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.

Ultra-processed food exposure and adverse health outcomes: umbrella review of epidemiological meta-analyses.

OBJECTIVE: To evaluate the existing meta-analytic evidence of associations between exposure to ultra-processed foods, as defined by the Nova food classification system, and adverse health outcomes. DESIGN: Systematic umbrella review of existing meta-analyses. DATA SOURCES: MEDLINE, PsycINFO, Embase, and the Cochrane Database of Systematic Reviews, as well as manual searches of reference lists from 2009 to June 2023. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Systematic reviews and meta-analyses of cohort, case-control, and/or cross sectional study designs. To evaluate the credibility of evidence, pre-specified evidence classification criteria were applied, graded as convincing ("class I"), highly suggestive ("class II"), suggestive ("class III"), weak ("class IV"), or no evidence ("class V"). The quality of evidence was assessed using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) framework, categorised as "high," "moderate," "low," or "very low" quality. RESULTS: The search identified 45 unique pooled analyses, including 13 dose-response associations and 32 non-dose-response associations (n=9 888 373). Overall, direct associations were found between exposure to ultra-processed foods and 32 (71%) health parameters spanning mortality, cancer, and mental, respiratory, cardiovascular, gastrointestinal, and metabolic health outcomes. Based on the pre-specified evidence classification criteria, convincing evidence (class I) supported direct associations between greater ultra-processed food exposure and higher risks of incident cardiovascular disease related mortality (risk ratio 1.50, 95% confidence interval 1.37 to 1.63; GRADE=very low) and type 2 diabetes (dose-response risk ratio 1.12, 1.11 to 1.13; moderate), as well as higher risks of prevalent anxiety outcomes (odds ratio 1.48, 1.37 to 1.59; low) and combined common mental disorder outcomes (odds ratio 1.53, 1.43 to 1.63; low). Highly suggestive (class II) evidence indicated that greater exposure to ultra-processed foods was directly associated with higher risks of incident all cause mortality (risk ratio 1.21, 1.15 to 1.27; low), heart disease related mortality (hazard ratio 1.66, 1.51 to 1.84; low), type 2 diabetes (odds ratio 1.40, 1.23 to 1.59; very low), and depressive outcomes (hazard ratio 1.22, 1.16 to 1.28; low), together with higher risks of prevalent adverse sleep related outcomes (odds ratio 1.41, 1.24 to 1.61; low), wheezing (risk ratio 1.40, 1.27 to 1.55; low), and obesity (odds ratio 1.55, 1.36 to 1.77; low). Of the remaining 34 pooled analyses, 21 were graded as suggestive or weak strength (class III-IV) and 13 were graded as no evidence (class V). Overall, using the GRADE framework, 22 pooled analyses were rated as low quality, with 19 rated as very low quality and four rated as moderate quality. CONCLUSIONS: Greater exposure to ultra-processed food was associated with a higher risk of adverse health outcomes, especially cardiometabolic, common mental disorder, and mortality outcomes. These findings provide a rationale to develop and evaluate the effectiveness of using population based and public health measures to target and reduce dietary exposure to ultra-processed foods for improved human health. They also inform and provide support for urgent mechanistic research. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023412732.

The effects of anodal tDCS on pain reduction in people with knee osteoarthritis: A systematic review and meta-analysis.

OBJECTIVES: To synthesise the literature on the efficacy of primary motor cortex anodal transcranial direct current stimulation (M1-a-tDCS), as a standalone or priming technique, for pain reduction in people with knee osteoarthritis (KOA). METHODS: The systematic literature search was conducted in MEDLINE, CINAHL, Embase and CENTRAL according to PRISMA statement. RESULTS: Fourteen studies involving 740 people with KOA were included. In the meta-analysis, six studies compared a-tDCS alone with sham stimulation, and five studies compared a-tDCS combined with other methods with sham stimulation. We found positive effect of a-tDCS alone on pain in KOA (standard mean difference (SMD) -0.52; 95% CI, -0.78 to -0.25; P=0.001; I2 = 69%). Further, a-tDCS with other treatments showed positive effect (SMD -1.23; 95% CI, -1.59 to -0.88; P<0.001; I2 = 48%) on pain in people with KOA. This evidence showed low certainty due to a high risk of bias and imprecision. DISCUSSION AND CONCLUSION: A-tDCS could be considered as standalone and an adjunct treatment for pain reduction in people with KOA. Future randomised studies should address quality issues, including small sample size, to enhance the overall certainty of the findings. SIGNIFICANCE: A-tDCS can be used as a standalone and adjunct treatment for KOA. STUDY REGISTRATION: PROSPERO number CRD42021255114.

Polyphenols as novel interventions for depression: Exploring the efficacy, mechanisms of action, and implications for future research.

Numerous animal and human studies have assessed the relationship between polyphenols and outcomes related to depression. However, no comprehensive synthesis of the main findings has been conducted. The aim of this manuscript was to systematically review the available evidence from animal and human studies on the association and the effects of dietary polyphenols on depression and provide recommendations for future research. We based our review on 163 preclinical animal, 16 observational and 44 intervention articles assessing the relationship between polyphenols and outcomes related to depression. Most animal studies demonstrated that exposure to polyphenols alleviated behaviours reported to be associated with depression. However, human studies are less clear, with some studies reporting an inverse relationship between the intake of some polyphenols, and polyphenol rich foods and depression risk and symptoms, while others reporting no association or effect. Hence, while there has been extensive research conducted in animals and there is some supporting evidence in humans, further human studies are required, particularly in younger and clinical populations.

Peri-Operative Risk Factors Associated with Post-Operative Cognitive Dysfunction (POCD): An Umbrella Review of Meta-Analyses of Observational Studies.

