Cannabis is the most widely used illicit drug in the world, but
there is increasing evidence that its use during adolescence may
increase the risk of developing psychosis later in life. Not all
cannabis smokers develop psychotic symptoms, however, and it has
been postulated that certain individuals may be genetically
vulnerable to its effects. Polymorphisms in several genes have
been linked with schizophrenia. Given the likely role of
dopaminergic dysfunction in the pathogenesis of psychosis, it is
no surprise that most genetic investigations have focussed on
variants in genes involved in dopamine neurotransmission. One
such gene, COMT, is located on chromosome 22q11, a region
highlighted in several genome scans of schizophrenia. COMT
encodes catechol-O-methyltransferase, an enzyme involved in the
metabolism of dopamine in the synapse. The COMT gene contains a
common missense mutation that causes a valine to methionine
substitution at codon 158, producing a less active enzyme.
Genetic association studies sugg