Abstract Mental disorders represent a significant public health burden worldwide due to their high prevalence, chronically disabling nature, and substantial impact on quality of life. Despite growing knowledge of the pathological mechanisms that underlie the development of these disorders, a high percentage of patients do not respond to first-line clinical treatments; thus, there is a strong need for alternative therapeutic approaches. During the past half-century, after the identification of the endocannabinoid system and its role in multiple physiological processes, both natural and synthetic cannabinoids have attracted considerable interest as putative medications in pathological conditions such as, but not exclusive to, mental disorders. Here, we...

Abstract Melanoma is the fourth most common type of cancer diagnosed in Australians after breast, prostate, and colorectal cancers. While there has been substantial progress in the treatment of cancer in general, malignant melanoma, in particular, is resistant to existing medical therapies requiring an urgent need to develop effective treatments with lesser side effects. Several studies have shown that “cannabinoids”, the major compounds of the Cannabis sativa L. plant, can reduce cell proliferation and induce apoptosis in melanoma cells. Despite prohibited use of Cannabis in most parts of the world, in recent years there have been renewed interests in exploiting the beneficial health effects of the Cannabis plant-derived compounds. Therefore, the...

Please use this link to access this publication. Abstract The legalization of cannabis in some states has intensified interest in the potential for cannabis and its constituents to lead to novel therapeutics for pain. Our understanding of the cellular mechanisms underlying cannabinoid actions in the brain have lagged behind opioids; however, the current opioid epidemic has also increased attention on the use of cannabinoids as alternatives to opioids for pain, especially chronic pain that requires long-term use. Endogenous cannabinoids are lipid signaling molecules that have complex roles in modulating neuronal function throughout the brain. In this review, we discuss cannabinoid functions in the descending pain modulatory pathway, a brain circuit that integrates...

Please use this link to access this publication. Abstract Prolonged status epilepticus (SE) in humans causes high mortality and brain inflammation–associated neuronal injury and morbidity in survivors. Currently, the only effective treatment is to terminate the seizures swiftly to prevent brain damage. However, reliance on acute therapies alone would be imprudent due to the required short response time. Follow-on therapies that can be delivered well after the SE onset are in an urgent need. Cannabinoid receptor type 2 (CB2), a G protein-coupled receptor that can be expressed by activated brain microglia, has emerged as an appealing anti-inflammatory target for brain conditions. In the current...

Please use this link to access this publication. Abstract Purpose Cannabinoids have been shown to exert analgesic and anti-inflammatory effects, and the effects of cannabinoids are mediated primarily by cannabinoid receptors 1 and 2 (CB1 and CB2). The objective of this study was to determine efficacy and mechanism of CB2 activation on cyclophosphamide (CYP)-induced cystitis in vivo. Methods Cystitis was induced by intraperitoneal (IP) injection of CYP in female C57BL/6J mice. Mice were pretreated with CB2 agonist JWH-133 (1 mg/kg, intraperitoneally), CB2 antagonist AM-630 (1 mg/kg, intraperitoneally) or autophagy inhibitor 3-methyladenine (3-MA) (50 mM, intraperitoneally) before IP injection of CYP. Peripheral nociception and spontaneous voiding were investigated...

Abstract Background: The widespread use of synthetic cannabinoids (SCs) among youth has become an important public health problem. Several life-threatening side effects of SC have been reported, including cardiovascular, gastrointestinal, neurological, renal, metabolic, ophthalmologic, and pulmonary effects, besides skin toxicity and hepatotoxicity. Methods: Given that high levels of SC can lead to oxidative stress, DNA damage, and inflammation, it has been aimed in this study to investigate the effects of SC in aspects of primary DNA damage, plasma total oxidant status (TOS)/total antioxidant status (TAS), thiol–disulfide homeostasis, myeloperoxidase (MPO) level, and cytokine levels (interleukin 1 beta (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor-alpha...

Please use this link to access this publication. Abstract Cannabinoids exert therapeutic effects on several diseases such as chronic pain and startle disease by targeting glycine receptors (GlyRs). Our previous studies have shown that cannabinoids target a serine residue at position 296 in the third transmembrane helix of the α1/α3 GlyR. This site is located on the outside of the ion channel protein at the lipid interface where the cholesterol concentrates. However, whether membrane cholesterol regulates cannabinoid-GlyR interaction remains unknown. Here, we show that GlyRs are closely associated with cholesterol/caveolin-rich domains at subcellular levels. Membrane cholesterol reduction significantly inhibits cannabinoid potentiation of glycine-activated currents...

Please use this link to access this publication. Abstract Synthetic cannabinoids (SC) have become increasingly popular in the last few years, especially among adolescents. Given ADHD is overrepresented in patients with substance use across adolescents compared to the general population, the current study aims were two-fold: i) examine structural brain network topology in SC users compared to healthy controls and, ii) examine the influence of ADHD on network topology in SC users. Diffusion-weighted magnetic resonance imaging scans were acquired from 27 SC users (14 without ADHD and 13 with ADHD combined type) and 13 controls. Structural networks were examined using network-based statistic and connectomic...

ABSTRACT Background: The endogenous cannabinoid system mediates the psychoactive effects of cannabis in the brain. It has been argued that this system may play a key role in the pathophysiology of schizophrenia. While some studies have consistently shown that the levels of anandamide, an endogenous cannabinoid ligand, are increased in the cerebrospinal fluid of schizophrenia patients, inconsistent results have been observed in studies measuring anandamide levels in the periphery. Here, we sought to determine if the assessment of peripheral anandamide levels in patients evaluated in a psychiatric emergency setting would show robust increases. Methods: One hundred seven patients with a schizophrenia-spectrum disorder from the psychiatric emergency...

Abstract Glaucoma is one of the principal causes of irreversible blindness worldwide. Yet, intraocular pressure (IOP) is the main modifiable risk factor for disease progression. In the never-ending challenge to develop new and effective drugs, several molecules have been tested as anti-glaucoma agents thanks to their pressure-lowering capabilities. Among these molecules, the cannabinoids have been investigated as possible anti-glaucoma drugs since the early 1970s. Cannabinoids are a large class of chemical compounds that exploit their effects by interaction with cannabinoid receptors 1 and 2. These receptors are widely expressed in the human retina where they may influence important functions such as photo-transduction, amacrine cell...