Risk of Motor Vehicle Collisions and Culpability among Older Drivers Using Cannabis: A Meta-Analysis

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Limited studies have investigated the effects of cannabis use on driving among older adults, who represent the fastest growing segment of drivers globally. We conducted a systematic review and meta-analysis to evaluate the effects of delta-9-tetrahydrocannabinol (THC) exposure on risks of (1) motor vehicle collisions (MVC) and (2) culpability for MVCs among adults 50 years and older. Three reviewers screened 7022 studies identified through MEDLINE, EMBASE, CENTRAL, and PsycINFO. Odds Ratios (OR) were calculated using the Mantel-Haenszel method in Review Manager 5.4.1. Heterogeneity was assessed using I . The National Heart, Lung, and Blood Institute tool was used to assess the quality of each study. Seven cross-sectional studies were included. Three studies evaluated culpability while four evaluated MVC. The pooled risk of MVC was not signifi- cantly different between THC-positive and THC-negative older drivers (OR, 95% CI 1.15 [0.40, 3.31]; I2 = 72%). In culpability studies, THC exposure was not significantly associated with an increased risk of being culpable for MVC among adults over the age of 50 (OR, 95% CI 1.24 [0.95, 1.61]; I2 = 0%). Inspection of funnel plots did not indicate publication bias. Our review found that THC exposure was not associated with MVC involvement nor with culpability for MVCs.

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Pathogenesis Underlying Neurological Manifestations of Long COVID Syndrome and Potential Therapeutics

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The development of long-term symptoms of coronavirus disease 2019 (COVID-19) more than four weeks after primary infection, termed “long COVID” or post-acute sequela of COVID-19 (PASC), can implicate persistent neurological complications in up to one third of patients and present as fatigue, “brain fog”, headaches, cognitive impairment, dysautonomia, neuropsychiatric symptoms, anosmia, hypogeusia, and peripheral neuropathy. Pathogenic mechanisms of these symptoms of long COVID remain largely unclear; however, several hypotheses implicate both nervous system and systemic pathogenic mechanisms such as SARS-CoV2 viral persistence and neuroinvasion, abnormal immunological response, autoimmunity, coagulopathies, and endotheliopathy. Outside of the CNS, SARS-CoV-2 can invade the support and stem cells of the olfactory epithelium leading to persistent alterations to olfactory function. SARS-CoV-2 infection may induce abnormalities in innate and adaptive immunity including monocyte expansion, T-cell exhaustion, and prolonged cytokine release, which may cause neuroinflammatory responses and microglia activation, white matter abnormalities, and microvascular changes. Additionally, microvascular clot formation can occlude capillaries and endotheliopathy, due to SARS-CoV-2 protease activity and complement activation, can contribute to hypoxic neuronal injury and blood–brain barrier dysfunction, respectively. Current therapeutics target pathological mechanisms by employing antivirals, decreasing inflammation, and promoting olfactory epithelium regeneration. Thus, from laboratory evidence and clinical trials in the literature, we sought to synthesize the pathophysiological pathways underlying neurological symptoms of long COVID and potential therapeutics.

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Rare Phytocannabinoids Exert Anti-Inflammatory Effects on Human Keratinocytes via the Endocannabinoid System and MAPK Signaling Pathway

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Increasing evidence supports the therapeutic potential of rare cannabis-derived phytocannabinoids (pCBs) in skin disorders such as atopic dermatitis, psoriasis, pruritus, and acne. However, the molecular mechanisms of the biological action of these pCBs remain poorly investigated. In this study, an experimental model of inflamed human keratinocytes (HaCaT cells) was set up by using lipopolysaccharide (LPS) in order to investigate the anti-inflammatory effects of the rare pCBs cannabigerol (CBG), cannabichromene (CBC), Δ9-tetrahydrocannabivarin (THCV) and cannabigerolic acid (CBGA). To this aim, pro-inflammatory interleukins (IL)-1β, IL-8, IL-12, IL-31, tumor necrosis factor (TNF-β) and anti-inflammatory IL-10 levels were measured through ELISA quantification. In addition, IL-12 and IL-31 levels were measured after treatment of HaCaT cells with THCV and CBGA in the presence of selected modulators of endocannabinoid (eCB) signaling.

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Cannabis and Public Health: A Study Assessing Regular Cannabis Users Through Health Indicators

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An increasing number of countries are deciding to regulate the medicinal and/or recreational use of cannabis (Cannabis sativa L.). However, there is a lack of information on the impact of regular consumption of this substance on public health. In this study, for the first time, regular cannabis consumers in Spain were assessed using health indicators, comparing these data with the general population.

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Is it the Ideal Time to Start Prescribing Cannabis Derivatives to Treat Endometriosis-associated Pain?

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Endometriosis affects 5%-10% of women of reproductive age and is often associated with painful symptoms like dysmenorrhea, dyschezia, dyspareunia, and even non cyclical pain. The disease is diagnosed in at least 20% of women with dysmenorrhea and/or non-menstrual pelvic pain, reaching a prevalence of 50% pain among adolescents. There is an alignment among international societies3,4 that the pre- sumed diagnosis of this disease is enough to start clinical treatment. Moreover, there seems to be a consensus that first-line treatment should be hormonal contraceptives since the efficacy is similar to that of surgery but with lower complication rates and costs. However, these drugs are
effective in only approximately two-thirds of patients, have limited long-term efficacy and may occasionally lead to undesirable side effects. Additionally, there are serious limitations in the interpretation of clinical trials.