This umbrella review aimed to systematically identify the peri-operative risk factors associated with post-operative cognitive dysfunction (POCD) using meta-analyses of observational studies. To date, no review has synthesised nor assessed the strength of the available evidence examining risk factors for POCD. Database searches from journal inception to December 2022 consisted of systematic reviews with meta-analyses that included observational studies examining pre-, intra- and post-operative risk factors for POCD. A total of 330 papers were initially screened. Eleven meta-analyses were included in this umbrella review, which consisted of 73 risk factors in a total population of 67,622 participants. Most pertained to pre-operative risk factors (74%) that were predominantly examined using prospective designs and in cardiac-related surgeries (71%). Overall, 31 of the 73 factors (42%) were associated with a higher risk of POCD. However, there was no convincing (class I) or highly suggestive (class II) evidence for associations between risk factors and POCD, and suggestive evidence (class III) was limited to two risk factors (pre-operative age and pre-operative diabetes). Given that the overall strength of the evidence is limited, further large-scale studies that examine risk factors across various surgery types are recommended.

Ultra-Processed Food Consumption and Mental Health: A Systematic Review and Meta-Analysis of Observational Studies.

Since previous meta-analyses, which were limited only to depression and by a small number of studies available for inclusion at the time of publication, several additional studies have been published assessing the link between ultra-processed food consumption and depression as well as other mental disorders. We aimed to build on previously conducted reviews to synthesise and meta-analyse the contemporary evidence base and clarify the associations between the consumption of ultra-processed food and mental disorders. A total of 17 observational studies were included (n = 385,541); 15 cross-sectional and 2 prospective. Greater ultra-processed food consumption was cross-sectionally associated with increased odds of depressive and anxiety symptoms, both when these outcomes were assessed together (common mental disorder symptoms odds ratio: 1.53, 95%CI 1.43 to 1.63) as well as separately (depressive symptoms odds ratio: 1.44, 95%CI 1.14 to 1.82; and, anxiety symptoms odds ratio: 1.48, 95%CI 1.37 to 1.59). Furthermore, a meta-analysis of prospective studies demonstrated that greater ultra-processed food intake was associated with increased risk of subsequent depression (hazard ratio: 1.22, 95%CI 1.16 to 1.28). While we found evidence for associations between ultra-processed food consumption and adverse mental health, further rigorously designed prospective and experimental studies are needed to better understand causal pathways.

Brain derived neurotrophic factor in perioperative neurocognitive disorders: Current evidence and future directions.

An increase in the age of surgical patients as well as the volume of surgeries is associated with a rise in perioperative neurocognitive disorders. These disorders encompass acute delirium and longer-term cognitive dysfunctions. Brain derived neurotrophic factor (BDNF) is a neurotrophin that plays a dynamic role in a series of neurological functions including neuroplasticity, neurogenesis and synaptic regulation. Given the possible alterations to brain physiology in response to surgery, this review aims to explore the relationship between changes in central and peripheral BDNF concentrations and perioperative neurocognitive disorders. Higher levels of Brain tissue and blood BDNF have been associated with better cognitive function; however, the nature of the association between BDNF and delirium is uncertain. Preclinical models point to a significant depletion in BDNF expression and signalling within the brain post-operatively, while preliminary human studies demonstrate depletions in serum BDNF concentration after surgery. These findings suggest that the reduced BDNF concentrations may be associated with post-operative cognitive dysfunction. Thus, understanding the BDNF expression/signalling pathways may present a promising avenue for managing perioperative neurocognitive disorders symptoms. Nonetheless, given that results were primarily derived from preclinical models, it is critical for these findings to be validated in humans to confirm the relevance of this promising target.

The Effects of Dietary Advanced Glycation End-Products on Neurocognitive and Mental Disorders.

Advanced glycation end products (AGEs) are glycated proteins or lipids formed endogenously in the human body or consumed through diet. Ultra-processed foods and some culinary techniques, such as dry cooking methods, represent the main sources and drivers of dietary AGEs. Tissue accumulation of AGEs has been associated with cellular aging and implicated in various age-related diseases, including type-2 diabetes and cardiovascular disease. The current review summarizes the literature examining the associations between AGEs and neurocognitive and mental health disorders. Studies indicate that elevated circulating AGEs are cross-sectionally associated with poorer cognitive function and longitudinally increase the risk of developing dementia. Additionally, preliminary studies show that higher skin AGE accumulation may be associated with mental disorders, particularly depression and schizophrenia. Potential mechanisms underpinning the effects of AGEs include elevated oxidative stress and neuroinflammation, which are both key pathogenetic mechanisms underlying neurodegeneration and mental disorders. Decreasing dietary intake of AGEs may improve neurological and mental disorder outcomes. However, more sophisticated prospective studies and analytical approaches are required to verify directionality and the extent to which AGEs represent a mediator linking unhealthy dietary patterns with cognitive and mental disorders.

Polyphenols as adjunctive treatments in psychiatric and neurodegenerative disorders: Efficacy, mechanisms of action, and factors influencing inter-individual response.

The pathophysiology of psychiatric and neurodegenerative disorders is complex and multifactorial. Polyphenols possess a range of potentially beneficial mechanisms of action that relate to the implicated pathways in psychiatric and neurodegenerative disorders. The aim of this review is to highlight the emerging clinical trial and preclinical efficacy data regarding the role of polyphenols in mental and brain health, elucidate novel mechanisms of action including the gut microbiome and gene expression, and discuss the factors that may be responsible for the mixed clinical results; namely, the role of interindividual differences in treatment response and the potentially pro-oxidant effects of some polyphenols. Further clarification as part of larger, well conducted randomized controlled trials that incorporate precision medicine methods are required to inform clinical efficacy and optimal dosing regimens.