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Yes / Medical cannabis is one of the most commonly reported therapeutic treatments sought for chronic pain. The wide acceptance and research in alternative medicine has put medical cannabis in the limelight, where researchers are widely examining the therapeutic benefits of medical cannabis and its association to treat chronic pain. Objective: The purpose of this scoping review is to provide an overview of the perspectives on CBD as an alternative treatment for chronic pain among health professionals and legal cannabis users.

Cannabidiol (CBD), a non-psychoactive cannabinoid found in cannabis suppresses vomiting in shrews (Suncus murinus, Parker et al., 2004), and conditioned gaping in rats (a selective measure of nausea-like behaviour, Parker et al., 2002). CBD‘s anti-emetic/anti-nausea mechanism of action is unknown. However, evidence suggests that CBD may act as a somatodendritic 5-hydroxytryptamine 1A (5-HT1A) autoreceptor agonist in the dorsal raphe nucleus (DRN), because the anxiolytic (Campos and Guimaraes, 2008a) and neuroprotectant (Mishima et al., 2005) properties of CBD are 5-HT1A-mediated. Therefore, here we investigated if administration of 5-HT1A receptor antagonists, (WAY100135 or WAY100635) would block CBD‘s anti-emetic/anti-nausea-like effects. Systemic administration of WAY100135 prevented the anti-emetic effect of CBD in shrews, and WAY100135 and WAY100635 attenuated the anti-nausea-like effect of CBD in rats. The effect of CBD on conditioned gaping reactions was most likely the result of its action on somatodendritic 5-HT1A receptors in the DRN, because the anti-nausea-like action of systemic CBD was reversed by intra-DRN administration of WAY100635. As well, when administered into the DRN, CBD suppressed conditioned gaping, an effect that was blocked by systemic WAY100635. In vitro studies revealed that CBD enhanced the ability of 8-OH-DPAT to stimulate [35S]GTPS binding and in vivo studies revealed that systemic subthreshold doses of combined CBD and 8-OH-DPAT synergistically suppressed conditioned gaping. These results suggest that CBD produces its anti-emetic/anti-nausea-like effects by indirect receptor agonism of DRN somatodendritic 5-HT1A autoreceptors. CBD‘s mechanism of action was explored further, by examining its interaction with cannabigerol (CBG), another cannabinoid, which acts in vitro as a 5-HT1A receptor antagonist (Cascio et al., 2010). CBG blocked the systemic CBD-, and 8-OH-DPAT-induced suppression of gaping in rats, as well as the systemic CBD-induced suppression of vomiting in shrews. Therefore, CBG and CBD may be in opposition at the 5-HT1A receptor. These findings shed light on the mechanism of action of non-psychoactive cannabinoids in the cannabis plant, and their effect on nausea and vomiting. These results suggest CBD alone may be an effective treatment in reducing nausea and vomiting. / This research was supported by research grants from the Natural Sciences and Engineering Research Council (NSERC) of Canada to Dr. Parker, a scholarship from NSERC to Erin Rock, and a grant from NIDA to Dr. Mechoulam and Dr. Pertwee.

Estudios e investigaciones prueban que su uso es beneficioso para aliviar graves dolencias de salud, pero la legalidad de su uso aún se debate a nivel mundial. ¿Qué es el cannabis medicinal?

