How cannabinoids influence immune function has been examined extensively in the last 30 years. Studies on drug-abusing humans and animals, as well as in vitro models employing immune cell cultures, have shown that marijuana, natural and endogenous cannabinoid compounds are immunomodulators. These substances modulate host resistance to bacterial, protozoan and viral infections as well as they can profoundly affect the Th1/Th2 response. Recently, two types of cannabinoid receptor, CB1 and CB2, have been discovered. While CB1 is expressed primarily in the brain, CB2 is peculiar of the immune cells. Cannabinoid receptors have been shown to be involved in some but not all of immune...

Paediatric traumatic brain injury (TBI) is a leading cause of death and disability. Previous studies showed neuroprotection after TBI by (endo)cannabinoid mechanisms, suggesting involvement of cannabinoid receptors (CBR). We therefore determined CBR densities and expression of the translocator protein 18 kDA (TSPO) in newborn piglets after experimental TBI. Newborn female piglets were subjected to sham operation (n=6) or fluid-percussion (FP) injury (n=7) under controlled physiological conditions. After six hours, brains were frozen, sagittally cut and incubated with radioligands for CBR ([3 HCP55,940, [3 H]SR141716A) and TSPO ([3 H]PK11195), an indicator of gliosis/brain injury. Early after injury, FP-TBI elicited a significant ICP increase at a...

Cnr2 is one of two cannabinoid receptors known to regulate bone metabolism. Here, we compared the whole bone properties of femora and tibiae from three-month-old Cnr2−/− mice with wild-type controls using a C57BL/6 background. Bending stiffness was measured by three-point bending. The elastic modulus, density and mineral content were measured using ultrasound, Archimedes’ principle and ashing. Micro-CT was used to measure the second moment of area, inner and outer perimeters of the cortical shaft and trabecular parameters. Deleting Cnr2 increased the bending stiffness by increasing the second moment of area. Bone from affected male mice had a greater modulus than controls, although no difference...

Abstract Endocannabinoids and their attending cannabinoid type 1 (CB1) receptor have been implicated in animal models of post-traumatic stress disorder (PTSD). However, their specific role has not been studied in people with PTSD. Herein, we present an in vivo imaging study using positron emission tomography (PET) and the CB1-selective radioligand [(11)C]OMAR in individuals with PTSD, and healthy controls with lifetime histories of trauma (trauma-exposed controls (TC)) and those without such histories (healthy controls (HC)). Untreated individuals with PTSD (N=25) with non-combat trauma histories, and TC (N=12) and HC (N=23) participated in a magnetic resonance imaging scan and a resting PET scan with the CB1...

Abstract Muscle disuse has numerous physiological consequences that end up with significant catabolic metabolism and ultimately tissue atrophy. What is not known is how muscle atrophy affects the endocannabinoid (EC) system. Arachidonic acid (AA) is the substrate for anandamide (AEA) and 2-arachidonylgycerol (2-AG), which act as agonists for cannabinoid receptors CB1 and CB2 found in muscle. Diets with n-3 polyunsaturated fatty acids (PUFA) have been shown to reduce tissue levels of AA, AEA and 2-AG. Therefore, we hypothesized that hind limb suspension (HS)-induced muscle atrophy and intake of n-3 PUFA will change mRNA levels of the EC system. Mice were randomized and assigned to...

Abstract Purpose: Colon cancer is a major public health problem. Cannabis-based medicines are useful adjunctive treatments in cancer patients. Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD), here named CBD BDS, i.e. CBD botanical drug substance, on colorectal cancer cell proliferation and in experimental models of colon cancer in vivo. Methods: Proliferation was evaluated in colorectal carcinoma (DLD-1 and HCT116) as well as in healthy colonic cells using the MTT assay. CBD BDS binding was evaluated by its ability to displace [(3)H]CP55940 from human cannabinoid CB1 and CB2 receptors. In vivo, the effect of CBD BDS...

A nascent literature has postulated endocannabinoids (eCBs) as strong sleep-inducing lipids, particularly rapid-eye-movement sleep (REMs), nevertheless the exact mechanisms behind this effect remain to be determined. Anandamide and 2-arachidonyl glycerol, two of the most important eCBS, are synthesized in the hippocampus. This structure also expresses a high concentration of cannabinoid receptor 1 (CB1). Recent extensive literature supports eCBs as important regulators of hippocampal activity. It has also been shown that these molecules vary their expression on the hippocampus depending on the light–dark cycle. In this context we decided to analyze the effect of intrahippocampal administration of the eCB anandamide (ANA) on the sleep–waking cycle...

Cannabis is the most commonly used illicit substance among pregnant women. Human epidemiological and animal studies have found that prenatal cannabis exposure influences brain development and can have long-lasting impacts on cognitive functions. Exploration of the therapeutic potential of cannabis-based medicines and synthetic cannabinoid compounds has given us much insight into the physiological roles of endogenous ligands (endocannabinoids) and their receptors. In this article, we examine human longitudinal cohort studies that document the longterm influence of prenatal exposure to cannabis, followed by an overview of the molecular composition of the endocannabinoid system and the temporal and spatial changes in their expression during brain development....

Aims/hypothesis: We examined the presence of functional cannabinoid receptors 1 and 2 (CB1, CB2) in isolated human islets, phenotyped the cells producing cannabinoid receptors and analysed the actions of selective cannabinoid receptor agonists on insulin, glucagon and somatostatin secretion in vitro. We also described the localisation on islet cells of: (1) the endocannabinoid-producing enzymes Nacyl-phosphatidyl ethanolamine-hydrolysing phospholipase D and diacylglycerol lipase; and (2) the endocannabinoiddegrading enzymes fatty acid amidohydrolase and monoacyl glycerol lipase. Methods: Real-time PCR, western blotting and immunocytochemistry were used to analyse the presence of endocannabinoid-related proteins and genes. Static secretion experiments were used to examine the effects of activating CB1 or...

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,...