The Level Upper in A Certain Scientific Railgun is a sound file that amplifies the powers of any esper that listens to it. However, it comes with the side-effect of causing its users to collapse into a coma. It's distributed illegally throughout Academy City by shady people and it's generally treated as if it were a deadly drug.
In the Welcome to the NHK light novel and manga, nearly the first thing we see the protagonist do is snort a small amount of a 'legal drug' he 'brought off the internet'. In the anime, the drug was removed, and the resulting trip was changed from a drug-induced hallucination into a psychotic hallucination.
Chitose in Yuru-Yuri gets drunk off chocolates as well, and has a tendency to kiss anyone in the vicinity when she does it.
Chihiro Kawai from Pretty Sammy has an extreme addiction to karaoke, at one point going through withdrawals after her new computer (which she mistook for a high-tech karaoke machine) breaks. In a later episode she even ties up and gags a bus attendant and steals the woman's microphone so she can lead a tour bus in a rendition of one of her songs.
One chapter of Oh My Goddess! started with Belldandy first drinking everyone under the table at a party, and she explains that alcohol simply has no effect on her. Then she has one can of cola and is instantly intoxicated. Hilarity Ensues.
Dandelions were implied to be hallucinogenic, addictive and self-destructive in Bloom County several times.
Frequently in Peanuts, whenever Linus is without his blanket, he suffers painful-looking withdrawal symptoms. In one sequence Charlie Brown agrees to keep Linus company during a night in which his blanket is missing. Charlie explains as the punchline, "The first night without the blanket is going to be the hardest."
Archibald Snatcher, the Big Bad of The Boxtrolls, is obsessed with cheese as a status symbol, even though eating it causes a violent allergic reaction that not only makes his face swell up in a nasty fashion, but causes him to act like a surly drunk and even hallucinate at one point. One of his lackeys, Mr. Pickles, even wars him "You know what cheese does to you..."
Films - Live-Action
Repo! The Genetic Opera averted this hard with Zydrate. The promo stuff made it seem G-rated, but then it's first appearance in the actual movie was when Grave-Robber extracted it from a corpse, and it has some pretty nightmarish effects. Towards the finale, Amber Sweet, the daughter of the owner of Gene Co, Rotti Largo, has her face fall off because of a shoddy, last-minute surgery to fix her accidentally-scarred face right before the opera. The really nightmarish thing is that she isn't screaming because she's so high off Zydrate.
The nightmarish effects are because, when you're extracting it from a corpse, it's bound to be a little less than 99 44/100% pure. The official Gene Co version just seems to be a very effective (and incidentally addictive) painkiller.
El Indio in For a Few Dollars More smokes what is presumably marijuana, but it's never mentioned exactly what it is. There's a few points where we see him so stoned he falls asleep with his eyes open or ends up giggling uncontrollably, but other than that the film deliberately makes it unclear whether Indio's psychotic behavior is caused by the drugs, or whether he's actually medicating a mental illness with them and without them he'd be even worse. (The fact that he twitchily requests joints from his underlings after killing people for trivial reasons supports this interpretation). Presumably, the intention was to placate Moral Guardians in America, without ending up in the Reefer Madness hysteria school by claiming weed will turn you into a bipolar rapist.
The drug-fueled, hallucination-laden madness that is Naked Lunch (the film, at least) revolves around Lee's addiction to... extermination powder? Granted, it was meant as an indirect adaptation of the original novel, in which heroin was the culprit.
In the less than mediocre Chuck E. Cheese in the Galaxy 5000, there's "Zoom Gas." The antagonists flood their cockpit with it then start acting all giddy and driving at absurd speeds. Hmmm....
Radagast in The Hobbit feels the effects of Gandalf's pipe-weed, and Saruman later comments disapprovingly on his consumption of mushrooms.
At the risk of informing you of something you already know: Tolkien unambiguously intended "pipe-weed" to be interpreted as Nicotiana, not Cannabis. Though tobacco does contain, as the genus name indicates, nicotine, and that can give people who aren't used to it a "buzz".
