Researchers from Monash and Melbourne universities took high-tech images of the brains of 155 primary school students when they were 12.
Four years later when they reached their milestone 16th birthday, the students were asked whether they had used cannabis.
Of 121 who responded, 28 admitted to using the drug.
When the researchers checked the scans taken when those students were 12, they found a part of the frontal lobe area in their brains was smaller than those in teens who steered clear of cannabis.
Lead researcher Prof Dan Lubman said the students with abnormalities in the orbitofrontal cortex - the brain region involved in memory, reward and decision making - were more prone to using cannabis.
"What we found is that only the orbitofrontal cortex predicted later cannabis use, suggesting that this particular part of the frontal lobe increases an adolescent's vulnerability to cannabis use," the Herald Sun quoted him as saying.
The study is the first to examine whether existing brain abnormalities have a role in whether teens start using cannabis.
The finding was published online by the journal Biological Psychiatry.