New Advances of Cannabinoid Receptors in Health and Disease

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 15 July 2024 | Viewed by 13845

Special Issue Editor


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Guest Editor
1. Department of Psychiatry, New York University Langone Medical Center, New York City, NY, USA
2. Scientist, Faculty at Columbia University Medical Center, Center for Dementia Research, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA
Interests: endocannabinoids; synaptic plasticity; FASD; AUD; neurodegeneration; learning and memory; epigenetics; gene expression; behavior
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Special Issue Information

Dear Colleagues,

Over the last 30 years, the endocannabinoid system (that includes cannabinoid receptors) has become an imperative neuromodulatory system having been shown to play an essential role in health and diseases. Cannabinoid receptors have been implicated in multiple pathophysiological events, ranging from addiction, alcohol abuse, and neurodegeneration to memory-related disorders. Significant knowledge has been accomplished over the last 25 years. However, much more research is still indispensable to fully appreciate the complex functions of cannabinoid receptors, particularly in vivo, and to unravel their true potential as a source of therapeutic targets.

This Special Issue of Biomolecules aims to present a collection of studies focusing on the most recent advancements in cannabinoid receptor structure, signaling, and function in health and disease, including developmental and adult-associated research. Authors are invited to submit cutting-edge reviews, original research articles, and meta-analyses of large existing datasets advancing the field towards a greater understanding of its fundamental and pathophysiological mechanisms. Publication topics include, but are not limited to, studies concerning epidemiology, cancer biology, neuropsychology, neurobehavior, neuropharmacology, epigenetics, genetics and genomics, brain imaging, molecular neurobiology, experimental models, and clinical investigations in the format of full-length reviews or original articles. However, other formats reduced in length could also be considered, such as brief reports, short notes, communications, or commentaries, as long as the manuscript presents innovative and perceptive content that competently suits the topic of this Special Issue.

Dr. Balapal S. Basavarajappa
Guest Editor

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Keywords

  • neurodegeneration
  • alcohol
  • addiction
  • signaling
  • structure–function

Published Papers (6 papers)

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Research

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17 pages, 2258 KiB  
Article
Effects of Cannabidiol, ∆9-Tetrahydrocannabinol, and WIN 55-212-22 on the Viability of Canine and Human Non-Hodgkin Lymphoma Cell Lines
by Saba Omer, Suhrud Pathak, Mahmoud Mansour, Rishi Nadar, Dylan Bowen, Muralikrishnan Dhanasekaran, Satyanarayana R. Pondugula and Dawn Boothe
Biomolecules 2024, 14(4), 495; https://doi.org/10.3390/biom14040495 - 19 Apr 2024
Viewed by 257
Abstract
In our previous study, we demonstrated the impact of overexpression of CB1 and CB2 cannabinoid receptors and the inhibitory effect of endocannabinoids (2-arachidonoylglycerol (2-AG) and Anandamide (AEA)) on canine (Canis lupus familiaris) and human (Homo sapiens) non-Hodgkin lymphoma [...] Read more.
In our previous study, we demonstrated the impact of overexpression of CB1 and CB2 cannabinoid receptors and the inhibitory effect of endocannabinoids (2-arachidonoylglycerol (2-AG) and Anandamide (AEA)) on canine (Canis lupus familiaris) and human (Homo sapiens) non-Hodgkin lymphoma (NHL) cell lines’ viability compared to cells treated with a vehicle. The purpose of this study was to demonstrate the anti-cancer effects of the phytocannabinoids, cannabidiol (CBD) and ∆9-tetrahydrocannabinol (THC), and the synthetic cannabinoid WIN 55-212-22 (WIN) in canine and human lymphoma cell lines and to compare their inhibitory effect to that of endocannabinoids. We used malignant canine B-cell lymphoma (BCL) (1771 and CLB-L1) and T-cell lymphoma (TCL) (CL-1) cell lines, and human BCL cell line (RAMOS). Our cell viability assay results demonstrated, compared to the controls, a biphasic effect (concentration range from 0.5 μM to 50 μM) with a significant reduction in cancer viability for both phytocannabinoids and the synthetic cannabinoid. However, the decrease in cell viability in the TCL CL-1 line was limited to CBD. The results of the biochemical analysis using the 1771 BCL cell line revealed a significant increase in markers of oxidative stress, inflammation, and apoptosis, and a decrease in markers of mitochondrial function in cells treated with the exogenous cannabinoids compared to the control. Based on the IC50 values, CBD was the most potent phytocannabinoid in reducing lymphoma cell viability in 1771, Ramos, and CL-1. Previously, we demonstrated the endocannabinoid AEA to be more potent than 2-AG. Our study suggests that future studies should use CBD and AEA for further cannabinoid testing as they might reduce tumor burden in malignant NHL of canines and humans. Full article
(This article belongs to the Special Issue New Advances of Cannabinoid Receptors in Health and Disease)
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11 pages, 1160 KiB  
Article
Non-Psychoactive Cannabinoid Modulation of Nociception and Inflammation Associated with a Rat Model of Pulpitis
by Elana Y. Laks, Hongbo Li and Sara Jane Ward
Biomolecules 2023, 13(5), 846; https://doi.org/10.3390/biom13050846 - 16 May 2023
Cited by 1 | Viewed by 2105
Abstract
Despite advancements in dental pain management, one of the most common reasons for emergency dental care is orofacial pain. Our study aimed to determine the effects of non-psychoactive Cannabis constituents in the treatment of dental pain and related inflammation. We tested the therapeutic [...] Read more.
Despite advancements in dental pain management, one of the most common reasons for emergency dental care is orofacial pain. Our study aimed to determine the effects of non-psychoactive Cannabis constituents in the treatment of dental pain and related inflammation. We tested the therapeutic potential of two non-psychoactive Cannabis constituents, cannabidiol (CBD) and β-caryophyllene (β-CP), in a rodent model of orofacial pain associated with pulp exposure. Sham or left mandibular molar pulp exposures were performed on Sprague Dawley rats treated with either vehicle, the phytocannabinoid CBD (5 mg/kg i.p.) or the sesquiterpene β-CP (30 mg/kg i.p.) administered 1 h pre-exposure and on days 1, 3, 7, and 10 post-exposure. Orofacial mechanical allodynia was evaluated at baseline and post-pulp exposure. Trigeminal ganglia were harvested for histological evaluation at day 15. Pulp exposure was associated with significant orofacial sensitivity and neuroinflammation in the ipsilateral orofacial region and trigeminal ganglion. β-CP but not CBD produced a significant reduction in orofacial sensitivity. β-CP also significantly reduced the expression of the inflammatory markers AIF and CCL2, while CBD only decreased AIF expression. These data represent the first preclinical evidence that non-psychoactive cannabinoid-based pharmacotherapy may provide a therapeutic benefit for the treatment of orofacial pain associated with pulp exposure. Full article
(This article belongs to the Special Issue New Advances of Cannabinoid Receptors in Health and Disease)
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Review