Annabeth: I think I figured it out, I know why we're here.
Percy: Why are we here?
Annabeth: To HAVE FUN!
The Extremis serum in Iron Man 3 has some hints of this. Jack Taggart very clearly seems to be going through withdrawal, and Aldrich Killian states that test subjects who can't regulate their dosage properly will be dropped from the trials, as addiction will not be tolerated.
In X-Men: Days of Future Past, Xavier being dependent on his medicine, and suffering intense pain from his powers returning when he stops taking it, is about the closest a PG-13 film can come to depicting the effects of drug abuse and withdrawal.
Animorphs, maple and ginger instant oatmeal is highly addictive to the Yeerks, unfortunately it also permanently removes their need to leave their hosts to feed, and drives them insane, although it does also weaken their ability to control the host's body.
In Kage Baker's Company series, the cyborg process gives (along with superpowers) immunity to all the usual drugs — but, unexpectedly, cyborgs get stoned on chocolate.
Touched on in The Dark Tower novel The Drawing of the Three. Roland is in the body of Eddie, a drug user who is currently drug running to get his fix. When Eddie gives Roland a hot dog and Pepsi, he has a major sugar rush and wonders, dumbfounded, why someone would need heroin when something like this (sugar) is widely and legally available.
In The Dresden Files, pizza is this for pixies. Harry Dresden keeps a small army of them on as retainers for recon work and other support jobs (plus picked up a faerie extermination squad to keep roaches and rats out) in exchange for a weekly "bribe" of hot, fresh pizza. Lampshaded in Changes when Harry does this in front of Sanya.
Sanya: You are a drug dealer. To tiny faeries. For shame.
The Strugatsky Brothers' novel The Final Circle Of Paradise has an agent being sent to a seaside resort to investigate a number of mysterious deaths that may indicate an overdose by a new drug. His goal is to find the suppliers and the manufacturers, so it can be shut down before spreading to other places. Everyone is reluctant to talk about it, but someone lets it slip that the drug is called "slug" (or "slag" in the original version), which turns out to be a "vacuum tubusoid", a cheaply-made commonly-available electronic component that someone accidentally inserted into a radio receiver (it has the same shape as a heterodyne receiver) while taking a bath, resulting in an LSD-like effect enhanced by adding aroma-salts to the bath water and taking a few anti-mosquito tablets. At the end, the agent fails to convince his superiors that this is not your typical drug ring and quits, deciding to fight the threat to human civilization (i.e. everybody spending their days in bathtubs with the "slug" plugged in) by changing the way people think.
In Hal Clement's "Iceworld" the aliens suffer a single dose activated addiction to nicotine that will kill them if they are not forever supplied with the drug.
Characters in Shades of Grey use different colours as recreational drugs. "Lime" is seen as a gateway drug, while "Lincoln" is more dangerous.
In Julie Cross's Tempest: A Novel Adam drinks a 6 pack of red bull and ends up wired for the rest of the night. It's stated that even a single can of coke keeps him up all night building bridges out of toothpicks.
In Worldwar by Harry Turtledove, it turns out that ginger is an extremely addictive drug to the Race (with effects similar to cocaine) and within a few months of the invasion, drug smuggling rings have sprung up and humans are exploiting the addiction. The bigger problems start when females arrive and it turns out that ginger sends them into estrus (they normally mate in seasons). This results in two new institutions among the Race: prostitution and romantic love.
In Mercedes Lackey's modern urban fantasy books, elves react to caffeine the way humans to cocaine. (Give an elf a can of cola and he'll be very happy. Give him a double shot of expresso, and it could kill him if he's not used to it.)
In Charlie and the Chocolate Factory, the tour passes by a room where the Oompa-Loompas are drinking "butterscotch and soda" and "buttergin and tonic", which make them "tiddly".
In The Heroes of Olympus, Dakota, a son of Bacchus, is addicted to Kool-Aid. With three times the normal sugar.
