scholarly journals Cannabinoids in Medicine: Cancer, Immunity, and Microbial Diseases

2020 ◽  
Vol 22 (1) ◽  
pp. 263
Author(s):  
Paweł Śledziński ◽  
Agnieszka Nowak-Terpiłowska ◽  
Joanna Zeyland
Keyword(s):  
Molecular Mechanisms ◽  
Cannabinoid Receptors ◽  
Therapeutic Potential ◽  
Inflammatory Diseases ◽  
Scientific Evidence ◽  
Endocannabinoid System ◽  
Molecular Response ◽  
Animal Cells ◽  
Microbial Diseases

Recently, there has been a growing interest in the medical applications of Cannabis plants. They owe their unique properties to a group of secondary metabolites known as phytocannabinoids, which are specific for this genus. Phytocannabinoids, and cannabinoids generally, can interact with cannabinoid receptors being part of the endocannabinoid system present in animals. Over the years a growing body of scientific evidence has been gathered, suggesting that these compounds have therapeutic potential. In this article, we review the classification of cannabinoids, the molecular mechanisms of their interaction with animal cells as well as their potential application in the treatment of human diseases. Specifically, we focus on the research concerning the anticancer potential of cannabinoids in preclinical studies, their possible use in cancer treatment and palliative medicine, as well as their influence on the immune system. We also discuss their potential as therapeutic agents in infectious, autoimmune, and gastrointestinal inflammatory diseases. We postulate that the currently ongoing and future clinical trials should be accompanied by research focused on the cellular and molecular response to cannabinoids and Cannabis extracts, which will ultimately allow us to fully understand the mechanism, potency, and safety profile of cannabinoids as single agents and as complementary drugs.

Cannabinoids and the Brain

2017 ◽  
Author(s):  
Linda A. Parker
Keyword(s):  
Cannabinoid Receptors ◽  
Legal Status ◽  
Therapeutic Potential ◽  
Scientific Discovery ◽  
Scientific Evidence ◽  
Endocannabinoid System ◽  
Preclinical Research ◽  
Pain Anxiety ◽  
Scientific Investigations ◽  
The Brain

Cannabinoids and the Brain introduces an informed general audience to the scientific discovery of the endocannabinoid system and recent preclinical research that explains its importance in brain functioning. The endocannabinoids, anandamide and 2-AG, act on the same cannabinoid receptors, that are activated by the primary psychoactive compound found in marijuana, Δ‎9-tetrahydrocannabinol (THC). Therefore, the scientific investigations of the functions of the endocannabinoid system are guided by the known effects of marijuana on the brain and body. The book reviews the scientific evidence of the role that the endocannabinoid system plays in regulating emotion, anxiety, depression, psychosis, reward and addiction, learning and memory, feeding, nausea/vomiting, pain, epilepsy, and other neurological disorders. Anecdotal reports are linked with the current scientific literature on the medicinal benefits of marijuana. Cannabis contains over 80 chemicals that have closely related structures, called cannabinoids, but the only major mood-altering constituent is THC. Another major plant cannabinoid is cannabidiol (CBD), which is not psychoactive; yet, considerable recent preclinical research reviewed in various chapters reveals that CBD has promising therapeutic potential in treatment of pain, anxiety, nausea and epilepsy. Only recently, has research been conducted with some of the other compounds found in cannabis. The subject matter of the book is extremely timely in light of the current ongoing debate not only about medical marijuana, but also about its legal status.

scholarly journals Therapeutic Attributes of Endocannabinoid System against Neuro-Inflammatory Autoimmune Disorders

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3389
Author(s):  
Ishtiaq Ahmed ◽  
Saif Ur Rehman ◽  
Shiva Shahmohamadnejad ◽  
Muhammad Anjum Zia ◽  
Muhammad Ahmad ◽  
...  
Keyword(s):  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Therapeutic Potential ◽  
Endocannabinoid System ◽  
Cell Types ◽  
Autoimmune Disorders ◽  
Specific Receptors ◽  
Different Cell Types

