title: Cannabis and schizophrenia.
abstract: BACKGROUND
  Schizophrenia is a mental illness causing disordered beliefs, ideas and sensations. Many people with schizophrenia smoke cannabis, and it is unclear why a large proportion do so and if the effects are harmful or beneficial. It is also unclear what the best method is to allow people with schizophrenia to alter their cannabis intake.
  
  
  OBJECTIVE
  To assess the effects of specific psychological treatments for cannabis reduction in people with schizophrenia.To assess the effects of antipsychotics for cannabis reduction in people with schizophrenia.To assess the effects of cannabinoids (cannabis related chemical compounds derived from cannabis or manufactured) for symptom reduction in people with schizophrenia.
  
  
  METHODS
  We searched the Cochrane Schizophrenia Group Trials Register, 12 August 2013, which is based on regular searches of BIOSIS, CINAHL, EMBASE, MEDLINE, PUBMED and PsycINFO.We searched all references of articles selected for inclusion for further relevant trials. We contacted the first author of included studies for unpublished trials or data.
  
  
  METHODS
  We included all randomised controlled trials involving cannabinoids and schizophrenia/schizophrenia-like illnesses, which assessed:1) treatments to reduce cannabis use in people with schizophrenia;2) the effects of cannabinoids on people with schizophrenia.
  
  
  METHODS
  We independently inspected citations, selected papers and then re-inspected the studies if there were discrepancies, and extracted data. For dichotomous data we calculated risk ratios (RR) and for continuous data, we calculated mean differences (MD), both with 95% confidence intervals (CI) on an intention-to-treat basis, based on a fixed-effect model. We excluded data if loss to follow-up was greater than 50%. We assessed risk of bias for included studies and used GRADE to rate the quality of the evidence.
  
  
  RESULTS
  We identified eight randomised trials, involving 530 participants, which met our selection criteria.For the cannabis reduction studies no one treatment showed superiority for reduction in cannabis use. Overall, data were poorly reported for many outcomes of interest. Our main outcomes of interest were medium-term data for cannabis use, global state, mental state, global functioning, adverse events, leaving the study early and satisfaction with treatment. 1. Reduction in cannabis use: adjunct psychological therapies (specifically about cannabis and psychosis) versus treatment as usualResults from one small study showed people receiving adjunct psychological therapies specifically about cannabis and psychosis were no more likely to reduce their intake than those receiving treatment as usual (n = 54, 1 RCT, MD -0.10, 95% CI -2.44 to 2.24, moderate quality evidence). Results for other main outcomes at medium term were also equivocal. No difference in mental state measured on the PANSS positive were observed between groups (n = 62, 1 RCT, MD -0.30 95% CI -2.55 to 1.95, moderate quality evidence). Nor for the outcome of general functioning measured using the World Health Organization Quality of Life BREF (n = 49, 1 RCT, MD 0.90 95% CI -1.15 to 2.95, moderate quality evidence). No data were reported for the other main outcomes of interest 2. Reduction in cannabis use: adjunct psychological therapy (specifically about cannabis and psychosis) versus adjunct non-specific psychoeducation One study compared specific psychological therapy aimed at cannabis reduction with general psychological therapy. At three-month follow-up, the use of cannabis in the previous four weeks was similar between treatment groups (n = 47, 1 RCT, RR 1.04 95% CI 0.62 to 1.74, moderate quality evidence). Again, at a medium-term follow-up, the average mental state scores from the Brief Pscychiatric Rating Scale-Expanded were similar between groups (n = 47, 1 RCT, MD 3.60 95% CI - 5.61 to 12.81, moderate quality evidence). No data were reported for the other main outcomes of interest: global state, general functioning, adverse events, leaving the study early and satisfaction with treatment. 3. Reduction in cannabis use: antipsychotic versus antipsychotic In a small trial comparing effectiveness of olanzapine versus risperidone for cannabis reduction, there was no difference between groups at medium-term follow-up (n = 16, 1 RCT, RR 1.80 95% CI 0.52 to 6.22, moderate quality evidence). The number of participants leaving the study early at medium term was also similar (n = 28, 1 RCT, RR 0.50 95% CI 0.19 to 1.29, moderate quality evidence). Mental state data were reported, however they were reported within the short term and no difference was observed. No data were reported for global state, general functioning, and satisfaction with treatment.With regards to adverse effects data, no study reported medium-term data. Short-term data were presented but overall, no real differences between treatment groups were observed for adverse effects. 4. Cannabinoid as treatment: cannabidiol versus amisulprideAgain, no data were reported for any of the main outcomes of interest at medium term. There were short-term data reported for mental state using the BPRS and PANSS, no overall differences in mental state were observed between treatment groups.
  
  
  CONCLUSIONS
  Results are limited and inconclusive due to the small number and size of randomised controlled trials available and quality of data reporting within these trials. More research is needed to a) explore the effects of adjunct psychological therapy that is specifically about cannabis and psychosis as currently there is no evidence for any novel intervention being better than standard treatment,for those that use cannabis and have schizophrenia b) decide the most effective drug treatment in treating those that use cannabis and have schizophrenia, and c) assess the effectiveness of cannabidiol in treating schizophrenia. Currently evidence is insufficient to show cannabidiol has an antipsychotic effect.
authors.affiliation: School of Medicine, The University of Nottingham, Queens Medical Centre, Nottingham, Nottinghamshire, UK, NG7 2UH.
authors.forename: Benjamin C
authors.initials: BC
authors.lastname: McLoughlin
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Pushpa-Rajah
authors.forename: Donna
authors.initials: D
authors.lastname: Gillies
authors.forename: John
authors.initials: J
authors.lastname: Rathbone
authors.forename: Hannele
authors.initials: H
authors.lastname: Variend
authors.forename: Eliana
authors.initials: E
authors.lastname: Kalakouti
authors.forename: Katerina
authors.initials: K
authors.lastname: Kyprianou
mesh_terms: D000077582:Amisulpride; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000627:therapeutic use; D002186:Cannabinoids / Q000627:therapeutic use*; D006801:Humans; D002189:Marijuana Abuse / Q000523:psychology / Q000628:therapy*; D064086:Medical Marijuana / Q000627:therapeutic use*; D000077152:Olanzapine; D011613:Psychotherapy; D016032:Randomized Controlled Trials as Topic; D018967:Risperidone / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy*; D013469:Sulpiride / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D014150:Antipsychotic Agents; D002186:Cannabinoids; D064086:Medical Marijuana; D001569:Benzodiazepines; D013469:Sulpiride; D000077582:Amisulpride; D018967:Risperidone; D000077152:Olanzapine