Mr Tulip in the Discworld novel The Truth is addicted to the idea of drugs, and is noted several times as taking various substances as if they were drugs, regardless of what effects such substances might actually have. He's been known to snort things like mothballs, for example.
Dinosaurs had an episode about thornoids, which were sentient drugs meant to increase strength and muscles size, but had a side-effect of growing thorns.
Another episode focused on Robbie and Spike happening upon a plant in the forest which they eat, and become high. Robbie brings it back home and soon Earl and Charlene get high on it, and Earl brings it to work where everyone there eats it too—including his boss Mr. Richfield—and they're in a marijuana-like high for most of the episode, eventually running out of food in the house. In the end, they go back to the forest to find more of the plant, only to find Spike—who never left where he was—covered in dirt and leaves after just being high in the forest for a week. Robbie then lampshades this by breaking the fourth wall and telling the audience that drugs are bad because drug use compels sitcoms like Dinosaurs to do obligatory drug-PSA episodes like this one.
How I Met Your Mother plays this for laughs, having the father refer to marijuana as "sandwiches" in order to avoid outright mentioning the drug to his kids, and the live action has the characters puffing on them as though they were blunts. In one episode they baked a bag of "sandwiches" into brownies.
Small Wonder had an episode called "Vicki and the Pusher." Instead of consuming the drug she obtained in the schoolyard, Vicki hid it in a flowerpot.
Welcome Back, Kotter: The episode "What Goes Up ..." featured Freddie (one of the show's four main students) becoming addicted to painkillers after being prescribed them to heal a basketball injury. He convinces a scared Horshack that the pills are really just "vitamins" (but is unsuccessful with his teacher or other friends), only seeing the light when Horshack tries to contact the pusher who sold Freddie the pills.
In Family Ties, Alex Keaton becomes addicted to unspecified "diet pills" (in the days when this would likely be an amphetamine or NDRI) which operate as a stimulant, in an attempt to handle the stress of scholastic life. He eventually crashes, missing the big exam that has been the build-up of the entire sequence.
In the show California Dreams they had a very special episode in which one of the girls is convinced to take steroids to qualify for an Olympic volleyball team. She's eventually found out, and has an intervention (complete with breakdown in the middle of the local teen hangout) after which it is never referred to again.
Fraggle Rock had "Wembley's wonderful whoopie water" although the episode that featured it was NOT about drugs.
ALF once got addicted to cotton, where the effects seem like a combination of being both high and drunk.
The Young Ones: "Vyv - can you actually, like, kill yourself with laxative pills?"
The Gaia Memories in Kamen Rider Double give their users superpowers, but improper use results in addiction, insanity, and withdrawal symptoms. It doesn't help that people who use them are called Dopants. Don't even think about mainlining one; it will mess up your body. And may your deity of choice help you if you get an adulterated Gaia Memory from a shadier-than-usual dealer...
And most Dopants only use one Memory for a VERY good reason, the only one shown to have used more than one (in fact a large number) got a VERY disturbing death.
Zodiarts Switches in Kamen Rider Fourze have a very similar effect to the aforementioned Gaia Memories, with the major difference being that Zodiarts Switches are Magical Space Drugs instead of Magical Earth Drugs.
Lock Seeds in Kamen Rider Gaim don't have any drug-like effects with their usual use of summoning Invase Mons, but they're sold by a shady character named Sid, who dresses and behaves suspiciously like a drug dealer. It doesn't help that Sid and his superiors have an ulterior motive and specifically target kids because they're immature and don't know better.
...But for less usual uses, the drug effects become more apparent. For starters, any Invase that eats a Lock Seed goes One-Winged Angel. The Riders also use Drivers to use the Seeds' powers on themselves; and when one gets his Driver destroyed he definitely seems to be going through power withdrawl (including hallucinations). And then there's the fruit that the Seeds come from, which is supernaturally tempting and - while apparently safe for Invase to eat - causes a transformation into a mad Invase when consumed by humans.
Star Trek: The Next Generation had an episode called "The Game" that did it with a video game that directly affected neurotransmitters in all kinds of ways and was described constantly as addictive.