In humans, various sites like cannabinoid receptors (CBR) having a binding affinity with cannabinoids are distributed on the surface of different cell types, where endocannabinoids (ECs) and derivatives of fatty acid can bind. The binding of these substance(s) triggers the activation of specific receptors required for various physiological functions, including pain sensation, memory, and appetite. The ECs and CBR perform multiple functions via the cannabinoid receptor 1 (CB1); cannabinoid receptor 2 (CB2), having a key effect in restraining neurotransmitters and the arrangement of cytokines. The role of cannabinoids in the immune system is illustrated because of their immunosuppressive characteristics. These characteristics include inhibition of leucocyte proliferation, T cells apoptosis, and induction of macrophages along with reduced pro-inflammatory cytokines secretion. The review seeks to discuss the functional relationship between the endocannabinoid system (ECS) and anti-tumor characteristics of cannabinoids in various cancers. The therapeutic potential of cannabinoids for cancer—both in vivo and in vitro clinical trials—has also been highlighted and reported to be effective in mice models in arthritis for the inflammation reduction, neuropathic pain, positive effect in multiple sclerosis and type-1 diabetes mellitus, and found beneficial for treating in various cancers. In human models, such studies are limited; thereby, further research is indispensable in this field to get a conclusive outcome. Therefore, in autoimmune disorders, therapeutic cannabinoids can serve as promising immunosuppressive and anti-fibrotic agents.

The Molecular targets of Cannabinoids in the treatment of Cancer and Inflammation

2021 ◽  
Vol 27 ◽  
Author(s):  
Alenabi Aylar ◽  
Malekinejad Hassan
Keyword(s):  
Cannabinoid Receptors ◽  
Inflammatory Diseases ◽  
Biological Effects ◽  
Synthetic Cannabinoids ◽  
Endocannabinoid System ◽  
Anticancer Effects ◽  
Anti Cancer ◽  
Culture Models ◽  
Cancer And Inflammation ◽  
G Protein Coupled

Objective: In this review we discuss the emerging evidence for the effectiveness of cannabinoids in the treatment of cancer and inflammation. The remarkable effects complete the traditional evidence for their successful application in the treatment of pain and cancer-related side effects. Methods: we searched Pub Med (132 articles) and Google scholar (9 articles) databases and gathered the clinical (4 articles), preclinical (28 articles) studies, reports on cell culture models (30 articles) and other original and review articles (78 articles) related to inflammation, cancer and cannabinoids. Results: Cannabinoids are described in three different forms, comprising endo- phyto- and synthetic compounds that exert biological effects. The molecular and cellular pathways of endogenous cannabinoids in the maintenance of homeostasis are well documented. In addition to classical cannabinoid receptors type 1 and 2, Vanilloid receptors and G protein-coupled receptor 55 were identified as common receptors. Subsequently, the effectiveness of phyto- and synthetic cannabinoids mediated by cannabinoid receptors has been demonstrated in the treatment of inflammatory diseases including neurodegenerative diseases as well as gastrointestinal and respiratory inflammations. Another accepted property of cannabinoids is their anti-cancer effects. Cannabinoids were found to be effective in the treatment of lung, colorectal, prostate, breast, pancreas and hepatic cancers. The anticancer effects of cannabinoids were characterized by their anti-proliferative property, inhibition of cancer cells migration, suppression of vascularization and induction of apoptosis. Conclusion: The current review provides and overview the role of endocannabinoid system in the mediation of physiological functions, the type and expression of cannabinoids receptors under physiological and pathological conditions. In additions, the molecular pathways involved in the effects of cannabinoids and the effectiveness of cannabinoids in the treatment of inflammations and cancers are highlighted.

scholarly journals Cannabinoid Receptors: An Update on Cell Signaling, Pathophysiological Roles and Therapeutic Opportunities in Neurological, Cardiovascular, and Inflammatory Diseases

2020 ◽  
Vol 21 (20) ◽  
pp. 7693
Author(s):  
Dhanush Haspula ◽  
Michelle A. Clark
Keyword(s):  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Inflammatory Diseases ◽  
Endocannabinoid System ◽  
Future Directions ◽  
The Past ◽  
Health And Disease ◽  
Made In

