Tag Archives: endocannabinoid system

The antitumor activity of cannabidiol on lung cancer cell lines A549 and H1299: the role of apoptosis

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Publication Cover“In the recent years, the application of new antitumor drugs has focused on the replacement of conventional chemotherapeutics with compounds derived from natural products.

Cannabidiol (CBD) is one of the 113 cannabinoids derived from the plant Cannabis sativa and is characterized with complex and not entirely understood biological function. Unlike the other most abundant cannabinoid in Cannabis sativa – tetrahydrocannabinol, cannabidiol has low affinity to the endocannabinoid receptors and the manifestation of its activity does not appear to rely on the endocannabinoid system.

Cannabidiol is used in the treatment of many diseases including some types of cancer.

The aim of our study was to evaluate the cytotoxic activity of cannabidiol and its effect on the process of programmed cell death. This process is directly involved in the antitumor effect of many drugs.

We found that CBD treatment led to a dose-dependant apoptosis increase in p53 positive A549 cells.

Several studies have demonstrated that cannabinoids also have antineoplastic effect and are usually accompanied with no negative side effects such as the ones produced by the conventional chemotherapy treatment.”

https://www.tandfonline.com/doi/full/10.1080/13102818.2021.1915870

The Endocannabinoid System: A Potential Target for the Treatment of Various Diseases

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ijms-logo“The Endocannabinoid System (ECS) is primarily responsible for maintaining homeostasis, a balance in internal environment (temperature, mood, and immune system) and energy input and output in living, biological systems.

In addition to regulating physiological processes, the ECS directly influences anxiety, feeding behaviour/appetite, emotional behaviour, depression, nervous functions, neurogenesis, neuroprotection, reward, cognition, learning, memory, pain sensation, fertility, pregnancy, and pre-and post-natal development.

The ECS is also involved in several pathophysiological diseases such as cancer, cardiovascular diseases, and neurodegenerative diseases. In recent years, genetic and pharmacological manipulation of the ECS has gained significant interest in medicine, research, and drug discovery and development.

The distribution of the components of the ECS system throughout the body, and the physiological/pathophysiological role of the ECS-signalling pathways in many diseases, all offer promising opportunities for the development of novel cannabinergic, cannabimimetic, and cannabinoid-based therapeutic drugs that genetically or pharmacologically modulate the ECS via inhibition of metabolic pathways and/or agonism or antagonism of the receptors of the ECS. This modulation results in the differential expression/activity of the components of the ECS that may be beneficial in the treatment of a number of diseases.

This manuscript in-depth review will investigate the potential of the ECS in the treatment of various diseases, and to put forth the suggestion that many of these secondary metabolites of Cannabis sativa L. (hereafter referred to as “C. sativa L.” or “medical cannabis”), may also have potential as lead compounds in the development of cannabinoid-based pharmaceuticals for a variety of diseases.”

https://pubmed.ncbi.nlm.nih.gov/34502379/

https://www.mdpi.com/1422-0067/22/17/9472

“Cannabis sativa L. as a Natural Drug Meeting the Criteria of a Multitarget Approach to Treatment”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7830475/

Lifestyle Interventions Improving Cannabinoid Tone During COVID-19 Lockdowns May Enhance Compliance With Preventive Regulations and Decrease Psychophysical Health Complications

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CrossFit | 190629“Studies investigating the psychosomatic effects of social isolation in animals have shown that one of the physiologic system that gets disrupted by this environment-affective change is the Endocannabinoid System. As the levels of endocannabinoids change in limbic areas and prefrontal cortex during stressful times, so is the subject more prone to fearful and negative thoughts and aggressive behavior. The interplay of social isolation on the hypothalamic-pituitary-adrenal axis and cannabinoid tone triggers a vicious cycle which further impairs the natural body’s homeostatic neuroendocrine levels and provokes a series of risk factors for developing health complications. In this paper, we explore the psychosomatic impact of prolonged quarantine in healthy individuals, and propose management and coping strategies that may improve endocannabinoid tone, such as integration of probiotics, cannabidiol, meditation, and physical exercise interventions with the aim of supporting interpersonal, individual, and professional adherence with COVID-19 emergency public measures whilst minimizing their psycho-physical impact.”

https://pubmed.ncbi.nlm.nih.gov/34335317/

https://www.frontiersin.org/articles/10.3389/fpsyt.2021.565633/full

 

Cannabis sativa L. as a Natural Drug Meeting the Criteria of a Multitarget Approach to Treatment

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ijms-logo“Cannabis sativa L. turned out to be a valuable source of chemical compounds of various structures, showing pharmacological activity. The most important groups of compounds include phytocannabinoids and terpenes.

