1. confounders
   1. socioeconomic (Philip and Johnson)
   2. demographic
   3. common genetic factors (Tsung)
   4. dysregulation of neural circuitory mediating drug reward and reinforcement (Chambers, 01)
2. hypotheses
   1. vulnerability hypothesis
      1. Use of cannabis actually increases the risk of S
      2. predicts the risk of S should be higher in users
   2. self medication hypothesis
      1. Pt with S take drugs to reduce S/S or ADR
3. support
   1. cannabis intox leads to brief psycho episode (mahters and godse)
   2. or recurrence of psychosis in people with history of psychosis
   3. IV THC exacerbates +ve s/s in pt and induces them in controls (D'Douza 2000)
   4. NEUROIMAGING
      1. lllar in Fn network impaired by cannabis and those implicated in pathogenesis of S (leuber, todd, 99)
   5. cannabinoid agonists impair cog that are hallmark s/s of S (Emrich, 97)
   6. ENDOGENOUS CANNABINOIDS
      1. ? aetiological role in S
      2. Increase in CSF of S, independent of age, gender or Rx (Leweke, 99)
   7. POST MORTEM STUDIES
      1. Increase binding of CRA in DLPFC of S independent of recent use (Dean 01)
      2. Increases binding of CRA in cingulate cortex of S compared with controls (Zavitsanou)
4. Sweedish Conscript Cohort (Andreasson, 87)
5. Other studies
   1. subjects with high vulnerability would report more perceived hostility, strange or unusual impressions (Amorin)
   2. experience sampling (Verdoux, 03)
      1. acute effects of cannabis were modified by vulnerability of psychosis
   3. Neuroimaging
      1. use before age 17 -- low % of cortical grey matter (Wilson, 2000)
   4. Mathematecal modelling study
      1. - cannabis ppt psychosis in vulnerables - use is more likely in S - DID NOT SUPPORT CAUSAL LINK (dEGENHARDT 03)
6. SR & MA (Semple, Lawrie, McIntosh, 05)
   1. case- contol studies (11)
      1. consistent unadj OR acoss all pop group studied NO BIAS, NO HETEROGENITY
      2. MA of OR (7)
         1. SIMILAR fixed and random effects OR
   2. 6 case control Studies that rated psychotic S/s in users compared to non-useres
      1. High risk pop
         1. did not find increased risk ; possible dose-response relationship
      2. general pop (LARGEST CROSS-SEC STUDY, dEGENHARDT 01)
         1. POSSIBLE dose related effect
   3. Prosp long study (Furguson, 03)
      1. Greater vuln to cannabis in early adolescence
7. Floating Topic
8. initial evidence of asso of cannabis and psychosis (Bowers 01)
   1. case reports of cannabis preceeding schizohrenia
   2. psychosis in community survey of cannabis users
   3. obs studies of psychosis in cannabis users