TNG also had the first season episode "Symbiosis", which featured a planet of people addicted to the narcotic "felicium" because it was a virus cure (and therefore invoking this trope) and another planet that did nothing but supply the drug even after the disease it was supposed to treat had long been eradicated, since the residents were so addicted to it.
The TV series Dollhouse features a mysterious "memory drug" in the season one episode "Echoes". Supposedly, it triggers suppressed memories. Effectively, the characters in contact with it act like they are on a strong psychotic substances like mescaline.
Sliders has an episode where the main characters slide into a Prohibition-like world, where caffeine has taken the place of alcohol. Along with the clothing and music styles of the 20s, they also got speakeasies, where coffee is sold in tiny bags for $5 each, gangsters, and corrupt cops.
Another episode had the opposite. A world where there are no illegal drugs, and being an addict is mandatory. Cops walk around with tranq guns to calm down those who have gone off meds, until they can get an implant that allows easy injections directly into the bloodstream.
In an episode of Mythbusters, Tory Grant and Kari tested a myth about smugglers smuggling contraband across borders by driving with no lights on to evade detection. The (theoretical) contraband being smuggled in this scenario? Canadian maple syrup.
For some reason, in the original Hawaii Five-O episode "Up Tight", every reference to LSD was removed and the word "speed" substituted. The women's behavior when they were using it, and the charismatic Leary-like guru who dispensed it, all indicated LSD, not speed.
An early First Wave episode reveals that ordinary table salt has a cocaine-like effect on the Gua (either that or it's an unintended side-effect of their Half-Human Hybrid husks). Later, Gua salt dens are found. It's shown that any Gua caught ingesting salt is executed.
In Farscape, one episode has the crew travelling back in time to Earth through a wormhole. They arrive on Halloween, and Rygel gets hopped up on sugar, acting a bit like a crack/speed addict.
Rygel: Chrichton! How illegal is this dren?
Children's radio show Jungle Jam and Friends had an episode in which characters discover that they get a pleasant buzz from being knocked on the head by a falling coconut, a practice they refer to as "clunking." What follows is a perfect metaphor for the controversy surrounding the consumption of cigarettes, complete with political rallies, discussions about the dangers of "second-hand clunking," and the eventual revelation of a fatal outcome for the clunker: terminal hiccups.
Heavy Rain has Norman Jayden, an FBI agent with a Boston accent that comes in and out from line to line and a powerful addiction to blue luminescent powders, even more over the top in the end because it's hard to know what's coming from the drugs/withdrawal, his magic sunglasses from the future or the way he himself seems a bit unhinged to begin with.
The addiction is treated as something akin to an addiction to painkillers, since he takes the medication to stave off the side effects of using his future police glasses (which include blinding headaches, nausea, and occasional loss of basic motor functions). Throughout the whole game he walks a fine line between using the glasses too much and taking too much medication to compensate. There is actually at least one instance where the player can make the choice to press on with the case (and risk further damage to Nahman's system) or to quit and save him the trouble (at which point the player switches to another one of the playable characters).
Monster Party used 'pills' that turned Mark into a flying gargoyle that would shoot lasers, essential making him a much more powerful character. The effect would be temporary and would often leave the player scrambling for another pill.
The Warriors (the video game) has a healing drug called "Flash" that is sniffed.
The later installments of Mega Man Battle Network have a variant in the form of Dark Chips. The chips are extremely powerful when used in battle, but harms the NetNavi to use them; said NetNavi becomes addicted to them with repeated use, until they are too far gone for their operator and they eventually get deleted.
All of the Fallout games use made-up drugs with drastic effects far beyond those of real-world drugs (for example, drinking a beer will make the character objectively stronger for a short time, letting him/her carry more and use heavier equipment). Fallout 3 was set to contain real-world morphine, but Australian Moral Guardians led to the game being banned until "morphine" was replaced with the generic "Med-X." Fallout: New Vegas even introduces "Fixer," an anti-drug that will kick your addictions in exchange for some Interface Screw.