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Prenatal cannabis use and its impact on offspring neuro-behavioural outcomes: A systematic review

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Cannabis is a widely used substance in pregnancy, yet there is a paucity of literature addressing the neuro-behavioural consequences for prenatally exposed children. Our systematic review synthesizes currently available data for the impact of prenatal cannabis use on offspring intelligence and cognitive functioning.

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Anticancer properties of cannabidiol and Δ9-tetrahydrocannabinol and synergistic effects with gemcitabine and cisplatin in bladder cancer cell lines

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With the legalization of cannabis in multiple jurisdictions throughout the world, a larger proportion of the population consumes cannabis. Several studies have demonstrated anti-tumor effects of components present in cannabis in different models. Unfortunately, little is known about the potential anti-tumoral effects of cannabinoids in bladder cancer, and how cannabinoids could potentially synergize with chemotherapeutic agents. Our study aims to identify whether a combination of cannabinoids, like cannabidiol and Δ9-tetrahydrocannabinol with agents commonly used to treat bladder cancer, such as gemcitabine and cisplatin, is able to produce desirable synergistic effects. We also evaluated whether co-treatment of different cannabinoids also generated synergistic effects.

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Cannabidiol for the Treatment of Brain Disorders: Therapeutic Potential and Routes of Administration

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The use of cannabidiol (CBD) for treating brain disorders has gained increasing interest. While the mechanism of action of CBD in these conditions is still under investigation, CBD has been shown to affect numerous different drug targets in the brain that are involved in brain disorders. Here we review the preclinical and clinical evidence on the potential therapeutic use of CBD in treating various brain disorders. Moreover, we also examine various drug delivery approaches that have been applied to CBD. Due to the slow absorption and low bioavailability with the current oral CBD therapy, more efficient routes of administration to bypass hepatic metabolism, particularly pulmonary delivery, should be considered. Comparison of pharmacokinetic studies of different delivery routes highlight the advantages of intranasal and inhalation drug delivery over other routes of administration (oral, injection, sublingual, buccal, and transdermal) for treating brain disorders. These two routes of delivery, being non-invasive and able to achieve fast absorption and increase bioavailability, are attracting increasing interest for CBD applications, with more research and development expected in the near future.

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Cannabinoids as a Potential Alternative to Opioids in the Management of Various Pain Subtypes: Benefits, Limitations, and Risks

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Pain is a global phenomenon encompassing many subtypes that include neuropathic, musculoskeletal, acute postoperative, cancer, and geriatric pain. Traditionally, opioids have been a mainstay pharmacological agent for managing many types of pain. However, opioids have been a subject of controversy with increased addiction, fatality rates, and cost burden on the US healthcare system. Cannabinoids have emerged as a potentially favorable alternative or adjunctive treatment for various types of acute and chronic pain. This narrative review seeks to describe the efficacy, risks, and benefits of cannabinoids as an adjunct or even potential replacement for opioids in the treatment of various subtypes of pain.

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Cannabidiol as a potential novel treatment for endometriosis by its anti-inflammatory, antioxidative and anti-angiogenic effects in an experimental rat model

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Can cannabidiol (CBD) be used in the treatment of endometriosis by its anti-inflammatory, antioxidative, and anti-angiogenic effects? Endometrial implants were surgically induced in 36 female Wistar-Albino rats. After confirmation of endometriotic foci, the rats were randomized into four groups. In leuprolide acetate (LA) group, rats were given a single 1mg/kg subcutaneous LA injection. Other groups were 5 mg/kg CBD (CBD5), saline solution (SS), and 20 mg/kg CBD (CBD20) and daily intra-peritoneal injections were applied for seven days. After 21 days, the rats were sacrificed, and total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) measurements in blood and peritoneal fluid samples, and immunohistochemical staining for TNF-α, IL-6 and vascular endothelial growth factor (VEGF) of endometriotic tissues were evaluated.

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Endocannabinoids are potential inhibitors of glioblastoma multiforme proliferation

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Globally, it is evident that glioblastoma multiforme (GBM) is an aggressive malignant cancer with a high mortality rate and no effective treatment options. Glioblastoma is classified as the stage-four progression of a glioma tumor, and its diagnosis results in a shortened life expectancy. Treatment options for GBM include chemotherapy, immunotherapy, surgical intervention, and conventional pharmacotherapy; however, at best, they extend the patient’s life by a maximum of 5 years. GBMs are considered incurable due to their high recurrence rate, despite various aggressive therapeutic approaches which can have many serious adverse effects. Ceramides, classified as endocannabinoids, offer a promising novel therapeutic approach for GBM. Endocannabinoids may enhance the apoptosis of GBM cells but have no effect on normal healthy neural cells.

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Do tobacco and cannabis use and co-use predict lung function: A longitudinal study

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Use of tobacco and cannabis is common and has been reported to predict lung function. Less is known about co-use of tobacco and cannabis and their impact on changes in lung function to early adulthood.The study examines whether cigarette smoking or cannabis use and co-use are each associated with lung function in a population sample of young adults.Data are from a prospective cohort study of cigarette smoking, cannabis use and co-use at 21 and 30 years of age and lung function (FVC, FEV1, FEV1/FVC) measured at 30 years. Lung function results are transformed using Global Lung Function Formulae. Subjects are the children of pregnant women who were recruited into the cohort study over the period 1981–3. Respondents were administered a spirometry assessment at 21 and 30 years of age. These respondents completed a smoking and cannabis use questionnaire at 21- and 30-year follow-ups.

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