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Endocannabinoid System in Health and Disease: Current Situation and Future...
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Endocannabinoid System in Health and Disease: Current Situation and Future Perspectives 4.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (15 July 2022) | Viewed by 16057

Special Issue Editor

Dr. Rosaria Meccariello

E-Mail Website
Guest Editor
Department of Movement and Wellness Sciences, Parthenope University of Naples, Via Medina 40, I-80133 Naples, Italy
Interests: endocannabinoid system; endocannabinoids–GnRH–steroids crosstalk; kisspeptins; reproduction; HPG axis; spermatogenesis; spermatozoa; endocrine disruptors; epigenetics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The discovery of the endocannabinoid system (ECS), comprising cannabinoid receptors, their endogenous ligands (endocannabinoids), and synthetic and metabolizing enzymes, triggered a large number of studies in cell lines, animal models, and humans. The ECS modulates many physiological and pathological processes, both in the peripheral and central nervous systems and in peripheral organs. This signaling system has a recognized activity on nervous system development, synaptic plasticity, learning and memory, neuroinflammation, pain and neurodegeneration, stress responsivity, mood and behavior, food intake and metabolism, reproduction, fertility and pregnancy, immune response, cardiac functions, cancer progression, and so much more. As a consequence, the modulation of ECS signaling has potential therapeutic application for a broad range of diseases, including neurodegenerative, reproductive, cardiovascular, and inflammatory disorders, metabolic syndrome and obesity, and cancer. However, despite experimental evidence, the molecular and epigenetic regulatory mechanisms of ECS activity remain to be fully elucidated, hence the need to fill this gap in order to devise clinically successful treatment strategies.

This 4th Special Issue aims at expanding the current knowledge on the ECS in both physiological and pathological conditions and on its possible therapeutic exploitation. Experimental studies in in vitro and in vivo models, review articles, and clinical studies are all welcome for consideration.

Dr. Rosaria Meccariello
Guest Editor

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Keywords

  • Endocannabinoids
  • Endocannabinoid system
  • Synaptic plasticity
  • Neurological diseases
  • Energy balance, food intake, and metabolic disorders
  • Reproduction, fertility, and pregnancy
  • Immune response
  • Cardiac functions
  • Stress
  • Pain
  • Cancer progression

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Published Papers (4 papers)

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Research

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15 pages, 2247 KiB  
Article
Cannabinoid CB1 Receptor Deletion from Catecholaminergic Neurons Protects from Diet-Induced Obesity
by Raj Kamal Srivastava, Inigo Ruiz de Azua, Andrea Conrad, Martin Purrio and Beat Lutz
Int. J. Mol. Sci. 2022, 23(20), 12635; https://doi.org/10.3390/ijms232012635 - 20 Oct 2022
Cited by 5 | Viewed by 2398
Abstract
High-calorie diets and chronic stress are major contributors to the development of obesity and metabolic disorders. These two risk factors regulate the activity of the sympathetic nervous system (SNS). The present study showed a key role of the cannabinoid type 1 receptor (CB1) [...] Read more.
High-calorie diets and chronic stress are major contributors to the development of obesity and metabolic disorders. These two risk factors regulate the activity of the sympathetic nervous system (SNS). The present study showed a key role of the cannabinoid type 1 receptor (CB1) in dopamine β-hydroxylase (dbh)-expressing cells in the regulation of SNS activity. In a diet-induced obesity model, CB1 deletion from these cells protected mice from diet-induced weight gain by increasing sympathetic drive, resulting in reduced adipogenesis in white adipose tissue and enhanced thermogenesis in brown adipose tissue. The deletion of CB1 from catecholaminergic neurons increased the plasma norepinephrine levels, norepinephrine turnover, and sympathetic activity in the visceral fat, which coincided with lowered neuropeptide Y (NPY) levels in the visceral fat of the mutant mice compared with the controls. Furthermore, the mutant mice showed decreased plasma corticosterone levels. Our study provided new insight into the mechanisms underlying the roles of the endocannabinoid system in regulating energy balance, where the CB1 deletion in dbh-positive cells protected from diet-induced weight gain via multiple mechanisms, such as increased SNS activity, reduced NPY activity, and decreased basal hypothalamic-pituitary-adrenal (HPA) axis activity. Full article
(This article belongs to the Special Issue Endocannabinoid System in Health and Disease: Current Situation and Future Perspectives 4.0)
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13 pages, 619 KiB  
Article
Effect of CB2 Stimulation on Gene Expression in Pediatric B-Acute Lymphoblastic Leukemia: New Possible Targets
by Francesca Punzo, Maura Argenziano, Chiara Tortora, Alessandra Di Paola, Margherita Mutarelli, Elvira Pota, Martina Di Martino, Daniela Di Pinto, Maria Maddalena Marrapodi, Domenico Roberti and Francesca Rossi
Int. J. Mol. Sci. 2022, 23(15), 8651; https://doi.org/10.3390/ijms23158651 - 3 Aug 2022
Cited by 3 | Viewed by 2360
Abstract
Acute lymphoblastic leukemia type B (B-ALL) is the most common kind of pediatric leukemia, characterized by the clonal proliferation of type B lymphoid stem cells. Important progress in ALL treatments led to improvements in long-term survival; nevertheless, many adverse long-term consequences still concern [...] Read more.
Acute lymphoblastic leukemia type B (B-ALL) is the most common kind of pediatric leukemia, characterized by the clonal proliferation of type B lymphoid stem cells. Important progress in ALL treatments led to improvements in long-term survival; nevertheless, many adverse long-term consequences still concern the medical community. Molecular and cellular target therapies, together with immunotherapy, are promising strategies to overcome these concerns. Cannabinoids, enzymes involved in their metabolism, and cannabinoid receptors type 1 (CB1) and type 2 (CB2) constitute the endocannabinoid system, involved in inflammation, immune response, and cancer. CB2 receptor stimulation exerts anti-proliferative and anti-invasive effects in many tumors. In this study, we evaluated the effects of CB2 stimulation on B-ALL cell lines, SUP-B15, by RNA sequencing, Western blotting, and ELISA. We observe a lower expression of CB2 in SUP-B15 cells compared to lymphocytes from healthy subjects, hypothesizing its involvement in B-ALL pathogenesis. CB2 stimulation reduces the expression of CD9, SEC61G, TBX21, and TMSB4X genes involved in tumor growth and progression, and also negatively affects downstream intracellular pathways. Our findings suggest an antitumor role of CB2 stimulation in B-ALL, and highlight a functional correlation between CB2 receptors and specific anti-tumoral pathways, even though further investigations are needed. Full article
(This article belongs to the Special Issue Endocannabinoid System in Health and Disease: Current Situation and Future Perspectives 4.0)
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Review

