Endocannabinoid System in Health and Disease

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Pharmaceutical Science".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 9441

Special Issue Editors


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Guest Editor
Helmholtz-Zentrum Dresden-Rossendorf Institute for Radiopharmaceutical Cancer Research, 01328 Dresden, Germany
Interests: preclinical Imaging; PET; cancer; inflammation; metabolism; metastases

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Guest Editor
Department of Nuclear Medicine, University Medical Center Göttingen (UMG), 37075 Göttingen, Germany
Interests: preclinical imaging; PET imaging; Alzheimer’s disease; dementia; imaging of inflammation; endocannabinoid system

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Guest Editor
Helmholtz-Zentrum Dresden-Rossendorf Institute for Radiopharmaceutical Cancer Research, 01328 Dresden, Germany
Interests: cannabinoids; tetrahydrocannabinol (THC); medicinal chemistry; pharmacology; natural products; radiochemistry; neuroradiopharmacy

Special Issue Information

Dear Colleagues,

The hemp plant Cannabis sativa has been used as a medicine for analgesic, anticonvulsive, and antiphlogistic applications for centuries. It exerts its pharmacological activity through bioactive natural compounds, or so-called called cannabinoids, by modulating the endogenous cannabinoid system (ECS). The ECS is involved in the modulation of various physiological functions, such as brain development, memory, cognition, emotion, pain control, and inflammatory processes. However, until today, the ECS partially demystified with some blurry spots that needs to be cleared for the understanding of its role in health and disease. Evident benefits of using cannabinoids as therapeutic agents could already be shown as exemplified by tetrahydrocannabinol (∆9-THC) in neuropathic pain, multiple sclerosis and palliative care. To deepen our understanding of the role of the ECS in other diseases, such as addiction, anxiety, neurodegenerative diseases, and the treatment of cancer, further research must be conducted. The alterations of the ECS could thus present new diagnostic and therapeutic options for various diseases, by targeting cannabinoid receptors. Formulations based on cannabinoids are approved for human use, and synthetic compounds with a high specificity and high affinity towards cannabinoid receptors are available. Furthermore, new pharmaceuticals based on different lead compounds are being developed.

In order to enlighten the dark spots of the ECS, we encourage you to share your recent work on new therapeutic and diagnostic approaches using cannabinoids by submitting your manuscripts to this peer-reviewed Special Issue.

Dr. Daniel Gündel
Dr. Caroline Bouter
Dr. Rareş-Petru Moldovan
Guest Editors

Manuscript Submission Information

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Keywords

  • cannabinoids
  • cannabinoid receptors
  • signal transduction under healthy and pathologic conditions
  • imaging
  • natural and synthetic compounds
  • drug development

Published Papers (4 papers)