The pharmacological activity of Cannabis (in epilepsy, sclerosis multiplex (SM), vomiting and nausea, pain, appetite loss, inflammatory bowel diseases (IBDs), Parkinson’s disease, Tourette’s syndrome, schizophrenia, glaucoma, and coronavirus disease 2019 (COVID-19)), which has been proven so far, results from the affinity of these compounds predominantly for the receptors of the endocannabinoid system (the cannabinoid receptor type 1 (CB1), type two (CB2), and the G protein-coupled receptor 55 (GPR55)) but, also, for peroxisome proliferator-activated receptor (PPAR), glycine receptors, serotonin receptors (5-HT), transient receptor potential channels (TRP), and GPR, opioid receptors.

The synergism of action of phytochemicals present in Cannabis sp. raw material is also expressed in their increased bioavailability and penetration through the blood-brain barrier. This review provides an overview of phytochemistry and pharmacology of compounds present in Cannabis extracts in the context of the current knowledge about their synergistic actions and the implications of clinical use in the treatment of selected diseases.”

https://pubmed.ncbi.nlm.nih.gov/33466734/

https://www.mdpi.com/1422-0067/22/2/778

In quest of a new therapeutic approach in COVID-19: the endocannabinoid system

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Publication Cover“The SARS-Cov-2 virus caused a high morbidity and mortality rate disease, that is the COVID-19 pandemic. Despite the unprecedented research interest in this field, the lack of specific treatments leads to severe complications in a high number of cases.

Current treatment includes antivirals, corticosteroids, immunoglobulins, antimalarials, interleukin-6 inhibitors, anti-GM-CSF, convalescent plasma, immunotherapy, antibiotics, circulation support, oxygen therapy, and circulation support. Due to the limited results, until specific treatments are available, other therapeutic approaches need to be considered.

The endocannabinoid system is found in multiple systems within the human body, including the immune system. Its activation can lead to beneficial results such as decreased viral entry, decreased viral replication, and a decrease in pro-inflammatory cytokines such as IL-2, IL-4, IL-6, IL-12, TNF-α, or IFN-γ. Moreover, endocannabinoid system activation can lead to an increase in anti-inflammatory cytokines, mainly represented by IL-10.

Overall, the cannabinoid system can potentially reduce pulmonary inflammation, increase the immunomodulatory effect, decrease PMN infiltration, reduce fibrosis, and decrease viral replication, as well as decrease the ‘cytokine storm’. Although the cannabinoid system has many mechanisms to provide certain benefits in the treatment of SARS-CoV-2 infected patients, research in this field is needed for a better understanding of the cannabinoid impact in this situation.”

https://pubmed.ncbi.nlm.nih.gov/33683968/

“Concerning the SARS-CoV-2 infection, the cannabinoid effects on the immune system have the potential to limit the abnormal function of the immune system and therefore decrease the overall mortality.”

https://www.tandfonline.com/doi/full/10.1080/03602532.2021.1895204

Cannabinoids for skin diseases and hair regrowth

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“The use of cannabis for skin diseases and hair regrowth is at the preliminary stage.

Legalization: Many countries have approved cannabis for medical use; however, four countries Canada, Uruguay, South Africa, and Georgia have legalized it for both medical and recreational purposes.

The endocannabinoid system: The endocannabinoid system may maintain skin homeostasis; two notable endocannabinoids include 2-Arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (AEA).

Routes of administration and pharmacokinetics: Topical cannabinoids can avoid the first-pass metabolism and reduce respiratory side effects; however, the high hydrophobicity of cannabinoids may hinder percutaneous absorption.

Skin disorders and hair growth: Human clinical studies suggest that cannabinoids may be used in eczema, acne, pruritus, and systemic sclerosis treatment. Cannabidiol (CBD) may enhance hair growth via multiple mechanisms.

Safety: Topical cannabis may cause mild side effects such as pruritus, burning, erythema, and stinging; they are relatively safer than inhalation and oral cannabis. Cannabis use may be associated with allergic symptoms and reduced immune response to live vaccination.

Cannabinoids in practice: Despite growing interest, dermatologists should be cautious prescribing cannabinoids due to insufficient clinical data on both efficacy and safety.”

https://pubmed.ncbi.nlm.nih.gov/34363728/

https://onlinelibrary.wiley.com/doi/10.1111/jocd.14352

 

An overview on plants cannabinoids endorsed with cardiovascular effects

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Biomedicine & Pharmacotherapy“Nowadays cardiovascular diseases (CVDs) are the major causes for the reduction of the quality of life.

