Are Younger Medical Cannabis Users at Risk? Comparing Patterns of Use and Mental Health in Younger and Older Medical Cannabis Dispensary Users

While there has been a considerable amount of research on recreational cannabis use in youth to date, much less is known about patterns of medical cannabis use in youth. Adult medical versus recreational cannabis users may differ in how they use the product on important factors such as dose, frequency and route of ingestion, and so it is important to understand whether adolescents and young adults differ in how they use medical cannabis compared to adults, and if this increases risk of impaired mental health. In the present study, one hundred members of a community cannabis dispensary who endorsed cannabis use for medical purposes were assessed for major psychiatric disorders, and completed questionnaires related to stress, depression, sleep and somatic symptoms. Detailed information about cannabis use was collected. In the sample, 35% were aged 19-24 years old, and 24% were aged 25-30 (categorized as youth/young adults). In comparison to the older medical cannabis users, there were unexpectedly few differences, both in mental health status as well as pattern of medical cannabis use. These findings contrast with those of recreational cannabis users, and indicate that medical cannabis in youth may be as effective and well-tolerated as in older adults

Exploring medical cannabis use in individuals with a traumatic brain injury

Aim: Traumatic brain injury (TBI) is a common neurological condition, which can present with a wide range of neuropsychological symptoms. Treating this broad spectrum of symptoms represents a significant medical challenge. In part because of this, there is growing interest in the use of medical cannabis to treat the sequelae of TBI, as medical cannabis has been used to treat multiple associated conditions, such as pain. However, medical cannabis represents a heterogeneous collection of therapies, and relatively little is known about their effectiveness in treating TBI symptoms. The aim of the present study was therefore to assess medical cannabis use in patients with TBI. Methods: In the present study, a retrospective chart review was conducted of patterns of cannabis use and TBI symptoms in individuals who used medical cannabis to treat TBI-related symptoms. All subjects were recruited from a medical cannabis clinic, where cannabis was authorized by physicians, using licensed cannabis products. A total of 53 subjects provided written consent to have their charts reviewed. Results: Neuropsychiatric conditions, including depression, pain, and anxiety were frequent in this group. The most common forms of medical cannabis consumption at intake included smoking, vaping, and oral ingestion. Patients used a combination of high tetrahydrocannabinol (THC)/low cannabidiol (CBD) and low THC/high CBD products, typically 1–3 times per day. Medical cannabis appeared to be relatively well-tolerated in subjects, with few serious side effects. At follow-up, subjects self-reported improvements in TBI symptoms, although these were not statistically significant when assessed using validated questionnaires. Conclusions: Overall findings indicate modest potential benefits of medical cannabis for TBI, but further research will be required to validate these results

Niche-specific regulation of central metabolic pathways in a fungal pathogen

To establish an infection, the pathogen Candida albicans must assimilate carbon and grow in its mammalian host. This fungus assimilates six-carbon compounds via the glycolytic pathway, and two-carbon compounds via the glyoxylate cycle and gluconeogenesis. We address a paradox regarding the roles of these central metabolic pathways in C. albicans pathogenesis: the glyoxylate cycle is apparently required for virulence although glyoxylate cycle genes are repressed by glucose at concentrations present in the bloodstream. Using GFP fusions, we confirm that glyoxylate cycle and gluconeogenic genes in C. albicans are repressed by physiologically relevant concentrations of glucose, and show that these genes are inactive in the majority of fungal cells infecting the mouse kidney. However, these pathways are induced following phagocytosis by macrophages or neutrophils. In contrast, glycolytic genes are not induced following phagocytosis and are expressed in infected kidney. Mutations in all three pathways attenuate the virulence of this fungus, highlighting the importance of central carbon metabolism for the establishment of C. albicans infections. We conclude that C. albicans displays a metabolic program whereby the glyoxylate cycle and gluconeogenesis are activated early, when the pathogen is phagocytosed by host cells, while the subsequent progression of systemic disease is dependent upon glycolysis

Mycobacterium ulcerans in Mosquitoes Captured during Outbreak of Buruli Ulcer, Southeastern Australia

Mosquitoes positive for M. ulcerans were linked to outbreaks of Buruli ulcer in humans

Risk of Buruli Ulcer and Detection of Mycobacterium ulcerans in Mosquitoes in Southeastern Australia

