title: [Cannabinoids in palliative care: Systematic review and meta-analysis of efficacy, tolerability and safety].
abstract: BACKGROUND
  Cannabinoids have multiple medical indications in palliative care, such as relief of pain or nausea or increase of appetite and weight stabilisation. The value of cannabinoids for these indications is not resolved sufficiently for palliative patients. A systematic review with meta-analysis of the efficacy, tolerability and safety on the basis of randomised controlled studies (RCT) or randomised open label or crossover studies has not yet been conducted.
  
  
  METHODS
  An extensive search for RCTs, randomised open label or crossover studies dealing with the underlying question was performed in the databases of Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PsycINFO, PubMed, Scopus and Clinicaltrials.gov up to April 2015. Studies with a duration of ≥ 2 weeks and ≥ 10 participants per treatment group were included into analysis. Using a random effects model, pooled estimates of event rates for categorical data and standardized mean differences (SMD) for continuous variables and risk differences (RD) for dichotomous variables were calculated.
  
  
  RESULTS
  Out of initially 108 studies 9, with a total of 1561 participants suffering from advanced or end stage diseases, were included. The median study duration of the cancer research was 8 weeks (16 days-11 weeks), of the HIV research 6 weeks (3-12 weeks) and of the study concentrating on Alzheimer's 2 × 6 weeks. The outcome results for cannabis/cannabinoids vs. placebo in patients with cancer were not significant for the 30 % decrease in pain (RD: 0.07; 95 % confidence interval (CI): - 0.01 to 0.16; p = 0.07), caloric intake (SMD: 0.2; 95 % CI: - 0.66 to 1.06; p = 0.65) or sleep problems (SMD: - 0.09; 95 % CI: - 0.62 to 0.43; p = 0.72). In the treatment of HIV cannabinoids were superior to placebo for the outcome of weight change (SMD: 0.57; 95 % CI: 0.22-0.92; p = 0.001). Change in appetite was significant for the treatment of HIV (SMD: 0.57; 95 % CI: 0.11-1.03; p = 0.02), but not for treatment of cancer (SMD: 0.81; 95 % CI: - 1.14 to 2.75; p = 0.42). Nausea/vomiting (SMD: 0.20; 95 % CI: - 0.03 to 0.44; p = 0.09) and health-related quality of life (HRQoL; SMD: 0.00; 95 % CI: - 0.19 to 0.18; p = 0.98) did not show significant differences in the therapy of the two diseases. For the outcomes of tolerability the results were not significant for occurrence of dizziness (RD: 0.03; 95 % CI: - 0.02 to 0.08; p = 0.23) or psychiatric diseases, such as hallucinations or psychosis (RD: - 0.01; 95 % CI: - 0.04 to 0.03; p = 0.69) in the therapy of cancer. The outcome of psychiatric diseases in the treatment of HIV was significant (RD: 0.05; 95 % CI: 0.00-0.11; p = 0.05). The number of withdrawals due to adverse events, as a marker for tolerability, and the reports of serious adverse events as a measure of safety was not significantly different (RD: 1.20; 95 % CI: 0.85-1.71; p = 0.30 and RD: 1.15; 95 % CI: 0.88-1.49; p = 0.30, respectively). Dronabinol vs. megestrol acetate showed a superiority of megestrol in the therapy of cancer-associated anorexia for the endpoints change of appetite (49 vs. 75 %; p = 0.0001), weight gain (3 vs. 11 %; p = 0.02), HRQoL (p = 0.003) and tolerability (p = 0.03). There was no difference in the safety of the therapies (p = 0.12). In the treatment of HIV-associated wasting syndrome megestrol acetate was better than dronabinol for the endpoint of weight gain (p = 0.0001), whereas tolerability and safety did not differ. In the therapy of Alzheimer's dronabinol was better than placebo in the endpoint of weight gain according to one study (n = 15). A difference between herbal cannabis and synthetic cannabinoids, analysed by one study (n = 62) could not be found.
  
  
  CONCLUSIONS
  Cannabinoids can lead to an increase in appetite in patients with HIV wasting syndrome but the therapy with megestrol acetate is superior to treatment with cannabinoids. The included studies were not of sufficient duration to answer questions concerning the long-term efficacy, tolerability and safety of therapy with cannabis or cannabinoids. Due to the sparse amount of data it is not possible to recommend a favoured use of cannabis or cannabinoids at this point.
authors.affiliation: Klinik für Palliativmedizin, Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Deutschland. martin.muecke@ukb.uni-bonn.de.|Institut für Hausarztmedizin, Medizinische Fakultät, Universität Bonn, Bonn, Deutschland. martin.muecke@ukb.uni-bonn.de.|Zentrum für Seltene Erkrankungen (ZSEB), Universitätsklinikum Bonn, Bonn, Deutschland. martin.muecke@ukb.uni-bonn.de.
authors.forename: M
authors.initials: M
authors.lastname: Mücke
authors.affiliation: Klinik für Palliativmedizin, Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Deutschland.
authors.forename: C
authors.initials: C
authors.lastname: Carter
authors.affiliation: Klinik für Palliativmedizin, Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Deutschland.
authors.forename: H
authors.initials: H
authors.lastname: Cuhls
authors.affiliation: Charité Centrum Innere Medizin mit Gastroenterologie und Nephrologie, Universitätsmedizin Berlin, Berlin, Deutschland.
authors.forename: M
authors.initials: M
authors.lastname: Prüß
authors.affiliation: Klinik für Palliativmedizin, Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Deutschland.|Zentrum für Palliativmedizin, Malteser Krankenhaus Seliger Gerhard Bonn/Rhein-Sieg, Bonn, Deutschland.
authors.forename: L
authors.initials: L
authors.lastname: Radbruch
authors.affiliation: Innere Medizin I, Klinikum Saarbrücken gGmbH, Saarbrücken, Deutschland.|Klinik für Psychosomatische Medizin und Psychotherapie, Technische Universität München, München, Deutschland.
authors.forename: W
authors.initials: W
authors.lastname: Häuser
mesh_terms: D002186:Cannabinoids / Q000009:adverse effects* / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D006801:Humans; D010166:Palliative Care / Q000379:methods*; D016896:Treatment Outcome
chemical_list: D002186:Cannabinoids
keywords: Alzheimer disease; HIV; Neoplasms; Palliative medicine; Symptom control
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