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13 pages, 988 KiB  
Review
The Main Therapeutic Applications of Cannabidiol (CBD) and Its Potential Effects on Aging with Respect to Alzheimer’s Disease
by Václav Trojan, Leoš Landa, Alexandra Šulcová, Jiří Slíva and Radovan Hřib
Biomolecules 2023, 13(10), 1446; https://doi.org/10.3390/biom13101446 - 26 Sep 2023
Viewed by 2163
Abstract
The use of cannabinoids (substances contained specifically in hemp plants) for therapeutic purposes has received increased attention in recent years. Presently, attention is paid to two main cannabinoids: delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). With respect to the psychotropic effects and dependence potential of [...] Read more.
The use of cannabinoids (substances contained specifically in hemp plants) for therapeutic purposes has received increased attention in recent years. Presently, attention is paid to two main cannabinoids: delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). With respect to the psychotropic effects and dependence potential of THC (though it is very mild), its use is associated with certain restrictions, and thus the therapeutic properties of CBD are frequently emphasized because there are no limitations associated with the risk of dependence. Therefore, this review covers the main pharmacodynamic and pharmacokinetic features of CBD (including characteristics of endocannabinoidome) with respect to its possible beneficial effects on selected diseases in clinical practice. A substantial part of the text deals with the main effects of CBD on aging, including Alzheimer’s disease and related underlying mechanisms. Full article
(This article belongs to the Special Issue New Advances of Cannabinoid Receptors in Health and Disease)
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45 pages, 1740 KiB  
Review
Cannabinoids in Medicine: A Multifaceted Exploration of Types, Therapeutic Applications, and Emerging Opportunities in Neurodegenerative Diseases and Cancer Therapy
by Victor Voicu, Felix-Mircea Brehar, Corneliu Toader, Razvan-Adrian Covache-Busuioc, Antonio Daniel Corlatescu, Andrei Bordeianu, Horia Petre Costin, Bogdan-Gabriel Bratu, Luca-Andrei Glavan and Alexandru Vlad Ciurea
Biomolecules 2023, 13(9), 1388; https://doi.org/10.3390/biom13091388 - 14 Sep 2023
Cited by 6 | Viewed by 3088
Abstract
In this review article, we embark on a thorough exploration of cannabinoids, compounds that have garnered considerable attention for their potential therapeutic applications. Initially, this article delves into the fundamental background of cannabinoids, emphasizing the role of endogenous cannabinoids in the human body [...] Read more.
In this review article, we embark on a thorough exploration of cannabinoids, compounds that have garnered considerable attention for their potential therapeutic applications. Initially, this article delves into the fundamental background of cannabinoids, emphasizing the role of endogenous cannabinoids in the human body and outlining their significance in studying neurodegenerative diseases and cancer. Building on this foundation, this article categorizes cannabinoids into three main types: phytocannabinoids (plant-derived cannabinoids), endocannabinoids (naturally occurring in the body), and synthetic cannabinoids (laboratory-produced cannabinoids). The intricate mechanisms through which these compounds interact with cannabinoid receptors and signaling pathways are elucidated. A comprehensive overview of cannabinoid pharmacology follows, highlighting their absorption, distribution, metabolism, and excretion, as well as their pharmacokinetic and pharmacodynamic properties. Special emphasis is placed on the role of cannabinoids in neurodegenerative diseases, showcasing their potential benefits in conditions such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and multiple sclerosis. The potential antitumor properties of cannabinoids are also investigated, exploring their potential therapeutic applications in cancer treatment and the mechanisms underlying their anticancer effects. Clinical aspects are thoroughly discussed, from the viability of cannabinoids as therapeutic agents to current clinical trials, safety considerations, and the adverse effects observed. This review culminates in a discussion of promising future research avenues and the broader implications for cannabinoid-based therapies, concluding with a reflection on the immense potential of cannabinoids in modern medicine. Full article
(This article belongs to the Special Issue New Advances of Cannabinoid Receptors in Health and Disease)
