Abstract Background and Purpose Obesity, an important risk factor for developing chronic kidney disease (CKD), affects the kidneys by two main molecular signalling pathways: the endocannabinoid/CB1 receptor system, whose activation in obesity promotes renal inflammation, fibrosis, and injury, and the inducible NOS (iNOS), which generates ROS resulting in oxidative stress. Hence, a compound that inhibits both peripheral CB1 receptors and iNOS may serve as an effective therapeutic agent against obesity-induced CKD. Experimental Approach Here, we describe the effect of a novel peripherally restricted, orally bioavailable dual CB1 receptor/iNOS antagonist, MRI-1867 (3 mg·kg−1), in ameliorating obesity-induced CKD, and compared its metabolic and renal efficacies to a stand-alone peripheral CB1 receptor...

ABSTRACT Background: Gilles de la Tourette syndrome (GTS) is a neuropsychiatric disorder of unknown etiology, although a major role of genetic factors has been established. Cannabis-based medicines may alleviate GTS-associated tics and variants of CNR1 gene encoding central cannabinoid receptor (CB1) are believed to be a risk factor for the development of some neurodevelopmental diseases. Our aim was to test the association of selected CNR1 gene variants with GTS. Material and Methods: The cohort of GTS cases comprised 262 unrelated patients aged 3–53 years (mean age: 18.3 ± 9.1 years; 204 males (77.9%), 126 (48.1%) adults defined as ≥18 years). As a control group we enrolled 279 unrelated,...

Please use this link to access this publication. Abstract The human endocannabinoid system (ECS) is a complex signalling network involved in many key physiological processes. The ECS includes the cannabinoid receptors, the endocannabinoid ligands, and the enzymes related to their synthesis and degradation. Other cannabinoids encompass the phytocannabinoids from Cannabis sativa L.(marijuana) and the synthetic cannabinoids. Alterations in the ECS are associated with different diseases, including inflammatory and immune-mediated disorders such as allergy. Allergy is a global health problem of increasing prevalence with high socio-economic impact. Different studies have convincingly demonstrated that cannabinoids play a role in allergy, but their actual contribution is still controversial. It...

Abstract Cannabinoid CB2 receptor (CB2) agonists are potential analgesics void of psychotropic effects. Peripheral immune cells, neurons and glia express CB2; however, the involvement of CB2 from these cells in neuropathic pain remains unresolved. We explored spontaneous neuropathic pain through on-demand self-administration of the selective CB2 agonist JWH133 in wild-type and knockout mice lacking CB2 in neurons, monocytes or constitutively. Operant self-administration reflected drug-taking to alleviate spontaneous pain, nociceptive and affective manifestations. While constitutive deletion of CB2 disrupted JWH133-taking behavior, this behavior was not modified in monocyte-specific CB2 knockouts and was increased in mice defective in neuronal CB2 knockouts suggestive of increased spontaneous pain. Interestingly, CB2-positive lymphocytes infiltrated the injured nerve...

Abstract In this study, we investigated locomotor activity and responses to repeated light and dark stimuli to assess cannabinoid-induced abnormal behavior in zebrafish larvae (Danio rerio), as an alternative to standard rodent models. To induce the desired responses, we used cannabidiol and WIN55,212–2, two major cannabinoid components. A repeated light and dark test was used to assess how drug exposure influences locomotory responses. Larvae were examined after moderate cannabidiol and WIN55,212–2 exposure and at 24 h after transfer to untreated water. We found that cannabidiol did not produce a dose-dependent inhibitory effect on locomotor activity, with both 0.5 and 10 μg/mL concentrations reducing movement...

Abstract Olfaction has a direct influence on behavior and cognitive processes. There are different neuromodulatory systems in olfactory circuits that control the sensory information flowing through the rest of the brain. The presence of the cannabinoid type-1 (CB1) receptor, (the main cannabinoid receptor in the brain), has been shown for more than 20 years in different brain olfactory areas. However, only over the last decade have we started to know the specific cellular mechanisms that link cannabinoid signaling to olfactory processing and the control of behavior. In this review, we aim to summarize and discuss our current knowledge about the presence of CB1 receptors,...

Abstract Background and Purpose Marijuana is the illicit drug most commonly used among pregnant and breastfeeding women. Different studies reported long-term adverse effects induced by in utero exposure to the main component of marijuana, Δ9-tetrahydrocannabinol (THC), both in rodents and in humans. However, little is known about any potential sex-dependent effects of marijuana consumption during pregnancy on newborns at early developmental ages. Experimental Approach We studied the effects of prenatal exposure to the cannabinoid receptor agonist WIN55,212-2 (WIN; 0.5 mg·kg−1 from GD5 to GD20) on the emotional reactivity and cognitive performance of male and female rat offspring from infancy through adolescence and tested the role of mGlu5 receptor...

Please use this link to access this publication. Abstract Synthetic cannabinoid receptor agonists (SCRAs) are an evolving class of new psychoactive substances (NPS) with structurally diverse compounds emerging each year. Due to the rapid pace at which these drugs enter the market, there is often little or nil information regarding the pharmacology of these substances despite widespread human use. In this study, 12 recently emerged SCRAs (reported between 2018 and 2020) were synthesized, analytically characterized, and pharmacologically evaluated using a live cell-based nanoluciferase complementation reporter assay that monitors in vitro cannabinoid receptor type 1 (CB1) activation via its interaction with β-arrestin 2 (βarr2). All synthesized SCRAs...

Abstract Breast cancer (BC) is the most common cancer in women worldwide. Approximately 70–80% of BCs express estrogen receptors (ER), which predict the response to endocrine therapy (ET), and are therefore hormone receptor-positive (HR+). Endogenous cannabinoids together with cannabinoid receptor 1 and 2 (CB1, CB2) constitute the basis of the endocannabinoid system. Interactions of cannabinoids with hypothalamic–pituitary–gonadal axis hormones are well documented, and two studies found a positive correlation between peak plasma endogenous cannabinoid anandamide with peak plasma 17β-estradiol, luteinizing hormone and follicle-stimulating hormone levels at ovulation in healthy premenopausal women. Do cannabinoids have an effect on HR+ BC? In this paper we review...