Does medicinal cannabis affect depression, anxiety, and stress in people with cancer? A systematic review and meta-analysis of intervention studies.

INTRODUCTION: Medicinal cannabis might have a role in supporting the mental health of people with cancer. This systematic review and meta-analysis examined the efficacy and safety of medicinal cannabis, compared with any control, as an intervention for depression, anxiety, and stress symptoms in people living with cancer. A secondary aim was to examine the effect of low versus high Δ9-tetrahydrocannabinol (THC) dose on these outcomes. METHODS: Five databases were systematically searched, and complemented with a snowball search from inception to May 2023, for any type of interventional study that included humans of any age with any cancer type. Primary outcomes were incidence and severity of depression, anxiety, and stress symptoms. Secondary outcomes were mood, cognition, quality of life, appetite, nutrition status, gastrointestinal symptoms, and adverse events. Data were pooled using Review Manager. Evidence was appraised using Cochrane risk of bias tools. Confidence in the estimated effect of pooled outcomes was assessed using Grading of Recommendations, Assessment, Development and Evaluation (GRADE). RESULTS: Fifteen studies (n = 11 randomized trials, n = 4 non-randomized trials) of 18 interventions (N = 1898 total participants; 100 % ≥18 years of age) were included. Ten studies examined THC (70 % synthetic), two synthetic cannabidiol with or without THC, and six whole-plant extracts. No clinically significant effects of medicinal cannabis were found on primary outcomes. The likelihood of anxiety events increased with higher-dose synthetic THC compared with a lower dose (OR: 2.0; 95 % CI: 1.4, 2.9; p < 0.001; Confidence: very low). Medicinal cannabis (THC, cannabidiol, and whole-plant extract) increased the likelihood of improved appetite (OR: 12.3; 95 % CI: 3.5, 45.5; p < 0.001; n = 3 interventions; Confidence: moderate) and reduced severity of appetite loss (SMD: -0.4; 95 % CI: -0.8, -0.1; p = 0.009; Confidence: very low). There was very low confidence that higher doses of synthetic THC increased the likelihood of any adverse event (OR: 0.5; 95 % CI: 0.3, 0.7; p < 0.001). Medicinal cannabis had no effect on emotional functioning, mood changes, confusion, disorientation, quality of life, and gastrointestinal symptoms. Confidence in findings was limited by some studies having high or unclear risk of bias and imprecise pooled estimates. CONCLUSIONS: There was insufficient evidence to determine the efficacy and safety of medicinal cannabis as a therapeutic intervention for depression, anxiety, or stress in people with active cancer. Further research should explore whether medicinal cannabis might improve and maintain appetite and if high-dose synthetic THC might increase the incidence of side-effects, including anxiety. To inform clinical practice, well-powered and rigorously designed trials are warranted that evaluate the effects of medicinal cannabis prescribed to target anxiety, depression, and stress.

Effect of a Standardized Ginger Root Powder Regimen on Chemotherapy-Induced Nausea and Vomiting: A Multicenter, Double-Blind, Placebo-Controlled Randomized Trial.

BACKGROUND: There is substantial interest in the role of ginger as an adjuvant therapy for chemotherapy-induced nausea and vomiting (CINV). However, available evidence lacks robust methodology. OBJECTIVE: To assess the effect of adjuvant ginger compared with placebo on chemotherapy-induced nausea-related quality of life (QoL) and CINV-related outcomes. DESIGN: A parallel, double-blind, placebo-controlled randomized trial with 1:1 allocation was conducted. PARTICIPANTS/SETTING: One hundred three chemotherapy-naïve adults scheduled to receive moderately to highly emetogenic chemotherapy at two hospitals in Australia were enrolled and analyzed. INTERVENTION: Four standardized ginger capsules (totaling 84 mg/day active gingerols/shogaols), or placebo, were administered commencing the day of chemotherapy and continuing for 5 days for chemotherapy cycles 1 through 3. MAIN OUTCOME MEASURES: The primary outcome was chemotherapy-induced nausea-related QoL. Secondary outcomes were vomiting- and CINV-related QoL; anticipatory, acute, and delayed nausea and vomiting; fatigue; nutritional status; depression and anxiety; health-related QoL; and adverse events. STATISTICAL ANALYSES PERFORMED: Intention-to-treat analysis was performed. Mixed analysis of variance with repeated measures determined differences between groups. The null hypothesis was no difference between groups. After applying a Bonferroni multiple testing correction, evidence against the null hypothesis was considered at P= 0.003. RESULTS: One hundred three participants (ginger: n = 52; placebo: n = 51) were enrolled and analyzed. There was clinically relevant evidence against the null hypothesis, favoring ginger, in change scores for nausea-related QoL (F[df] = 9.34[1,101]; P = 0.003; partial η2 = 0.09), overall CINV-related QoL (F[df] = 12.26[1,101]; P < 0.001; partial η2 = 0.11), delayed nausea severity (F[df] = 9.46[1,101]; P = 0.003; partial η2 = 0.09), and fatigue (F[df] = 10.11[1,101]; P = 0.002; partial η2 = 0.09). There was a clinically meaningful lower incidence of delayed nausea and vomiting in the ginger group at Cycle 2 (53% vs 75%; P = 0.020 and 4% vs 27%; P = 0.001, respectively) and Cycle 3 (49% vs 79%; P = 0.002 and 2% vs 23%; P = 0.001, respectively). There was a clinically meaningful lower incidence of malnutrition in the ginger group at Cycle 3 (18% vs. 41%; P = 0.032) and in change scores for Patient-Generated Subjective Global Assessment (F[df)] = 4.32[1,100]; P = 0.040; partial η2 = 0.04). Change scores between groups favored ginger for vomiting-related QoL and number of vomiting episodes; however, findings were not clinically meaningful. There was no effect of ginger on anticipatory or acute CINV, health-related QoL, anxiety, or depression. No serious adverse events were reported. CONCLUSIONS: Ginger supplementation was a safe adjuvant to antiemetic medications for CINV that enhanced QoL during chemotherapy treatment. Future trials are needed to examine dose-dependent responses to verify optimal dosing regimens.