The endocannabinoid system is an attractive therapeutic target for the treatment of cardiovascular disorders due to its involvement in vasomotor control, cardiac contractility, blood pressure and vascular inflammation. Alteration in cannabinoid signalling can be often related to cardiotoxicity, circulatory shock, hypertension, and atherosclerosis.

Plants have been the major sources of medicines until modern eras in which researchers are experiencing a rediscovery of natural compounds as novel therapeutics.

One of the most versatile plant is Cannabis sativa L., containing phytocannabinoids that may play a role in the treatment of CVDs.

The aim of this review is to collect and investigate several less studied plants rich in cannabinoid-like active compounds able to interact with cannabinoid system; these plants may play a pivotal role in the treatment of disorders related to the cardiovascular system.”

https://pubmed.ncbi.nlm.nih.gov/34332376/

“Cannabis sativa L. is the most investigated source of phytocannabinoids. Other plants are a rich source of cannabinoid-like compounds. Cannabinoid-like compounds may interact with cannabinoid system. Most of them may exhibit a protective role on cardiovascular system.” 

https://www.sciencedirect.com/science/article/pii/S0753332221007459?via%3Dihub

 

Therapeutic Attributes of Endocannabinoid System against Neuro-Inflammatory Autoimmune Disorders

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molecules-logo“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.”

https://pubmed.ncbi.nlm.nih.gov/34205169/

https://www.mdpi.com/1420-3049/26/11/3389

Epigenetic Regulation of Cannabinoid-Mediated Attenuation of Inflammation and Its Impact on the Use of Cannabinoids to Treat Autoimmune Diseases

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ijms-logo“Chronic inflammation is considered to be a silent killer because it is the underlying cause of a wide range of clinical disorders, from cardiovascular to neurological diseases, and from cancer to obesity. In addition, there are over 80 different types of debilitating autoimmune diseases for which there are no cure. Currently, the drugs that are available to suppress chronic inflammation are either ineffective or overtly suppress the inflammation, thereby causing increased susceptibility to infections and cancer. Thus, the development of a new class of drugs that can suppress chronic inflammation is imperative.

Cannabinoids are a group of compounds produced in the body (endocannabinoids) or found in cannabis (phytocannabinoids) that act through cannabinoid receptors and various other receptors expressed widely in the brain and immune system. In the last decade, cannabinoids have been well established experimentally to mediate anti-inflammatory properties. Research has shown that they suppress inflammation through multiple pathways, including apoptosis and inducing immunosuppressive T regulatory cells (Tregs) and myeloid-derived suppressor cells (MDSCs).

Interestingly, cannabinoids also mediate epigenetic alterations in genes that regulate inflammation. In the current review, we highlight how the epigenetic modulations caused by cannabinoids lead to the suppression of inflammation and help identify novel pathways that can be used to target autoimmune diseases.”

https://pubmed.ncbi.nlm.nih.gov/34298921/

https://www.mdpi.com/1422-0067/22/14/7302

Cannabinoids and their derivatives in struggle against melanoma

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SpringerLink“Melanoma is one of the most aggressive malignances in human. Recently developed therapies improved overall survival rate, however, the treatment of melanoma still remains a challenging issue.

This review attempts to summarize recent advances in studies on cannabinoids used in the setting of melanoma treatment.

Conclusions after analysis of available data suggest that cannabinoids limit number of metastasis, and reduce growth of melanoma. The findings indicate that cannabinoids induce apoptosis, necrosis, autophagy, cell cycle arrest and exert significant interactions with tumor microenvironment.

Cannabinoids should be rather considered as a part of multi-targeted anti-tumor therapy instead of being standalone agent. Moreover, cannabinoids are likely to improve quality of life in patients with cancer, due to different supportive effects, like analgesia and/or anti-emetic effects.

In this review, it was pointed out that cannabinoids may be potentially useful in the melanoma therapy. Nevertheless, due to limited amount of data, great variety of cannabinoids available and lack of clinical trials, further studies are required to determine an exact role of cannabinoids in the treatment of melanoma.”

https://pubmed.ncbi.nlm.nih.gov/34264513/

“The endocannabinoid system is dysregulated in numerous pathological conditions, including malignancies. Recently, cannabinoids have received increasing amount of interest in the setting of treatment of various cancers.  Cannabinoids seem to be promising agents in the setting of melanoma treatment. In the case of melanoma, most important actions of cannabinoids described so far are decrease of cells viability by increase of apoptosis, necrosis and cell cycle arrest. Moreover, cannabinoids slow down disease progress by reduction of metastasis and tumor vascularization. Due to large variety of cannabinoids, there are many potential derivatives, which may be found useful in the therapy of melanoma.”

https://link.springer.com/article/10.1007%2Fs43440-021-00308-1