Fangame Sonic After The Sequel has the Sugar Splash Zone and the piles of sugar lying around the stage that give Sonic beady eyes and make him run faster when he runs into them. Cue cocaine jokes.
As mentioned above, Sergeant Schlock is addicted to Ovalkwik mix, which he eats directly from the can - although the ingredient statement suggests it might not be so G-rated, containing among other things nicotine, codeine, and something called "hyper-ephedrine."
Homestuck: Meulin and Kurloz apparently get stoned on catnip together. Catnip does have relaxing and euphoric effects similar to weed when smoked by humans in real life, but it's not potent enough to get anyone stoned enough to completely space out for about ten minutes like Meulin suspects 'nip' made her do. Damara is shown smoking a blunt and asks Meenah to get stoned with her, but it's never explained what exactly she is smoking.
Later, there is a powerful magic artifact known as a juju, shaped like a lollipop, the licking of which causes great power and great insanity. From an outside perspective, it resembles a powerful hallucinogen.
There's also Faygo, which affects trolls in a similar way to how alcohol affects humans. Eridan is fairly unimpressed by it, but Gamzee is more or less addicted to it and Terezi becomes so on the meteor.
Eerie Cuties: At one point, Nina switches bodies with her older sister Layla, but doesn't want Layla to wake up and realize what has happened, so right before she makes the switch, she consumes a heavy dose of the most powerful sedative she can imagine:
Nina(in Layla's body): Don't worry. I drank warm milk with extra honey. She'll be out for hours!
Housepets!: Orange Soda has the effect of making pets (King at least) drunk.
Fox's mentioning that "he (King) has only had one" seems to indicate that this happens to other pets. We also see one of the ferrets drunk off his gourd from orange soda (much to the confusion of the wolf he's speaking to).
An episode of Arthur featured a popular candy bar that contains a chemical which works almost exactly like a real drug (directly affecting the brain chemistry to make the person consuming the candy bar extremely happy but making the consumer feel sad when the chemical wears off until they get more of it) and the in show explanation on how said chemical works sounds like an extremely simplified way of explaining how real drugs work.
The trope is then subverted when it's revealed the candy actually has drugs in it.
Clone High parodied this in an episode revolving around Abe's destructive addiction to smoking raisins. After learning that you can't actually get high on raisins, the students decide to kick the habit for good and "smoke crack, instead!"
Tiny Toon Adventures used alcohol, yet with amusingly sarcastic bookend scenes; Buster points out the obvious hyperbole in them doing a Very Special Episode and closes by optimistically assuming they'll get to do a "funny" episode again.
An episode of Disney's Doug centered on Nic-Nacs, a legal, gum-like "relaxant" that was clearly tobacco in all but name (its main ingredient was "nicoglutenousmonopexterate"). The episode was a pretty heavy-handed screed against the tobacco industry for a kids' show.
There was an episode of Static Shock featuring a Bang Baby with the ability to give other people super powers temporarily...at the price of not telling anyone where they got them; oh, and they have to steal stuff for him. Well, if you want to get high—I mean, get super powers...
There are a couple of examples, both played surprisingly somber and serious for the show, in that the substances themself might be goofy or fantastical, but the consequences are appropriately dire. In one episode Mojo Jojo offers 4 disabled kids Chemical X-induced, temporary superpowers. Before long they are willing to kill the Powerpuff Girls for the next fix.
In the episode "Candy is Dandy" where the mayor starts rewarding the girls with candy for their heroics, not only the effect is disturbinly similair to a drug high, but the Girls are also willing to abandon their morals to get more, such as striking a deal with Mojo Jojo and then beat him to the inch of his life, when he steals the candy.
Root beer is often used in place of beer in 1990s Television prorgrams. In the Dexter's Laboratory episode "Dexter's Rival", in the end, Dexter has a toast with one of his inventions in which he pours root beer in a glass that's usually used for drinking liquor.
