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  • Muscular, Skeletal System
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Cannabis for pain in orthopedics: a systematic review focusing on study methodology

Abstract Background Medical cannabis use is an emerging topic of interest in orthopedics. Although there is a large amount of literature on medical cannabis use for managing various types of pain, few studies have focused on orthopedic conditions. There is little high-quality evidence in core orthopedic areas. The objective of this study was to summarize the literature on the efficacy of cannabis use for pain related to orthopedic conditions. Methods We conducted a systematic review of the literature on the use of cannabinoids for pain management in core orthopedic conditions. Two independent reviewers extracted information on reporting quality, risk of bias, drugs, population, control,...
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Cannabis against chronic musculoskeletal pain: a scoping review on users and their perceptions

Abstract Background Chronic musculoskeletal pain (CMP) may lead to reduced physical function and is the most common cause of chronic non-cancer pain. Currently, the pharmacotherapeutic options against CMP are limited and frequently consist of pain management with non-steroidal anti-inflammatories, gabapentinoids, or opioids, which carry major adverse effects. Although the effectiveness of medical cannabis (MC) for CMP still lacks solid evidence, several patients suffering from it are exploring this therapeutic option with their physicians. Objectives Little is known about patients’ perceptions of their MC treatment for CMP. We aimed to increase this knowledge, useful for healthcare professionals and patients considering this treatment, by conducting a...
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Cannabidiol inhibits the skeletal muscle Nav1.4 by blocking its pore and by altering membrane elasticity

Abstract Cannabidiol (CBD) is the primary nonpsychotropic phytocannabinoid found in Cannabis sativa, which has been proposed to be therapeutic against many conditions, including muscle spasms. Among its putative targets are voltage-gated sodium channels (Navs), which have been implicated in many conditions. We investigated the effects of CBD on Nav1.4, the skeletal muscle Nav subtype. We explored direct effects, involving physical block of the Nav pore, as well as indirect effects, involving modulation of membrane elasticity that contributes to Nav inhibition. MD simulations revealed CBD’s localization inside the membrane and effects on bilayer properties. Nuclear magnetic resonance (NMR) confirmed these results, showing CBD localizing below...
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Patient Experience and Perspective on Medical Cannabis as an Alternative for Musculoskeletal Pain Management

Abstract Introduction: The current rate of opioid prescription is disquieting because of their high abuse potential, adverse effects, and thousands of overdose deaths. This situation imposes urgency in seeking alternatives for adequate pain management. From this perspective, this study aimed to evaluate the experience and the perceived analgesic efficacy of medical cannabis in managing the pain associated with musculoskeletal conditions. Methods: A 28-question survey was distributed to patients at a major medical cannabis center in Puerto Rico for 2 months. Demographics, medical history, cannabis usage, cannabis use perspective, and analgesic efficacy were assessed in the questionnaire. Results: One hundred eighty-four patients completed our survey....
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Molecular Mechanisms Through Which Cannabidiol May Affect Skeletal Muscle Metabolism, Inflammation, Tissue Regeneration, and Anabolism: A Narrative Review

Please use this link to access this publication. Abstract Background: Cannabidiol (CBD), a nonintoxicating constituent of the cannabis plant, recently gained a lot of interest among athletes, since it is no longer considered as a prohibited substance by the World Anti-Doping Agency. The increasing prevalence of CBD use among athletes is driven by a perceived improvement in muscle recovery and a reduction in pain. However, compelling evidence from intervention studies is lacking and the precise mechanisms through which CBD may improve muscle recovery remain unknown. This highlights the need for more scientific studies and an evidence-based background. In the current review, the state-of-the-art knowledge on...
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Cannabidiol (CBD) Dosing: Plasma Pharmacokinetics and Effects on Accumulation in Skeletal Muscle, Liver and Adipose Tissue

Abstract Oral cannabidiol (CBD) consumption is widespread in North America and Europe, as it has analgesic, neuroprotective and antitumor effects. Although oral CBD consumption in humans affords beneficial effects in epileptic and inflammatory states, its pharmacokinetics and subsequent uptake into tissue are largely unknown. This study investigated plasma pharmacokinetics and accumulation of CBD in gastrocnemius muscle, liver and adipose tissue in adult rats following oral gavage. CBD was fed relative to body mass at 0 (control), 30, 115, or 230 mg/Kg/day for 28 days; with 6 males and 6 females per dosing group. Pharmacokinetics were assessed on day 1 and day 28 in the...
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Endocannabinoid Anandamide Mediates the Effect of Skeletal Muscle Sphingomyelins on Human Energy Expenditure

Abstract   Context: Skeletal muscle endocannabinoids and sphingolipids (particularly sphingomyelins) are inversely associated with sleeping energy expenditure (SLEEP) in humans. The endocannabinoid system may increase sphingolipid synthesis via cannabinoid receptor-1.   Objective: To investigate in human skeletal muscle whether endocannabinoids are responsible for the effect of sphingomyelins on SLEEP.   Design: Muscle endocannabinoid [anandamide (AEA), 2-arachidonoylglycerol (2-AG)], endocannabinoid congeners [oleoylethanolamide (OEA), palmitoylethanolamide (PEA)], and sphingomyelin content were measured with liquid chromatography/mass spectrometry. SLEEP was assessed in a whole-room indirect calorimeter. Mediation analyses tested whether the inverse associations between sphingomyelins and SLEEP depended on endocannabinoids and endocannabinoid-related OEA and PEA.   Setting: Inpatient study.   Participants: Fifty-three Native Americans who...
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The cannabinoid CB1 receptor regulates bone formation by modulating adrenergic signaling

We have recently reported that in bone the cannabinoid CB1 receptor is present in sympathetic terminals. Here we show that traumatic brain injury (TBI), which in humans enhances peripheral osteogenesis and fracture healing, acutely stimulates bone formation in a distant skeletal site. At this site we demonstrate i) a high level of the main endocannabinoid, 2-arachidonoylglycerol (2-AG), and expression of diacylglycerol lipases, enzymes essential for 2-AG synthesis; ii) that the TBIinduced increase in bone formation is preceded by elevation of the 2-AG and a decrease in norepinephrine (NE) levels. The TBI stimulation of bone formation was absent in CB1-null mice. In wild-type animals it...
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The Role of Type 2 Cannabinoid Receptor in Bone Metabolism

Cannabinoid receptors play an important role in regulating bone mass and bone turnover. Studies in our laboratories have shown that young mice lacking type 1 cannabinoid receptor (CNR1-/-) had increased bone mass and were resistant to ovariectomy-induced bone loss. Other workers have reported that type 2 cannabinoid receptor knockout mice (CNR2-/-) develop age-related osteoporosis. The aim of this PhD thesis was to further investigate the role of CNR2 in bone metabolism in vitro and in vivo, using genetic and pharmacological approaches.
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Activation of Cannabinoid Receptor 2 Enhances Osteogenic Differentiation of Bone Marrow Derived Mesenchymal Stem Cells

Bone marrow derived mesenchymal stem cells (BM-MSCs) are considered as the most promising cells source for bone engineering. Cannabinoid (CB) receptors play important roles in bone mass turnover. The aim of this study is to test if activation of CB2 receptor by chemical agonist could enhance the osteogenic differentiation and mineralization in bone BM-MSCs. Alkaline phosphatase (ALP) activity staining and real time PCR were performed to test the osteogenic differentiation. Alizarin red staining was carried out to examine the mineralization. Small interference RNA (siRNA) was used to study the role of CB2 receptor in osteogenic differentiation. Results showed activation of CB2 receptor increased ALP...
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