Cannabis use and psychosis onset: from epidemiology to clinical practice

Objectives The aim of this study is to review the most recent literature data regarding association between use of cannabis and psychotic disorders, especially highlighting epidemiological, neurobiological and clinical data. Methods A MEDLINE search of the international literature data was performed. The following keywords were used: "cannabis use", "onset psychosis", "high risk of psychosis", "at risk mental state", "epidemiology", "neurobiology" and "clinical features". All studies from the years 2000 to 2011, except for epidemiological studies, were selected. Finally, the most relevant literature was chosen. Results Cannabis use is associated with a 2- to 3- fold increase in the relative risk for psychosis in individuals with familial and genetic vulnerability. The results of several prospective studies also show a dose-response relationship between exposure to cannabis and the risk of psychosis after exposure. Many neurobiological studies reported that the Delta(9)-tetrahydrocannabinol (Delta(9)-THC) is the component of cannabis with the most psychotropic effects that can mediate psychotic onset through alteration of the endocannabinoid signal. A key role in genetic vulnerability to these effects is supported by polymorphisms of the gene for catechol-Omethyl-transferase (i.e., the presence of the gene variant Val/Val compared to Met/Met). More recent studies have shown how the use of cannabis preparations with higher concentrations of Delta(9)-THC (e.g., skunk vs. resin vs. leaves) is more associated with onset of psychosis. Conclusions According to literature data, we predict an increase in the rates of psychosis over the next 10 years. However, the possibility to eliminate the cannabis use is fairly remote, and clinicians should concentrate their attention on individuals with genetic vulnerability for psychosis and adolescents. In this latter population, increased use and reduction in the age of first consumption has been observed. Therefore, prevention campaigns in schools to reduce the use of cannabis and the risk of psychopathological consequences linked to it are needed. In subjects at risk for psychosis, defined according to the genetic risk (family) for psychosis or the presence of an at-risk mental state, proper psychoeducation on cannabis use is necessary to prevent the onset of overt symptoms and improve long-term outcomes.