“Cannabinoid receptors type 1 (CB1) and 2 (CB2) are widely expressed in the human body, and are attractive drug targets in the prevention and management of central nervous system (CNS) and immune system dysfunction, respectively. Recent breakthroughs in the structural elucidation of cannabinoid receptors and their signaling complexes with G proteins, provide the important molecular basis of ligand-receptor interactions, activation and signaling mechanism, which will facilitate the next-generation drug design and the precise modulation of the endocannabinoid system. Here, we provide an overview on the structural features of cannabinoid receptors in different functional states and the diverse ligand binding modes. The major challenges and new strategies for future therapeutic applications targeting the endocannabinoid system (ECS) are also discussed.”
https://pubmed.ncbi.nlm.nih.gov/32739033/
“Cannabinoid receptors as key components of the endocannabinoid system are involved in regulating a variety of physiological and pathological activities, and their ligands are regarded as potential drug candidates for the treatment of many diseases.”
“Cannabinoid receptors (CB1 and CB2), as part of the endocannabinoid system, play a critical role in numerous human physiological and pathological conditions. Thus, considerable efforts have been made to develop ligands for CB1 and CB2, resulting in hundreds of phyto- and synthetic cannabinoids which have shown varying affinities relevant for the treatment of various diseases. However, only a few of these ligands are clinically used.
“Cholesterol plays vital roles in many central physiological and pathological processes. As a key component in the cell membrane, cholesterol can regulate a variety of ion channels, including ligand-gated ion channels (LGICs). However, relatively little is known about the molecular detail and in vivo consequence of cholesterol-LGIC interaction. Here, we reveal that membrane cholesterol depletion significantly inhibits the potentiating effects of dehydroxylcannabidiol (DH-CBD) on glycine-activated currents (IGly) in HEK 293T cells expressing α1/α3 glycine receptors (GlyRs). Simvastatin considerably decreases cholesterol levels and DH-CBD-induced potentiation of IGly in the spinal cord of mice. Simvastatin also significantly decreases DH-CBD analgesia in acute and chronic pain of mice. The cholesterol levels in the dorsal horn of spinal cord, measured by mass spectrometry imaging, are specifically correlated with cannabinoid potentiation of spinal GlyRs and cannabinoid-induced analgesia. These findings suggest that spinal cholesterol is critical for the efficacy of glycinergic cannabinoid-induced analgesia.”
“Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder linked to various converging toxic mechanisms. Evidence suggests that hyperglycemia induces oxidative stress, mitochondrial dysfunction, inflammation and excitotoxicity, all of which play important roles in the onset and progression of AD pathogenesis.
“Cannabis has been used for its medicinal purposes since ancient times. Its consumption leads to the activation of Cannabis receptors CB1 and CB2 that, through specific mechanisms can lead to modulation and progression of inflammation or repair. The novel findings are linked to the medical use of Cannabis in gastrointestinal (GI) system.
“Chronic hepatitis C virus (HCV) infection is a risk factor of insulin resistance, and HCV-infected patients are at a high risk of developing diabetes.
“Purpose of review: To evaluate the impact of flavonoids and cannabinoids as anti-inflammatory and antiallergic treatments on the anterior surface of the eye.
“The contribution of substance use disorders to the burden of severe maternal morbidity in the United States is poorly understood. The objective was to estimate the independent association between substance use disorders during pregnancy and risk of severe maternal morbidity.
“Although several lines of evidence support the hypothesis of a dysregulation of serotoninergic neurotransmission in the pathophysiology of obsessive-compulsive disorder (OCD), there is also evidence for an involvement of other pathways such as the GABAergic, glutamatergic, and dopaminergic systems.
“Methicillin-resistant Staphylococcus aureus (MRSA) has proven to be an imminent threat to public health, intensifying the need for novel therapeutics.