Tag Archives: therapeutic

The Endocannabinoid System Alleviates Pain in a Murine Model of Cancer-Induced Bone Pain.

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Journal of Pharmacology and Experimental Therapeutics: 372 (3)“Metastatic breast cancer is prevalent worldwide, and one of the most common sites of metastasis are long bones. Of patients with disease, the major symptom is pain, yet current medications fail to adequately result in analgesic efficacy and present major undesirable adverse effects.

In our study we investigate the potential of a novel monoacylglycerol lipase (MAGL) inhibitor, MJN110, in a murine model of cancer induced bone pain (CIBP). Literature has previously demonstrated that MAGL inhibitors function to increase the endogenous concentrations of 2-arachydonylglycerol, which then activate CB1 and CB2 receptors inhibiting inflammation and pain.

Together, these data support the application for MJN110 as a novel therapeutic for cancer induced bone pain.

SIGNIFICANCE STATEMENT: Current standard of care for metastatic breast cancer pain is opioid-based therapies with adjunctive chemotherapy, which have highly addictive and other deleterious side effects. The need for effective, non-opioid based therapies is essential and harnessing the endogenous cannabinoid system is proving to be a new target to treat various types of pain conditions. We present a novel drug targeting the endogenous cannabinoid system that is effective at reducing pain in a mouse model of metastatic breast cancer to bone.”

https://www.ncbi.nlm.nih.gov/pubmed/32054717

http://jpet.aspetjournals.org/content/early/2020/02/13/jpet.119.262337

Mechanisms of Cannabinoids and Potential Applicability to Skin Diseases.

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SpringerLink“The legalisation of cannabis in a growing number of jurisdictions has led to increasing interest in its potential therapeutic effects in a range of disorders, including cutaneous conditions. Cannabinoids have been used as natural medicines for centuries; however, their biological activity in the skin is a new area of study.

Recent data suggest that cannabinoids are involved in neuro-immuno-endocrine modulation of skin functioning, yet their effect on the features of dermatologic conditions is unclear. This article sought to review the mechanisms by which cannabinoids regulate skin functioning through the lens of relevance to treatment of dermatologic diseases looking at the effects of cannabinoids on a range of cellular activities and dermatologic conditions both in vitro and in vivo.

We identified studies demonstrating an inhibitory effect of cannabinoids on skin inflammation, proliferation, fibrosis, pain, and itch-biological mechanisms involved in the pathogenesis of many dermatologic conditions.

Cannabinoids have the potential to expand the therapeutic repertoire of a wide spectrum of skin disorders. Given their widespread unregulated use by the general public, basic and clinical studies are required to elucidate the effectiveness and long-term effects of topical and systemic cannabinoids in cutaneous disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/32060787
https://link.springer.com/article/10.1007%2Fs40261-020-00894-7

“The endocannabinoid system of the skin. A potential approach for the treatment of skin disorders.” https://www.ncbi.nlm.nih.gov/pubmed/30138623

Possible therapeutic applications of cannabis in the neuropsychopharmacology field.

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European Neuropsychopharmacology“Cannabis use induces a plethora of actions on the CNS via its active chemical ingredients, the so-called phytocannabinoids.

These compounds have been frequently associated with the intoxicating properties of cannabis preparations. However, not all phytocannabinoids are psychotropic, and, irrespective of whether they are psychotropic or not, they have also shown numerous therapeutic properties.

These properties are mostly associated with their ability to modulate the activity of an intercellular communication system, the so-called endocannabinoid system, which is highly active in the CNS and has been found altered in many neurological disorders.

Specifically, this includes the neuropsychopharmacology field, with diseases such as schizophrenia and related psychoses, anxiety-related disorders, mood disorders, addiction, sleep disorders, post-traumatic stress disorder, anorexia nervosa and other feeding-related disorders, dementia, epileptic syndromes, as well as autism, fragile X syndrome and other neurodevelopment-related disorders.

Here, we gather, from a pharmacological and biochemical standpoint, the recent advances in the study of the therapeutic relevance of the endocannabinoid system in the CNS, with especial emphasis on the neuropsychopharmacology field. We also illustrate the efforts that are currently being made to investigate at the clinical level the potential therapeutic benefits derived from elevating or inhibiting endocannabinoid signaling in animal models of neuropsychiatric disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/32057592

https://www.sciencedirect.com/science/article/abs/pii/S0924977X20300365?via%3Dihub

Inhibition of autophagic flux differently modulates cannabidiol-induced death in 2D and 3D glioblastoma cell cultures.

