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Girls – Substance Lyrics 15 years ago
Yes, it's a reference to substance use. The song opens with someone (his inner monologue?) suggesting that a substance will take the edge off, make everything easier, etc. The substance is the key to this carefree life (or the illusion thereof, as the lyrics "you could have nothing," "just give up," and the final line suggest).

There is also car-related imagery throughout the song, such as "down the road," "let go of the wheel," "simple ride," and taking the key is a continuation of this.

The word "key" is also loaded with drug entendres, as others stated, such as slang for a kilo or the practice of using a key to scoop the substance. Though he's probably not literally talking about a kilo of anything in his hand, these connotations add an extra layer of depth to the lyrics.

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