BACKGROUND: Medicinal cannabinoids, including medicinal cannabis and pharmaceutical cannabinoids and their synthetic derivatives, such as tetrahydrocannabinol (THC) and cannabidiol (CBD), have been suggested to have a therapeutic role in certain mental disorders. We analysed the available evidence to ascertain the effectiveness and safety of all types of medicinal cannabinoids in treating symptoms of various mental disorders.
METHODS: For this systematic review and meta-analysis we searched MEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled Clinical Trials, and the Cochrane Database of Systematic Reviews for studies published between Jan 1, 1980, and April 30, 2018. We also searched for unpublished or ongoing studies on ClinicalTrials.gov, the EU Clinical Trials Register, and the Australian and New Zealand Clinical Trials Registry. We considered all studies examining any type and formulation of a medicinal cannabinoid in adults (≥18 years) for treating depression, anxiety, attention-deficit hyperactivity disorder (ADHD), Tourette syndrome, post-traumatic stress disorder, or psychosis, either as the primary condition or secondary to other medical conditions. We placed no restrictions on language, publication status, or study type (ie, both experimental and observational study designs were included). Primary outcomes were remission from and changes in symptoms of these mental disorders. The safety of medicinal cannabinoids for these mental disorders was also examined. Evidence from randomised controlled trials was synthesised as odds ratios (ORs) for disorder remission, adverse events, and withdrawals and as standardised mean differences (SMDs) for change in symptoms, via random-effects meta-analyses. The quality of the evidence was assessed with the Cochrane risk of bias tool and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. This study is registered with PROSPERO (CRD42017059372, CRD42017059373, CRD42017059376, CRD42017064996, and CRD42018102977).
FINDINGS: 83 eligible studies (40 randomised controlled trials, n=3067) were included: 42 for depression (23 randomised controlled trials; n=2551), 31 for anxiety (17 randomised controlled trials; n=605), eight for Tourette syndrome (two randomised controlled trials; n=36), three for ADHD (one randomised controlled trial; n=30), 12 for post-traumatic stress disorder (one randomised controlled trial; n=10), and 11 for psychosis (six randomised controlled trials; n=281). Pharmaceutical THC (with or without CBD) improved anxiety symptoms among individuals with other medical conditions (primarily chronic non-cancer pain and multiple sclerosis; SMD -0·25 [95% CI -0·49 to -0·01]; seven studies; n=252), although the evidence GRADE was very low. Pharmaceutical THC (with or without CBD) worsened negative symptoms of psychosis in a single study (SMD 0·36 [95% CI 0·10 to 0·62]; n=24). Pharmaceutical THC (with or without CBD) did not significantly affect any other primary outcomes for the mental disorders examined but did increase the number of people who had adverse events (OR 1·99 [95% CI 1·20 to 3·29]; ten studies; n=1495) and withdrawals due to adverse events (2·78 [1·59 to 4·86]; 11 studies; n=1621) compared with placebo across all mental disorders examined. Few randomised controlled trials examined the role of pharmaceutical CBD or medicinal cannabis.
INTERPRETATION: There is scarce evidence to suggest that cannabinoids improve depressive disorders and symptoms, anxiety disorders, attention-deficit hyperactivity disorder, Tourette syndrome, post-traumatic stress disorder, or psychosis. There is very low quality evidence that pharmaceutical THC (with or without CBD) leads to a small improvement in symptoms of anxiety among individuals with other medical conditions. There remains insufficient evidence to provide guidance on the use of cannabinoids for treating mental disorders within a regulatory framework. Further high-quality studies directly examining the effect of cannabinoids on treating mental disorders are needed.
FUNDING: Therapeutic Goods Administration, Australia; Commonwealth Department of Health, Australia; Australian National Health and Medical Research Council; and US National Institutes of Health.
