INTRODUCTION: Chemotherapy-induced nausea and vomiting (CINV) is a burdensome adverse event frequently associated with chemotherapy treatment of cancer. Evidence suggests that cannabinoid CB2 receptors are present in brainstem neurons, and thus, there may exist a role for cannabinoids to counter CINV. The aim of this paper is to conduct a systematic review and meta-analysis of the efficacy and safety of oral cannabinoids compared with other treatments as documented in randomized controlled trials (RCTs).
METHODS: A literature search was conducted using Ovid MEDLINE up until December 31, 2018; Embase Classic and Embase up until 2018 week 53; and Cochrane Central Register of Controlled Trials up until November 2018. Study data were extracted and included in this meta-analysis if they reported on at least one of the following efficacy endpoints: no nausea and no vomiting, no nausea, and no vomiting. The Mantel-Haenszel method and random effects analysis model were used, to generate odds ratio (OR) and accompanying 95% confidence intervals (CI).
RESULTS: In the setting of prophylactic treatment against both nausea and vomiting, oral cannabinoid was more efficacious than placebo or other studied antiemetic treatments. When controlling for vomiting, oral cannabinoid was equally as efficacious as others. Against nausea, oral cannabinoid was equally as effective as other treatments. A greater percentage of patients administered oral cannabinoid for CINV experienced dysphoria, euphoria, and sedation.
CONCLUSION: Although there exists some evidence suggesting that oral cannabinoids may have a role in controlling for emesis from a neurophysiological perspective, these conclusions are currently not mirrored in the published RCTs to date. However, there exists only a limited number of RCTs, comparisons with older treatment regimens and a lack of standard reporting practice across published literature. Further RCTs should investigate the efficacy and safety of oral cannabinoids, to secure a better picture of the efficacy of oral cannabinoids against CINV.
PURPOSE: This systematic literature review examines research into the use of medicinal cannabis in cancer management. The aim was to identify the gaps in knowledge on the dose, dosing schedule and absorption of the administration routes of medicinal cannabis use in oncology.
METHODS: A comprehensive search of the literature was conducted across six databases to identify original data reporting the pharmacology of medicinal cannabis in oncology.
RESULTS: Eighteen articles were selected for review. Of the selected articles, ten were identified as randomised control trials, two experimental studies, two retrospective cohort studies and four case studies. Four articles reported absorption data and one drug interaction study was identified.
CONCLUSIONS: There is little evidence reported in the literature on the absorption of medicinal cannabis in cancer populations. Various reasons are explored for the lack of pharmacokinetic studies for medicinal cannabis in cancer populations, including the availability of assays to accurately assess cannabinoid levels, lack of clinical biomarkers and patient enrolment for pharmacokinetic studies.
Abstract Background Anti-inflammatory, analgesic, anticonvulsant, and other effects have been attributed to cannabis, and so it has been widely used to treat several diseases. Objective To assess the use and therapeutic effects of cannabinoid drugs and the cannabis plant in several diseases. Method We carried out a narrative review of the literature that has reported the use of the cannabis plant (marijuana) and cannabinoid drugs (nabilone, cannabinol and dronabinol, among others). We conducted a search in Medline, Cochrane, SciELO and other web sites. Clinical, controlled, double-blind and randomized studies were included. The route of administration and the cannabinoid drugs used were assessed too. Results Thirty-four studies were included. Nabilone was the cannabinoid drug more commonly used (12 studies), followed by delta-9-tetrahydrocannabinol (THC) (11 studies). It was also found that the marijuana plant and cannabinoid drugs were used to treat many symptoms or diseases. Two studies were reported for Gilles de la Tourette's syndrome. Discussion and conclusion Many scientific studies on the marijuana plant and cannabinoid drugs conclude that these are not as effective as conventional medications and thus their benefits should be taken with caution.
The purpose of this report is to present a review of the medical uses, efficacy, and adverse effects of the three approved cannabis-based medications and ingested marijuana. A literature review was conducted utilizing key search terms: dronabinol, nabilone, nabiximols, cannabis, marijuana, smoke, efficacy, toxicity, cancer, multiple sclerosis, nausea, vomiting, appetite, pain, glaucoma, and side effects. Abstracts of the included literature were reviewed, analyzed, and organized to identify the strength of evidence in medical use, efficacy, and adverse effects of the approved cannabis-based medications and medical marijuana. A total of 68 abstracts were included for review. Dronabinol's (Marinol) most common medical uses include weight gain, chemotherapy-induced nausea and vomiting (CINV), and neuropathic pain. Nabiximol's (Sativex) most common medical uses include spasticity in multiple sclerosis (MS) and neuropathic pain. Nabilone's (Cesamet) most common medical uses include CINV and neuropathic pain. Smoked marijuana's most common medical uses include neuropathic pain and glaucoma. Orally ingested marijuana's most common medical uses include improving sleep, reducing neuropathic pain, and seizure control in MS. In general, all of these agents share similar medical uses. The reported adverse effects of the three cannabis-based medications and marijuana show a major trend in central nervous system (CNS)-related adverse effects along with cardiovascular and respiratory related adverse effects. Marijuana shares similar medical uses with the approved cannabis-based medications dronabinol (Marinol), nabiximols (Sativex), and nabilone (Cesamet), but the efficacy of marijuana for these medical uses has not been fully determined due to limited and conflicting literature. Medical marijuana also has similar adverse effects as the FDA-approved cannabis-based medications mainly consisting of CNS related adverse effects but also including cardiovascular and respiratory related adverse effects. Finally, insufficient higher-order evidence to support the widespread use of medical marijuana was found, but a limited amount of moderate-level evidence supports its use in pain and seizure management.