Therapeutic health effects of ginger (Zingiber officinale): updated narrative review exploring the mechanisms of action.

Ginger (Zingiber officinale) has been investigated for its potentially therapeutic effect on a range of chronic conditions and symptoms in humans. However, a simplified and easily understandable examination of the mechanisms behind these effects is lacking and, in turn, hinders interpretation and translation to practice, and contributes to overall clinical heterogeneity confounding the results. Therefore, drawing on data from nonhuman trials, the objective for this narrative review was to comprehensively describe the current knowledge on the proposed mechanisms of action of ginger on conferring therapeutic health effects in humans. Mechanistic studies support the findings from human clinical trials that ginger may assist in improving symptoms and biomarkers of pain, metabolic chronic disease, and gastrointestinal conditions. Bioactive ginger compounds reduce inflammation, which contributes to pain; promote vasodilation, which lowers blood pressure; obstruct cholesterol production, which regulates blood lipid profile; translocate glucose transporter type 4 molecules to plasma membranes to assist in glycemic control; stimulate fatty acid breakdown to aid weight management; and inhibit serotonin, muscarinic, and histaminergic receptor activation to reduce nausea and vomiting. Additional human trials are required to confirm the antimicrobial, neuroprotective, antineoplastic, and liver- and kidney-protecting effects of ginger. Interpretation of the mechanisms of action will help clinicians and researchers better understand how and for whom ginger may render therapeutic effects and highlight priority areas for future research.

What is the efficacy of dietary, nutraceutical, and probiotic interventions for the management of gastroesophageal reflux disease symptoms? A systematic literature review and meta-analysis.

BACKGROUND: Treatments for Gastroesophageal Reflux Disease (GERD) symptoms include pharmaceutical, surgical, dietary, and lifestyle behaviors; however, dietary interventions lack evidence synthesis. RESEARCH QUESTION: What is the effect of dietary, probiotic, and nutraceutical interventions on GERD symptoms, with or without pharmaceutical therapy, in adults with a history of GERD or functional dyspepsia compared to no intervention, placebo, or usual care? METHOD: A systematic review and meta-analysis was performed according to PRISMA. The search strategy was implemented in MEDLINE, CINAHL, CENTRAL, and Embase on the 28th October 2020 and updated to 27th July 2021. Intervention studies were eligible if they evaluated the effect of a dietary, nutraceutical, or probiotic intervention on GERD symptoms in adults with a history of GERD or functional dyspepsia. The internal validity of studies was assessed using the Academy Quality Criteria Checklist; Review Manager software was used to perform meta-analysis; and certainty in the body of evidence was assessed using GRADE. RESULTS: 6,608 study records were retrieved from the search, with 21 studies (n = 24 highly heterogenous intervention groups) included (n = 10 restrictive dietary interventions; n = 3 non-restrictive dietary interventions; n = 8 nutraceutical interventions; and n = 3 probiotic interventions). GERD symptoms were clinically and statistically improved by a test-based elimination diet (n = 1 study), low nickel diet (n = 1 study), probiotic yoghurt (n = 1 study), psyllium husk (n = 1 study), prickly pear and olive leaf extract supplement (n = 1 study), and melatonin, amino acid and b-group vitamin supplement (n = 1 study) according to qualitative synthesis. Ginger-containing supplements could be meta-analyzed, and improved incidence of GERD symptom alleviation (n = 2 studies, OR: 7.50 [95%CI: 3.62-15.54], GRADE: high). No clinically and/or statistically significant effects were found for the remaining n = 16 highly heterogenous interventions. CONCLUSION: Evidence to guide the dietary management of GERD symptoms is limited in scope, quality, and feasibility. Based on the limited evidence available, dietary GERD management should be long-term, individualized, and consider both dietary restrictions and/or additions. PROSPERO ID: CRD42021224082.

