In recent years, a growing interest has been dedicated to the study of the endocannabinoid system. The isolation of Cannabis sativa main psychotropic compound, Δ9 -tetrahydrocannabinol (THC), has led to the discovery of an atypical neurotransmission system that modulates the release of other neurotransmitters and participates in many biological processes, including the cascade of inflammatory responses. In this context, cannabinoids have been studied for their possible therapeutic properties in neuroinflammatory diseases. In this review, historic and biochemical aspects of cannabinoids are discussed, as well as their function as modulators of inflammatory processes and therapeutic perspectives for neurodegenerative disorders, particularly, multiple sclerosis.

Research into the pharmacology of individual cannabinoids that began in the 1940s, several decades after the presence of a cannabinoid was first detected in cannabis, is concisely reviewed. Also described is how this pharmacological research led to the discovery of cannabinoid CB1 and CB2 receptors and of endogenous ligands for these receptors, to the development of CB1- and CB2-selective agonists and antagonists and to the realization that the endogenous cannabinoid system has significant roles in both health and disease, and that drugs which mimic, augment or block the actions of endogenously released cannabinoids must have important therapeutic applications. Some goals for future research are...

Background: Some of cannabinoids, which are chemical compounds contained in marijuana, are immunosuppressive. One of the receptors, CB receptor 1 (CB1), is expressed predominantly by the cells in the central nervous system, whereas CB receptor 2 (CB2) is expressed primarily by immune cells. Theoretically, selective CB2 agonists should be devoid of psychoactive effects. In this study, we investigated therapeutic effects of a selective CB2 agonist on arthritis. Methods: The expression of CB2 was analyzed with immunohistochemistry and Western blotting. Interleukin (IL)-6, matrix metalloproteinase-3 (MMP-3), and chemokine (C-C motif) ligand 2 (CCL2) were quantified with enzyme-linked immunosorbent assays (ELISA). Osteoclastogenesis was assessed with tartrate-resistant acid...

Fluorouracil is the main chemotherapeutic drug used for gastrointestinal cancers, which suffers the important problem of treatment resistance. There is little information whether cannabinoid agonists can be used as an alternative drug for fluorouracil-resistant gastric cancer cells. In this study, we investigated the effects of a cannabinoid agonist, WIN-55,212-2, on 5-fluorouracil (5-FU)-resistant human gastric cancer cells, to examine whether the cannabinoid agonist may be an alternative therapy. Survival of the 5-FUresistant gastric cancer cell line, SNU-620-5FU/1000, was not significantly reduced even by a high dose of 5-FU treatment. However, WIN-55,212-2 inhibited the proliferation of SNU-620-5FU/1000 and enhanced their apoptosis, as indicated by an increase...

Objectives: The endocannabinoid system is an endogenous lipid signalling network comprising arachidonic-acid-derived ligands, cannabinoid (CB) receptors, transporters and endocannabinoid degrading enzymes. The CB1 receptor is predominantly expressed in neurons but is also co-expressed with the CB2 receptor in peripheral tissues. In recent years, CB receptor ligands, including D 9 -tetrahydrocannabinol, have been proposed as potential anticancer agents. Key findings: This review critically discusses the pharmacology of CB receptor activation as a novel therapeutic anticancer strategy in terms of ligand selectivity, tissue specificity and potency. Intriguingly, antitumour effects mediated by cannabinoids are not confined to inhibition of cancer cell proliferation; cannabinoids also reduce angiogenesis, cell...

Abstract In the last 25 years data has grown exponentially dealing with the discovery of the endocannabinoid system consisting of specific cannabinoid receptors, their endogenous ligands, and enzymatic systems of their biosynthesis and degradation. Progress is being made in the development of novel agonists and antagonists with receptor subtype selectivity which should help in providing a greater understanding of the physiological role of the endocannabinoid system and perhaps also in a broad number of pathologies. This could lead to advances with important therapeutic potential of drugs modulating activity of endocannabinoid system as hypnotics, analgesics, antiemetics, antiasthmatics, antihypertensives, immunomodulatory drugs, antiphlogistics, neuroprotective agents, antiepileptics, agents...

It is now well established that the psychoactive effects of Cannabis sativa are primarily mediated through neuronal CB1 receptors, while its therapeutic immune properties are primarily mediated through CB2 receptors. Two endocannabinoids, arachidonoylethanolamide and 2-arachidonoylglycerol, have been identifi ed, their action on CB1 and CB2 thoroughly characterized, and their production and inactivation elucidated. However, many signifi cant exceptions to these rules exist. Here we review the evidence suggesting that cannabinoids can modulate synaptic transmission, the cardiovascular system, and the immune system through receptors distinct from CB1 and CB2, and that an additional “ independent ” endocannabinoid signaling system that involves palmitoylethanolamide may exist.

Rationale. The cannabinoid system consists of a complex array of receptors, substances with agonist/antagonist properties for those receptors, biosynthetic machineries and mechanisms for cellular uptake and degradation for endocannabinoids. This system is in interrelation with other systems that comprise lipid mediators like prostaglandins/leukotrienes systems. A clear antagonist, additive or synergic effect of nonsteroidal anti-inflammatory drugs (NSAIDs)-cannabinoid associations was not yet demonstrated. Aim. The present study tried to summarize the existent data on NSAIDS-cannabinoid system interactions. Methods and results. A bibliographic research in Medline, Scirus, Embase was made using as keywords cannabinoid, nonsteroidal anti-inflammatory drugs, aspirin, ibuprofen, flurbiprofen, diclofenac, indomethacin, acetaminophen, coxibs, antinociceptive, antinociception, analgesia....

Objective: Interleukin-1b (IL-1b) is involved in the up-regulation of matrix metalloproteinases (MMPs) leading to cartilage degradation. Cannabinoids are anti-inflammatory and reduce joint damage in animal models of arthritis. This study aimed to determine a mechanism whereby the synthetic cannabinoid WIN-55,212-2 mesylate (WIN-55) may inhibit cartilage degradation. Methods: Effects of WIN-55 were studied on IL-1b stimulated production of MMP-3 and -13 and their inhibitors TIMP-1 and -2 in human chondrocytes. Chondrocytes were obtained from articular cartilage of patients undergoing total knee replacement. Chondrocytes were grown in monolayer and 3D alginate bead cultures. Real-time polymerase chain reaction (PCR) was used to determine the gene expression of...

In recent years, cannabinoids (the active components of Cannabis sativa) and their derivatives have received considerable interest due to findings that they can affect the viability and invasiveness of a variety of different cancer cells. Moreover, in addition to their inhibitory effects on tumor growth and migration, angiogenesis and metastasis, the ability of these compounds to induce different pathways of cell death has been highlighted. Here, we review the most recent results generating interest in the field of death mechanisms induced by cannabinoids in cancer cells. In particular, we analyze the pathways triggered by cannabinoids to induce apoptosis or autophagy and investigate the interplay...