Answer questions and earn CME/CNE Marijuana has been used for centuries, and interest in its medicinal properties has been increasing in recent years. Investigations into these medicinal properties has led to the development of cannabinoid pharmaceuticals such as dronabinol, nabilone, and nabiximols. Dronabinol is best studied in the treatment of nausea secondary to cancer chemotherapy and anorexia associated with weight loss in patients with acquired immune deficiency syndrome, and is approved by the US Food and Drug Administration for those indications. Nabilone has been best studied for the treatment of nausea secondary to cancer chemotherapy. There are also limited studies of these drugs for other conditions. Nabiximols is only available in the United States through clinical trials, but is used in Canada and the United Kingdom for the treatment of spasticity secondary to multiple sclerosis and pain. Studies of marijuana have concentrated on nausea, appetite, and pain. This article will review the literature regarding the medical use of marijuana and these cannabinoid pharmaceuticals (with emphasis on indications relevant to oncology), as well as available information regarding adverse effects of marijuana use. CA Cancer J Clin 2015;65: 109-122.
BACKGROUND: Cannabis has a long history of medicinal use. Cannabis-based medications (cannabinoids) are based on its active element, delta-9-tetrahydrocannabinol (THC), and have been approved for medical purposes. Cannabinoids may be a useful therapeutic option for people with chemotherapy-induced nausea and vomiting that respond poorly to commonly used anti-emetic agents (anti-sickness drugs). However, unpleasant adverse effects may limit their widespread use.
OBJECTIVES: To evaluate the effectiveness and tolerability of cannabis-based medications for chemotherapy-induced nausea and vomiting in adults with cancer.
SEARCH METHODS: We identified studies by searching the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO and LILACS from inception to January 2015. We also searched reference lists of reviews and included studies. We did not restrict the search by language of publication.
SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared a cannabis-based medication with either placebo or with a conventional anti-emetic in adults receiving chemotherapy.
DATA COLLECTION AND ANALYSIS: At least two review authors independently conducted eligibility and risk of bias assessment, and extracted data. We grouped studies based on control groups for meta-analyses conducted using random effects. We expressed efficacy and tolerability outcomes as risk ratio (RR) with 95% confidence intervals (CI).
MAIN RESULTS: We included 23 RCTs. Most were of cross-over design, on adults undergoing a variety of chemotherapeutic regimens ranging from moderate to high emetic potential for a variety of cancers. The majority of the studies were at risk of bias due to either lack of allocation concealment or attrition. Trials were conducted between 1975 and 1991. No trials involved comparison with newer anti-emetic drugs such as ondansetron. Comparison with placebo People had more chance of reporting complete absence of vomiting (3 trials; 168 participants; RR 5.7; 95% CI 2.6 to 12.6; low quality evidence) and complete absence of nausea and vomiting (3 trials; 288 participants; RR 2.9; 95% CI 1.8 to 4.7; moderate quality evidence) when they received cannabinoids compared with placebo. The percentage of variability in effect estimates that was due to heterogeneity rather than chance was not important (I(2) = 0% in both analyses).People had more chance of withdrawing due to an adverse event (2 trials; 276 participants; RR 6.9; 95% CI 1.96 to 24; I(2) = 0%; very low quality evidence) and less chance of withdrawing due to lack of efficacy when they received cannabinoids, compared with placebo (1 trial; 228 participants; RR 0.05; 95% CI 0.0 to 0.89; low quality evidence). In addition, people had more chance of 'feeling high' when they received cannabinoids compared with placebo (3 trials; 137 participants; RR 31; 95% CI 6.4 to 152; I(2) = 0%).People reported a preference for cannabinoids rather than placebo (2 trials; 256 participants; RR 4.8; 95% CI 1.7 to 13; low quality evidence). Comparison with other anti-emetics There was no evidence of a difference between cannabinoids and prochlorperazine in the proportion of participants reporting no nausea (5 trials; 258 participants; RR 1.5; 95% CI 0.67 to 3.2; I(2) = 63%; low quality evidence), no vomiting (4 trials; 209 participants; RR 1.11; 95% CI 0.86 to 1.44; I(2) = 0%; moderate quality evidence), or complete absence of nausea and vomiting (4 trials; 414 participants; RR 2.0; 95% CI 0.74 to 5.4; I(2) = 