There was an episode which depicts Bart as addicted to Focusyn, which seems to be a stand-in for Ritalin until the end of the episode where Marge says she's getting Bart off of Focusyn... and back on Ritalin.
In the episode where Bleedin' Gums Murphy dies, he mentions squandering money on his "$1500 a day habit." Cut to a flashback of him buying Faberge Eggs.
The episode "Hell Is Other Robots" has Bender get addicted to electricity, which leads to the first appearance of the "Fry-fro", a funny hairstyle Fry gets on occasion. After an intervention, the main plot plays out when Bender decides to convert to a robot religion.
Lampshaded in a later episode, where Bender tries electricity again and gets arrested for "possession of something analogous to drugs".
"The Butterjunk Effect" has this in the form of a nectar found on Kif's home planet, which acts like steroids, including the deepening of one's voice. Leela and Amy began to use nectar to win in Butterfly Derby matches, but it makes them meaner, especially towards Fry and Kif. It also makes them attracted to Fry after a vicious, giant butterfly sprays him with its butterjunk.
Futurama also features Slurm, whose tagline is "It's highly addictive!" Fry is shown to be extremely addicted to Slurm - even after he finds out what it's made of. When going more than twenty minutes without a Slurm he starts to twitch and get shakes. It doesn't help that he's tasted the super-addictive Super-Slurm.
Apparently there are no bad drugs in that time. Hermes smokes pot (and doesn't lose it when his young son steals a "cigar" and smokes it). Crack is sold in vending machines, as well as crack mansions. Robots are fueled by alcohol. Bender becomes Iron Cook/Zinc Saucier by (unknowingly) dosing the meal with large amounts of LSD; once the Professor analyzes the liquid, Bender offers to cook a meal knowingly dosed, and everyone accepts eagerly.
Interestingly, since Bender runs on alcohol, he gets drunk when he doesn't drink for a while!
In He-Man and the Masters of the Universe (1983), the episode "A Friend in Need" has Ileena become addicted to a blue potion given to her by a "sorceress" who uses her addiction to try getting her to steal the Transmutator. She starts to suffer a withdrawal and Prince Adam becomes concerned...but obviously not much, since he coldly dismisses her instantly when the weeping girl says she can't tell him what's wrong!
While Fantastic Planet is hardly G-rated, the film abounds with drug imagery, drug effects, hallucinatory other-worlds - and yet, no real drugs.
South Park has had episodes based around people getting high on cough syrup ("Quest for Ratings") and cat urine ("Major Boobage"), and in another episode, Cartman snorts the skin off of illegally-obtained KFC ("Medicinal Fried Chicken"). "Medicinal Fried Chicken" additionally has a story where many of the male adults deliberately get testicular cancer so they can smoke all the medical marijuana they want.
You can get high off cough syrup. And if you buy the wrong kind, and ingest enough to get high, the additional chemicals can kill you.
Popeye. Come on, you honestly never thought of the spinach = steroids connection?
one Popeye cartoon has Bluto replacing Popeye's spinach with locoweed.
In the world of Regular Show, soda acts like beer, donuts may be dangerous, and coffee...
In the episode "Weekend at Benson's", the main characters drink a concoction of seafood, mayonaisse, and various spicy things called "Mississippi Queen". After hallucinating vividly, they wake up in the park, hung over and unable to remember what happened.
In Gold Watch, after eating hot wings Benson is told by Skips "a lot of people do things they regret on a belly full of wings" and he was told to take it easy on them. He wakes up not remembering anything after having too many.
Since Harry Osborn's amphetamine addiction was too touchy a subject to use in a cartoon aimed at children, The Spectacular Spider-Man compensated by having him instead develop an addiction to "Globulin Green," the serum that turns him into the Green Goblin.
Superboy's addiction to "Shields" (patches developed by Lex Luthor that give him access to Kryptonian-level abilities) is also treated like a metaphor for drug abuse. The whole subplot comes off like a cautionary tale about the dangers of steroids.