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Research

19 pages, 7846 KiB  
Article
The Abundant Phytocannabinoids in Rheumatoid Arthritis: Therapeutic Targets and Molecular Processes Identified Using Integrated Bioinformatics and Network Pharmacology
by Arijit Nandi, Anwesha Das, Yadu Nandan Dey and Kuldeep K. Roy
Life 2023, 13(3), 700; https://doi.org/10.3390/life13030700 - 5 Mar 2023
Cited by 5 | Viewed by 2526
Abstract
The endocannabinoid system consists of several phytocannabinoids, cannabinoid receptors, and enzymes that aid in numerous steps necessary to manifest any pharmacological activity. It is well known that the endocannabinoid system inhibits the pathogenesis of the inflammatory and autoimmune disease rheumatoid arthritis (RA). To [...] Read more.
The endocannabinoid system consists of several phytocannabinoids, cannabinoid receptors, and enzymes that aid in numerous steps necessary to manifest any pharmacological activity. It is well known that the endocannabinoid system inhibits the pathogenesis of the inflammatory and autoimmune disease rheumatoid arthritis (RA). To the best of our knowledge, no research has been done that explains the network-pharmacology-based anti-rheumatic processes by focusing on the endocannabinoid system. Therefore, the purpose of this study is to further our understanding of the signaling pathways, associated proteins, and genes underlying RA based on the abundant natural endocannabinoids. The knowledge on how the phytocannabinoids in Cannabis sativa affect the endocannabinoid system was gathered from the literature. SwissTarget prediction and BindingDB databases were used to anticipate the targets for the phytocannabinoids. The genes related to RA were retrieved from the DisGeNET and GeneCards databases. Protein–protein interactions (high confidence > 0.7) were carried out with the aid of the string web server and displayed using Cytoscape. The Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway analysis was used to perform enrichment analyses on the endocannabinoid–RA common targets. ShinyGO 0.76 was used to predict the biological processes listed in the Gene Ontology (GO) classification system. The binding affinity between the ligand and the receptors was precisely understood using molecular docking, induced-fit docking, and a molecular dynamics simulation. The network pharmacology analyses predicted that processes like response to oxygen-containing compounds and peptodyl-amino acid modification are related to the potential mechanisms of treatment for RA. These biological actions are coordinated by cancer, neuroactive ligand–receptor interaction, lipids and atherosclerosis, the calcium signaling pathway, and the Rap1 signaling pathway. According to the results of molecular docking, in the context of RA, phytocannabinoids may bind to important target proteins such PIK3CA, AKT1, MAPK9, PRKCD, BRAF, IGF1R, and NOS3. This entire study predicted the phytocannabinoids’ systemic biological characteristics. Future experimental research is needed, however, to confirm the results so far. Full article
(This article belongs to the Special Issue Endocannabinoid System in Health and Disease)
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20 pages, 7180 KiB  
Article
Understanding the Dynamics of the Structural States of Cannabinoid Receptors and the Role of Different Modulators
by Anjela Manandhar, Mona H. Haron, Michael L. Klein and Khaled Elokely
Life 2022, 12(12), 2137; https://doi.org/10.3390/life12122137 - 18 Dec 2022
Cited by 1 | Viewed by 2007
Abstract
The cannabinoid receptors CB1R and CB2R are members of the G protein-coupled receptor (GPCR) family. These receptors have recently come to light as possible therapeutic targets for conditions affecting the central nervous system. However, because CB1R is [...] Read more.
The cannabinoid receptors CB1R and CB2R are members of the G protein-coupled receptor (GPCR) family. These receptors have recently come to light as possible therapeutic targets for conditions affecting the central nervous system. However, because CB1R is known to have psychoactive side effects, its potential as a drug target is constrained. Therefore, targeting CB2R has become the primary focus of recent research. Using various molecular modeling studies, we analyzed the active, inactive, and intermediate states of both CBRs in this study. We conducted in-depth research on the binding properties of various groups of cannabinoid modulators, including agonists, antagonists, and inverse agonists, with all of the different conformational states of the CBRs. The binding effects of these modulators were studied on various CB structural features, including the movement of the transmembrane helices, the volume of the binding cavity, the internal fluids, and the important GPCR properties. Then, using in vitro experiments and computational modeling, we investigated how vitamin E functions as a lipid modulator to influence THC binding. This comparative examination of modulator binding to CBRs provides significant insight into the mechanisms of structural alterations and ligand affinity, which can directly help in the rational design of selective modulators that target either CB1R or CB2R. Full article
