The causes of paranoia are not clearly understood. Researchers have found that family history of paranoia is not greater in paranoid patients than in those without paranoia. However, studies of twins have shown a potential genetic influence on some paranoid symptoms in patients with schizophrenia. Other research has shown that paranoid disorders are much more common in relatives of people with schizophrenia.

The role of abnormal brain chemistry in paranoia remains unclear. Some research has indicated that paranoid schizophrenia has different biochemical characteristics than other nonparanoid forms of schizophrenia.

Use and abuse of certain substances may lead to symptoms of paranoid thinking or behavior. Examples include abuse of amphetamines, cocaine, steroids and alcohol. Research continues into how biochemical actions of these drugs may trigger paranoia.