Buruli ulcer (BU) is a destructive skin condition caused by infection with the environmental bacterium, Mycobacterium ulcerans. BU has been reported in more than 30 countries in Africa, the Americas, Asia and the Western Pacific. How people become infected with M. ulcerans is not completely understood, but numerous studies have explored the role of biting insects. In 2007, it was discovered that M. ulcerans could be detected in association with mosquitoes trapped in one town in southeastern Australia during a large outbreak of BU. In the present study we investigated whether there was a relationship between the incidence of BU in humans in several towns and the likelihood of detecting M. ulcerans in mosquitoes trapped in those locations. We found a strong association between the proportion of M. ulcerans-positive mosquitoes and the incidence of human disease. The results of this study strengthen the hypothesis that mosquitoes are involved in the transmission of M. ulcerans in southeastern Australia. This has implications for the development of strategies to control and prevent BU

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Cannabidiol-associated hepatotoxicity: a systematic review and meta-analysis.

BACKGROUND Findings of liver enzyme elevations in recent cannabidiol studies have raised concerns over liver safety. This study aimed to determine the association between cannabidiol use, liver enzyme elevation, and drug-induced liver injury (DILI). METHODS In this systematic review and meta-analysis, a search of EMBASE, CENTRAL, CINAHL, Clinicaltrials.gov, Medline, medRxiv, and Web of Science of records up to February 2022 was conducted. Clinical trials initiating daily cannabidiol treatment with serial liver enzyme measures were included. The proportion of liver enzyme elevations and DILI were independently extracted from published reports. Pooled proportions and probability meta-analyses were conducted. RESULTS Cannabidiol use was associated with an increased probability of liver enzyme elevation (N = 12 trials, n = 1229; OR = 5.85 95% CI = 3.84-8.92, p < 0.001) and DILI (N = 12 trials, n = 1229; OR = 4.82 95% CI = 2.46-9.45, p < 0.001) compared to placebo controls. In participants taking cannabidiol (N = 28 trials, n = 1533), the pooled proportion of liver enzyme elevations was 0.074 (95% CI 0.0448-0.1212), and DILI was 0.0296 (95% CI 0.0136-0.0631). High-dose CBD (≥1000 mg/day or ≥20 mg/kg/day) and concomitant antiepileptic drug use were identified as risk factors. No cases were reported in adults using cannabidiol doses <300 mg/day. No cases of severe DILI were reported. CONCLUSIONS Cannabidiol-associated liver enzyme elevations and DILI meet the criteria of common adverse drug events. Clinicians are encouraged to screen for cannabidiol use and monitor liver function in patients at increased risk

Exploratory factor analysis of the Dizziness Handicap Inventory (German version)

BACKGROUND: The Dizziness Handicap Inventory (DHI) is a validated, self-report questionnaire which is widely used as an outcome measure. Previous studies supported the multidimensionality of the DHI, but not the original subscale structure. The objectives of this survey were to explore the dimensions of the Dizziness Handicap Inventory - German version, and to investigate the associations of the retained factors with items assessing functional disability and the Hospital Anxiety and Depression Scale (HADS). Secondly we aimed to explore the retained factors according to the International Classification of Functioning, Disability and Health (ICF). METHODS: Patients were recruited from a tertiary centre for vertigo, dizziness or balance disorders. They filled in two questionnaires: (1) The DHI assesses precipitating physical factors associated with dizziness/unsteadiness and functional/emotional consequences of symptoms. (2) The HADS assesses non-somatic symptoms of anxiety and depression. In addition, patients answered the third question of the University of California Los Angeles-Dizziness Questionnaire which covers the impact of dizziness and unsteadiness on everyday activities. Principal component analysis (PCA) was performed to explore the dimensions of the DHI. Associations were estimated by Spearman correlation coefficients. RESULTS: One hundred ninety-four patients with dizziness or unsteadiness associated with a vestibular disorder, mean age (standard deviation) of 50.6 (13.6) years, participated. Based on eigenvalues greater one respectively the scree plot we analysed diverse factor solutions. The 3-factor solution seems to be reliable, clinically relevant and can partly be explained with the ICF. It explains 49.2% of the variance. Factor 1 comprises the effect of dizziness and unsteadiness on emotion and participation, factor 2 informs about specific activities or effort provoking dizziness and unsteadiness, and factor 3 focuses on self-perceived walking ability in relation to contextual factors. The first factor correlates moderately with disability and the HADS (values >/=0.6). The second factor is comparable with the original physical subscale of the DHI and factors retained in previous studies. CONCLUSIONS: The results of the present survey can not support the original subscale structure of the DHI. Therefore only the total scale should be used. We discuss a possible restructuring of the DHI