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 Scientific Reports“Radiotherapy combined with chemotherapy is the major treatment modality for human glioblastoma multiforme (GBM). GBMs eventually relapse after treatment and the average survival of GBM patients is less than two years.

There is some evidence that cannabidiol (CBD) can induce cell death and increases the radiosensitivity of GBM by enhancing apoptosis. Beside initiation of death, CBD has been demonstrated as an inducer of autophagy.

In the present study, we address the question whether CBD simultaneously induces a protective effect in GBM by upregulating autophagy. Addition of chloroquine that suppressed autophagic flux to 2D GBM cultures increased CBD-induced cell death, presenting proof for the protective autophagy.

Blockage of autophagy upregulated radiation-induced cytotoxicity but only modestly affected the levels of cell death in CBD- or CBD/γ-irradiated 3D GBM cultures. Furthermore, CBD enhanced the pro-apoptotic activities of JNK1/2 and MAPK p38 signaling cascades while partially downregulated the pro-survival PI3K-AKT cascade, thereby changing a balance between cell death and survival.

Suppression of JNK activation partially reduced CBD-induced cell death in 3D GBM cultures. In contrast, co-treatment of CBD-targeted cells with inhibitors of PI3K-AKT-NF-κB, IKK-NF-κB or JAK2-STAT3 pathways killed surviving GBM cells in both 2D and 3D cultures, potentially improving the therapeutic ratio of GBM.”

https://www.ncbi.nlm.nih.gov/pubmed/32060308

“Killing efficiency of cannabinoids (CBD, THC and their combination CBD+THC) against GBM in vitro and in animal experiments has been elucidated in numerous studies during the last 15 years. Additional investigations also confirmed a cytotoxic role of cannabinoids for several other types of cancer. A number of studies demonstrated the efficiency of combined treatments of cannabinoids together with γ-irradiation in both cell culture and in animal experiments.”

https://www.nature.com/articles/s41598-020-59468-4

Cannabidiol treatment in an adolescent with multiple substance abuse, social anxiety and depression.

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 “In this report, we present a case of a 16,9-year-old patient with multiple substance use disorder (cannabis, MDMA, cocaine, ecstacy), severe depression, social phobia and narcissistic personality disorder.We administered Cannabidiol (CBD) capsules in different dosages (starting dosage 100 mg up to 600 mg over 8 weeks) after unsuccessful treatment with antidepressants.

CBD was a safe and well tolerated medication for this patient. Upon treatment with CBD and cessation of the antidepressant medication, the patient improved regarding depressive as well as anxiety symptoms including simple phobias and symptoms of paranoia and dissociation.

Furthermore, the patient quit abusing illegal drugs including THC without showing withdrawal symptoms. This is the first report of CBD medication in a patient with multiple substance use disorder with a positive outcome.Until today it is not clear if CBD holds promise as a therapeutic option in substance use disorder as RCTs are lacking, but in this single case the substance seems to work in various domains.”

https://www.ncbi.nlm.nih.gov/pubmed/32052321

https://link.springer.com/article/10.1007%2Fs40211-020-00334-0

Cannabinoids in the Pathophysiology of Skin Inflammation.

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molecules-logo“Cannabinoids are increasingly-used substances in the treatment of chronic pain, some neuropsychiatric disorders and more recently, skin disorders with an inflammatory component.

This paper aims to detail and clarify the complex workings of cannabinoids in the molecular setting of the main dermatological inflammatory diseases, and their interactions with other substances with emerging applications in the treatment of these conditions. Also, the potential role of cannabinoids as antitumoral drugs is explored in relation to the inflammatory component of skin cancer.

In vivo and in vitro studies that employed either phyto-, endo-, or synthetic cannabinoids were considered in this paper. Cannabinoids are regarded with growing interest as eligible drugs in the treatment of skin inflammatory conditions, with potential anticancer effects, and the readiness in monitoring of effects and the facility of topical application may contribute to the growing support of the use of these substances.