The phytocannabinoid cannabidiol (CBD) has a complex pharmacology which is thought to include, but is not limited to, an ability to act as an inverse agonist at the CB1 and CB2 receptors and an antagonist of GPR55. Moreover, is has been shown to reduce infarct size and ameliorate reductions in left ventricular function in vivo. These improvements in the pathogenesis of experimental MI are accompanied by a reduction in inflammatory cell migration to the area at risk. More recently it has been shown that CBD is anti-arrhythmic in acute experimental MI. Thus, it was suggested that the cardioprotective effects of CBD might be due to an anti-inflammatory action. In addition, GPR55 receptor activation is acknowledged to mediate mobilisation of intracellular Ca2+ (Ca2+i) which could potentially be pro-arrhythmic and so CBD, as an antagonist may confer cardioprotection via GPR55. However, the receptors and/or mechanisms responsible for mediating the cardioprotective effects of CBD are get to be determined. The present studies were therefore performed to; (1) better understand the pharmacology of CBD by assessing haemodynamic responses to CBD and other cannabinoids ligands in anaesthetised rats, (2) investigate the receptors involved in the anti-arrhythmic effect of CBD in a rat model of coronary artery occlusion (CAO), and (3) investigate if CBD can alter [Ca2+]i in isolated rat cardiomyocytes. The characterisation of the pharmacology of CBD in vivo showed that; firstly, CB1 receptor activation causes a hypotensive response which can be dose-dependently inhibited by AM251; secondly, both CBD and AM251 alone (a CB1 receptor antagonist and GPR55 agonist) can induce vasodepressor responses and finally, CBD can potentiate the AM251-mediated hypotension when co-administered, suggesting possible cross-talk between the CB1 and GPR55. Results from CAO studies showed that CBD and AM251 each have the capacity to reduce arrhythmias. Moreover, when CBD and AM251 were co-administered the anti-arrhythmic capacity of either alone was potentiated. However, the degree of potentiation was dependent on the order of administration, suggesting that more than one receptor is involved in the summative anti-arrhythmic effects. The investigation of cardiomyocyte [Ca2+]i suggested that AM251 can modulate [Ca2+]i at the level of the cardiomyocyte, while CBD cannot. These data give novel insight into the anti-arrhythmic effects of CBD and, moreover, for the first time demonstrate that AM251 is anti-arrhythmic. In addition, these data suggest a role for GPR55 in increasing [Ca2+]i via AM251.

Cannabidiol (CBD) is one of over 80 active cannabinoids found in Cannabis Sativa and is the second most abundant cannabinoid derived from the plant following d(9)-Tetrahydrocannabinol (THC). As opposed to THC, CBD does not appear to have any psychotropic effects, rather CBD is often utilized for its therapeutic properties, which include effects such as antinociception, anti-convulsion, and anti-inflammation. During the extraction of CBD from plant material, THC may be co-extracted. Therefore, screening and quantitating potential THC levels in individuals using CBD products is important in instances where the legality of use of THC does not match that of CBD. In recent years, oral fluid has gained recognition as a non-invasive and expedient matrix for both drug testing and forensic casework. Due to its relevance, oral fluid was selected for analysis. This project evaluated the detection and quantitation of CBD, THC, and two primary metabolites in oral fluid samples of a therapeutic-use cannabidiol donor using Biotage Supported Liquid Extraction (SLE) and subsequent testing by PerkinElmer QSight 220 CR LC-MS/MS in positive ionization mode All calibrators and quality controls were prepared by fortifying synthetic oral fluid with certified reference standards. Standards and samples were prepared in a 1:3 dilution with extraction buffer. Calibrators were prepared at 0.25, 0.5, 1, 5, 10, 50, 100, 200, 300, 400, and 500 ng/mL, with quality controls analyzed at 0.75, 70, and 425 ng/mL. Internal standard was added to the appropriate samples to account for any variation produced by sample preparation. SLE was performed using ISOLUTE SLE+ 1 mL columns with elution in hexane:ethyl acetate:methyl tert-butyl ether (80:10:10), followed by evaporation using an Organomation Multivap Nitrogen Evaporator (Berlin, Massachusetts). All samples were reconstituted in 100 uL of 0.1% formic acid in deionized water:0.1% formic acid in acetonitrile (70:30). Validation parameters were assessed using Academy Standards Board (ASB) Standard 036-Standard Practices for Method Validation in Forensic Toxicology, including linear dynamic range (LDR), limit of detection (LOD), limit of quantitation (LOQ), analyte recovery, ion suppression/enhancement, and carryover. Following reconstitution, samples were placed onto the autosampler for injection and subsequent chromatographic separation using a PerkinElmer Brownlee C18 2.1x50 millimeter (mm), 2.7 micrometer (um) column. Analysis of the samples by mass spectrometry was performed in positive mode with multiple reaction monitoring (MRM). Total run time including equilibration was 10.5 minutes. All compounds were quantified using linear calibration models with 1/X weighting (1/concentration) and measured values were normalized by their respective internal standards. The LDR was determined to be 0.25 to 500 ng/mL. For all analytes, LOD was assessed and determined to be 0.25 ng/mL with an LOQ of 1 ng/mL. Carryover was assessed by running a double blank following a sample spiked at 500 ng/mL with no analytes observed. The donor samples were collected at several timepoints around the oral administration of an 8 mg dose of CBD. These timepoints included: prior to administration, at the time of administration, 30 minutes post-administration, 45 minutes post-administration, 60 minutes post-administration, 90 minutes post-administration, and 120 minutes post-administration. CBD was quantified within the diluted oral fluid samples from below LOQ to 325.75 ng/mL. THC was detected above LOD but below LOQ, concentrations which lie below typical cut-offs used in both workplace drug testing and forensic casework. The two metabolites were not detected above the LOD. As such, the CBD product can be concluded to be of reasonable purity as it relates to legal implications. Overall, the use of laminar flow mass spectrometry was effective in detecting various cannabinoids in oral fluid samples following SLE sample extraction.

