“Epilepsy contributes to approximately 1% of the global disease burden. By affecting especially young children as well as older persons of all social and racial variety, epilepsy is a present disorder worldwide. Currently, only 65% of epileptic patients can be successfully treated with antiepileptic drugs. For this reason, alternative medicine receives more attention.
Cannabis has been cultivated for over 6000 years to treat pain and insomnia and used since the 19th century to suppress epileptic seizures.
The two best described phytocannabinoids, (-)-trans-Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are claimed to have positive effects on different neurological as well as neurodegenerative diseases, including epilepsy.
There are different cannabinoids which act through different types of receptors and channels, including the cannabinoid receptor 1 and 2 (CB1, CB2), G protein-coupled receptor 55 (GPR55) and 18 (GPR18), opioid receptor µ and δ, transient receptor potential vanilloid type 1 (TRPV1) and 2 (TRPV2), type A γ-aminobutyric acid receptor (GABAAR) and voltage-gated sodium channels (VGSC).
The mechanisms and importance of the interaction between phytocannabinoids and their different sites of action regarding epileptic seizures and their clinical value are described in this review.”
“Diabetes is a chronic disease associated with a high number of complications such as peripheral neuropathy, which causes sensorial disturbances and may lead to the development of diabetic neuropathic pain (DNP). The current treatment for DNP is just palliative and the drugs may cause severe adverse effects, leading to discontinuation of treatment. Thus, new therapeutic targets need to be urgently investigated.
“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.”
“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.
“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 ethanol abuse can lead to harmful consequences for the heart, resulting in systolic dysfunction, variability in the heart rate, arrhythmia, and cardiac remodelling. However, the precise molecular mechanism responsible for ethanol-induced cardiomyopathy is poorly understood. In this regard, the present study aimed to describe the RIP1/RIP3/MLKL-mediated necroptotic cell death that may be involved in ethanol-induced cardiomyopathy and characterize CBR-mediated effects on the signalling pathway and myocardial injury.
“Cannabinoids (CBs), analgesic drugs used for thousands of years, were first found in Cannabis sativa, and the multiple CBs used medicinally, such as tetrahydrocannabinol (THC), cannabidiol (CBD) and dozens more, have complex structures. In addition to their production by plants, CBs are naturally present in the nerves and immune systems of humans and animals.
“During the last decades, researchers have investigated the functional relevance of adult hippocampal neurogenesis in normal brain function as well as in the pathogenesis of diverse psychiatric conditions.
“Like most modern molecular biology and natural product chemistry, understanding cannabinoid pharmacology centers around molecular interactions, in this case, between the cannabinoids and their putative targets, the G-protein coupled receptors (GPCRs) cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2). Understanding the complex structure and interplay between the partners in this molecular dance is required to understand the mechanism of action of synthetic, endogenous, and phytochemical cannabinoids. This review, with 91 references, surveys our understanding of the structural biology of the cannabinoids and their target receptors including both a critical comparison of the extant crystal structures and the computationally derived homology models, as well as an in-depth discussion about the binding modes of the major cannabinoids. The aim is to assist in situating structural biochemists, synthetic chemists, and molecular biologists who are new to the field of cannabis research.”