Despite the promising early results, further controlled human studies are required to establish the definitive role of these products in the pathophysiology of skin inflammation and their usefulness in the clinical setting.”

https://www.ncbi.nlm.nih.gov/pubmed/32033005

https://www.mdpi.com/1420-3049/25/3/652

“Cannabinoid Signaling in the Skin: Therapeutic Potential of the “C(ut)annabinoid” System” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6429381/

Cannabinoid receptor 2 activation alleviates septic lung injury by promoting autophagy via inhibition of inflammatory mediator release.

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Cellular Signalling“Septic lung injury is one of main causes of high mortality in severe patients. Inhibition of excessive inflammatory response is considered as an effective strategy for septic lung injury.

Previous studies have shown that cannabinoid receptor 2 (CB2), a G protein-coupled receptor, play an important role in immunosuppression.

Whether CB2 can be used as a therapeutic target for septic lung injury is unclear. The aim of this study is to explore the role of CB2 in sepsis and its potential mechanism.

These results suggest that CB2 serves as a protective target for septic lung injury by decreasing inflammatory factors, which is associated with the enhancement of autophagy.”

https://www.ncbi.nlm.nih.gov/pubmed/32027949

“Activation of cannabinoid receptor 2 can alleviate sepsis-induced lung injury.”

https://www.sciencedirect.com/science/article/abs/pii/S0898656820300334?via%3Dihub

Endocannabinoids as Therapeutic Targets.

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Archives of Medical Research“Most of the drugs of abuse affect the brain by interacting with naturally expressed molecular receptors. Marihuana affects a series of receptors including cannabinoid receptor 1 (CB1R) and CB2R, among others. Endogenous molecules with cannabinoid activity interact with these receptors naturally. Receptors, ligands, synthesizing and degrading enzymes, as well as transporters, have been described.

This endocannabinoid system modulates behaviors and physiological processes, i.e. food intake, the sleep-waking cycle, learning and memory, motivation, and pain perception, among others. The rather broad distribution of endocannabinoids in the brain explains the different effects marihuana induces in its users. However, this very same anatomical and physiological distribution makes this system a useful target for therapeutic endeavors.

In this review, we briefly discuss the potential of small molecules that target the endocannabinoids as therapeutic tools to improve behaviors and treat illnesses. We believe that under medical supervision, endocannabinoid targets offer new advantages for patients for controlling multiple medical disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/32028095

https://www.sciencedirect.com/science/article/abs/pii/S0188440919304746?via%3Dihub

Medical Cannabis for Intractable Epilepsy in Childhood: A Review.

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 Logo of rmmj“In recent years, cannabis has been gaining increasing interest in both the medical research and clinical fields, with regard to its therapeutic effects in various disorders. One of the major fields of interest is its role as an anticonvulsant for refractory epilepsy, especially in the pediatric population. This paper presents and discusses the current accumulated knowledge regarding artisanal cannabis and Epidiolex®, a United States Food and Drug Administration (FDA)-approved pure cannabidiol (CBD), in epilepsy management in pediatrics, by reviewing the literature and raising debate regarding further research directions.”

https://www.ncbi.nlm.nih.gov/pubmed/32017679

Uncovering the hidden antibiotic potential of Cannabis.

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 Go to Volume 0, Issue ja“The spread of antimicrobial resistance continues to be a priority health concern worldwide, necessitating exploration of alternative therapies.

Cannabis sativa has long been known to contain antibacterial cannabinoids, but their potential to address antibiotic resistance has only been superficially investigated.

Here, we show that cannabinoids exhibit antibacterial activity against MRSA, inhibit its ability to form biofilms and eradicate pre-formed biofilms and stationary phase cells persistent to antibiotics.

We show that the mechanism of action of cannabigerol is through targeting the cytoplasmic membrane of Gram-positive bacteria and demonstrate in vivo efficacy of cannabigerol in a murine systemic infection model caused by MRSA.

We also show that cannabinoids are effective against Gram-negative organisms whose outer membrane is permeabilized, where cannabigerol acts on the inner membrane.

Finally, we demonstrate that cannabinoids work in combination with polymyxin B against multi-drug resistant Gram-negative pathogens, revealing the broad-spectrum therapeutic potential for cannabinoids.”

https://www.ncbi.nlm.nih.gov/pubmed/32017534

https://pubs.acs.org/doi/10.1021/acsinfecdis.9b00419