Even Hey Arnold! had this, with chocolate. Regular chocolate. Chocolate Boy once went into a withdrawal, curling up into a ball and shivering when he didn't have it, as well as digging through dumpsters to find some.
The Smoggies had purple silly sauce, which was a G-Rated Drug powerful enough to contaminate an eco system and cause whomever came into contact with it to involuntarily sing and dance perpetually, even in diluted amounts. The song they would sing, "The Purple Rag" was an Ear Worm as well as being a state of And I Must Scream.
Mac on Foster's Home for Imaginary Friends gets hyperactive when he eats sugar. In an episode where Bloo throws a massive rave at Foster's, Mac unwillingly ingests sugar, then proceeds to go through a climbing-the-walls-nude drug trip from the effects. The post-rush withdrawal reduces him to a shivering wreck that's equal parts jonesing junkie and Gollum parody.
The episode "Cookie Dough" has Frankie devour thousands of boxes of her grandmother's cookies, which she has loved since she was a baby.
Beavis' alternate persona, The Great Cornholio, is created due to a large consumption of caffeine. One episode had Beavis having a sugar crash and was given a powerful cappuccino to keep going (he was in a poetry night thing. Don't ask) and, in the movie, he downs a number of caffeine pills after a well-meaning old woman gives him some to help him (first to help with airsickness, the second after the bus driver kicks his ass).
In Transformers Prime, Ratchet creates Synthetic Energon and then injects himself with it, causing him to gain immense strength, but renders his mind unstable, making him aggressive and incredibly arrogant.
An episode of The Looney Tunes Show has Bugs Bunny addicted to Spargle, an energy drink he acquires from Yosemite Sam. He is extremely hyper, euphoric and over-productive when he consumes large amounts of it and freaks out when his supply runs out to the point of threatening Sam for more. Subverted when it turns out that Sparkle's secret ingredient is an illegal drug.
Galaxy High had an episode where Doyle becomes addicted to "Brainwaves" administered through a device called a "Brain Blaster", so that he could pass a test and retain his sports eligibility.
One episode of King of the Hill has Bobby getting addicted to New York-style deli food, which ends up giving him Gout. When the chef making the food suggests that maybe he should stop eating, Bobby angrily screams out "I'll tell you when I've had enough!"
The Double Dragon cartoon series, notable for having An Aesop at the end of every episode, had an episode that focused on the Shadow Master producing a designer drug, known as Euphoria, which turned users into wide-eyed, green-eyed zombified people. Presumably in attempt to avoid portraying real drug abuse methods, the green liquid Euphoria was not ingested nor injected, but rather poured onto bare skin, though it was often applied this way to the forearm.
Later on, the Shadow Master was back in the business, selling RPM.note Stored in glass balls, they were broken and the drug inhaled. Billy looked horrible when forcibly dosed. The drug acted very much like steroids.
Gravity Falls had "Smile Dip", a banned German confectionery (and a parody of the real life candy Fun Dip) that caused Mabel to hallucinate. Although, eating bleven-teen packages of it probably didn't help matters either.
In "Hooked Up" The villain Spellbinder opens a VR arcade, where people can experience their greatest fantasies. The massive doses of endorphins released by living out these fantasies, however, make these simulators extremely addictive. As soon as people leave his VR machines, they experience intense withdrawal symptoms. He uses this to get people to steal and commit other crimes for him.
"The Winning Edge" is actually an aversion of the "G-rated" part as it features steroids (a "steroidal compound" according to Bruce Wayne's files on it) taken like nicotine patches via adhesive pads called "slappers." It turns out they're based on Bane's Venom, which has rendered him a comatose junkie and invalid after decades of abuse.
The Dexter's Laboratory episode "Beard to be Feared" has Dexter getting roped into breaking up a band of flour smugglers.
In the My Little Pony: Friendship Is Magic episode Inspiration Manifestation, the spellbook effectively serves as this for Rarity. Under its influence, she stops eating, grows increasingly manic in her behavior, and is only free of it when Spike finally stops enabling her and makes her realize how harmful it is.