Dietary strategies for chemotherapy-induced nausea and vomiting: A systematic review.

BACKGROUND & AIMS: Chemotherapy-induced nausea and vomiting (CINV) is one of the most distressing cancer treatment side effects, affecting 20-70% of patients despite routine antiemetic prescription. Although dietary modifications are routinely recommended in clinical practice, there is lack of data synthesis to determine which dietary strategies for managing CINV are supported by quality evidence. This systematic review was conducted to examine the effect of dietary strategies on incidence and severity of CINV in adults compared with no intervention, usual care, or alternative strategies. METHODS: Five electronic databases were searched from inception to 15th July 2021 for original research studies of interventional or observational design assessing dietary strategies for CINV. The quality of evidence was appraised, data were synthesized narratively, and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) assessment of the certainty of the evidence was applied. RESULTS: Twenty-one studies were included, 10 (48%) interventional studies and 11 (52%) observational studies. Most interventional and observational studies had a high or neutral risk of bias (70% and 72%, respectively). Of the interventions studied, strongest evidence with highest certainty was found for the very large positive effect of CINV-specific education and support with a personalized meal plan from a dietician, implemented in person or in writing, for reducing the severity of nausea and overall CINV (effect size: very large; GRADE: high). A statistically significant very large positive effect of ginger tea consumption was also found on overall CINV severity; however, certainty in this effect was very low. Although confidence in the findings from observational studies was very low to low, a statistically significant positive association was also found between a moderate intake of alcohol and incidence of nausea, vomiting, or overall CINV as well as nausea severity; the Mediterranean diet and nausea incidence and severity; and adequate intake of energy, protein, fat, or carbohydrate and nausea or vomiting incidence. CONCLUSION: Improved CINV was associated with CINV-specific nutrition education and support from health professionals. Non-restrictive dietary patterns that include adequate energy and macronutrient intakes, particularly protein, and include ginger, and Mediterranean diet concepts may benefit CINV; however, the confidence in the body of evidence to inform these conclusions is mostly very low to moderate. Future rigorous trials with adequate sample sizes, clearly defined dietary strategies, and valid outcome measures are warranted prior to dietary strategies being routinely prescribed alongside antiemetic regimens.

Efficacy and safety of biophenol-rich nutraceuticals in adults with inflammatory gastrointestinal diseases or irritable bowel syndrome: A systematic literature review and meta-analysis.

AIM: Biophenol-rich nutraceuticals may be an adjuvant treatment for Crohn's disease (CD), ulcerative colitis (UC), symptomatic uncomplicated diverticular disease (SUDD), and irritable bowel syndrome (IBS). This systematic review and meta-analysis aimed to determine the efficacy and safety of biophenol-rich nutraceutical supplementation on CD, UC, SUDD, and IBS on gastrointestinal symptoms (GIS), quality of life (QoL), inflammatory and oxidative stress biomarkers, and adverse events compared to usual care or placebo. METHODS: PubMed, Embase, CINAHL, and CENTRAL were searched for randomised controlled trials until 27 April 2020. Outcomes were GIS, inflammatory and oxidative stress markers, QoL, and adverse events. The Cochrane Risk of Bias tool and GRADE were used to appraise studies. Data were pooled using Revman. RESULTS: Twenty-three trials in CD, UC, and IBS patients were included. Compared with placebo, biophenol-rich nutraceuticals improved GIS (SMD: 0.43 [95%CI: 0.22, 0.63]; GRADE: very low) in UC, CD, and IBS participants. In UC and CD participants, biophenol-rich nutraceuticals improved CRP by 1.6 mg/L [95%CI:0.08, 3.11; GRADE: low], malondialdehyde by 1 mmol/L [95%CI:0.55, 1.38; GRADE: low]; but only resveratrol improved QoL (SMD: -0.84 [95%CI: -1.24, -0.44; GRADE: high). Resveratrol (for UC and CD participants) and peppermint oil (for IBS participants) had greater certainty in the evidence for improving GIS and QoL (GRADE: moderate to high). There was no effect on adverse events (P > .05). CONCLUSIONS: Biophenol-rich nutraceuticals may be an effective and safe adjuvant treatment for the management of CD, UC, and IBS; with higher certainty of evidence for resveratrol for UC and CD and peppermint oil for IBS.