Adequate evidence exists in the literature indicating a relatively positive shift with regards to the legal acceptance of cannabis and cannabis-derived products for medicinal purposes in some countries. Concomitantly, scientists are showing renewed interest in cannabis-related research work. Over the years, clinical and preclinical studies have demonstrated the therapeutic significance of cannabinoids for diverse indications. Additionally, efforts are being made to develop cannabis-related products into acceptable prescription products. FDA authorization for the commercial use of four cannabinoid-derived products, available as oral dosage forms is a significant progress already. However, there are certain drawbacks associated with the conventional delivery forms of cannabinoids. These include low oral bioavailability due to hepatic degradation, gastric instability, poor water solubility, and the side effects experienced upon the use of high doses of psychotropic cannabinoids associated with heightened plasma concentrations of the drug. These are however, limitable with the aid of transcutaneous drug delivery. Emerging topical and transdermal strategies could be exploited for the successful development of highly effective delivery systems for cannabinoids. This review discusses the feasibility of delivering therapeutic cannabinoids via skin and provides a comprehensive account of the supporting research studies that have been reported in the literature till date.

No description available.

Alcohol use disorder (AUD) and post-traumatic stress disorder (PTSD) are debilitating conditions that often co-occur, with an estimated 41-79% comorbidity rate. A major concern with the co-occurrence of these disorders is the tendency for one to exacerbate the other. Specifically, symptoms related to PTSD are a significant risk factor for the development of AUD, and alcohol abuse worsens PTSD symptoms. This cycle, along with a lack of effective pharmacological treatment options, leads to significant behavioral and physiological deficits. Additionally, remission for comorbid AUD and PTSD is much more difficult to attain due to exacerbated symptomology and a lack of FDA-approved medications. In recent years, cannabidiol (CBD), a non-psychoactive compound found in cannabis, has been a focus of study due to its therapeutic potential. Researchers have demonstrated the anxiolytic and anti-inflammatory effects of CBD in both humans and animals, showing its promise as a novel therapeutic agent in the treatment of psychiatric disorders. The purpose of this study is to investigate the hypothesis that CBD will reduce fear-related behaviors and neuroinflammation in a rat model of comorbid AUD and PTSD. Our AUD/PTSD model utilized restraint stress and chronic intermittent ethanol exposure procedures. To investigate changes in future stress sensitivity all animals were exposed to a contextual fear conditioning paradigm, which was used to train the animals to associate environmental and auditory cues (environment appearance and tone) with an aversive stimulus (mild foot-shock). 30 minutes prior to each conditioning session, rats received an intraperitoneal injection of CBD (20mg/kg) or 0.9% Saline. Once the animals learned to associate the cues with a shock, they were exposed to an extinction learning procedure that involved presentation of the cue alone (no shock). This procedure parallels exposure therapy in humans, allowing for the assessment adaptations to fear learning. The amount of time the rats remain still (freezing) during the tone represents fear-related behavior. Our current results indicate rats with a history of stress and alcohol exposure displayed significantly higher freezing behaviors and this effect was significantly decreased with CBD treatment. This suggests that when CBD is administered during fear learning, it is able to attenuate heightened stress sensitivity associated with AUD/PTSD. To evaluate how CBD mediates the neuroinflammatory response associated with AUD and PTSD, brains from the rats were extracted and analyzed for the inflammatory cytokine tumor necrosis factor a (TNF-a). Specific regions of interest included the medial prefrontal cortex and hippocampus, areas associated with anxiety, memory, and addiction. Neuroinflammation analyses are still ongoing, however it is predicted that rats who received CBD will show a reduction in inflammation in the medial prefrontal cortex and hippocampus. Taken together, the current results show promise for CBD to reduce enhanced fear-related behavior associated with comorbid AUD and PTSD.

