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Journal ArticleDOI

Cannabinoids for Medical Use: A Systematic Review and Meta-analysis.

23 Jun 2015-JAMA (American Medical Association)-Vol. 313, Iss: 24, pp 2456-2473

TL;DR: There was moderate- quality evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity and low-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in HIV infection, sleep disorders, and Tourette syndrome.
Abstract: Importance Cannabis and cannabinoid drugs are widely used to treat disease or alleviate symptoms, but their efficacy for specific indications is not clear. Objective To conduct a systematic review of the benefits and adverse events (AEs) of cannabinoids. Data Sources Twenty-eight databases from inception to April 2015. Study Selection Randomized clinical trials of cannabinoids for the following indications: nausea and vomiting due to chemotherapy, appetite stimulation in HIV/AIDS, chronic pain, spasticity due to multiple sclerosis or paraplegia, depression, anxiety disorder, sleep disorder, psychosis, glaucoma, or Tourette syndrome. Data Extraction and Synthesis Study quality was assessed using the Cochrane risk of bias tool. All review stages were conducted independently by 2 reviewers. Where possible, data were pooled using random-effects meta-analysis. Main Outcomes and Measures Patient-relevant/disease-specific outcomes, activities of daily living, quality of life, global impression of change, and AEs. Results A total of 79 trials (6462 participants) were included; 4 were judged at low risk of bias. Most trials showed improvement in symptoms associated with cannabinoids but these associations did not reach statistical significance in all trials. Compared with placebo, cannabinoids were associated with a greater average number of patients showing a complete nausea and vomiting response (47% vs 20%; odds ratio [OR], 3.82 [95% CI, 1.55-9.42]; 3 trials), reduction in pain (37% vs 31%; OR, 1.41 [95% CI, 0.99-2.00]; 8 trials), a greater average reduction in numerical rating scale pain assessment (on a 0-10-point scale; weighted mean difference [WMD], −0.46 [95% CI, −0.80 to −0.11]; 6 trials), and average reduction in the Ashworth spasticity scale (WMD, −0.12 [95% CI, −0.24 to 0.01]; 5 trials). There was an increased risk of short-term AEs with cannabinoids, including serious AEs. Common AEs included dizziness, dry mouth, nausea, fatigue, somnolence, euphoria, vomiting, disorientation, drowsiness, confusion, loss of balance, and hallucination. Conclusions and Relevance There was moderate-quality evidence to support the use of cannabinoids for the treatment of chronic pain and spasticity. There was low-quality evidence suggesting that cannabinoids were associated with improvements in nausea and vomiting due to chemotherapy, weight gain in HIV infection, sleep disorders, and Tourette syndrome. Cannabinoids were associated with an increased risk of short-term AEs.
Topics: Nabiximols (55%), Nausea (54%), Euphoriant (53%), Randomized controlled trial (52%), Chronic pain (51%)
Citations
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Journal ArticleDOI
01 Dec 2018-
TL;DR: Despite increased cannabis use and a changing state-level policy landscape, conclusive evidence regarding the shortand long-term health effects—both harms and benefits—of cannabis use remains elusive.
Abstract: Recent years have seen a rapid rise in the medical and recreational use of cannabis: a broad term that can be used to describe the various products and chemical compounds (e.g., marijuana, cannabinoids) derived from different species of the cannabis plant. Despite increased cannabis use and a changing state-level policy landscape, conclusive evidence regarding the shortand long-term health effects—both harms and benefits—of cannabis use remains elusive.

724 citations


Cites background from "Cannabinoids for Medical Use: A Sys..."

  • ...In their review, de Carvalho et al. (2015) noted several limitations particular to individual studies....

    [...]


