Macklemore has struggled with drug abuse in the past and publicly spoken about the issue, including in previous songs such as "Otherside".

[5] In the first verse, Macklemore addresses the political pull of pharmaceutical companies,[3][5] the drug-related deaths of musicians Prince, Michael Jackson, Whitney Houston, Amy Winehouse, Heath Ledger, Pimp C, ASAP Yams and DJ AM,[3][5][6] and the ongoing opioid epidemic in the United States.

[2][3][5][6] Following the hook, Macklemore covers his own struggles with addiction ("Four Horseman, they won't let me forget / I wanna forge a prescription, cause doctor I need some more of it / When morphine and heroin is more viewer budget / I said I'd never use a needle, but sure, fuck it")[3][4] and the consequences of opioids.

[7][8][9][10][11] Throughout the video, he is shown sitting, lying, tossing and turning in a stripped down mattress and sweating,[7][10][11][12][13] in a room surrounded by drugs;[10] his eyes are swollen and filled with tears.

[14][15] On November 16, 2016, Macklemore performed the song with Ariana DeBoo and The Roots on The Tonight Show Starring Jimmy Fallon.