This review examines evidence cannabinoids in chronic non-cancer pain (CNCP), and addresses gaps in the literature by: considering differences in outcomes based on cannabinoid type and specific CNCP condition; including all study designs; and following IMMPACT guidelines. MEDLINE, Embase, PsycINFO, CENTRAL and clinicaltrials.gov were searched in July 2017. Analyses were conducted using Revman 5.3 and Stata 15.0. A total of 91 publications containing 104 studies were eligible (n = 9958 participants), including 47 RCTs and 57 observational studies. Forty-eight studies examined neuropathic pain, seven studies examined fibromyalgia, one rheumatoid arthritis, and 48 other CNCP (13 MS-related pain, 6 visceral pain, and 29 samples with mixed or undefined CNCP). Across RCTs, PERs for 30% reduction in pain were 29.0% (cannabinoids) vs 25.9% (placebo), significant effect for cannabinoids, number needed to treat to benefit (NNTB): 24 (95%CI 15-61); for 50% reduction in pain, PERs were 18.2% vs. 14.4%; no significant difference. Pooled change in pain intensity (standardised mean difference: -0.14, 95%CI -0.20, -0.08) was equivalent to 3mm on a 100mm visual analogue scale greater than placebo. In RCTs, PERs for all-cause AEs were 81.2% vs. 66.2%; number needed to treat to harm (NNTH): 6 (95%CI 5-8). There were no significant impacts upon physical or emotional functioning, and low-quality evidence of improved sleep and patient global impression of change. Evidence for effectiveness of cannabinoids in CNCP is limited. Effects suggest NNTB are high, and NNTH low, with limited impact on other domains. It appears unlikely that cannabinoids are highly effective medicines for CNCP.
Antecedentes: El dolor abdominal es frecuentemente reportado por personas con enfermedad inflamatoria intestinal (EII), incluso en remisión. El dolor es un síntoma poco tratado. OBJETIVO: Revisar sistemáticamente las pruebas sobre las intervenciones (excluyendo las intervenciones modificadoras de la enfermedad) para el tratamiento del dolor abdominal en la EII. MÉTODOS: Se realizaron búsquedas en bases de datos (MEDLINE, EMBASE, PsycInfo, CINAHL, Scopus, Cochrane Library) (febrero de 2016). Dos investigadores seleccionaron independientemente las referencias y extrajeron los datos. RESULTADOS: Se incluyeron 15 trabajos: 13 estudios de intervención y 2 estudios transversales. Se informó de una variedad de intervenciones psicológicas, dietéticas y farmacológicas. Cuatro de seis estudios informaron reducción del dolor con intervención psicológica incluyendo relajación individualizada y en grupo, terapia cognitiva conductual relacionada con la ansiedad de la enfermedad y manejo del estrés. Tanto el manejo del estrés dirigido por el psicólogo como el autodirigido en la enfermedad de Crohn inactiva redujeron el dolor en comparación con los controles (índice de reducción de la frecuencia de los síntomas = -26,7, -11,3 y 17,2 a los 6 meses de seguimiento, respectivamente). Dos intervenciones dietéticas (bebidas alcohólicas con alto contenido de azúcar y carbohidratos fermentables con propiedades prebióticas) tuvieron un efecto sobre el dolor abdominal. Los antibióticos (para los pacientes con sobrecrecimiento bacteriano) y parches transdérmicos de nicotina redujeron el dolor abdominal. Los usuarios de cannabis actuales y pasados informan que alivia el dolor. Un ensayo controlado de cannabis redujo las puntuaciones de dolor SF-36 y EQ-5D (1,84 y 0,7, respectivamente). Estos resultados deben ser tratados con precaución: los datos se obtuvieron a partir de estudios predominantemente pequeños no controlados de moderada a baja calidad. Conclusiones: Pocas intervenciones han sido probadas para el dolor abdominal IBD. La limitada evidencia sugiere que la relajación y las cogniciones cambiantes son prometedoras, posiblemente con cambios dietéticos individualizados. Existe la necesidad de desarrollar intervenciones para el manejo del dolor abdominal en la EII.
INTRODUCCIÓN: El uso de cannabis o cannabinoides para tratar condiciones médicas y / o aliviar síntomas es cada vez más frecuente. Sin embargo, el impacto de este uso en los resultados informados por los pacientes, como la calidad de vida relacionada con la salud (CVRS), sigue siendo poco claro. MÉTODOS: Realizamos una revisión sistemática y metanálisis, empleando directrices de Preferred Reporting Items for Systematic Reviews and Meta -Analyses (PRISMA). Se categorizaron los estudios basados en el diseño, la condición de enfermedad objetivo, y el tipo de cannabis o cannabinoide utilizado. Se realizaron estudios basados en la calidad y el riesgo de sesgo. Después de eliminar algunos estudios debido a la mala calidad o la insuficiencia de datos, realizamos meta-análisis de los estudios restantes basados en el diseño. Resultados: Veinte estudios cumplieron con nuestros criterios de selección predefinidos. Once estudios fueron ensayos controlados aleatorios (ECA, 2322 participantes); Los estudios restantes fueron de cohorte y diseño transversal. Los estudios de cannabinoides fueron en su mayoría ECA de mayor calidad de diseño que los estudios de cannabis, que utilizaron muestras auto-seleccionadas más pequeñas en estudios observacionales. Aunque no descubrimos una asociación significativa entre el cannabis y los cannabinoides para las condiciones médicas y la CVRS, algunos pacientes que los usaron para tratar el dolor, la esclerosis múltiple y los trastornos inflamatorios de la orilla han informado pequeñas mejoras en la CVRS, mientras que algunos pacientes con VIH han reportado una HRQoL reducida. CONCLUSIÓN: La relación entre la CVRS y el uso de cannabis o cannabinoides para condiciones médicas no es concluyente. Algunas poblaciones de pacientes informan mejoras, mientras que otras informan reducciones en la CVRS. Con el fin de informar a los usuarios, profesionales y formuladores de políticas más claramente, los estudios futuros deben cumplir con directrices de calidad de investigación más estrictas y más claramente informar los resultados de los pacientes.
