Localisation of Cannabinoid and Cannabinoid-Related Receptors in the Horse Ileum

Journal of Equine Veterinary Science“Colic is a common digestive disorder in horses and one of the most urgent problems in equine medicine. A growing body of literature has indicated that the activation of cannabinoid receptors could exert beneficial effects on gastrointestinal inflammation and visceral hypersensitivity.

The localisation of cannabinoid and cannabinoid-related receptors in the intestine of the horse has not yet been investigated. The purpose of this study was to immunohistochemically localise the cellular distribution of canonical and putative cannabinoid receptors in the ileum of healthy horses.

Distal ileum specimens were collected from six horses at the slaughterhouse. The tissues were fixed and processed to obtain cryosections which were used to investigate the immunoreactivity of canonical cannabinoid receptors 1 (CB1R) and 2 (CB2R), and three putative cannabinoid-related receptors: nuclear peroxisome proliferator-activated receptor-alpha (PPARα), transient receptor potential ankyrin 1 and serotonin 5-HT1a receptor (5-HT1aR).

Cannabinoid and cannabinoid-related receptors showed a wide distribution in the ileum of the horse.

The epithelial cells showed immunoreactivity for CB1R, CB2R and 5-HT1aR. Lamina propria inflammatory cells showed immunoreactivity for CB2R and 5-HT1aR. The enteric neurons showed immunoreactivity for CB1R, transient receptor potential ankyrin 1 and PPARα. The enteric glial cells showed immunoreactivity for CB1R and PPARα. The smooth muscle cells of the tunica muscularis and the blood vessels showed immunoreactivity for PPARα.

The present study represents a histological basis which could support additional studies regarding the distribution of cannabinoid receptors during gastrointestinal inflammatory diseases as well as studies assessing the effects of non-psychotic cannabis-derived molecules in horses for the management of intestinal diseases.”

https://pubmed.ncbi.nlm.nih.gov/34416995/

“Horses are often affected by gastrointestinal pathologies. Researchers are searching for new therapies for equine gastrointestinal diseases. New products with cannabinoid receptor agonists have been produced for horses. Cannabinoid receptors showed a wide distribution in the ileum of the horse. Activation of cannabinoids receptors could attenuate intestinal inflammation.”

https://www.sciencedirect.com/science/article/abs/pii/S073708062100318X?via%3Dihub

 

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Use of complementary therapies for chronic pain management in patients with reported Ehlers-Danlos syndrome or hypermobility spectrum disorders

American Journal of Medical Genetics Part A“Ehlers-Danlos Syndromes (EDS) and related Hypermobility Spectrum Disorders (HSD) are debilitating connective tissue disorders that feature a prominent pain component for which there are limited therapeutic options for pain management.

Consequently, many patients try various non-prescribed treatments, including complementary and alternative therapies that have not been well studied in the EDS/HSD patient population. We surveyed over 500 individuals through the EDS Society who reported having been diagnosed with EDS or HSD to ascertain what complementary and alternative therapies were used and their reported effectiveness in alleviating pain and improving quality of life.

Specifically, we focused on the use of traditional Chinese therapies, herbal medications, and marijuana.

The most commonly reported therapies, used by 70-92% of participants, were non-steroidal anti-inflammatory drugs, acetaminophen, opioids, and physical therapy.

Therapies rated by participants as most efficacious were opioids, physical therapy, and marijuana with 10-24% of those using these therapies rating them as extremely helpful.

Patient-initiated complementary therapy use in EDS/HSD patients is widespread at 56%. Complementary therapies were largely utilized by EDS/HSD patients with higher reported pain levels. Providers caring for EDS/HSD patients should be aware of these data showing broad usage of predominantly non-prescribed therapies and be prepared to consider such usage in working collaboratively with these patients to develop comprehensive treatment plans to manage their chronic pain complications.”

https://pubmed.ncbi.nlm.nih.gov/32909698/

https://onlinelibrary.wiley.com/doi/10.1002/ajmg.a.61837

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

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

molecules-logo“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.”

https://pubmed.ncbi.nlm.nih.gov/34063214/

https://www.mdpi.com/1420-3049/26/9/2668

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Topical Cannabis-Based Medicines – A Novel Adjuvant Treatment for Venous Leg Ulcers: An Open-Label Trial

“Venous Leg Ulcers are highly prevalent lower limb integumentary wounds that remain challenging to heal despite the use of evidence-based compression therapies. A multitude of adjuvant treatments have been studied but none have demonstrated enough efficacy to gain adoption into treatment guidelines.

