Modulating the activity of the endocannabinoid system influences various gastrointestinal physiological and pathophysiological processes, and cannabinoid receptors as well as regulatory enzymes responsible for the synthesis or degradation of endocannabinoids representing potential targets to reduce the development of gastrointestinal mucosal lesions, hemorrhage and inflammation. Direct activation of CB1 receptors by plant-derived, endogenous or synthetic cannabinoids effectively reduces both gastric acid secretion and gastric motor activity, and decreases the formation of gastric mucosal lesions induced by stress, pylorus ligation, nonsteroidal anti-inflammatory drugs (NSAIDs) or alcohol, partly by peripheral, partly by central mechanisms. Similarly, indirect activation of cannabinoid receptors through elevation of endocannabinoid levels by globally...

There is a growing body of evidence to suggest that cannabinoids are beneficial for a range of clinical conditions, including pain, inflammation, epilepsy, sleep disorders, the symptoms of multiple sclerosis, anorexia, schizophrenia and other conditions. The transformation of cannabinoids from herbal preparations into highly regulated prescription drugs is therefore progressing rapidly. The development of such drugs requires well-controlled clinical trials to be carried out in order to objectively establish therapeutic efficacy, dose ranges and safety. The low oral bioavailability of cannabinoids has led to feasible methods of administration, such as the transdermal route, intranasal administration and transmucosal adsorption, being proposed. The highly lipophilic nature...

Since the discovery of the cannabinoid receptors and their endogenous ligands, significant advances have been made in studying the physiological function of the endocannabinoid system. The presence of cannabinoid receptors on cells of the immune system and anecdotal and historical evidence suggesting that cannabis use has potent immuno-modulatory effects, has led to research directed at understanding the function and role of these receptors within the context of immunological cellular function. Studies from chronic cannabis smokers have provided much of the evidence for immunomodulatory effects of cannabis in humans, and animal and in vitro studies of immune cells such as T cells and macrophages have...

Cannabinoid agonists such as Δ(9)-tetrahydrocannabinol (THC) are more potent and/or efficacious antinociceptive agents in female than male rats using acute pain models. We tested the hypothesis that THC is more effective in females than males using a model of longer-lasting, inflammatory pain. THC's anti-allodynic, anti-hyperalgesic, and anti-edema effects were examined 1, 3, and 7 days after injection of complete Freund's adjuvant (CFA) into the hind paw. Systemically administered THC (0.32-3.2mg/kg, intraperitoneally [i.p.], same dose each day) was significantly more effective in females than males in attenuating CFA-induced thermal hyperalgesia, but was also more sedative in females. When administered locally into the inflamed hind paw,...

Cannabinoids are a group of compounds that mediate their effects through cannabinoid receptors. The discovery of Δ9 -tetrahydrocannabinol (THC) as the major psychoactive principle in marijuana, as well as the identification of cannabinoid receptors and their endogenous ligands, has led to a significant growth in research aimed at understanding the physiological functions of cannabinoids. Cannabinoid receptors include CB1, which is predominantly expressed in the brain, and CB2, which is primarily found on the cells of the immune system. The fact that both CB1 and CB2 receptors have been found on immune cells suggests that cannabinoids play an important role in the regulation of the...

Interleukin-6 (IL-6) is a multifunctional cytokine which contributes to inXammation and tissue injury in several diseases. Thus, inhibition of IL-6 production may be a useful strategy for treatment of patients with diseases such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). A synthetic nonpsychoactive cannabinoid, ajulemic acid (AjA), prevents joint damage in experimental arthritis. Results of experiments presented here indicate that addition of AjA (3–30 M) to human monocyte derived macrophages in vitro reduces steady state levels of IL-6 mRNA and the subsequent secretion of IL-6 from LPS stimulated cells. Although AjA binds to and activates PPAR, its anti IL-6 eVects are PPAR...

Background: Dimethylheptyl-cannabidiol (DMH-CBD), a non-psychoactive, synthetic derivative of the phytocannabinoid cannabidiol (CBD), has been reported to be antiinflammatory in RAW macrophages. Here, we evaluated the effects of DMH-CBD at the transcriptional level in BV-2 microglial cells as well as on the proliferation of encephalitogenic T cells. Methods: BV-2 cells were pretreated with DMH-CBD, followed by stimulation with the endotoxin lipopolysaccharide (LPS). The expression levels of selected genes involved in stress regulation and inflammation were determined by quantitative real-time PCR. In addition, MOG35–55-reactive T cells (TMOG) were cultured with antigen-presenting cells in the presence of DMH-CBD and MOG35–55 peptide, and cell proliferation was determined by...

Cannabis sativa has been used as an anti-inflammatory plant for millennia. However until the elucidation of the chemistry of its constituents and the discovery of the endogenous cannabinoid system only a limited amount of research had been done on the effects of the plant or its constituents on inflammation. In the present overview we summarize our work on the effects of the non-psychotropic cannabidiol (CBD) and of a synthetic cannabidiol-derived acid (HU-320) in animal models of arthritis. Both compounds block progression of the disease, when administered after its onset. Cannabidiol was equally effective was administered i.p. or orally. Significant protection of the joints against...