According to researchers, young people with cannabis-dependence have an altered brain function that may be the source of emotional disturbances and increased psychosis risk.
The alterations were most pronounced in people who started using cannabis at a young age.
The findings reveal potential negative long-term effects of heavy cannabis use on brain function and behaviour.
Study authors Dr Peter Manza, Dardo Tomasi and Nora Volkow of the National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, assessed 441 young adults and compared a smaller set of 30 people who met criteria for cannabis abuse with 30 controls.
People with heavy cannabis use had abnormally high connectivity in brain regions important for reward processing and habit formation.
The same regions have also been pegged in the development of psychosis in previous research.
Dr Cameron Carter explained, "These brain imaging data provide a link between changes in brain systems involved in reward and psychopathology and chronic cannabis abuse, suggesting a mechanism by which heavy use of this popular drug may lead to depression and other even more severe forms of mental illness".
The brain alterations were also associated with heightened feelings of negative emotionality, especially alienation, where one feels a sense of hostility or rejection from others.
The link points to a potential biological mechanism for why feelings of alienation are often profoundly increased in people with cannabis dependence.
"Interestingly, the hyperconnectivity was strongest in the individuals who began using cannabis in early adolescence", Dr Manza added.
Adolescence is a critical period of brain development, making early use of cannabis particularly detrimental, they noted.
The research appears in Biological Psychiatry: Cognitive Neuroscience and Neuroimaging journal.