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  • ∆9-tetrahydrocannabinol (THC), analgesia, Cannabidiol (CBD), Cannabinoid receptor/s, Cannabis, Endocannabinoid/s, inflammatory pain, neuropathic pain
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Role of the Cannabinoid System in Pain Control and Therapeutic Implications for the Management of Acute and Chronic Pain Episodes

Abstract Cannabis extracts and synthetic cannabinoids are still widely considered illegal substances. Preclinical and clinical studies have suggested that they may result useful to treat diverse diseases, including those related with acute or chronic pain. The discovery of cannabinoid receptors, their endogenous ligands, and the machinery for the synthesis, transport, and degradation of these retrograde messengers, has equipped us with neurochemical tools for novel drug design. Agonist-activated cannabinoid receptors, modulate nociceptive thresholds, inhibit release of pro-inflammatory molecules, and display synergistic effects with other systems that influence analgesia, especially the endogenous opioid system. Cannabinoid receptor agonists have shown therapeutic value against inflammatory and neuropathic pains,...
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Safety and Side Effects of Cannabidiol, a Cannabis sativa Constituent

Cannabidiol (CBD), a major nonpsychotropic constituent of Cannabis, has multiple pharmacological actions, including anxiolytic, antipsychotic, antiemetic and anti-inflammatory properties. However, little is known about its safety and side effect profile in animals and humans. This review describes in vivo and in vitro reports of CBD administration across a wide range of concentrations, based on reports retrieved from Web of Science, Scielo and Medline. The keywords searched were “cannabinoids”, “cannabidiol” and “side effects”. Several studies suggest that CBD is non-toxic in non-transformed cells and does not induce changes on food intake, does not induce catalepsy, does not affect physiological parameters (heart rate, blood pressure and...
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Studies Investigating the Mechanisms of the Cardioprotective Effects of Cannabidiol

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...
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Symptomatic therapy in multiple sclerosis: the role of cannabinoids in treating spasticity

Abstract A large proportion of patients with multiple sclerosis (MS) have spasticity, which has a marked impact on their quality of life. Anecdotal evidence suggests a beneficial effect of cannabis on spasticity as well as pain. Recently, randomized, double-blind, placebo-controlled studies have confirmed the clinical efficacy of cannabinoids for the treatment of spasticity in patients with MS. Based on these data, nabiximols (Sativex), a 1:1 mix of Δ-9-tetrahydrocannabinol and cannabidiol extracted from cloned Cannabis sativa chemovars, received approval for treating MS-related spasticity in various countries around the globe. In this article we review the current understanding of cannabinoid biology and the value of cannabinoids as a...
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Taming THC: potential cannabis synergy and phytocannabinoid-terpenoid entourage effects

Abstract Tetrahydrocannabinol (THC) has been the primary focus of cannabis research since 1964, when Raphael Mechoulam isolated and synthesized it. More recently, the synergistic contributions of cannabidiol to cannabis pharmacology and analgesia have been scientifically demonstrated. Other phytocannabinoids, including tetrahydrocannabivarin, cannabigerol and cannabichromene, exert additional effects of therapeutic interest. Innovative conventional plant breeding has yielded cannabis chemotypes expressing high titres of each component for future study. This review will explore another echelon of phytotherapeutic agents, the cannabis terpenoids: limonene, myrcene, α-pinene, linalool, β-caryophyllene, caryophyllene oxide, nerolidol and phytol. Terpenoids share a precursor with phytocannabinoids, and are all flavour and fragrance components common to human...
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The Antitumor Activity of Plant-Derived Non-Psychoactive Cannabinoids

As a therapeutic agent, most people are familiar with the palliative effects of the primary psychoactive constituent of Cannabis sativa (CS), Δ9 -tetrahydrocannabinol (THC), a molecule active at both the cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptor subtypes. Through the activation primarily of CB1 receptors in the central nervous system, THC can reduce nausea, emesis and pain in cancer patients undergoing chemotherapy. During the last decade, however, several studies have now shown that CB1 and CB2 receptor agonists can act as direct antitumor agents in a variety of aggressive cancers. In addition to THC, there are many other cannabinoids found in CS, and...
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The cannabinoids: an overview. Therapeutic implications in vomiting and nausea after cancer chemotherapy, in appetite promotion, in multiple sclerosis and in neuroprotection

The present paper describes the historical use of cannabis, starting with its use in Assyria and China. Recent advances in the understanding of the molecular basis of cannabis action are explained, including the identification of the cannabinoid receptors CB(1) and CB(2), as well as the isolation of endogenous cannabinoids from the brain and periphery. The use of delta(9)-tetrahydrocannabinol as an anti-vomiting and anti-nausea drug for cancer chemotherapy, and as an appetite-enhancing agent is described. Clinical work in multiple sclerosis, which may lead to the approval of tetrahydrocannabinol as a drug for this condition, is presented. Preclinical and clinical investigations with cannabidiol, a non-psychotropic cannabis...
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The case for assessing cannabidiol in epilepsy

Intractable epilepsies have an extraordinary impact on cognitive and behavioral function and quality of life, and the treatment of seizures represents a challenge and a unique opportunity. Over the past few years, considerable attention has focused on cannabidiol (CBD), the major nonpsychotropic compound of Cannabis sativa. Basic research studies have provided strong evidence for safety and anticonvulsant properties of CBD. However, the lack of pure, pharmacologically active compounds and legal restrictions have prevented clinical research and confined data on efficacy and safety to anecdotal reports. Pure CBD appears to be an ideal candidate among phytocannabinoids as a therapy for treatment-resistant epilepsy. A first step...
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The Development of Cannabidiol as a Psychiatric Therapeutic: A Review of Its Antipsychotic Efficacy and Possible Underlying Pharmacodynamic Mechanisms

Cannabidiol (CBD), a once-considered inert cannabis constituent, is one of two primary constituents of cannabis, alongside delta-9-tetrahydrocannabinol (∆9-THC/THC). In the last 30 years, CBD has become implicated with a range of pharmaceutical mechanisms of great therapeutic interest and utility. This review details the literature speculating CBD’s attenuation of psychotic symptoms, particularly in light of a marked elevation in mean THC concentrations, and a concomitant decline in CBD concentrations in the prevalent U.K street market cannabis derivatives since c. 2000. CBD is purported to exhibit pharmacology akin to established atypical antipsychotics, whilst THC has been implicated with the precipitation of psychosis, and the induction of...
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The effects of cannabidiol and its synergism with bortezomib in multiple myeloma cell lines. A role for transient receptor potential vanilloid type-2

Multiple myeloma (MM) is a plasma cell (PC) malignancy characterised by the accumulation of a monoclonal PC population in the bone marrow (BM). Cannabidiol (CBD) is a non-psychoactive cannabinoid with antitumoural activities, and the transient receptor potential vanilloid type-2 (TRPV2) channel has been reported as a potential CBD receptor. TRPV2 activation by CBD decreases proliferation and increases susceptibility to drug-induced cell death in human cancer cells. However, no functional role has been ascribed to CBD and TRPV2 in MM. In this study, we identified the presence of heterogeneous CD1381TRPV21 and CD1381TRPV22 PC populations in MM patients, whereas only the CD1381 TRPV22 population was present...
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