In the Repentance expansion, a cutscene playing after defeating Mother reveals a interaction between Isaac and his mom, where she finds an unflattering image of herself that Isaac has drawn and punishes him by locking him in his closet and saying he's 'just like his father,' which are both abusive behaviours.
One of the “chest” endings has Isaac obtain a needle full of what’s implied to be heroin, before cutting to a shot of him where his appearance looks dishevelled in a similar way to someone who is addicted to heroin.
There are several syringes that can be taken as upgrades, as well as multiple pills that you take as consumables. There's also a "spun" transformation that gives the player an erratic look with needles stuck in their arms. There are also items like "Mom's bottle of pills" and "Mom's coin purse" that spawns a couple of pills around the player with the caption "What's all this?"
I get why most say No", because no horses die in the story, but there are bosses made after the 4 horsemen of the apocalypse who ride hobby-horses that look like dead/demonic horse heads or skeleton horse heads. Also 2 items in the game which are these hobby-horses that look like severed horse heads.
Isaac's cat, Guppy, plays a big role in the game, with several of his body parts serving as items found in treasure chests. One ending in the remake also shows what is implied to be Guppy's corpse locked in the toy chest with Isaac.
There are a number of worm-like enemies, and while these are not snakes, some of them have variations that look more snake-like. Of particular note are the skeletal variations, where a snake skeleton stands in for the skeletonless worm.
Some enemies either lose their heads after taking enough damage, are missing them to begin with, or are severed heads themselves. This includes some bosses, such as Famine and Pestilence.
The item Isaac's Fork could imply that loosely, but its actual behaviour more resembles vampirism than cannibalism. No actual cannibalism is seen, you just replenish health upon killing enemies as a video game mechanic.
If you count Mom's foot being able to stomp the player character to death in a boss fight, yes. Falling rocks can also kill you in certain fights. It is, however, not graphic, and Isaac will do his standard death animation.
Certain power-ups remove Isaac's body parts or resemble missing limbs, purely for cosmetic purposes. Others (most notably Scissors and Leprosy) temporarily remove body parts to weaponize them.
All of the "greed" enemies and one player character that's meant to be one of them have nooses around their necks. This also applies to the shopkeepers because they appear to be greeds.
Issac hangs himself in one normal ending and at the end of Greed Mode IIRC. He also suffocates to death inside of a toy chest.
Not at this time, though given the game's penchant for gross-out humor and bug-like enemies, I don't think it's safe to assume that this will not change.
Pills are encountered throughout the game, and they can give a variety of effects from good to bad, or even comedic.
One item, "Mom's Purse," drops a handful of pills, implying Isaac's mother is a drug abuser.
Another consists of a mushroom, which will overlay the screen with psychedelic effects, which intensify the more it is used. This wears off if the mushroom is not used continuously.
There is 2 unlockable characters (The Lost and The Soul) who are explicitly ghosts (The latter being bound to his still-walking skeleton, The Forgotten) a few items turn Isaac into a ghost, and several enemies are ghosts, most notably the Haunt boss and it's variants.
After beating the boss Mom’s Heart 6 times, a cutscene will play which shows the protagonist, Isaac, opening a chest. He turns towards the player and his face turns green and his cheeks puff up (as if he is holding vomit in his mouth). He turns back to the chest and vomits into the chest. The vomit cannot be seen coming out of Isaac’s mouth directly, but audio can be heard and some vomit is visible splashing out the side of the chest.
Poop and potty humor are abundant in this game. Piles of poop appear frequently that can be destroyed and sometimes drop items, there are several poop-themed enemies, and there are items relating to poop in the item pools (The Poop, Butt Bombs, No. 2, Montezuma's Revenge, etc)
[Repentance] In the boss fight against Rotgut, the player is swallowed after the first phase and the fight is continued in its insides. It's possible to escape, though.
No. However Isaac does cross dress which it’s implied he’s made fun of for by his peers and is seen as mentally disturbed behaviour by his mother. (Note: Isaac is explicitly not trans, he just crossdresses while roleplaying as characters. This is shown in how the “other” selectable playable characters are; they are all just Isaac in a different wig and costume rather than a different person entirely.)
Synthoil, Speed Ball, Experimental Treatment, Anaesthesia, Adrenaline, Roid Rage, The Virus, Growth Hormones and the Spun transformation are all present.
Some of the items include used tampons and pads. Also I’m not sure if this counts, but one of the enemy types is a walking vagina with legs that fires a blood laser at you.
Someone is portrayed as hearing a "message from god" that urges them to kill someone. They are shown to be delusional and violent, and they attempt to carry it out in a sort of cartoonishly-depicted way later on.
The entire game save for some cutscenes takes place in Isaac’s mind as he suffocates to death, resulting in some things getting strange or not making sense. This becomes most glaring in “The void,” where the game becomes a random mishmash of the previous levels, enemies, and bosses.
The Ultra Greed boss fight outro depicts Isaac appearing to be trapped under rubble and suffocating. The Delirium boss fight outro depicts Isaac being suffocated in a toy chest.
Suicide is a major theme throughout the game, with several items such as "Transcendence", (A noose that is explicitly used to hang Isaac) "Plan C", (Kills all enemies in the room, then kills Isaac 3 seconds later) and the "Suicide King" card (Spawns a lot of items and then kills Isaac). This is not even scratching the surface of the amount of suicide, both implicit and explicit, in this game.
[Repentance] Adds more screen shakes to explosions. Adds the Wavy Cap item, which causes increasingly flashing lights and wavy vision the more times it is used. Adds TMTRAINER and the Delete This challenge, both of which have a chance to copy the screen effects of Wavy Cap without warning.
[+REPENTANCE] An unlockable item, Larynx, makes Isaac shout to damage enemies. Area of effect, damage, and shout intensity, depend on the item's charge upon usage.
It isn't a common thing in gameplay, not necessarily by design, but certain extreme power-up combinations can cause the game to start glitching out and flashing in a strobe-like fashion.
It's difficult. One of the bosses is Isaac's evil mother, Magdalene. After she's defeated, in the next chapter, which is the womb, you have to battle an undeveloped fetus, so technically, yes
Mom calls Isaac Isaac, even if they currently roleplay as a female character (like Maggy or Eve). This could affect people who are sensitive to dead-naming.
The main character can probably be considered LGBT, as Maggy and Eve are alter egos of Isaac and they're also seen wearing a dress and wig in a cut scene. Isaac can and will obviously die, depending on how well you play.
Not sure if it counts, and it's more of an in-universe thing, but one scene that can appear between levels shows kids laughing at Isaac for wearing a feminine wig.
The item "Shoop da Whoop" references a meme that has its roots in blackface. This does not appear to be intentional on the part of the game developers, but it's still there.
there are huge sections of the game based around demons and hell. several playable characters are demons or can be turned into demons. there is an abundance of demonic imagery and satan is a focal point regularly.
Isaac is fully naked throughout almost the entire game, but not in an explicit or provocative manner. His genitals are not visible in-game, though are comically depicted as a tiny line in a few cutscenes.
Nothing graphic. All the characters are naked, but lack genitals and other parts of that caliber.
The item "Gimpy" puts a gimp mask on the character.
The levels called womb/utero have a red, fleshy appearance to the rooms, and you later fight either a heart or a fetus.
While not dementia, there is a boss named Delirium, which represents just that. It references Isaac going insane as he is slowly deprived of oxygen in his canonical death.
There are certainly a lot of fetuses floating around, in the manner of some infamous types of anti-abortion advertising. This is not necessarily presented as an anti-abortion message -like most things in the game it's played for laughs- but some people may find it uncomfortably similar.