resistance to the drug, its effects wore off and they all went back to sleep.
Happened to yet another patient of his with a different disease: syphilis. Some forms of syphilis can cause mental problems, such as dementia and seizures. For this patient, though, she actually liked the effects so far - she was adapting to the disease fine, it was just making her slightly manic. The challenge for her and Dr. Sacks was to find a treatment that would prevent the disease from getting any worse, but not reverse the effects so far.
The trick to it is that the neurological damage caused by syphilis is irreversible. The standard penicillin regiment used to treat the disease anyways, should have accomplished exactly what they wanted.
Dr. Sacks did indeed give her penicillin when she requested treatment, and she stayed "frisky" (to use her words) without fear of getting worse.
People whose severe ADHD responds very well to medication can get something like this effect. While it doesn't change their personalities, it can make them so much less impulsive, and make it so much easier to concentrate, that they seem like completely different people while taking medication. But it's not all positive—ADHD on medication may let you concentrate when you like, but many say they lose some of their creativity, as well as losing the ability to "hyperfocus" (to concentrate exclusively on one thing, forgetting the rest of the world even exists) in exchange for a more typical type of concentration. Not to mention withdrawal symptoms which can range from fatigue to thoughts of suicide.
Bipolar disorder, too. Nobody's disputing that going manic and hallucinating that you're the Virgin Mary is a bad thing, but there's also no denying that being manic feels good and makes you very creative, outgoing, and generally more fun to be around (at least before you get paranoid or get the delusion you're invulnerable and kill yourself by accident...) People with bipolar disorder often miss their manias while they're on medication, and stopping medication can get really tempting.
A lot of people have discovered that, despite the lack of enhanced creativity, they are far more productive while stabilised by medication. Why? Turtle beats the hare; being able to steadily work on things all the time gets more done than occasional hyperactive spurts (which get gradually more incoherent) followed by long periods of depression. Which makes the disorder an example of the trope done well.
People who suffer from depression often feel that the emotions they experience during a "down" period, while terrible, are at least authentic and so preferable to the artificial sense of complacency they get while on medication. Some refuse to take medication for this reason.
Reports of this happening with Prozac are quite common; in fact one scientist wrote a book about the subject called Listening to Prozac.