Juggling cancer and life in survivorship: The role of general practitioners.

BACKGROUND: The number of cancer survivors in Australia is growing. General practitioners (GPs) have a key role in providing holistic care to people experiencing a cancer diagnosis, receiving treatment or enduring long-term effects of cancer and its treatment. Cancer survivors experience a range of unique biopsychosocial issues, requiring significant and coordinated care to optimise their quality of life. OBJECTIVE: The aim of this article is to provide an overview of management strategies for GPs in addressing three highly distressing cancer-related issues: fear of cancer recurrence, financial toxicity and management of relationships. DISCUSSION: Recommendations are provided for effective screening and monitoring of cancer-related issues, with management strategies outlined to facilitate GP-initiated discussions and referral to credible resources and other health services. Useful materials relevant to the Australian primary care setting are presented together with an overview of information to support GP provision of cancer survivorship care for fear of cancer recurrence, financial toxicity and relationship issues.

"It's natural so it shouldn't hurt me": Chemotherapy patients' perspectives, experiences, and sources of information of complementary and alternative medicines.

BACKGROUND AND PURPOSE: Minimal evidence regarding the safety and efficacy of complementary and alternative medicine (CAM) use during chemotherapy is accompanied with a high prevalence of use and nondisclosure to health professionals. This study aimed to explore patients' perspectives, experiences, support needs, and sources of information regarding CAM use during chemotherapy. MATERIALS AND METHODS: Semi-structured interviews with ten adult participants who recently completed chemotherapy treatment at a large hospital in Australia were transcribed verbatim. Three investigators thematically analysed the interviews. RESULTS: These participants receiving chemotherapy valued CAMs as a natural complement to chemotherapy to improve wellbeing, with their use most strongly influenced by past experiences rather than expert advice. CONCLUSION: Health professionals would benefit from education on how to best inform patients of the potential risks, harms and lack of efficacy for CAM use during chemotherapy in a way that does not lead to patient non-disclosure of CAM use.

Efficacy of Ginger (Zingiber officinale) in Ameliorating Chemotherapy-Induced Nausea and Vomiting and Chemotherapy-Related Outcomes: A Systematic Review Update and Meta-Analysis.

BACKGROUND: Ginger has been proposed as an adjuvant treatment for chemotherapy-induced nausea and vomiting. OBJECTIVE: The aim of this systematic review with meta-analyses is to evaluate, in adult cancer patients receiving chemotherapy, the effects of ginger supplementation dose and duration on the incidence, duration, and severity of chemotherapy-induced nausea and vomiting and outcomes related to chemotherapy-induced nausea and vomiting (eg, quality of life and fatigue), compared with placebo or standard antiemetic medication. METHOD: Five electronic databases were searched from database inception to April 2018. The quality of evidence was appraised with the Cochrane Risk of Bias tool and Grading of Recommendations, Assessment, Development, and Evaluation level. Data were pooled using Revman software. RESULTS: Eighteen articles were analyzed. The likelihood of acute vomiting was reduced by 60% with ginger supplementation ≤1 g/day for duration >3 days, compared with control groups (odds ratio 0.4, 95% CI 0.17 to 0.81; P=0.01; n=3 studies; n=3 interventions; n=301 participants; I2=20%; Grading of Recommendations, Assessment, Development, and Evaluation level: Moderate). The likelihood of fatigue was reduced by 80% with ginger supplementation of any dose for duration <3 days (odds ratio 0.2, 95% CI, 0.03 to 0.87; P=0.03; n=1 studies; n=2 interventions; n=219 participants; I2=0%; Grading of Recommendations, Assessment, Development, and Evaluation level: Low). No statistically significant association was found between ginger and likelihood of overall or delayed vomiting, likelihood or severity of nausea, or other outcomes related to chemotherapy-induced nausea and vomiting. CONCLUSIONS: Ginger supplementation might benefit chemotherapy-induced vomiting as well as fatigue. Due to clinical heterogeneity, this systematic review update found no association between ginger and chemotherapy-induced nausea and other chemotherapy-induced nausea and vomiting-related outcomes. The results of this systematic review and meta-analysis provide a rationale for further research with stronger study designs, adequate sample sizes, standardized ginger products, and validated outcome measures to confirm efficacy of ginger supplementation and optimal dosing regimens.