Abstract The endocannabinoid system has been shown to be involved in various skin functions, such as melanogenesis and the maintenance of redox balance in skin cells exposed to UV radiation, as well as barrier functions, sebaceous gland activity, wound healing and the skin’s immune response. In addition to the potential use of cannabinoids in the treatment and prevention of skin cancer, cannabinoid compounds and derivatives are of interest as potential systemic and topical applications for the treatment of various inflammatory, fibrotic and pruritic skin conditions. In this context, cannabinoid compounds have been successfully tested as a therapeutic option for the treatment of androgenetic alopecia,...

Abstract In the brain, hippocampal circuits are crucial for cognitive performance (e.g., memory) and deeply affected in pathological conditions (e.g., epilepsy, Alzheimer). Specialized molecular mechanisms regulate different cell types underlying hippocampal circuitries functions. Among them, cannabinoid receptors exhibit various roles depending on the cell type (e.g., neuron, glial cell) or subcellular organelle (e.g., mitochondria). Determining the site of action and precise mechanisms triggered by cannabinoid receptor activation at a local cellular and subcellular level helps us understand hippocampal pathophysiological states. In doing so, past and current research have advanced our knowledge of cannabinoid functions and proposed novel routes for potential therapeutics. By outlining these...

Abstract Cannabidiol (CBD), a non-psychotomimetic phytocannabinoid found in the Cannabis plant, has emerged as a potential therapeutic agent for psychostimulant use disorders. In recent work, we demonstrated that CBD is able to attenuate the expression of locomotor sensitization and the enhanced metabolic activity in the nucleus accumbens (NAc) generated by the combination of cocaine and caffeine. CDB interacts directly or indirectly with several molecular targets, so the underlying mechanisms of its beneficial effects are hard to determine. Here we used high-throughput RNA-sequencing in mice’s NAc after a sensitization protocol with combined cocaine plus caffeine and a CBD pre-treatment, to identify the major pathways and genes involved...

Abstract Type 2 immunity in the lung protects against pathogenic infection and facilitates tissue repair, but its dysregulation may lead to severe human diseases. Notably, cannabis usage for medical or recreational purposes has increased globally. However, the potential impact of the cannabinoid signal on lung immunity is incompletely understood. Here, we report that cannabinoid receptor 2 (CB2) is highly expressed in group 2 innate lymphoid cells (ILC2s) of mouse and human lung tissues. Of importance, the CB2 signal enhances the IL-33-elicited immune response of ILC2s. In addition, the chemogenetic manipulation of inhibitory G proteins (Gi) downstream of CB2 produces a similarly promotive effect. Conversely, the genetic deletion of CB2 mitigates the IL-33-elicited type 2...

Abstract Endometriosis, a chronic condition affecting around 10–14% of women, is challenging to manage, due to its complex pathogenesis and limited treatment options. Research has suggested a potential role of the gut microbiota and the endocannabinoid system in the development and progression of endometriosis. This narrative review aims to explore the role of, and any potential interactions between, the endocannabinoid system (ECS) and the gut microbiota in endometriosis. This review found that both the ECS and microbiota influence endometriosis, with the former regulating inflammation and pain perception and the latter influencing immune responses and hormonal balance. There is evidence that a dysregulation of the...

Abstract The study was evaluated the impact of cannabidiol (CBD) on thyroid hormones by modulation cannabinoid receptor-2 (CB2) and vitamin D receptor (VDR) in rats fed with vitamin D3 deficiency diet (VDD). CB2-receptors were analyzed by RT-PCR method and others biomarkers by ELISA. The relative expression of CB2 (thyroid ~ 4 folds), VDR protein (liver, 151.72%), and (kidney, 66%) was significantly increased in CBD-60 compared to VDD. Vitamin D3 metabolites were significantly increased serum (189.42%), kidney (73.84%), and liver (58.11%) in CBD-60 than VDD. Increased thyroxine (59.9%) and calcitonin (213.59%); while decreased thyroid-stimulating hormone (36.15%) and parathyroid hormone (38.64%) was observed CBD treatment in VDD rats. In conclusion,...

Abstract   Cannabinoids have long been used for their psychotropic and possible medical properties of symptom relief. In the past few years, a vast literature shows that cannabinoids are neuroprotective under different pathological situations. Most of the effects of cannabinoids are mediated by the well-characterized cannabinoid receptors, the cannabinoid type 1 receptor (CB1R) and cannabinoid type 2 receptor (CB2R). Even though CB1Rs are highly expressed in the central nervous system (CNS), the adverse central side effects and the development of tolerance resulting from CB1R activation may ultimately limit the clinical utility of CB1R agonists. In contrast to the ubiquitous presence of CB1Rs, CB2Rs are...

The entourage effect was a proposed explanation for biological observations that endocannabinoid ligand activities can be modified by other lipids released from cells at the same time. An increasing volume of anecdotal reports and interest in the plant have provoked research into the activity of minor chemical constituents of the plant—including volatile terpenoids such as myrcene, α- and β- pinene, β-caryophyllene, and limonene. However, to date, no clear interaction has been identified. The current study was designed to determine whether terpenes in the cannabis plant have detectable receptor-mediated activity, or modify the activity of Δ9-tetrahydrocannabinol, cannabidiol, or the endocannabinoid 2-arachidonylglycerol at the cannabinoid receptors....

CB2cannabinoid receptor-selective agonists are promising candidates for the treatment of pain. CB2receptor activation inhibits acute, inflammatory, and neuropathic pain responses but does not cause central nervous system (CNS) effects, consistent with the lack of CB2receptors in the normal CNS. To date, there has been virtually no information regarding the mechanism of CB2receptor-mediated inhibition of pain responses. Here, we test the hypothesis that CB2receptor activation stimulates release from keratinocytes of the endogenous opioid
-endorphin, which then acts atopioid receptors on primary afferent neurons to inhibit nociception. The antinociceptive effects of the CB2receptor-selective agonist AM1241 were prevented in rats when naloxone or anti-serum to
-endorphin was injected in...

Abstract   Cannabinoids have been increasingly gaining attention for their therapeutic potential in treating various cardiovascular disorders. These disorders include myocardial infarction, hypertension, atherosclerosis, arrhythmias, and metabolic disorders. The aim of this review is to cover the main actions of cannabinoids on the cardiovascular system by examining the most recent advances in this field and major literature reviews. It is well recognized that the actions of cannabinoids are mediated by either cannabinoid 1 or cannabinoid 2 receptors (CB2 Rs). Endocannabinoids produce a triphasic response on blood pressure, while synthetic cannabinoids show a tissue‑specific and species‑specific response. Blocking cannabinoid 1 receptors have been shown to...