Global attention on cannabis-based therapies is increasing and has been driven by quantum scientific advancements in the understanding of the endocannabinoid signalling system. Topical Cannabis-Based Medicines represent a novel treatment paradigm for venous leg ulcers in terms of promoting wound closure.

Fourteen complex patients with sixteen recalcitrant leg ulcers were treated with Topical Cannabis-Based Medicines in conjunction with compression bandaging, every second day, to both wound bed and peri-wound tissues. The cohort had a mean age of 75.8 years and was medically complex as reflected by a mean M3 multimorbidity index score of 2.94 and a mean Palliative Performance Scale score of 67.1%.

Complete wound closure, defined being fully epithelialized, was achieved among 11 patients (79%) and 13 wounds (81%) within a median of 34 days. All three remaining patients demonstrated progressive healing trends but were lost to follow-up. The treatments were well tolerated, and no significant adverse reactions were experienced.

The rapid wound closure of previously non-healing venous leg ulcers among elderly and highly complex patients suggests that Topical Cannabis-Based Medicines may become effective adjuvants in conjunction with compression therapy. This may also indicate that they may have an even broader role within integumentary and wound management. Therefore, this treatment paradigm warrants being subjected to controlled trials.”

https://pubmed.ncbi.nlm.nih.gov/34013652/

https://onlinelibrary.wiley.com/doi/10.1111/exd.14395

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Cannabinoid Receptor Type-2 in B Cells Is Associated with Tumor Immunity in Melanoma

cancers-logo“Agents targeting the endocannabinoid system (ECS) have gained attention as potential cancer treatments. Given recent evidence that cannabinoid receptor 2 (CB2R) regulates lymphocyte development and inflammation, we performed studies on CB2R in the immune response against melanoma. Analysis of The Cancer Genome Atlas (TCGA) data revealed a strong positive correlation between CB2R expression and survival, as well as B cell infiltration in human melanoma. In a murine melanoma model, CB2R expression reduced the growth of melanoma as well as the B cell frequencies in the tumor microenvironment (TME), compared to CB2R-deficient mice. In depth analysis of tumor-infiltrating B cells using single-cell RNA sequencing suggested a less differentiated phenotype in tumors from Cb2r-/- mice. Thus, in this study, we demonstrate for the first time a protective, B cell-mediated role of CB2R in melanoma. This gained insight might assist in the development of novel, CB2R-targeted cancer therapies.”

https://pubmed.ncbi.nlm.nih.gov/33923757/

“In this study we investigated the role of cannabinoid receptor 2 (CB2R) on immune cells in melanoma and found significantly improved overall survival in patients with high intra-tumoral CB2R gene expression. In human melanoma, CB2R is predominantly expressed in B cells, as shown using a previously published single-cell RNA sequencing (scRNA-seq) dataset and by performing RNAscope. In a murine melanoma model, tumor growth was enhanced in CB2R-deficient mice. In-depth analysis of tumor-infiltrating lymphocytes using scRNA-seq showed less differentiated B cells in CB2R-deficient tumors, favoring the induction of regulatory T cells (Treg) and an immunosuppressive tumor microenvironment. Taken together, these data indicate a central role of CB2R on B cells in regulating tumor immunity. These results contribute to the understanding of the role of CB2R in tumor immunity and facilitate the development of new CB2R-targeted anti-cancer drugs.”