Medicinal cannabinoids, including medicinal cannabis and pharmaceutical cannabinoids and their synthetic derivatives, such as tetrahydrocannabinol (THC) and cannabidiol (CBD), have been suggested to have a therapeutic role in certain mental disorders. We analysed the available evidence to ascertain the effectiveness and safety of all types of medicinal cannabinoids in treating symptoms of various mental disorders.
METHODS:
For this systematic review and meta-analysis we searched MEDLINE, Embase, PsycINFO, the Cochrane Central Register of Controlled Clinical Trials, and the Cochrane Database of Systematic Reviews for studies published between Jan 1, 1980, and April 30, 2018. We also searched for unpublished or ongoing studies on ClinicalTrials.gov, the EU Clinical Trials Register, and the Australian and New Zealand Clinical Trials Registry. We considered all studies examining any type and formulation of a medicinal cannabinoid in adults (≥18 years) for treating depression, anxiety, attention-deficit hyperactivity disorder (ADHD), Tourette syndrome, post-traumatic stress disorder, or psychosis, either as the primary condition or secondary to other medical conditions. We placed no restrictions on language, publication status, or study type (ie, both experimental and observational study designs were included). Primary outcomes were remission from and changes in symptoms of these mental disorders. The safety of medicinal cannabinoids for these mental disorders was also examined. Evidence from randomised controlled trials was synthesised as odds ratios (ORs) for disorder remission, adverse events, and withdrawals and as standardised mean differences (SMDs) for change in symptoms, via random-effects meta-analyses. The quality of the evidence was assessed with the Cochrane risk of bias tool and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. This study is registered with PROSPERO (CRD42017059372, CRD42017059373, CRD42017059376, CRD42017064996, and CRD42018102977).
FINDINGS:
83 eligible studies (40 randomised controlled trials, n=3067) were included: 42 for depression (23 randomised controlled trials; n=2551), 31 for anxiety (17 randomised controlled trials; n=605), eight for Tourette syndrome (two randomised controlled trials; n=36), three for ADHD (one randomised controlled trial; n=30), 12 for post-traumatic stress disorder (one randomised controlled trial; n=10), and 11 for psychosis (six randomised controlled trials; n=281). Pharmaceutical THC (with or without CBD) improved anxiety symptoms among individuals with other medical conditions (primarily chronic non-cancer pain and multiple sclerosis; SMD -0·25 [95% CI -0·49 to -0·01]; seven studies; n=252), although the evidence GRADE was very low. Pharmaceutical THC (with or without CBD) worsened negative symptoms of psychosis in a single study (SMD 0·36 [95% CI 0·10 to 0·62]; n=24). Pharmaceutical THC (with or without CBD) did not significantly affect any other primary outcomes for the mental disorders examined but did increase the number of people who had adverse events (OR 1·99 [95% CI 1·20 to 3·29]; ten studies; n=1495) and withdrawals due to adverse events (2·78 [1·59 to 4·86]; 11 studies; n=1621) compared with placebo across all mental disorders examined. Few randomised controlled trials examined the role of pharmaceutical CBD or medicinal cannabis.
INTERPRETATION:
There is scarce evidence to suggest that cannabinoids improve depressive disorders and symptoms, anxiety disorders, attention-deficit hyperactivity disorder, Tourette syndrome, post-traumatic stress disorder, or psychosis. There is very low quality evidence that pharmaceutical THC (with or without CBD) leads to a small improvement in symptoms of anxiety among individuals with other medical conditions. There remains insufficient evidence to provide guidance on the use of cannabinoids for treating mental disorders within a regulatory framework. Further high-quality studies directly examining the effect of cannabinoids on treating mental disorders are needed.
FUNDING:
Therapeutic Goods Administration, Australia; Commonwealth Department of Health, Australia; Australian National Health and Medical Research Council; and US National Institutes of Health.
