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Identification of the TRPA1 cannabinoid-binding site

Abstract Chronic pain accounts for nearly two-thirds of conditions eligible for medical cannabis licenses, yet the mechanisms underlying cannabis-induced analgesia remain poorly understood. The principal phytocannabinoids, the psychoactive Δ9-tetrahydrocannabinol (THC) and non-psychoactive cannabidiol (CBD), exhibit comparable efficacy in pain management. Notably, THC functions as an agonist of cannabinoid receptor 1 (CB1), whereas CBD shows minimal activity on CB1 and CB2 receptors. Elucidating the molecular targets through which phytocannabinoids modulate the pain system is required for advancing our understanding of the pain pathway and optimizing medical cannabis therapies. Transient receptor potential ankyrin 1 (TRPA1), a pivotal chemosensor in the pain pathway, has been identified as...
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Cannabis and cannabinoid-microbiome interactions in varied clinical contexts: A comprehensive systematic review

Abstract With legalisation of cannabis for both medicinal and recreational use expanding to more world nations, grasping its effects on the human body is vital. The microbiome is critical to human health and disease, and accumulating data suggests that it is influenced by a variety of external variables, including marijuana/cannabis and cannabinoids. We therefore conducted a comprehensive assessment of the literature to analyse cannabis and cannabinoid effects on the human microbiota. We searched PubMed, Embase and Cochrane Library CENTRAL databases for studies involving the use of marijuana, medical cannabis, cannabinoids and cannabinoid-like lipid mediators on microbiota, across all clinical conditions. Nine studies were identified:...
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Cannabinoids Used for Medical Purposes in Children and Adolescents A Systematic Review and Meta-Analysis

Please use this link to access this publication. Key Points Question  What is the adverse event profile of cannabinoids used for medical purposes in children and adolescents? Findings  In this systematic review and meta-analysis of 23 randomized clinical trials including 3612 participants, cannabinoids used for medical purposes in children and adolescents were associated with increased risk of adverse events, serious adverse events, and withdrawals due to adverse events compared with the control group. Meaning  The findings suggest that physicians considering cannabinoids for medical purposes in children and adolescents should weigh the risk and benefit profile of cannabinoids and available therapeutic options as well as the individual’s underlying...
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Use of Cannabis-Based Medical Products for Pediatric Health Conditions: A Systematic Review of the Recent Literature

Abstract Introduction: Cannabis policy is rapidly changing in the USA and across the globe, with 24 states legalizing cannabis for adult use and 38 states making medical cannabis available for those with qualified conditions. Building on prior evidence, we reviewed the recently published literature (from the past 5 years) focused on the treatment effects of naturally derived medical cannabis products within the pediatric population. Methods: We conducted a systematic literature review of three electronic databases using MeSH terms and free-text. A study was eligible for inclusion if it investigated the efficacy of medical cannabis for any condition, it was published in 2019 or later, and the mean...
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Medical cannabis use in oncology and associated outcomes: A scoping review

Please use this link to access this publication. Abstract Background Natural and synthetic cannabinoids are being used worldwide to treat various symptoms in cancer patients. This study aims to map the therapeutic benefits and adverse effects associated with the use of cannabis-based drugs in these outcomes. Methods Following Joanna Briggs Institute guidelines a scoping review was conducted. The study protocol was available in the Open Science Framework public repository. An extensive search strategy involving databases like Cochrane Library, Embase, CINAHL, Medline/PubMed, Lilacs, Google Scholar, and Open Gray for gray literature analysis was executed by a skilled librarian. The inclusion criteria were primary studies (observational...
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Cannabinoids in attention-deficit/hyperactivity disorder: A randomised-controlled trial

Please use this link to access this publication. Abstract Adults with ADHD describe self-medicating with cannabis, with some reporting a preference for cannabis over ADHD medications. A small number of psychiatrists in the US prescribe cannabis medication for ADHD, despite there being no evidence from randomised controlled studies. The EMA-C trial (Experimental Medicine in ADHD-Cannabinoids) was a pilot randomised placebo-controlled experimental study of a cannabinoid medication, Sativex Oromucosal Spray, in 30 adults with ADHD. The primary outcome was cognitive performance and activity level using the QbTest. Secondary outcomes included ADHD and emotional lability (EL) symptoms. From 17.07.14 to 18.06.15, 30 participants were randomly assigned to the active (n=15) or...
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Cannabinoids for skin diseases and hair regrowth

Please use this link to access this publication. Abstract The use of cannabis for skin diseases and hair regrowth is at the preliminary stage. Legalization Many countries have approved cannabis for medical use; however, four countries Canada, Uruguay, South Africa, and Georgia have legalized it for both medical and recreational purposes. The endocannabinoid system The endocannabinoid system may maintain skin homeostasis; two notable endocannabinoids include 2-Arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (AEA). Routes of administration and pharmacokinetics Topical cannabinoids can avoid the first-pass metabolism and reduce respiratory side effects; however, the high hydrophobicity of cannabinoids may hinder percutaneous absorption. Skin disorders and hair growth Human clinical studies...
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Positive Effect of Cannabis sativa L. Herb Extracts on Skin Cells and Assessment of Cannabinoid-Based Hydrogels Properties

Abstract The skin is an organ that is constantly exposed to many external factors that can affect its structure and function. Due to the presence of different cannabinoid receptors on many types of skin cells, cannabinoids can interact directly with them. Therefore, as part of this work, the impact of two types of Cannabis sativa L. herb extracts on keratinocytes and fibroblasts was assessed. The content of biologically active compounds such as phenols, flavonoids, chlorophylls and cannabinoids was evaluated. The antioxidant capacity of prepared extracts using the DPPH radical, H2DCFDA probe and measurement of superoxide dismutase activity was also assessed. The cytotoxicity of hemp extracts was...
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Cannabis and Cannabinoids in Reproduction and Fertility: Where We Stand

Please use this link to access this publication. Abstract Although cannabis use is increasing in general population, their prevalence among young adults is remarkably high. In recent years, their medical use gained a renewed interest. However, it can underline the reputation of cannabis being a harmless drug. Between cannabinoids, uniquely found on the cannabis plant, Δ9-tetrahydrocannabinol (THC) is the well-studied compound. It is responsible for the psychoactive effects via central cannabinoid receptors. Nevertheless, cannabinoids interact with other chemical signalling systems such as the hypothalamic–pituitary–gonadal axis. THC indirectly decreases gonadotropin-releasing hormone (GnRH) secretion by the hypothalamus. The consequences are diverse, and several key hormones are...
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Molecular Targets of Minor Cannabinoids in Breast Cancer: In Silico and In Vitro Studies

Abstract Background: Breast cancer therapy has been facing remarkable changes. Classic treatments are now combined with other therapies to improve efficacy and surpass resistance. Indeed, the emergence of resistance demands the development of novel therapeutic approaches. Due to key estrogen signaling, estrogen receptor-positive (ER+) breast cancer treatment has always been focused on aromatase inhibition and ER modulation. Lately, the effects of phytocannabinoids, mainly Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), have been evaluated in different cancers, including breast. However, Cannabis sativa contains more than 120 phytocannabinoids less researched and understood. Methods: Here, we evaluated, both in silico and in vitro, the ability of 129 phytocannabinoids to modulate important molecular...
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