Cannabinoids for Medical Use: A Systematic Review and Meta-analysis.
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.
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01 Jan 2011
2,529 citations
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.
977 citations
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.
921 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....
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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.
488 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)....
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...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)....
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TL;DR: This Review discusses maladaptive structural plasticity in neural circuits of pain, spanning multiple anatomical and spatial scales in animal models and human patients, and addresses key questions on structure–function relationships.
Abstract: Chronic pain is not simply a temporal continuum of acute pain. Studies on functional plasticity in neural circuits of pain have provided mechanistic insights and linked various modulatory factors to a change in perception and behaviour. However, plasticity also occurs in the context of structural remodelling and reorganisation of synapses, cells and circuits, potentially contributing to the long-term nature of chronic pain. This Review discusses maladaptive structural plasticity in neural circuits of pain, spanning multiple anatomical and spatial scales in animal models and human patients, and addresses key questions on structure-function relationships.
409 citations
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TL;DR: The cannabinoids tested in these trials may be useful as mood enhancing adjuvants for controlling chemotherapy related sickness and potentially serious adverse effects, even when taken short term orally or intramuscularly are likely to limit their widespread use.
Abstract: Objective: To quantify the antiemetic efficacy and adverse effects of cannabis used for sickness induced by chemotherapy. Design: Systematic review. Data sources: Systematic search (Medline, Embase, Cochrane library, bibliographies), any language, to August 2000. Studies: 30 randomised comparisons of cannabis with placebo or antiemetics from which dichotomous data on efficacy and harm were available (1366 patients). Oral nabilone, oral dronabinol (tetrahydrocannabinol), and intramuscular levonantradol were tested. No cannabis was smoked. Follow up lasted 24 hours. Results: Cannabinoids were more effective antiemetics than prochlorperazine, metoclopramide, chlorpromazine, thiethylperazine, haloperidol, domperidone, or alizapride: relative risk 1.38 (95% confidence interval 1.18 to 1.62), number needed to treat 6 for complete control of nausea; 1.28 (1.08 to 1.51), NNT 8 for complete control of vomiting. Cannabinoids were not more effective in patients receiving very low or very high emetogenic chemotherapy. In crossover trials, patients preferred cannabinoids for future chemotherapy cycles: 2.39 (2.05 to 2.78), NNT 3. Some potentially beneficial side effects occurred more often with cannabinoids: “high” 10.6 (6.86 to 16.5), NNT 3; sedation or drowsiness 1.66 (1.46 to 1.89), NNT 5; euphoria 12.5 (3.00 to 52.1), NNT 7. Harmful side effects also occurred more often with cannabinoids: dizziness 2.97 (2.31 to 3.83), NNT 3; dysphoria or depression 8.06 (3.38 to 19.2), NNT 8; hallucinations 6.10 (2.41 to 15.4), NNT 17; paranoia 8.58 (6.38 to 11.5), NNT 20; and arterial hypotension 2.23 (1.75 to 2.83), NNT 7. Patients given cannabinoids were more likely to withdraw due to side effects 4.67 (3.07 to 7.09), NNT 11. Conclusions: In selected patients, the cannabinoids tested in these trials may be useful as mood enhancing adjuvants for controlling chemotherapy related sickness. Potentially serious adverse effects, even when taken short term orally or intramuscularly, are likely to limit their widespread use. What is already known on this topic Requests have been made for legalisation of cannabis (marijuana) for medical use Long term smoking of cannabis can have physical and neuropsychiatric adverse effects Cannabis may be useful in the control of chemotherapy related sickness What this study adds Oral nabilone and dronabinol and intramuscular levonantradol are superior to conventional antiemetics (such as prochlorperazine or metoclopramide) in chemotherapy Side effects are common with cannabinoids, and although some may be potentially beneficial (euphoria, “high,” sedation), others are harmful (dysphoria, depression, hallucinations) Many patients have a strong preference for cannabinoids
546 citations
TL;DR: Spasticity VAS scores were significantly reduced by CBME (Sativex) in comparison with placebo (P- 0.001), there were no significant adverse effects on cognition or mood and intoxication was generally mild.
Abstract: The objective was to determine whether a cannabis-based medicinal extract (CBME) benefits a range of symptoms due to multiple sclerosis (MS). A parallel group, double-blind, randomized, placebo-controlled study was undertaken in three centres, recruiting 160 outpatients with MS experiencing significant problems from at least one of the following: spasticity, spasms, bladder problems, tremor or pain. The interventions were oromucosal sprays of matched placebo, or whole plant CBME containing equal amounts of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) at a dose of 2.5-120 mg of each daily, in divided doses. The primary outcome measure was a Visual Analogue Scale (VAS) score for each patient's most troublesome symptom. Additional measures included VAS scores of other symptoms, and measures of disability, cognition, mood, sleep and fatigue. Following CBME the primary symptom score reduced from mean (SE) 74.36 (11.1) to 48.89 (22.0) following CBME and from 74.31 (12.5) to 54.79 (26.3) following placebo [ns]. Spasticity VAS scores were significantly reduced by CBME (Sativex) in comparison with placebo (P =0.001). There were no significant adverse effects on cognition or mood and intoxication was generally mild.
510 citations
TL;DR: It is shown that THC:CBD extract is efficacious for relief of pain in patients with advanced cancer pain not fully relieved by strong opioids.
463 citations
TL;DR: Dronabinol was found to be safe and effective for anorexia associated with weight loss in patients with AIDS and was associated with increased appetite above baseline and decreased nausea.
461 citations
TL;DR: Dronabinol has a modest but clinically relevantanalgesic effect on central pain in patients with multiple sclerosis and on the SF-36 quality of life scale, the two items bodily pain and mental health indicated benefits from active treatment compared with placebo.
Abstract: Objective To evaluate the effect of the oral synthetic δ-9-tetrahydrocannabinol dronabinol on central neuropathic pain in patients with multiple sclerosis.
Design Randomised double blind placebo controlled crossover trial.
Setting Outpatient clinic, University Hospital of Aarhus, Denmark.
Participants 24 patients aged between 23 and 55 years with multiple sclerosis and central pain.
Intervention Orally administered dronabinol at a maximum dose of 10 mg daily or corresponding placebo for three weeks (15-21 days), separated by a three week washout period.
Main outcome measure Median spontaneous pain intensity (numerical rating scale) in the last week of treatment.
Results Median spontaneous pain intensity was significantly lower during dronabinol treatment than during placebo treatment (4.0 (25th to 75th centiles 2.3 to 6.0) v 5.0 (4.0 to 6.4), P = 0.02), and median pain relief score (numerical rating scale) was higher (3.0 (0 to 6.7) v> 0 (0 to 2.3), P = 0.035). The number needed to treat for 50% pain relief was 3.5 (95% confidence interval 1.9 to 24.8). On the SF-36 quality of life scale, the two items bodily pain and mental health indicated benefits from active treatment compared with placebo. The number of patients with adverse events was higher during active treatment, especially in the first week of treatment. The functional ability of the multiple sclerosis patients did not change.
Conclusions Dronabinol has a modest but clinically relevant analgesic effect on central pain in patients with multiple sclerosis. Adverse events, including dizziness, were more frequent with dronabinol than with placebo during the first week of treatment.
437 citations