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21 pages, 3391 KiB  
Review
Antitumor Effects of Cannabis sativa Bioactive Compounds on Colorectal Carcinogenesis
by Rita Silva-Reis, Artur M. S. Silva, Paula A. Oliveira and Susana M. Cardoso
Biomolecules 2023, 13(5), 764; https://doi.org/10.3390/biom13050764 - 28 Apr 2023
Cited by 4 | Viewed by 3110
Abstract
Cannabis sativa is a multipurpose plant that has been used in medicine for centuries. Recently, considerable research has focused on the bioactive compounds of this plant, particularly cannabinoids and terpenes. Among other properties, these compounds exhibit antitumor effects in several cancer types, including [...] Read more.
Cannabis sativa is a multipurpose plant that has been used in medicine for centuries. Recently, considerable research has focused on the bioactive compounds of this plant, particularly cannabinoids and terpenes. Among other properties, these compounds exhibit antitumor effects in several cancer types, including colorectal cancer (CRC). Cannabinoids show positive effects in the treatment of CRC by inducing apoptosis, proliferation, metastasis, inflammation, angiogenesis, oxidative stress, and autophagy. Terpenes, such as β-caryophyllene, limonene, and myrcene, have also been reported to have potential antitumor effects on CRC through the induction of apoptosis, the inhibition of cell proliferation, and angiogenesis. In addition, synergy effects between cannabinoids and terpenes are believed to be important factors in the treatment of CRC. This review focuses on the current knowledge about the potential of cannabinoids and terpenoids from C. sativa to serve as bioactive agents for the treatment of CRC while evidencing the need for further research to fully elucidate the mechanisms of action and the safety of these compounds. Full article
(This article belongs to the Special Issue New Advances of Cannabinoid Receptors in Health and Disease)
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20 pages, 596 KiB  
Review
Molecular Insights into Epigenetics and Cannabinoid Receptors
by Balapal S. Basavarajappa and Shivakumar Subbanna
Biomolecules 2022, 12(11), 1560; https://doi.org/10.3390/biom12111560 - 26 Oct 2022
Cited by 7 | Viewed by 2447
Abstract
The actions of cannabis are mediated by G protein-coupled receptors that are part of an endogenous cannabinoid system (ECS). ECS consists of the naturally occurring ligands N-arachidonylethanolamine (anandamide) and 2-arachidonoylglycerol (2-AG), their biosynthetic and degradative enzymes, and the CB1 and CB2 [...] Read more.
The actions of cannabis are mediated by G protein-coupled receptors that are part of an endogenous cannabinoid system (ECS). ECS consists of the naturally occurring ligands N-arachidonylethanolamine (anandamide) and 2-arachidonoylglycerol (2-AG), their biosynthetic and degradative enzymes, and the CB1 and CB2 cannabinoid receptors. Epigenetics are heritable changes that affect gene expression without changing the DNA sequence, transducing external stimuli in stable alterations of the DNA or chromatin structure. Cannabinoid receptors are crucial candidates for exploring their functions through epigenetic approaches due to their significant roles in health and diseases. Epigenetic changes usually promote alterations in the expression of genes and proteins that can be evaluated by various transcriptomic and proteomic analyses. Despite the exponential growth of new evidence on the critical functions of cannabinoid receptors, much is still unknown regarding the contribution of various genetic and epigenetic factors that regulate cannabinoid receptor gene expression. Recent studies have identified several immediate and long-lasting epigenetic changes, such as DNA methylation, DNA-associated histone proteins, and RNA regulatory networks, in cannabinoid receptor function. Thus, they can offer solutions to many cellular, molecular, and behavioral impairments found after modulation of cannabinoid receptor activities. In this review, we discuss the significant research advances in different epigenetic factors contributing to the regulation of cannabinoid receptors and their functions under both physiological and pathological conditions. Increasing our understanding of the epigenetics of cannabinoid receptors will significantly advance our knowledge and could lead to the identification of novel therapeutic targets and innovative treatment strategies for diseases associated with altered cannabinoid receptor functions. Full article
(This article belongs to the Special Issue New Advances of Cannabinoid Receptors in Health and Disease)
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