Schizophrenia Bulletin Advance Access published December 30, 2014 Schizophrenia Bulletin doi:10.1093/schbul/sbu168
Cannabis and Schizophrenia
Jonathan A. Pushpa-Rajah*,1,6, Benjamin C. McLoughlin1,6, Donna Gillies2, John Rathbone3, Hannele Variend4, Eliana Kalakouti5, and Katerina Kyprianou5 Queens Medical Centre, School of Medicine, The University of Nottingham, Nottinghamshire, UK; 2Western Sydney Local Health District—Mental Health, Parramatta, Australia; 3Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Australia; 4 Becklin Centre, CRHT, Leeds, UK; 5Department of Medicine, University of Nottingham, Nottingham, UK; 6Pushpa-Rajah and Benjamin Mcloughin were co-lead authors. 1
Background: 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. Objectives: 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. Search Methods: We searched the Cochrane Schizophrenia Group Trials Register (August 2013) and all references of articles selected for further relevant trials. We contacted the first author of included studies for unpublished trials or data. Selection Criteria: We included all randomized controlled trials involving cannabinoids and schizophrenia/schizophrenia-like illnesses, which assessed: (1) treatments to reduce cannabis use in people with schizophrenia and (2) the effects of cannabinoids on people with schizophrenia. Conclusions: Results are limited and inconclusive due to the small number and size of randomized controlled trials available and quality of data reporting within these trials. Currently, there is no evidence to demonstrate that one type of adjunct psychological therapy or one type of drug therapy is more effective than another. There is also insufficient evidence to show that cannabidiol has an antipsychotic effect. Selection Criteria We included all randomized controlled trials (RCTs) involving cannabinoids and schizophrenia/schizophrenia-like illnesses, which assessed:
Treatments to reduce cannabis use in people with 1. schizophrenia. The effects of cannabinoids on people with 2. schizophrenia. Data Collection and Analysis We independently inspected citations, selected articles and then reinspected the studies if there were discrepancies, and extracted data. For dichotomous data, we calculated risk ratios (RRs) and for continuous data, we calculated mean differences (MDs), both with 95% CI on an intention-to-treat basis, based on a fixed-effect model. Main Results We identified 8 relevant randomized trials (involving 530 participants). Overall, data were poorly reported for many outcomes of interest. Reduction in Cannabis Use: Adjunct Psychological Therapies (Specifically About Cannabis and Psychosis) vs Treatment As Usual Results from one small study showed that 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 Positive and Negative Syndrome Scale (PANSS) positive was 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
© The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: [email protected]
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Downloaded from http://schizophreniabulletin.oxfordjournals.org/ at University of Sussex on January 15, 2015
*To whom correspondence should be addressed; Queens Medical Centre, School of Medicine, The University of Nottingham, Nottingham, Nottinghamshire NG7 2UH, UK; tel: 44-115- 8231287, e-mail: [email protected]
J. A. Pushpa-Rajah et al
of Life Brief (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. Reduction in Cannabis Use: Adjunct Psychological Therapy (Specifically About Cannabis and Psychosis) vs Adjunct Nonspecific Psychoeducation
Reduction in Cannabis Use: Antipsychotic vs Antipsychotic In a small trial comparing effectiveness of olanzapine vs risperidone for cannabis reduction for people with schizophrenia, there was no difference between groups at medium-term follow-up (n = 16, 1 RCT, RR: 1.80, 95% CI: 0.52–6.22, 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: 0.19–1.29, 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 regard 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.
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There were short-term (1 RCT, n = 42, 28 days) data reported for mental state using the Brief Psychiatric Rating Scale-Expanded (BPRS) and Positive and Negative Syndrome Scale (PANSS). No overall differences in mental state were observed between treatment groups. Again, no data were reported for any of the main outcomes of interest at medium term. Conclusions Results are limited and inconclusive. Trials are few, small, and the quality of reporting is poor. There are very few studies relevant to people those who use cannabis and have schizophrenia to help then decide the most effective drug treatment for their psychosis while continuing to use cannabis. More research is needed to explore the effects of adjunct psychological therapies specifically designed to help people with psychosis deal with their cannabis use—there is no evidence for any novel intervention being better than standard treatment. Data on cannabidiol vs amisulpride demonstrated encouraging results regarding the antipsychotic properties of cannabidiol, but these must be viewed with caution given the size and length of the single study involved. Full details are published in the complete review.1 Acknowledgment The authors have declared that there are no conflicts of interest in relation to the subject of this study. Reference 1. McLoughlin BC, Pushpa-Rajah JA, Gillies D, et al. Cannabis and schizophrenia. Cochrane Database Syst Rev. 2014;(10):CD004837. doi:10.1002/14651858.CD004837. pub3.
Downloaded from http://schizophreniabulletin.oxfordjournals.org/ at University of Sussex on January 15, 2015
One study compared specific psychological therapy aimed at cannabis reduction with general psychological therapy. At 3-month follow-up, the use of cannabis in the previous 4 weeks was similar between treatment groups (n = 47, 1 RCT, RR: 1.04, 95% CI: 0.62–1.74, moderate quality evidence). Again, at a medium-term follow-up, the average mental state scores from the Brief Psychiatric Rating ScaleExpanded 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.
