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Drugs and Alcohol
Alcohol abuse is everywhere in Love Medicine, particularly among the male characters, and that definitely contributes to our overall sense that these characters are not happy campers. As Nector himself says, alcohol represented an escape for him as a young man, and it seems like a lot of the other dudes on the reservation felt the same way.
Not surprisingly, alcohol abuse gets worse as the characters get more and more unhappy. Take Gordie, for example, who apparently turned to alcohol after June's death, and ended up so desperate for a high that he did all kinds of dangerous stuff (like driving drunk in search of more liquor, and drinking Lysol).
The novel's focus on alcoholism is definitely related to the symbol of water—they call it "drowning your sorrows" when you drink a lot, right? The novel's consistent return to the topic of drowning is definitely related to the characters' use and abuse of alcohol.
Alcohol abuse is a big theme because it emphasizes the intensity of the characters' sadness/depression.
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