The identification of the human cannabinoid receptors and their roles in health and disease, has been one of the most significant biochemical and pharmacological advancements to have occurred in the past few decades. In spite of the major strides made in furthering endocannabinoid research, therapeutic exploitation of the endocannabinoid system has often been a challenging task. An impaired endocannabinoid tone often manifests as changes in expression and/or functions of type 1 and/or type 2 cannabinoid receptors. It becomes important to understand how alterations in cannabinoid receptor cellular signaling can lead to disruptions in major physiological and biological functions, as they are often associated with the pathogenesis of several neurological, cardiovascular, metabolic, and inflammatory diseases. This review focusses mostly on the pathophysiological roles of type 1 and type 2 cannabinoid receptors, and it attempts to integrate both cellular and physiological functions of the cannabinoid receptors. Apart from an updated review of pre-clinical and clinical studies, the adequacy/inadequacy of cannabinoid-based therapeutics in various pathological conditions is also highlighted. Finally, alternative strategies to modulate endocannabinoid tone, and future directions are also emphasized.

scholarly journals The Endocannabinoid System Contributes to Electroacupuncture Analgesia

2021 ◽  
Vol 14 ◽  
Author(s):  
Iona J. MacDonald ◽  
Yi-Hung Chen
Keyword(s):  
Cognitive Processes ◽  
Cannabinoid Receptors ◽  
Scientific Evidence ◽  
Antinociceptive Effect ◽  
Synthetic Cannabinoids ◽  
Behavioral Responses ◽  
Endocannabinoid System ◽  
Extensive Involvement ◽  
Effective Analgesia

The extensive involvement of the endocannabinoid system (ECS) in vital physiological and cognitive processes of the human body has inspired many investigations into the role of the ECS and drugs, and therapies that target this system and its receptors. Activation of cannabinoid receptors 1 and 2 (CB1 and CB2) by cannabinoid treatments, including synthetic cannabinoids, alleviates behavioral responses to inflammatory and neuropathic pain. An increasing body of scientific evidence details how electroacupuncture (EA) treatments achieve effective analgesia and reduce inflammation by modulating cannabinoid signaling, without the adverse effects resulting from synthetic cannabinoid administration. CB1 receptors in the ventrolateral area of the periaqueductal gray are critically important for the mechanisms of the EA antinociceptive effect, while peripheral CB2 receptors are related to the anti-inflammatory effects of EA. This review explores the evidence detailing the endocannabinoid mechanisms involved in EA antinociception.

Endocannabinoid Signalling in Atherosclerosis and Related Metabolic Complications

2019 ◽  
Vol 119 (04) ◽  
pp. 567-575 ◽  
Author(s):  
Raquel Guillamat-Prats ◽  
Martina Rami ◽  
Stephan Herzig ◽  
Sabine Steffens
Keyword(s):  
Cannabinoid Receptors ◽  
Cholesterol Metabolism ◽  
Therapeutic Potential ◽  
Vascular Inflammation ◽  
Visceral Obesity ◽  
Endocannabinoid System ◽  
Metabolic Complications ◽  
Altered Expression ◽  
Pathophysiological Role ◽  
Liver And Pancreas

AbstractEndocannabinoids are a group of arachidonic acid-derived lipid mediators binding to cannabinoid receptors CB1 and CB2. An overactivity of the endocannabinoid system plays a pathophysiological role in the development of visceral obesity and insulin resistance. Moreover, elevated circulating endocannabinoid levels are also prevalent in atherosclerosis. The pathophysiological increase of endocannabinoid levels is due to an altered expression of endocannabinoid synthesizing and degrading enzymes induced by inflammatory mediators such as cytokines or lipids. Emerging experimental evidence suggests that enhanced endocannabinoid signalling affects atherosclerosis via multiple effects, including a modulation of vascular inflammation, leukocyte recruitment, macrophage cholesterol metabolism and consequently atherosclerotic plaque stability. In addition, recent findings in various metabolic disease models highlight the relevance of peripheral CB1 cannabinoid receptors in adipose tissue, liver and pancreas, which crucially regulate lipid and glucose metabolism as well as macrophage properties in these organs. This suggests that targeting the endocannabinoid system in the vasculature and peripheral organs might have a therapeutic potential for atherosclerosis by inhibiting vascular inflammation and improving metabolic risk factors. This review will provide a brief update on the effects of endocannabinoid signalling in atherosclerosis and related metabolic complications.

scholarly journals Pharmacological Properties, Therapeutic Potential and Molecular Mechanisms of JWH133, a CB2 Receptor-Selective Agonist