(This article belongs to the Special Issue Endocannabinoid System in Health and Disease)
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11 pages, 799 KiB  
Article
A Pilot Study on the Use of Low Doses of CBD to Control Seizures in Rare and Severe Forms of Drug-Resistant Epilepsy
by Gabriela Pesántez Ríos, Luciana Armijos Acurio, Ruth Jimbo Sotomayor, Victor Cueva, Ximena Pesántez Ríos, Hugo Navarrete Zambrano, Samuel Pascual and Galo Pesántez Cuesta
Life 2022, 12(12), 2065; https://doi.org/10.3390/life12122065 - 9 Dec 2022
Cited by 3 | Viewed by 2504
Abstract
Due to its anticonvulsant properties, cannabidiol can be supportive as an adjuvant therapy in the management of drug resistant epilepsy. This retrospective observational study evaluates the intensity and frequency of the seizures of patients with drug-resistant epilepsy that have been treated with antiepileptic [...] Read more.
Due to its anticonvulsant properties, cannabidiol can be supportive as an adjuvant therapy in the management of drug resistant epilepsy. This retrospective observational study evaluates the intensity and frequency of the seizures of patients with drug-resistant epilepsy that have been treated with antiepileptic medication associated with CBD in low doses for at least 12 months. Thirty-four patients were included in the study. The most frequent diagnosis of epilepsy was focal symptomatic epilepsy and Lennox–Gastaut syndrome (35.2%). During the follow-up, there was a statistically significant decrease in the seizure frequency (t student p < 0.001). A high proportion of patients, 16, concluded the study with a total control of the seizures reaching a 100% improvement, 12 reported ≥ 75% improvement, 3 ≥ 50%, and 2 ≥ 25%; only 1 patient had an improvement of less than 25%. This is the first Latin American study that demonstrates that long-term CBD added to the usual drugs significantly reduces the frequency, duration, and type of seizures in the different etiologies of epilepsy, being especially effective on the seizures that are the most incapacitating, improving the quality of life of the individual and their family. Full article
(This article belongs to the Special Issue Endocannabinoid System in Health and Disease)
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13 pages, 2989 KiB  
Article
The Neuroprotective Effect of NEUROMIDE, a Compound Bioidentical to Commensal Bacteria Metabolites
by Yoonhee Seo, Hyunji Tak, Dohee Park, Hyejin Song, Sooyoung Choe, Chaehyeong Park and Byeongdeog Park
Life 2022, 12(10), 1529; https://doi.org/10.3390/life12101529 - 30 Sep 2022
Cited by 1 | Viewed by 1746
Abstract
GPR119 is a novel cannabinoid receptor that is primarily expressed in the pancreas and gastrointestinal tract and has beneficial effects on glucose homeostasis exerted through the stimulation of GLP-1 secretion, as demonstrated in the rodent brain. GLP-1 also has important anti-inflammatory effects in [...] Read more.
GPR119 is a novel cannabinoid receptor that is primarily expressed in the pancreas and gastrointestinal tract and has beneficial effects on glucose homeostasis exerted through the stimulation of GLP-1 secretion, as demonstrated in the rodent brain. GLP-1 also has important anti-inflammatory effects in chronic inflammatory diseases, including type 1 and 2 diabetes, asthma, psoriasis, and neurodegenerative disorders. Recently, there has been increasing interest in the effect of the gut microbiota on both the gut and the brain. However, few studies have examined how gut microbes affect brain health through the endocannabinoid system. NEUROMIDE is a compound that shares a bioidentical structure with certain commensal bacterial metabolites, acting as a CB1 and GPR119 agonist. In an in vitro system exposed to reactive oxygen species (ROS), pretreatment with NEUROMIDE resulted in a significant increase in cell viability. The ROS-exposed system also showed decreased acetylcholine and an increase in inflammatory cytokines such as IL-1β, changes that were counteracted in a dose-dependent manner in the NEUROMIDE treatment groups. To measure the effectiveness of NEUROMIDE in an in vivo system, we used scopolamine-treated mice as a neurodegenerative disease model and performed a series of passive avoidance tests to observe and quantify the cognitive impairment of the mice. Mice in the NEUROMIDE treatment group had increased latency time, thus indicating an improvement in their cognitive function. Furthermore, the NEUROMIDE treatment groups showed dose-dependent increases in acetylcholine along with decreases in TNF-α and IL-1β. These experiments demonstrate that NEUROMIDE can potentially be used for neuroprotection and the improvement of cognitive ability. Full article
(This article belongs to the Special Issue Endocannabinoid System in Health and Disease)
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