Does dopamine sensitization underlie the association between schizophrenia and drug abuse?

Drugs that release dopamine, such as amphetamines and cocaine, have long been known to be associated with schizophrenia. As Professor Stefanis pointed out many years ago, people with schizophrenia also commonly consume cannabis, which, like the psychostimulants, also enhances dopaminergic activity. Several theories have been put forward to explain the association between psychostimulants and cannabis on the one hand and schizophrenia on the other, notably the self-medication and vulnerability hypotheses. Recent evidence from both experimental and prospective studies supports the latter, and clearly demonstrates that the use of these drugs increases the risk of schizophrenia. Here we point out that dopamine sensitization plays a central role in explaining this, in that its development underlies both a craving for drugs and the positive symptoms of schizophrenia. The parts played by glutamate and the dopamine D-3 receptor in dopamine sensitization are currently receiving much attention.