Nabilone, a synthetic cannabinoid, is approved in many countries including, but not limited to, Canada, the United States, Mexico, and the United Kingdom for the treatment of severe nausea and vomiting associated with chemotherapy. Clinical evidence is emerging for its use in managing pain conditions with different etiologies. We review the efficacy and safety of nabilone for various types of pain as well as its abuse potential, precautions and contraindications, and drug interactions; summarize pertinent clinical practice guidelines; and provide recommendations for dosing, monitoring, and patient education. Citations involving nabilone were identified through systematic reviews evaluating cannabinoids for pain. A systematic search (updated July 23, 2015) of the Ovid MEDLINE, EMBASE, PubMed, and Cochrane Library databases was performed. Eight randomized controlled trials, two prospective cohort trials, and one retrospective chart review were retrieved. Cancer pain, chronic noncancer pain, neuropathic pain, fibromyalgia, and pain associated with spasticity were the pain conditions evaluated. Nabilone was most commonly used as adjunctive therapy and led to small but significant reductions in pain. The most common adverse drug reactions included euphoria, drowsiness, and dizziness. Nabilone was rarely associated with severe adverse drug reactions requiring drug discontinuation, and the likelihood of abuse was thought to be low. Although the optimal role of nabilone in the management of pain is yet to be determined, certain clinical practice guidelines consider nabilone as a third-line agent.
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.
MATERIALS AND 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.
CONCLUSION: 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.
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 systemsis: 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, −0.36 [95%CI, −0.69 to −0.05]; 7 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. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
SETTING: Cannabis preparations have been used as a remedy for thousands of years in traditional medicine. Clinical use of cannabinoid substances is restricted, due to legal and ethical reasons, as well as limited evidence showing benefits. OBJECTIVE: To assess the efficacy and harms of cannabis preparations in the treatment of chronic pain. DESIGN: Systematic review and meta-analysis of double-blind randomized controlled trials that compared any cannabis preparation to placebo among subjects with chronic pain. An electronic search was made in Medline/Pubmed, Embase, and The Cochrane Controlled Trials Register (TRIALS CENTRAL) of all literature published until February 2008, as well as specific web pages devoted to cannabis. Studies were cross-checked, selected, and assessed. RESULTS: Eighteen trials were included. The efficacy analysis (visual analog scales) displayed a difference in standardized means in favor of the cannabis arm of -0.61 (-0.84 to -0.37), with statistical homogeneity (I² = 0.0%;<i> P</i> = 0.50). For the analysis of harms, the following Odds Ratios (OR) and number needed to harm (NNH) were obtained: for events linked to alterations to perception, OR: 4.51 (3.05–6.66), NNH: 7 (6–9); for events affecting motor function, 3.93 (2.83–5.47), NNH: 5 (4–6); for events that altered cognitive function, 4.46 (2.37–8.37), NNH: 8 (6–12). CONCLUSIONS: Currently available evidence suggests that cannabis treatment is moderately efficacious for treatment of chronic pain, but beneficial effects may be partially (or completely) offset by potentially serious harms. More evidence from larger, well-designed trials is needed to clarify the true balance of benefits to harms. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
In order to assess the current knowledge on the therapeutic potential of cannabinoids, a meta-analysis was performed through Medline and PubMed up to July 1, 2005. The key words used were cannabis, marijuana, marihuana, hashish, hashich, haschich, cannabinoids, tetrahydrocannabinol, THC, dronabinol, nabilone, levonantradol, randomised, randomized, double-blind, simple blind, placebo-controlled, and human. The research also included the reports and reviews published in English, French and Spanish. For the final selection, only properly controlled clinical trials were retained, thus open-label studies were excluded. Seventy-two controlled studies evaluating the therapeutic effects of cannabinoids were identified. For each clinical trial, the country where the project was held, the number of patients assessed, the type of study and comparisons done, the products and the dosages used, their efficacy and their adverse effects are described. Cannabinoids present an interesting therapeutic potential as antiemetics, appetite stimulants in debilitating diseases (cancer and AIDS), analgesics, and in the treatment of multiple sclerosis, spinal cord injuries, Tourette's syndrome, epilepsy and glaucoma.
Investigated whether cannabis is an effective and safe treatment option in the management of pain. Trials of cannabis given by any route of administration (experimental intervention) with any analgesic or placebo (control intervention) in patients with acute, chronic non-malignant, or cancer pain were conducted. Outcomes examined were pain intensity scores, pain relief scores, and adverse effects. 20 randomised controlled trials were identified, 11 of which were excluded. Of the 9 included trials (222 patients), 5 trials related to cancer pain, 2 to chronic non-malignant pain, and 2 to acute postoperative pain. No randomised controlled trials evaluated cannabis; all tested active substances were cannabinoids. Oral delta-9-tetrahydrocannabinol (THC) 5–20 mg, an oral synthetic nitrogen analogue of THC 1 mg, and intramuscular levonantradol 1.5–3 mg were about as effective as codeine 50–120 mg, and oral benzopyranoperidine 2–4 mg was less effective than codeine 60–120 mg and no better than placebo. Adverse effects, most often psychotropic, were common. It is concluded that cannabinoids are no more effective than codeine in controlling pain and have depressant effects on the central nervous system that limit their use. (PsycInfo Database Record (c) 2021 APA, all rights reserved)
Nabilone, a synthetic cannabinoid, is approved in many countries including, but not limited to, Canada, the United States, Mexico, and the United Kingdom for the treatment of severe nausea and vomiting associated with chemotherapy. Clinical evidence is emerging for its use in managing pain conditions with different etiologies. We review the efficacy and safety of nabilone for various types of pain as well as its abuse potential, precautions and contraindications, and drug interactions; summarize pertinent clinical practice guidelines; and provide recommendations for dosing, monitoring, and patient education. Citations involving nabilone were identified through systematic reviews evaluating cannabinoids for pain. A systematic search (updated July 23, 2015) of the Ovid MEDLINE, EMBASE, PubMed, and Cochrane Library databases was performed. Eight randomized controlled trials, two prospective cohort trials, and one retrospective chart review were retrieved. Cancer pain, chronic noncancer pain, neuropathic pain, fibromyalgia, and pain associated with spasticity were the pain conditions evaluated. Nabilone was most commonly used as adjunctive therapy and led to small but significant reductions in pain. The most common adverse drug reactions included euphoria, drowsiness, and dizziness. Nabilone was rarely associated with severe adverse drug reactions requiring drug discontinuation, and the likelihood of abuse was thought to be low. Although the optimal role of nabilone in the management of pain is yet to be determined, certain clinical practice guidelines consider nabilone as a third-line agent.