https://www.mdpi.com/2072-6694/13/8/1934

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Repurposing Cannabidiol as a Potential Drug Candidate for Anti-Tumor Therapies

biomolecules-logo“In recent years, evidence has accumulated that cannabinoids-especially the non-psychoactive compound, cannabidiol (CBD)-possess promising medical and pharmacological activities that might qualify them as potential anti-tumor drugs. This review is based on multiple studies summarizing different mechanisms for how CBD can target tumor cells including cannabinoid receptors or other constituents of the endocannabinoid system, and their complex activation of biological systems that results in the inhibition of tumor growth. CBD also participates in anti-inflammatory activities which are related to tumor progression, as demonstrated in preclinical models. Although the numbers of clinical trials and tested tumor entities are limited, there is clear evidence that CBD has anti-tumor efficacy and is well tolerated in human cancer patients. In summary, it appears that CBD has potential as a neoadjuvant and/or adjuvant drug in therapy for cancer.”

https://pubmed.ncbi.nlm.nih.gov/33921049/

“It has been shown that CBD, either alone or in combination with other therapies, has the potential to act as a novel anti-tumor, anti-inflammatory and anti-pain drug in preclinical studies and first clinical trials. A few clinical trials have now demonstrated beneficial pharmacokinetic and pharmacodynamic characteristics of the drug, and some anti-tumor activities at well-tolerated doses. Therefore, it can be assumed that CBD might be considered a potential candidate for neoadjuvant and/or adjuvant interventions in oncology.”

https://www.mdpi.com/2218-273X/11/4/582/htm

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Cannabidiol Treatment Results in a Common Gene Expression Response Across Aggressive Cancer Cells from Various Origins

View details for Cannabis and Cannabinoid Research cover image“We previously reported that cannabidiol (CBD), a cannabinoid with a low toxicity profile, downregulated the expression of the prometastatic gene inhibitor of DNA binding 1 (ID1) in cancer cells, leading to inhibition of tumor progression in vivo. While CBD is broadly used, including in the self-medication of cancer patients, and CBD-based therapies are undergoing clinical evaluation for cancer treatment, its mechanisms of action are still poorly understood. 

Methods: In this study, using microarray analysis and Western blot analysis for validation, we attempted to identify the full spectrum of genes regulated by CBD across various aggressive cancer cell lines, including the breast, brain, head and neck, and prostate. 

Results: We confirmed that ID1 was a major target downregulated by CBD and also discovered that CBD inhibited FOXM1 (Forkhead box M1), a transcriptional activator involved in cell proliferation, while simultaneously upregulating GDF15 (growth differentiation factor 15), a cytokine associated with tissue differentiation. 

Conclusion: Our results suggest that, by modulating expression of shared key cancer-driving genes, CBD could represent a promising nontoxic therapeutic for treating tumors of various origins.”

https://pubmed.ncbi.nlm.nih.gov/33912679/

https://www.liebertpub.com/doi/10.1089/can.2019.0081

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Cannabigerol Is a Potential Therapeutic Agent in a Novel Combined Therapy for Glioblastoma

cells-logo“Glioblastoma is the most aggressive cancer among primary brain tumours. As with other cancers, the incidence of glioblastoma is increasing; despite modern therapies, the overall mean survival of patients post-diagnosis averages around 16 months, a figure that has not changed in many years. Cannabigerol (CBG) has only recently been reported to prevent the progression of certain carcinomas and has not yet been studied in glioblastoma. Here, we have compared the cytotoxic, apoptotic, and anti-invasive effects of the purified natural cannabinoid CBG together with CBD and THC on established differentiated glioblastoma tumour cells and glioblastoma stem cells. CBG and THC reduced the viability of both types of cells to a similar extent, whereas combining CBD with CBG was more efficient than with THC. CBD and CBG, both alone and in combination, induced caspase-dependent cell apoptosis, and there was no additive THC effect. Of note, CBG inhibited glioblastoma invasion in a similar manner to CBD and the chemotherapeutic temozolomide. We have demonstrated that THC has little added value in combined-cannabinoid glioblastoma treatment, suggesting that this psychotropic cannabinoid should be replaced with CBG in future clinical studies of glioblastoma therapy.”