Increasing interest has emerged in the field of nutrition and its role in promoting skeletal muscle growth. Recently, studies using both in vitro and in vivo models have suggested that cannabidiol – a constituent of Cannabis Sativa – can increase the growth and regenerative capacity of skeletal muscle stem cells. Other isolated compounds, such as cannabinol, have demonstrated anti-inflammatory effects in vivo. Due to the potential benefits of both compounds, our primary objective was to further elucidate the effects of cannabidiol and cannabinol on murine C2C12 myoblast proliferation and differentiation. We hypothesized that supplementation of cannabidiol and cannabinol would augment gene expression of myogenin, leading to enhanced myotube formation; as well as, induce greater gene expression of Myf5 and MyoD, accompanied by increased cell proliferation. In relation to skeletal muscle growth, myostatin and follistatin can substantially impact the regulation of hypertrophy; with down-regulation of myostatin being a potent stimulus for muscle growth, and follistatin being the antagonist to myostatin, we therefore examined if cannabidiol or cannabinol influenced these two proteins, as a possible rationale for increased myogenesis. In this study, cells were treated with either: (1) cannabidiol, (2) cannabinol, (3) or vehicle control (methanol). Cells were grown for 48 hrs in their respective media, the MTT assay was used to assess proliferation. Muscle differentiation experiments required cells to grow for seven days with media supplemented with the respective compound. The media was changed every 48 hrs. The extent of muscle differentiation was assessed via immunocytochemical and qPCR analysis. In preliminary experiments, cell proliferation was influenced by the duration of which cells were exposed to the compound and concentration of the compound within the media. It was noted that changing growth media and compound every 24 hrs augmented the proliferative response compared to leaving it on for 48 hrs for both cannabidiol and cannabinol (p<0.05). Furthermore, supplementing cells with cannabidiol at a 1 or 5 uM concentration resulted in considerable cell growth compared to vehicle control (p<0.0001). Cannabinol at 5 uM showed the same effect (p<0.0001). We also quantified the mRNA expression of genes involved in the myogenic regulatory pathway in proliferating and differentiating cells. Herein we report that using a 5 uM concentration of cannabidiol or cannabinol did not increase the expression of any of these genes in proliferating or differentiating cells. These findings help further characterize the effects of cannabidiol and cannabinol on the myogenic response. / Thesis / Master of Science (MSc) / Nutrition impacts the regulation of skeletal muscle mass, with many individuals turning to supplements as a means to improve overall health. Cannabidiol – a constituent of the cannabis plant – has been used over the past several decades for its anti-inflammatory, neuroprotective, and anxiolytic properties; however, recent evidence has revealed its potential effectiveness in promoting muscle growth. If true, there is a possibility that it can be used to target the age-related loss of muscle mass, sarcopenia, or even improve athletic performance. Other derivatives, such as cannabinol, have seldom been studied but also demonstrate anti-inflammatory effects. Therefore, this thesis further elucidates the effects of cannabidiol and cannabinol on the myogenic signaling pathway. As a model, we used the murine C2C12 cell line that recapitulates the behaviour of human myoblasts. Interestingly, the data presented herein supports the notion that cannabidiol and cannabinol only promote cell growth and have no effect on myoblast maturation and myotube formation. These findings provide a better understanding of the potential for cannabidiol and cannabinol as a nutritional supplement targeting skeletal muscle.