2021 ◽  
Vol 12 ◽  
Author(s):  
Hebaallah Mamdouh Hashiesh ◽  
Charu Sharma ◽  
Sameer N. Goyal ◽  
Niraj Kumar Jha ◽  
Shreesh Ojha
Keyword(s):  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Therapeutic Potential ◽  
Neurological Diseases ◽  
Endocannabinoid System ◽  
Preclinical Studies ◽  
Cb2 Receptor ◽  
Comprehensive Overview ◽  
Pathological Conditions ◽  
Selective Agonists

The endocannabinoid system has attracted attention as a pharmacological target for several pathological conditions. Cannabinoid (CB2)-selective agonists have been the focus of pharmacological studies because modulation of the CB2 receptor (CB2R) can be useful in the treatment of pain, inflammation, arthritis, addiction, and cancer among other possible therapeutic applications while circumventing CNS-related adverse effects. Increasing number of evidences from different independent preclinical studies have suggested new perspectives on the involvement of CB2R signaling in inflammation, infection and immunity, thus play important role in cancer, cardiovascular, renal, hepatic and metabolic diseases. JWH133 is a synthetic agonist with high CB2R selectivity and showed to exert CB2R mediated antioxidant, anti-inflammatory, anticancer, cardioprotective, hepatoprotective, gastroprotective, nephroprotective, and immunomodulatory activities. Cumulative evidences suggest that JWH133 protects against hepatic injury, renal injury, cardiotoxicity, fibrosis, rheumatoid arthritis, and cancer as well as against oxidative damage and inflammation, inhibits fibrosis and apoptosis, and acts as an immunosuppressant. This review provides a comprehensive overview of the polypharmacological properties and therapeutic potential of JWH133. This review also presents molecular mechanism and signaling pathways of JWH133 under various pathological conditions except neurological diseases. Based on the available data, this review proposes the possibilities of developing JWH133 as a promising therapeutic agent; however, further safety and toxicity studies in preclinical studies and clinical trials in humans are warranted.

scholarly journals Cancer Initiation, Progression and Resistance: Are Phytocannabinoids from Cannabis sativa L. Promising Compounds?

Molecules ◽  
2021 ◽  
Vol 26 (9) ◽  
pp. 2668
Author(s):  
Ersilia Nigro ◽  
Marialuisa Formato ◽  
Giuseppina Crescente ◽  
Aurora Daniele
Keyword(s):  
Molecular Mechanisms ◽  
Cannabinoid Receptors ◽  
Cannabis Sativa ◽  
Current Knowledge ◽  
Endocannabinoid System ◽  
Peripheral Tissues ◽  
Positive Effects ◽  
Cancer Initiation

Cannabis sativa L. is a source of over 150 active compounds known as phytocannabinoids that are receiving renewed interest due to their diverse pharmacologic activities. Indeed, phytocannabinoids mimic the endogenous bioactive endocannabinoids effects through activation of CB1 and CB2 receptors widely described in the central nervous system and peripheral tissues. All phytocannabinoids have been studied for their protective actions towards different biological mechanisms, including inflammation, immune response, oxidative stress that, altogether, result in an inhibitory activity against the carcinogenesis. The role of the endocannabinoid system is not yet completely clear in cancer, but several studies indicate that cannabinoid receptors and endogenous ligands are overexpressed in different tumor tissues. Recently, in vitro and in vivo evidence support the effectiveness of phytocannabinoids against various cancer types, in terms of proliferation, metastasis, and angiogenesis, actions partially due to their ability to regulate signaling pathways critical for cell growth and survival. The aim of this review was to report the current knowledge about the action of phytocannabinoids from Cannabis sativa L. against cancer initiation and progression with a specific regard to brain, breast, colorectal, and lung cancer as well as their possible use in the therapies. We will also report the known molecular mechanisms responsible for such positive effects. Finally, we will describe the actual therapeutic options for Cannabis sativa L. and the ongoing clinical trials.

scholarly journals β-Caryophyllene, A Natural Dietary CB2 Receptor Selective Cannabinoid can be a Candidate to Target the Trinity of Infection, Immunity, and Inflammation in COVID-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Niraj Kumar Jha ◽  
Charu Sharma ◽  
Hebaallah Mamdouh Hashiesh ◽  
Seenipandi Arunachalam ◽  
MF Nagoor Meeran ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Immune Modulation ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Endocannabinoid System ◽  
Therapeutic Effects ◽  
Peroxisome Proliferator ◽  
Cb2 Receptors ◽  
Anti Inflammatory