60%; low quality evidence). Sensitivity analysis where the two parallel group trials were pooled after removal of the five cross-over trials showed no difference (RR 1.1; 95% CI 0.70 to 1.7) with no heterogeneity (I(2) = 0%).People had more chance of withdrawing due to an adverse event (5 trials; 664 participants; RR 3.9; 95% CI 1.3 to 12; I(2) = 17%; low quality evidence), due to lack of efficacy (1 trial; 42 participants; RR 3.5; 95% CI 1.4 to 8.9; very low quality evidence) and for any reason (1 trial; 42 participants; RR 3.5; 95% CI 1.4 to 8.9; low quality evidence) when they received cannabinoids compared with prochlorperazine.People had more chance of reporting dizziness (7 trials; 675 participants; RR 2.4; 95% CI 1.8 to 3.1; I(2) = 12%), dysphoria (3 trials; 192 participants; RR 7.2; 95% CI 1.3 to 39; I(2) = 0%), euphoria (2 trials; 280 participants; RR 18; 95% CI 2.4 to 133; I(2) = 0%), 'feeling high' (4 trials; 389 participants; RR 6.2; 95% CI 3.5 to 11; I(2) = 0%) and sedation (8 trials; 947 participants; RR 1.4; 95% CI 1.2 to 1.8; I(2) = 31%), with significantly more participants reporting the incidence of these adverse events with cannabinoids compared with prochlorperazine.People reported a preference for cannabinoids rather than prochlorperazine (7 trials; 695 participants; RR 3.3; 95% CI 2.2 to 4.8; I(2) = 51%; low quality evidence).In comparisons with metoclopramide, domperidone and chlorpromazine, there was weaker evidence, based on fewer trials and participants, for higher incidence of dizziness with cannabinoids.Two trials with 141 participants compared an anti-emetic drug alone with a cannabinoid added to the anti-emetic drug. There was no evidence of differences between groups; however, the majority of the analyses were based on one small trial with few events. Quality of the evidence The trials were generally at low to moderate risk of bias in terms of how they were designed and do not reflect current chemotherapy and anti-emetic treatment regimens. Furthermore, the quality of evidence arising from meta-analyses was graded as low for the majority of the outcomes analysed, indicating that we are not very confident in our ability to say how well the medications worked. Further research is likely to have an important impact on the results.
AUTHORS' CONCLUSIONS: Cannabis-based medications may be useful for treating refractory chemotherapy-induced nausea and vomiting. However, methodological limitations of the trials limit our conclusions and further research reflecting current chemotherapy regimens and newer anti-emetic drugs is likely to modify these conclusions.
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)
Chemotherapy-induced nausea and vomiting (CINV) is a burdensome adverse event frequently associated with chemotherapy treatment of cancer. Evidence suggests that cannabinoid CB2 receptors are present in brainstem neurons, and thus, there may exist a role for cannabinoids to counter CINV. The aim of this paper is to conduct a systematic review and meta-analysis of the efficacy and safety of oral cannabinoids compared with other treatments as documented in randomized controlled trials (RCTs).
METHODS:
A literature search was conducted using Ovid MEDLINE up until December 31, 2018; Embase Classic and Embase up until 2018 week 53; and Cochrane Central Register of Controlled Trials up until November 2018. Study data were extracted and included in this meta-analysis if they reported on at least one of the following efficacy endpoints: no nausea and no vomiting, no nausea, and no vomiting. The Mantel-Haenszel method and random effects analysis model were used, to generate odds ratio (OR) and accompanying 95% confidence intervals (CI).
RESULTS:
In the setting of prophylactic treatment against both nausea and vomiting, oral cannabinoid was more efficacious than placebo or other studied antiemetic treatments. When controlling for vomiting, oral cannabinoid was equally as efficacious as others. Against nausea, oral cannabinoid was equally as effective as other treatments. A greater percentage of patients administered oral cannabinoid for CINV experienced dysphoria, euphoria, and sedation.
CONCLUSION:
Although there exists some evidence suggesting that oral cannabinoids may have a role in controlling for emesis from a neurophysiological perspective, these conclusions are currently not mirrored in the published RCTs to date. However, there exists only a limited number of RCTs, comparisons with older treatment regimens and a lack of standard reporting practice across published literature. Further RCTs should investigate the efficacy and safety of oral cannabinoids, to secure a better picture of the efficacy of oral cannabinoids against CINV.