Journal ArticleDOI
01 Apr 2018-JAMA Psychiatry
TL;DR: Both anxious/distressed specifier and mixed-features specifier were associated with early onset, poor course and functioning, and suicidality in US adults, and much remains to be learned about the DSM-5 MDD specifiers in the general population.
Abstract: Importance No US national data are available on the prevalence and correlates of DSM-5 –defined major depressive disorder (MDD) or on MDD specifiers as defined in DSM-5 . Objective To present current nationally representative findings on the prevalence, correlates, psychiatric comorbidity, functioning, and treatment of DSM-5 MDD and initial information on the prevalence, severity, and treatment of DSM-5 MDD severity, anxious/distressed specifier, and mixed-features specifier, as well as cases that would have been characterized as bereavement in DSM-IV . Design, Setting, and Participants In-person interviews with a representative sample of US noninstitutionalized civilian adults (≥18 years) (n = 36 309) who participated in the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions III (NESARC-III). Data were collected from April 2012 to June 2013 and were analyzed in 2016-2017. Main Outcomes and Measures Prevalence of DSM-5 MDD and the DSM-5 specifiers. Odds ratios (ORs), adjusted ORs (aORs), and 95% CIs indicated associations with demographic characteristics and other psychiatric disorders. Results Of the 36 309 adult participants in NESARC-III, 12-month and lifetime prevalences of MDD were 10.4% and 20.6%, respectively. Odds of 12-month MDD were significantly lower in men (OR, 0.5; 95% CI, 0.46-0.55) and in African American (OR, 0.6; 95% CI, 0.54-0.68), Asian/Pacific Islander (OR, 0.6; 95% CI, 0.45-0.67), and Hispanic (OR, 0.7; 95% CI, 0.62-0.78) adults than in white adults and were higher in younger adults (age range, 18-29 years; OR, 3.0; 95% CI, 2.48-3.55) and those with low incomes ($19 999 or less; OR, 1.7; 95% CI, 1.49-2.04). Associations of MDD with psychiatric disorders ranged from an aOR of 2.1 (95% CI, 1.84-2.35) for specific phobia to an aOR of 5.7 (95% CI, 4.98-6.50) for generalized anxiety disorder. Associations of MDD with substance use disorders ranged from an aOR of 1.8 (95% CI, 1.63-2.01) for alcohol to an aOR of 3.0 (95% CI, 2.57-3.55) for any drug. Most lifetime MDD cases were moderate (39.7%) or severe (49.5%). Almost 70% with lifetime MDD had some type of treatment. Functioning among those with severe MDD was approximately 1 SD below the national mean. Among 12.9% of those with lifetime MDD, all episodes occurred just after the death of someone close and lasted less than 2 months. The anxious/distressed specifier characterized 74.6% of MDD cases, and the mixed-features specifier characterized 15.5%. Controlling for severity, both specifiers were associated with early onset, poor course and functioning, and suicidality. Conclusions and Relevance Among US adults, DSM-5 MDD is highly prevalent, comorbid, and disabling. While most cases received some treatment, a substantial minority did not. Much remains to be learned about the DSM-5 MDD specifiers in the general population.

523 citations


Journal ArticleDOI
Tian Hua1, Kiran Vemuri2, Mengchen Pu1, Lu Qu1  +22 moreInstitutions (6)
20 Oct 2016-Cell
TL;DR: The structure of the CB1-AM6538 complex reveals key features of the receptor and critical interactions for antagonist binding and provides insight into the binding mode of naturally occurring CB1 ligands, such as THC, and synthetic cannabinoids.
Abstract: Cannabinoid receptor 1 (CB1) is the principal target of Δ9-tetrahydrocannabinol (THC), a psychoactive chemical from Cannabis sativa with a wide range of therapeutic applications and a long history of recreational use. CB1 is activated by endocannabinoids and is a promising therapeutic target for pain management, inflammation, obesity, and substance abuse disorders. Here, we present the 2.8 A crystal structure of human CB1 in complex with AM6538, a stabilizing antagonist, synthesized and characterized for this structural study. The structure of the CB1-AM6538 complex reveals key features of the receptor and critical interactions for antagonist binding. In combination with functional studies and molecular modeling, the structure provides insight into the binding mode of naturally occurring CB1 ligands, such as THC, and synthetic cannabinoids. This enhances our understanding of the molecular basis for the physiological functions of CB1 and provides new opportunities for the design of next-generation CB1-targeting pharmaceuticals.

392 citations


Cites background from "Cannabinoids for Medical Use: A Sys..."

  • ...…has been widely used across many cultures to treat multiple conditions, with most of the results relayed via oral tradition, anecdote, political position, or with economic interest preventing an objective interpretation of therapeutic efficacy in any particular disease state (Whiting et al., 2015)....

    [...]

  • ...Marijuana has been widely used across many cultures to treat multiple conditions, with most of the results relayed via oral tradition, anecdote, political position, or with economic interest preventing an objective interpretation of therapeutic efficacy in any particular disease state (Whiting et al., 2015)....

    [...]


Journal ArticleDOI
02 Apr 2016-The Lancet
Abstract: The Johns Hopkins–Lancet Commission on Drug Policy and Health has sought to examine the emerging scientific evidence on public health issues arising from drug-control policy and to inform and encourage a central focus on public health evidence and outcomes in drug-policy debates, such as the important deliberations of the 2016 UNGASS on drugs. The Commission is concerned that drug policies are often coloured by ideas about drug use and dependence that are not scientifically grounded. The 1998 UNGASS declaration, for example, like the UN drug conventions and many national drug laws, does not distinguish between drug use and drug misuse. A 2015 report by the UN High Commissioner for Human Rights, by contrast, emphasised that drug use “is neither a medical condition, nor does it necessarily lead to drug dependence”. The idea that all drug use is dangerous and evil has led to enforcement-heavy policies and has made it difficult to see potentially dangerous drugs in the same light as potentially dangerous foods, tobacco, and alcohol, for which the goal of social policy is to reduce potential harms.

317 citations


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Book
Julian P T Higgins1, Sally GreenInstitutions (1)
23 Sep 2019-
TL;DR: The Cochrane Handbook for Systematic Reviews of Interventions is the official document that describes in detail the process of preparing and maintaining Cochrane systematic reviews on the effects of healthcare interventions.
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Performance
Metrics
No. of citations received by the Paper in previous years
YearCitations
20221
2021255
2020260
2019215
2018198
2017158