Please use this link to access this publication. Abstract Neuropathic pain (NP) is a complex and debilitating condition that is often refractory to currently available analgesic medications. Cannabis sativa extract (CSE) has been reported to exhibit analgesic properties across various pain models; however, the underlying mechanisms of action are not fully understood. This study aimed to investigate the involvement of the cannabinoid CB2 receptor in mediating the analgesic effects of CSE in a rat model of NP, where NP was induced in male Wistar rats through chronic constriction injury (CCI) of the sciatic nerve. Rats were randomly allocated into four groups: (1) Sham + vehicle, (2) CCI...

Abstract Obsessive Compulsive Disorder (OCD) is listed as one of the top 10 most disabling neuropsychiatric conditions in the world. The neurobiology of OCD has not been completely understood and efforts are needed in order to develop new treatments. Beside the classical neurotransmitter systems and signalling pathways implicated in OCD, the possible involvement of the endocannabinoid system (ECS) has emerged in pathophysiology of OCD. We report here selective downregulation of the genes coding for enzymes allowing the synthesis of the endocannabinoids. We found reduced DAGLα and NAPE-PLD in blood samples of individuals with OCD (when compared to healthy controls) as well as in the...

Abstract The therapeutic application of cannabinoids has gained traction in recent years. Cannabinoids interact with the human endocannabinoid system in the skin. A large body of research indicates that cannabinoids could hold promise for the treatment of eczema, psoriasis, acne, pruritus, hair disorders, and skin cancer. However, most of the available data are at the preclinical stage. Comprehensive, large-scale, randomized, controlled clinical trials have not yet been fully conducted. In this article, we describe new findings in cannabinoid research and point out promising future research areas.

Abstract Though there is limited research confirming the purported topical benefits of cannabinoids, it is certain that cutaneous biology is modulated by the human endocannabinoid system (ECS). Receptors from the ECS have been identified in the skin and systemic abuse of synthetic cannabinoids, and their analogs, have also been associated with the manifestation of dermatological disorders, indicating the effects of the ECS on cutaneous biology. In particular, cannabidiol (CBD), a non-psychoactive compound from the cannabis plant, has garnered significant attention in recent years for its anecdotal therapeutic potential for various pathologies, including skin and cosmetic disorders. Though a body of preclinical evidence suggests topical...

Please use this link to access this publication. Abstract Respiratory illnesses and its repercussions are becoming more prevalent worldwide. It is necessary to research both innovative treatment and preventative techniques. Millions of confirmed cases and fatalities from the COVID-19 epidemic occurred over the previous two years. According to the review research, cannabinoids are a class of medicines that should be considered for the treatment of respiratory conditions. Cannabinoids and inhibitors of endocannabinoid degradation have illustrated advantageous anti-inflammatory, asthma, pulmonary fibrosis, and pulmonary artery hypotension in numerous studies (in vitro and in vivo). It has been also noted that CB2 receptors on macrophages and T-helper cells may...

Abstract Introduction: Compounds present in Cannabis sativa such as phytocannabinoids and terpenoids may act in concert to elicit therapeutic effects. Cannabinoids such as Δ9-tetrahydrocannabinol (Δ9-THC) directly activate cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2); however, it is not known if terpenoids present in Cannabis also affect cannabinoid receptor signaling. Therefore, we examined six common terpenoids alone, and in combination with cannabinoid receptor agonists, on CB1 and CB2 signaling in vitro. Materials and Methods: Potassium channel activity in AtT20 FlpIn cells transfected with human CB1 or CB2 receptors was measured in real time using FLIPR® membrane potential dye in a FlexStation 3 plate reader. Terpenoids were tested individually and in combination for periods up to...

Abstract Introduction: Cannabis sativa produces hundreds of bioactive compounds, including cannabinoids and terpenoids. It has been proposed that cannabinoids act in synergy with terpenoids to produce the entourage effect, a concept used to explain the therapeutic benefits of medicinal cannabis. One molecular explanation for the entourage effect is that the terpenoids augment the actions of cannabinoids at their molecular drug targets in cells. We recently reported that terpenoids commonly found in cannabis do not influence the functional effects of Δ9-tetrahydrocannabinol (Δ9-THC) on cannabinoid 1 and cannabinoid 2 receptors. The present study aimed to extend on this research by examining whether terpenoids influence the effects of phytocannabinoids...

Abstract Background/Objective Patients with non-small cell lung cancer (NSCLC) develop resistance to antitumor agents by mechanisms that involve the epithelial-to-mesenchymal transition (EMT). This necessitates the development of new complementary drugs, e.g., cannabinoid receptors (CB1 and CB2) agonists including tetrahydrocannabinol (THC) and cannabidiol (CBD). The combined use of THC and CBD confers greater benefits, as CBD enhances the effects of THC and reduces its psychotropic activity. We assessed the relationship between the expression levels of CB1 and CB2 to the clinical features of a cohort of patients with NSCLC, and the effect of THC and CBD (individually and in combination) on proliferation, EMT and migration in vitro in A549, H460 and H1792 lung...

ABSTRACT Inspired by the medicinal properties of the plant Cannabis sativa and its principal component (−)-trans-Δ9-tetrahydrocannabinol (THC), researchers have developed a variety of compounds to modulate the endocannabinoid system in the human brain. Inhibitors of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL), which are the enzymes responsible for the inactivation of the endogenous cannabinoids anandamide and 2-arachidonoylglycerol, respectively, may exert therapeutic effects without inducing the adverse side effects associated with direct cannabinoid CB1 receptor stimulation by THC. Here we review the FAAH and MAGL inhibitors that have reached clinical trials, discuss potential caveats, and provide an outlook on where the field is headed.

Abstract Graft-versus-host disease (GVHD) pathophysiology is a complex interplay between cells that comprise the adaptive and innate arms of the immune system. Effective prophylactic strategies are therefore contingent upon approaches that address contributions from both immune cell compartments. In the current study, we examined the role of the type 2 cannabinoid receptor (CB2R), which is expressed on nearly all immune cells, and demonstrated that absence of the CB2R on donor CD4+ or CD8+ T cells or administration of a selective CB2R pharmacological antagonist exacerbated acute GVHD lethality. This was accompanied primarily by the expansion of proinflammatory CD8+ T cells, indicating that constitutive CB2R expression on T cells...