Quite simply, Dylan Ebdus and Mingus Rude are friends in The Fortress of Solitude. They grow up trying desperately to navigate the newly integrated neighborhoods of Brooklyn, New York and deal with their differences in race (Dylan is white and Mingus is black) with grace and style.
Dylan is the newcomer in the neighborhood and it isn't long before his mom deserts the family. Mingus, never having had a mother, bonds with Dylan over this desertion. Mingus, feeling sorry for Dylan, becomes a kind of big brother to him. As a result, Mingus protects Dylan from the notorious exploits of the neighborhood children.
As a result of their friendship, Dylan gets to experience things that are usually "forbidden" to whites. Probably the most important and unifying one of these experiences is "graffiti tagging." Mingus is already famous for this. Mingus' signature is the word/name "Dose." As a testament of friendship, Mingus asks Dylan to share the name instead of creating a new one.
[Dylan has] been allowed to merge his identity in this way with the black kid’s, to lose his funkymusicwhiteboy geekdom in the illusion that he and his friend Mingus Rude are both Dose, no more and no less. A team, a united front, a brand name, an idea.
Then there is the unifying persona of Aeroman, the dual superhero the boys create in order to fight small crime in their neighborhoods. They spend long hours "flying" around due to a ring given to Dylan that suppposedly has magic within it. Unfortunately, this unity doesn't last forever.
I would say that it is drugs that make "them eventually drift apart," as you ask in your question. Mingus is lured into the drug scene and rejects their Aeroman persona which causes Dylan to sell all of their beloved comics in an act of betrayal. Mingus, now seriously addicted to drugs, spirals downward and ends up as a criminal locked up for life in a New York State Penitentiary.
Fast forward to years in the future where Dylan is a rock critic in California still dealing with his past and now deeply cynical. His girlfriend (who is black) is always saying things like this:
What happened to you? ... Your childhood is some privileged sanctuary you live in all the time, instead of here with me.
Dylan endeavors to reconnect with Mingus and break him out of prison, claiming that Mingus is "the rejected idol of my entire youth, my best friend, my lover." During a visit at the prison, Dylan gives Mingus their old Aeroman ring. The failure of this plan is the end of their dreams and a sad truth about crime and its relation to poverty and racial division.