Coronavirus disease (COVID-19), caused by novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing pandemic and presents a public health emergency. It has affected millions of people and continues to affect more, despite tremendous social preventive measures. Identifying candidate drugs for the prevention and treatment of COVID-19 is crucial. The pathogenesis and the complications with advanced infection mainly involve an immune-inflammatory cascade. Therefore, therapeutic strategy relies on suppressing infectivity and inflammation, along with immune modulation. One of the most promising therapeutic targets for the modulation of immune-inflammatory responses is the endocannabinoid system, particularly the activation of cannabinoid type 2 receptors (CB2R), a G-protein coupled receptor which mediates the anti-inflammatory properties by modulating numerous signaling pathways. To pharmacologically activate the CB2 receptors, a naturally occurring cannabinoid ligand, beta-caryophyllene (BCP), received attention due to its potent anti-inflammatory, antiviral, and immunomodulatory properties. BCP is recognized as a full selective functional agonist on CB2 receptors and produces therapeutic effects by activating CB2 and the nuclear receptors, peroxisome proliferator-activated receptors (PPARs). BCP is regarded as the first dietary cannabinoid with abundant presence across cannabis and non-cannabis plants, including spices and other edible plants. BCP showed tissue protective properties and favorably modulates numerous signaling pathways and inhibits inflammatory mediators, including cytokines, chemokines, adhesion molecules, prostanoids, and eicosanoids. Based on its pharmacological properties, molecular mechanisms, and the therapeutic potential of BCP as an immunomodulator, anti-inflammatory, organ-protective, and antiviral, we hypothesize that BCP could be a promising therapeutic and/or preventive candidate to target the triad of infection, immunity, and inflammation in COVID-19. In line with numerous studies that proposed the potential of cannabinoids in COVID-19, BCP may be a novel candidate compound for pharmaceutical and nutraceutical development due to its unique functional receptor selectivity, wide availability and accessibility, dietary bioavailability, nonpsychoactivity, and negligible toxicity along with druggable properties, including favorable pharmacokinetic and physicochemical properties. Based on reasonable pharmacological mechanisms and therapeutic properties, we speculate that BCP has potential to be investigated against COVID-19 and will inspire further preclinical and clinical studies.

scholarly journals Innovative Therapeutic Potential of Cannabinoid Receptors as Targets in Alzheimer’s Disease and Less Well-Known Diseases

2019 ◽  
Vol 26 (18) ◽  
pp. 3300-3340 ◽  
Author(s):  
Juan A. Páez ◽  
Nuria E. Campillo
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Endocrine System ◽  
Endocannabinoid System ◽  
Energy Regulation ◽  
Endogenous Ligands

: The discovery of cannabinoid receptors at the beginning of the 1990s, CB1 cloned in 1990 and CB2 cloned in 1993, and the availability of selective and potent cannabimimetics could only be justified by the existence of endogenous ligands that are capable of binding to them. Thus, the characterisation and cloning of the first cannabinoid receptor (CB1) led to the isolation and characterisation of the first endocannabinoid, arachidonoylethanolamide (AEA), two years later and the subsequent identification of a family of lipid transmitters known as the fatty acid ester 2-arachidonoylglycerol (2-AG). : The endogenous cannabinoid system is a complex signalling system that comprises transmembrane endocannabinoid receptors, their endogenous ligands (the endocannabinoids), the specific uptake mechanisms and the enzymatic systems related to their biosynthesis and degradation. : The endocannabinoid system has been implicated in a wide diversity of biological processes, in both the central and peripheral nervous systems, including memory, learning, neuronal development, stress and emotions, food intake, energy regulation, peripheral metabolism, and the regulation of hormonal balance through the endocrine system. : In this context, this article will review the current knowledge of the therapeutic potential of cannabinoid receptor as a target in Alzheimer’s disease and other less well-known diseases that include, among others, multiple sclerosis, bone metabolism, and Fragile X syndrome. : The therapeutic applications will be addressed through the study of cannabinoid agonists acting as single drugs and multi-target drugs highlighting the CB2 receptor agonist.

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