Cannabinoid as Treatment: Cannabidiol vs Amisulpride
Cannabis and Schizophrenia
Jonathan A. Pushpa-Rajah*,1,6, Benjamin C. McLoughlin1,6, Donna Gillies2, John Rathbone3, Hannele Variend4, Eliana Kalakouti5, and Katerina Kyprianou5 Queens Medical Centre, School of Medicine, The University of Nottingham, Nottinghamshire, UK; 2Western Sydney Local Health District—Mental Health, Parramatta, Australia; 3Faculty of Health Sciences and Medicine, Bond University, Gold Coast, Australia; 4 Becklin Centre, CRHT, Leeds, UK; 5Department of Medicine, University of Nottingham, Nottingham, UK; 6Pushpa-Rajah and Benjamin Mcloughin were co-lead authors. 1
Background: 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. Objectives: 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. Search Methods: We searched the Cochrane Schizophrenia Group Trials Register (August 2013) and all references of articles selected for further relevant trials. We contacted the first author of included studies for unpublished trials or data. Selection Criteria: We included all randomized controlled trials involving cannabinoids and schizophrenia/schizophrenia-like illnesses, which assessed: (1) treatments to reduce cannabis use in people with schizophrenia and (2) the effects of cannabinoids on people with schizophrenia. Conclusions: Results are limited and inconclusive due to the small number and size of randomized controlled trials available and quality of data reporting within these trials. Currently, there is no evidence to demonstrate that one type of adjunct psychological therapy or one type of drug therapy is more effective than another. There is also insufficient evidence to show that cannabidiol has an antipsychotic effect. Selection Criteria We included all randomized controlled trials (RCTs) involving cannabinoids and schizophrenia/schizophrenia-like illnesses, which assessed:
Treatments to reduce cannabis use in people with 1. schizophrenia. The effects of cannabinoids on people with 2. schizophrenia. Data Collection and Analysis We independently inspected citations, selected articles and then reinspected the studies if there were discrepancies, and extracted data. For dichotomous data, we calculated risk ratios (RRs) and for continuous data, we calculated mean differences (MDs), both with 95% CI on an intention-to-treat basis, based on a fixed-effect model. Main Results We identified 8 relevant randomized trials (involving 530 participants). Overall, data were poorly reported for many outcomes of interest. Reduction in Cannabis Use: Adjunct Psychological Therapies (Specifically About Cannabis and Psychosis) vs Treatment As Usual Results from one small study showed that 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 Positive and Negative Syndrome Scale (PANSS) positive was 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
© The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: [email protected]
Page 1 of 2
Downloaded from http://schizophreniabulletin.oxfordjournals.org/ at University of Sussex on January 15, 2015
*To whom correspondence should be addressed; Queens Medical Centre, School of Medicine, The University of Nottingham, Nottingham, Nottinghamshire NG7 2UH, UK; tel: 44-115- 8231287, e-mail: [email protected]
J. A. Pushpa-Rajah et al
of Life Brief (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. Reduction in Cannabis Use: Adjunct Psychological Therapy (Specifically About Cannabis and Psychosis) vs Adjunct Nonspecific Psychoeducation
Reduction in Cannabis Use: Antipsychotic vs Antipsychotic In a small trial comparing effectiveness of olanzapine vs risperidone for cannabis reduction for people with schizophrenia, there was no difference between groups at medium-term follow-up (n = 16, 1 RCT, RR: 1.80, 95% CI: 0.52–6.22, 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: 0.19–1.29, 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 regard 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.
Page 2 of 2
There were short-term (1 RCT, n = 42, 28 days) data reported for mental state using the Brief Psychiatric Rating Scale-Expanded (BPRS) and Positive and Negative Syndrome Scale (PANSS). No overall differences in mental state were observed between treatment groups. Again, no data were reported for any of the main outcomes of interest at medium term. Conclusions Results are limited and inconclusive. Trials are few, small, and the quality of reporting is poor. There are very few studies relevant to people those who use cannabis and have schizophrenia to help then decide the most effective drug treatment for their psychosis while continuing to use cannabis. More research is needed to explore the effects of adjunct psychological therapies specifically designed to help people with psychosis deal with their cannabis use—there is no evidence for any novel intervention being better than standard treatment. Data on cannabidiol vs amisulpride demonstrated encouraging results regarding the antipsychotic properties of cannabidiol, but these must be viewed with caution given the size and length of the single study involved. Full details are published in the complete review.1 Acknowledgment The authors have declared that there are no conflicts of interest in relation to the subject of this study. Reference 1. McLoughlin BC, Pushpa-Rajah JA, Gillies D, et al. Cannabis and schizophrenia. Cochrane Database Syst Rev. 2014;(10):CD004837. doi:10.1002/14651858.CD004837. pub3.
Downloaded from http://schizophreniabulletin.oxfordjournals.org/ at University of Sussex on January 15, 2015
One study compared specific psychological therapy aimed at cannabis reduction with general psychological therapy. At 3-month follow-up, the use of cannabis in the previous 4 weeks was similar between treatment groups (n = 47, 1 RCT, RR: 1.04, 95% CI: 0.62–1.74, moderate quality evidence). Again, at a medium-term follow-up, the average mental state scores from the Brief Psychiatric Rating ScaleExpanded 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.
Cannabinoid as Treatment: Cannabidiol vs Amisulpride
