Cannabis use and the development of schizophrenic psychoses share a variety of similarities. Both start during late adolescence;
go along with neuropsychological deficits, reduced activity, motivation deficits, and hallucinations suggesting impairment of similar
brain structures. In cannabis heavy users diminished regional gray and white matter volume was reported. Similar alterations were observed
in the large literature addressing structural abnormalities in schizophrenia. Furthermore, in cannabis using schizophrenic patients,
these brain alterations were especially pronounced. Close relatives of schizophrenic patients showed greater cannabis-associated brain
tissue loss than non-relatives indicating a genetically mediated particular sensitivity to brain tissue loss.
Possible mechanisms for the induction of structural brain alterations are here discussed including impairments of neurogenesis, disturbance
of endocannabinoids and diminished neuroplasticity. Especially direct THC effects (or via endocannabinoids) may mediate diminished
glutamatergic neurotransmission usually driving neuroplasticity. Correspondingly, alterations of the kynurenic acid blocking
NMDA receptors may contribute to brain structure alterations. However, different cannabis compounds may exert opposite effects on the
neuroanatomical changes underlying psychosis. In particular, cannabidiol (CBD) was shown to prevent THC associated hippocampal
volume loss in a small pilot study. This finding is further supported by several animal experiments supporting neuroprotective properties
of CBD mainly via anti-oxidative effects, CB2 receptors or adenosine receptors. We will discuss here the mechanisms by which CBD
may reduce brain volume loss, including antagonism of THC, interactions with endocannabinoids, and mechanisms that specifically underlie
antipsychotic properties of CBD.