Caffeine. Just look at all the new products that have come into play over the last ten years. Yeah sure, we've always had coffee and tea, and Red Bull isn't exactly new, but whose bright idea was it to cram all the crap of an energy drink into a 2 oz. package?
Older than you think: Energy shots are derived from Japanese "tonics", which were small amounts of extremely potent liquid that would do different things. When Energy Drinks became popular, it was a no-brainer to combine "This drink that does something to you" and "This extremely potent drink that does something to you in small doses". It seems recent that energy shots have became prevalent in the west, but they've been fairly common in the Orient for a few decades now.
Interestingly, if caffeine had only been discovered in modern day, based on its bodily effects and addictive potential, it might've been evaluated as a dangerous/controlled substance.
Nutmeg contains a natural hallucinogen. The only problems: It tastes horrible by itself, it takes a huge dose to get anything, the "trip" is anti-euphoric, and the hangovers are debilitatingly awful.
One of Carl Barks' stories has Scrooge McDuck addicted... to nutmeg tea. It was "A Spicy Tale" from September, 1962.
In the movie The Wrong Box, old Joseph Finsbury attributes his brother's erratic behavior to a nutmeg poisoning (oblivious to the fact his brother is trying to kill him).
And in the movie Idle Hands, Anton is told by his stoner buddies that "I hear if you combine nutmeg and oregano you can get pretty wasted." He tries it, and it's apparently disgusting. Later when he's killing those same stoner friends, one of them, trying to call the cops, exclaims that "I think he smoked some nutmeg or something!"
Nepeta, also known as catnip. In humans it has "soothing" and numbing effects and is used as a flavoring in tea, it's also mixed with tobacco or marijuana and smoked. A study found that a 4-year-old child who had eaten 3 raisins soaked in the stuff got high. Why do you think cats like it so much? Has its own subtrope.
Calamus root. Theoretically, it's mildly stimulating and in large quantities becomes hallucinogenic. Practically, its taste is "interesting"—if you used to drink black coffee without sweets—but even then trying to chew that much of roots will probably sooner get your whole digestive tract (along with the taste center in brain and maybe skin on the back of your ears) tanned for good than it will make you really "high."
In Russia, extremely strong tea (leaves boiled to black sludge-strong) known as Chephyr, is sometimes used as substitute for Amphetamine in prisons.
For a more innocent example, the sunflower seeds ("semki") are immensly popular and are positively IMPOSIBLE to stop nibbling.
Salvia divinorum is still legal in most parts of the world, but produces an extremely intense half hour of hallucinations, euphoria, and/or panic when extractions are smoked.
It has no health effects and is not addictive. However, there's a media campaign against it.
People have been known to do bizarre things up to and including kill themselves or other people while under the influence of the stuff, but then again, alcohol can do that too...
Dextromethorphan is a cough medication available without prescription in most parts of the world - despite the fact that it's a potent debilitating hallucinogenic dissociative in high doses.
Subverted: At least in the USA, recent epidemics of teenagers chugging the syrup and tripping in school has caused companies to mark cough medications, and grocery stores to card youngsters for cough medicine the same way as they would for cigarettes or alcohol.
Benadryl, also known as diphenhydramine. Remember how your mom used to give it to you to sleep? People get high off of quantities around 700mg+. The catch? It's basically hell on earth. With spiders.
For diabetics, too much insulin causes symptoms that mimic drunkenness. Insulin shock is actually a medical emergency.
At least for Type 1, this is entirely because of low blood sugar. It's mostly blurry vision and tiredness.
Coca is an interesting case. In Peru, the leaves are commonly chewed directly or brewed into a tea. (It's quite common to see boxes of coca tea in the grocery store right next to the Earl Grey.) In normal amounts, this is said to prevent altitude sickness; larger doses can be somewhat intoxicating. Of course, grinding up and concentrating the leaves gives you a drug that's most certainly not G-rated. For this reason, trying to import even a commercially-packaged box of coca tea into the U.S. will, at the very least, result in confiscation and a long chat with a customs agent.