https://pubmed.ncbi.nlm.nih.gov/33562819/

“Among primary brain tumours, glioblastoma is the most aggressive. As early relapses are unavoidable despite standard-of-care treatment, the cannabinoids delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) alone or in combination have been suggested as a combined treatment strategy for glioblastomas. However, the known psychoactive effects of THC hamper its medical applications in these patients with potential cognitive impairment due to the progression of the disease. Therefore, nontoxic cannabigerol (CBG), being recently shown to exhibit anti-tumour properties in some carcinomas, is assayed here for the first time in glioblastoma with the aim to replace THC. We indeed found CBG to effectively impair the relevant hallmarks of glioblastoma progression, with comparable killing effects to THC and in addition inhibiting the invasion of glioblastoma cells. Moreover, CBG can destroy therapy-resistant glioblastoma stem cells, which are the root of cancer development and extremely resistant to various other treatments of this lethal cancer. CBG should present a new yet unexplored adjuvant treatment strategy of glioblastoma.”

https://www.mdpi.com/2073-4409/10/2/340

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Phytocannabinoid Pharmacology: Medicinal Properties of Cannabis sativa Constituents Aside from the “Big Two”

 Go to Volume 0, Issue 0“Plant-based therapies date back centuries. Cannabis sativa is one such plant that was used medicinally up until the early part of the 20th century.

Although rich in diverse and interesting phytochemicals, cannabis was largely ignored by the modern scientific community due to its designation as a schedule 1 narcotic and restrictions on access for research purposes. There was renewed interest in the early 1990s when the endocannabinoid system (ECS) was discovered, a complex network of signaling pathways responsible for physiological homeostasis. Two key components of the ECS, cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2), were identified as the molecular targets of the phytocannabinoid Δ9-tetrahydrocannabinol (Δ9-THC).

Restrictions on access to cannabis have eased worldwide, leading to a resurgence in interest in the therapeutic potential of cannabis. Much of the focus has been on the two major constituents, Δ9-THC and cannabidiol (CBD). Cannabis contains over 140 phytocannabinoids, although only a handful have been tested for pharmacological activity. Many of these minor cannabinoids potently modulate receptors, ionotropic channels, and enzymes associated with the ECS and show therapeutic potential individually or synergistically with other phytocannabinoids.

The following review will focus on the pharmacological developments of the next generation of phytocannabinoid therapeutics.”

https://pubmed.ncbi.nlm.nih.gov/33356248/

https://pubs.acs.org/doi/10.1021/acs.jnatprod.0c00965

Abstract Image

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Healing autism spectrum disorder with cannabinoids: a neuroinflammatory story

 Neuroscience & Biobehavioral Reviews“Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with a multifactorial etiology. Latest researches are raising the hypothesis of a link between the onset of the main behavioral symptoms of ASD and the chronic neuroinflammatory condition of the autistic brain; increasing evidence of this connection is shedding light on new possible players in the pathogenesis of ASD.

The endocannabinoid system (ECS) has a key role in neurodevelopment as well as in normal inflammatory responses and it is not surprising that many preclinical and clinical studies account for alterations of the endocannabinoid signaling in ASD. These findings lay the foundation for a better understanding of the neurochemical mechanisms underlying ASD and for new therapeutic attempts aimed at exploiting the renowned anti-inflammatory properties of cannabinoids to treat pathologies encompassed in the autistic spectrum.

This review discusses the current preclinical and clinical evidence supporting a key role of the ECS in the neuroinflammatory state that characterizes ASD, providing hints to identify new biomarkers in ASD and promising therapies for the future.”

https://pubmed.ncbi.nlm.nih.gov/33358985/

“Autism spectrum disorder has a multifactorial and complex etiology. Changes in the endocannabinoid system are found in autistic patients. Neuroinflammation is detected in autistic patients. The endocannabinoid system has a key role in neuroinflammation. Future therapies exploiting cannabinoid drugs.”

https://www.sciencedirect.com/science/article/abs/pii/S0149763420306850?via%3Dihub

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous