REVIEW | doi:10.20944/preprints202102.0030.v1
Subject: Biology, Anatomy & Morphology Keywords: AEA; 2-AG; CB1; CB2; endocannabinoid; regeneration; neurodevelopment; invertebrate
Online: 1 February 2021 (13:16:51 CET)
Cannabis has long been used for its medicinal and psychoactive properties. With the relatively new adoption of formal medicinal cannabis regulations worldwide, the study of cannabinoids, both endogenous and exogenous, has similarly flourished in more recent decades. In particular, research investigating the role of cannabinoids in regeneration and neurodevelopment has yielded promising results in vertebrate models. However, regeneration-competent vertebrates are few, whereas a myriad of invertebrate species have been established as superb models for regeneration. As such, this review aims to provide a comprehensive summary of the endocannabinoid system, with a focus on current advances in the area of endocannabinoid system contributions to invertebrate neurodevelopment and regeneration.
REVIEW | doi:10.20944/preprints202211.0122.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: Endocannabinoid system; receptor cannabinoid; endocannabinoids ligands; phytocannabinoids; Integrative and Complementary Health Practices
Online: 7 November 2022 (11:36:46 CET)
The endocannabinoid system (eCB) began to be studied from the identification of the molecular structures present in the cannabis sativa plant. The ECS is constituted of cannabinoid receptors, endogenous ligands and all the associated enzymatic apparatus responsible for maintaining homeostasis. Several physiological effects of cannabinoids are exerted through interaction with various receptors such as CB1 and CB2 receptors, vanilloid receptors, and the recently discovered [GPCRs (GPR55, GPR3, GPR6, GPR12 and GPR19). Endogenous ligands such anandamide and 2-arachidonoylglycerol might modulate these receptors. eCB has proved to play a critical role in some human diseases and has been extensively studied due to its wide therapeutic potential and because it is a promising target for the development of new drugs. Phytocannabinoids and synthetic cannabinoids have shown varied affinities to eCB, which are relevant to the treatment of various diseases. They may also have potential as lead compounds in the development of cannabinoid-based pharmaceuticals for a variety of diseases. Furthermore, Integrative and Complementary Health Practices (ICHP) appear to influence the endocannabinoid system through modulation. This review will show a description of ECS components and discuss how phytocannabinoids, other exogenous compounds, and PICS may operate the eCB balance.
REVIEW | doi:10.20944/preprints201911.0260.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: sepsis; endocannabinoid system; cannabinoids; cannabis sativa; THC; CBD
Online: 22 November 2019 (09:32:28 CET)
Critically ill patients with sepsis require a multidisciplinary approach, as this situation implies multiorgan distress, with most of the bodily biochemical and cellular systems being affected by the condition. Moreover, sepsis is characterized by a multitude of biochemical interactions and by dynamic changes of the immune system. At the moment, there is a gap in our understanding of the cellular, genetic, and molecular mechanisms involved in sepsis. One of the systems intensely studied in recent years is the endocannabinoid signaling pathway, as light was shed over a series of important interactions of cannabinoid receptors with biochemical pathways, specifically for sepsis. Furthermore, a series of important implications on inflammation and the immune system that are induced by the activity of cannabinoid receptors stimulated by the delta-9-tetrahidrocannabinol and cannabinol have been noticed. The aim of this review paper was to present, in detail, the important mechanisms modulated by the endocannabinoid signaling pathway, as well as of the molecular and cellular links it has with sepsis. At the same time, we wish to present the possible implications of cannabinoids in the most important biological pathways involved in sepsis, such as inflammation, redox activity, immune system, and epigenetic expression.
REVIEW | doi:10.20944/preprints201806.0001.v1
Subject: Medicine & Pharmacology, Obstetrics & Gynaecology Keywords: endocannabinoid system; gynaecological cancers; endometrial cancer; cervical cancer; ovarian cancer, CB1R; CB2R; FAAH;
Online: 1 June 2018 (05:45:19 CEST)
Background: The endocannabinoid system (ECS) is a very heterogeneous array consisting of many proteins like ligands, enzymes and receptors synthetized in various tissues and immunity cells. The main endogenous ligands are unsaturated fatty acid derivatives like anandamide(AEA), 2-arachidonoylglycerol(2-AG), but many others are under study. Endocannabinoids are involved in both physiological and pathological conditions. ECS plays an important role in the regulation of main processes which lead to cancer and also in sex steroid hormone-related cancers. Methods: With focus on gynaecological cancers, main papers and review articles, up to April 2018, on the role of the ECS, were acquired by PubMed searches using the search terms: ‘cancer’, ‘cannabinoid’, ‘endocannabinoid’, ‘gynaecology’ and ‘malignancy’. Results: The review of recent literature data showed the involvement of the endocannabinoid system in numerous physiological and pathological conditions of the female genital tract up to the development of gynaecological malignancy as cervical, endometrial and ovarian cancer. Conclusions: The endocannabinoid system has an important role in antitumor actions involving different signalling receptor and receptor-independent pathways. It represents an exciting challenge to researchers for its potential use in diagnosis and treatment of all gynaecological malignancies
ARTICLE | doi:10.20944/preprints201809.0222.v1
Subject: Medicine & Pharmacology, Pathology & Pathobiology Keywords: psoriasis, arthritis, inflammation, granulocytes, redox signaling, oxidative stress, lipid peroxidation, 4-hydroxynonenal, lipids, endocannabinoid system
Online: 12 September 2018 (13:43:16 CEST)
Inflammatory granulocytes are characterized by oxidative burst, which may promote oxidative stress and lipid modification both in affected tissues and on systemic level. On the other hand, redox signaling involving lipid peroxidation products acting as second messengers of free radicals play important, not yet fully understood, roles in pathophysiology of inflammation and various stress-associated disorders. Therefore, the aim of this study was to evaluate the onset of oxidative stress and alterations of enzyme-dependent lipid metabolism resulting from redox imbalance in granulocytes and plasma obtained from patients with psoriasis vulgaris or psoriatic arthritis, in comparison to the healthy subjects. The results obtained revealed enhanced activity of pro-oxidant enzymes NADPH and xanthine oxidases in granulocytes, with a decrease of enzymatic and non-enzymatic antioxidants in plasma of psoriatic patients. The Nrf2 and its regulators were increased in both forms of psoriasis, while HO-1 levels were increased only in psoriasis vulgaris. Redox imbalance was associated with decreased levels of phospholipids and of free PUFAs, but with enhanced activity of enzymes involved in lipid metabolism (PLA2, PAF-AH COX1/2) and increased lipid peroxidation products 4-hydroxynonenal (4-HNE), isoprostanes and neuroprostanes. Increased endocannabinoids and GPR55 were observed in both forms of the disease, while expression of CB1 was increased only in pateints with psoriatic arthritis, opposite to CB2, which was increased only in psoriasis vulgaris. Protein modifications by ROS and lipid peroxidation product 4-HNE promoted apoptosis of granulocytes by increased caspases in both forms of psoriasis. This study indicates that excessive activation of granulocytes, causing oxidative stress and lipid modifications, is an important pathophysiology of psoriasis. Consequently, lower Nrf2 activity and CB2 expression may promote progression of psoriasis into advanced, arthritic form of the disease.
REVIEW | doi:10.20944/preprints201906.0262.v1
Subject: Medicine & Pharmacology, Veterinary Medicine Keywords: endocannabinoid system; anandamide; 2-AG; cannabis; cannabinoid receptor 1; cannabinoid receptor 2; PPARSa, b; Ht1a; TRPV1; GPR55; cannabidiol; CBD; THC; CBG; CBC; tetrahydrocannabinol
Online: 26 June 2019 (07:28:52 CEST)
The endocannabinoid system has been found to be pervasive in mammalian species. It has also been described in invertebrate species primitive as the Hydra. Insects apparently are devoid of this otherwise ubiquitous system that provides homeostatic balance to the nervous and immune systems, as well as many other organ systems. The endocannabinoid system (ECS) has been defined to consist of three parts: 1. Endogenous ligands, 2. G-protein coupled receptors (GPCRs), and 3. Enzymes to degrade and recycle the ligands. Two endogenous molecules have been identified as ligands in the ECS to date. These are the endocannabinoids: Anandamide (arachidonoyl ethanolamide) and 2-AG (2-arachidonoyl glycerol). Two G-coupled protein receptors have been described as part of this system, with other putative GPC being considered. Coincidentally, the phytochemicals produced in large quantities by the Cannabis sativa L plant, and in lesser amounts by other plants, can interact with this system as ligands. These plant-based cannabinoids are termed, phytocannabinoids. The precise determination of the distribution of cannabinoid receptors in animal species is an ongoing project, with the canine cannabinoid receptor distribution currently receiving the most interest in non-human animals.
Subject: Medicine & Pharmacology, Allergology Keywords: Asian elephant; Elephas maximus; cannabidiol; cannabis; CBD; endocannabinoid system
Online: 16 June 2021 (11:59:03 CEST)
The Asian elephant (Elephas maximus) is one of the largest herbivore mammals in the world. A portion of the total elephant population is under human care, where health problems such as skin lesions and decreased appetite are reported. The objective of this study was to apply the therapeutic properties of cannabidiol (CBD) to aid treatment of palmar abscesses and a suboptimal food intake in a female Asian elephant in Mexico. A CBD-isolate compounded medication was administered orally at a dose of 0.05 mg/kg/day. CBD administration showed positive effects such as reduction in abscess size, decreased food selectivity, increased food intake, weight gain and increased mobility. More research in elephants is needed to understand their cannabinoid pharmacodynamics and pharmacokinetics and proposing a dosage range and therapeutic applications for this species.