Novel compounds that modulate PDE10A, a gene that is primarily expressed in medium spiny neurons of the mammalian striatum and has been found to inhibit striatal output by reducing spiny medium excitability and effect cAMP and cGMP signalling cascades in vivo in rats, and methods for treating psychosis and schizophrenia using the novel compounds. Methods for screening for further compounds to modulate PDE10A activity are also taught.