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16 pages, 783 KiB  
Review
Opioid and Cannabinoid Systems in Pain: Emerging Molecular Mechanisms and Use in Clinical Practice, Health, and Fitness
by Carmine Secondulfo, Filomena Mazzeo, Grazia Maria Giovanna Pastorino, Antonella Vicidomini, Rosaria Meccariello and Francesca Felicia Operto
Int. J. Mol. Sci. 2024, 25(17), 9407; https://doi.org/10.3390/ijms25179407 - 29 Aug 2024
Cited by 2 | Viewed by 1633
Abstract
Pain is an unpleasant sensory and emotional experience. Adequate pain control is often challenging, particularly in patients with chronic pain. Despite advances in pain management, drug addiction, overtreatment, or substance use disorders are not rare. Hence the need for further studies in the [...] Read more.
Pain is an unpleasant sensory and emotional experience. Adequate pain control is often challenging, particularly in patients with chronic pain. Despite advances in pain management, drug addiction, overtreatment, or substance use disorders are not rare. Hence the need for further studies in the field. The substantial progress made over the last decade has revealed genes, signalling pathways, molecules, and neuronal networks in pain control thus opening new clinical perspectives in pain management. In this respect, data on the epigenetic modulation of opioid and cannabinoid receptors, key actors in the modulation of pain, offered new perspectives to preserve the activity of opioid and endocannabinoid systems to increase the analgesic efficacy of opioid- and cannabinoid-based drugs. Similarly, upcoming data on cannabidiol (CBD), a non-psychoactive cannabinoid in the marijuana plant Cannabis sativa, suggests analgesic, anti-inflammatory, antioxidant, anticonvulsivant and ansiolitic effects and supports its potential application in clinical contexts such as cancer, neurodegeneration, and autoimmune diseases but also in health and fitness with potential use in athletes. Hence, in this review article, we summarize the emerging epigenetic modifications of opioid and cannabinoid receptors and focus on CBD as an emerging non-psychoactive cannabinoid in pain management in clinical practice, health, and fitness. Full article
(This article belongs to the Special Issue Endocannabinoid System in Health and Disease: Current Situation and Future Perspectives 4.0)
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27 pages, 2917 KiB  
Review
Cannabinoids Drugs and Oral Health—From Recreational Side-Effects to Medicinal Purposes: A Systematic Review
by Luigi Bellocchio, Alessio Danilo Inchingolo, Angelo Michele Inchingolo, Felice Lorusso, Giuseppina Malcangi, Luigi Santacroce, Antonio Scarano, Ioana Roxana Bordea, Denisa Hazballa, Maria Teresa D’Oria, Ciro Gargiulo Isacco, Ludovica Nucci, Rosario Serpico, Gianluca Martino Tartaglia, Delia Giovanniello, Maria Contaldo, Marco Farronato, Gianna Dipalma and Francesco Inchingolo
Int. J. Mol. Sci. 2021, 22(15), 8329; https://doi.org/10.3390/ijms22158329 - 3 Aug 2021
Cited by 15 | Viewed by 8741
Abstract
Background: marijuana, the common name for cannabis sativa preparations, is one of the most consumed drug all over the world, both at therapeutical and recreational levels. With the legalization of medical uses of cannabis in many countries, and even its recreational use in [...] Read more.
Background: marijuana, the common name for cannabis sativa preparations, is one of the most consumed drug all over the world, both at therapeutical and recreational levels. With the legalization of medical uses of cannabis in many countries, and even its recreational use in most of these, the prevalence of marijuana use has markedly risen over the last decade. At the same time, there is also a higher prevalence in the health concerns related to cannabis use and abuse. Thus, it is mandatory for oral healthcare operators to know and deal with the consequences and effects of cannabis use on oral cavity health. This review will briefly summarize the components of cannabis and the endocannabinoid system, as well as the cellular and molecular mechanisms of biological cannabis action in human cells and biologic activities on tissues. We will also look into oropharyngeal tissue expression of cannabinoid receptors, together with a putative association of cannabis to several oral diseases. Therefore, this review will elaborate the basic biology and physiology of cannabinoids in human oral tissues with the aim of providing a better comprehension of the effects of its use and abuse on oral health, in order to include cannabinoid usage into dental patient health records as well as good medicinal practice. Methods: the paper selection was performed by PubMed/Medline and EMBASE electronic databases, and reported according to the PRISMA guidelines. The scientific products were included for qualitative analysis. Results: the paper search screened a total of 276 papers. After the initial screening and the eligibility assessment, a total of 32 articles were considered for the qualitative analysis. Conclusions: today, cannabis consumption has been correlated to a higher risk of gingival and periodontal disease, oral infection and cancer of the oral cavity, while the physico-chemical activity has not been completely clarified. Further investigations are necessary to evaluate a therapeutic efficacy of this class of drugs for the promising treatment of several different diseases of the salivary glands and oral diseases. Full article
(This article belongs to the Special Issue Endocannabinoid System in Health and Disease: Current Situation and Future Perspectives 4.0)
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