THC Total Health Care

A comprehensive research archive dedicated to the science of cannabis

Peripheral endocannabinoid signaling controls hyperphagia in western diet-induced obesity.

Posted on January 10, 2017 by David Worrell

“The endocannabinoid system in the brain and periphery plays a major role in controlling food intake and energy balance. We reported that tasting dietary fats was met with increased levels of the endocannabinoids, 2-arachidonoyl-sn-glycerol (2-AG) and anandamide, in the rat upper small intestine, and pharmacological inhibition of this local signaling event dose-dependently blocked sham feeding of fats. We now investigated the contribution of peripheral endocannabinoid signaling in hyperphagia associated with chronic consumption of a western-style diet in mice ([WD] i.e., high fat and sucrose). These results suggest that endogenous activity at peripheral CB₁Rs in WD mice is critical for driving hyperphagia. In support of this hypothesis, levels of 2-AG and anandamide in both, jejunum mucosa and plasma, of ad-libitum fed WD mice increased when compared to SC mice. Furthermore, expression of genes for primary components of the endocannabinoid system (i.e., cannabinoid receptors, and endocannabinoid biosynthetic and degradative enzymes) was dysregulated in WD mice when compared to SC mice. Our results suggest that hyperphagia associated with WD-induced obesity is driven by enhanced endocannabinoid signaling at peripheral CB₁Rs.” https://www.ncbi.nlm.nih.gov/pubmed/28065722]]>

The Endocannabinoid System and Anxiety.

Posted on January 8, 2017 by David Worrell

“The medical properties of Cannabis sativa is known for centuries. Since the discovery and characterization of the endogenous cannabinoid system, several studies have evaluated how cannabinoid compounds and, particularly, how the modulation of the endocannabinoid (eCB) system influences a wide range of functions, from metabolic to mental disorders. Cannabinoids and eCB system often exert opposite effects on several functions, such as anxiety. Although the mechanisms are not completely understood, evidence points to different factors influencing those effects. In this chapter, the recent advances in research about the relationship between eCB system and anxiety disorders in humans, as well as in animal models, will be discussed. The recent data addressing modulation of the eCBs in specific brain areas, such as the medial prefrontal cortex, amygdaloid complex, bed nucleus of stria terminalis, hippocampus, and dorsal periaqueductal gray, will be summarized. Finally, data from animal models addressing the mechanisms through which the eCB system modulates anxiety-related behavior dependent on stressful situations, such as the involvement of different receptors, distinct eCBs, modulation of neurotransmitters release, HPA axis and immune system activation, and plastic mechanisms, will also be discussed.” https://www.ncbi.nlm.nih.gov/pubmed/28061971]]>

Association Between Use of Cannabis in Adolescence and Weight Change into Midlife.

Posted on January 7, 2017 by David Worrell

“Cannabis use has been found to stimulate appetite and potentially promote weight gain via activation of the endocannabinoid system. Despite the fact that the onset of cannabis use is typically during adolescence, the association between adolescence cannabis use and long-term change in body weight is generally unknown. This study aims to examine the association between adolescence cannabis use and weight change to midlife, while accounting for the use of other substances. In conclusion, this study does not provide evidence of an association between adolescence cannabis use and weight change from adolescence to midlife.”

https://www.ncbi.nlm.nih.gov/pubmed/28060830

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Therapeutic Use of Cannabis in Inflammatory Bowel Disease.

Posted on January 6, 2017 by David Worrell

“The marijuana plant Cannabis sativa and its derivatives, cannabinoids, have grown increasingly popular as a potential therapy for inflammatory bowel disease (IBD). Studies have shown that modulation of the endocannabinoid system, which regulates various functions in the body and has been shown to play a key role in the pathogenesis of IBD, has a therapeutic effect in mouse colitis. The plant Cannabis sativa has been used in medicinal practice for thousands of years. Anecdotal reports have suggested a therapeutic role for cannabis in the treatment of IBD for hundreds of years. A case report from 1990 describes patients with IBD maintaining remission of disease via cannabis use. Cannabinoids appear to have a clear role in gut pathology and offer a potential target for drug intervention in the treatment of IBD. Cannabis seems to be of symptomatic benefit to patients often refractory to conventional medicines.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5193087/]]>

A user's guide to cannabinoid therapies in oncology.

Posted on January 5, 2017 by David Worrell

“”Cannabinoid” is the collective term for a group of chemical compounds that either are derived from the Cannabis plant, are synthetic analogues, or occur endogenously. Although cannabinoids interact mostly at the level of the currently recognized cannabinoid receptors, they might have cross reactivity, such as at opioid receptors. Patients with malignant disease represent a cohort within health care that have some of the greatest unmet needs despite the availability of a plethora of guideline-driven disease-modulating treatments and pain and symptom management options. Cannabinoid therapies are varied and versatile, and can be offered as pharmaceuticals (nabilone, dronabinol, and nabiximols), dried botanical material, and edible organic oils infused with cannabis extracts. Cannabinoid therapy regimens can be creative, involving combinations of all of the aforementioned modalities. Patients with malignant disease, at all points of their disease trajectory, could be candidates for cannabinoid therapies whether as monotherapies or as adjuvants. The most studied and established roles for cannabinoid therapies include pain, chemotherapy-induced nausea and vomiting, and anorexia. Moreover, given their breadth of activity, cannabinoids could be used to concurrently optimize the management of multiple symptoms, thereby reducing overall polypharmacy. The use of cannabinoid therapies could be effective in improving quality of life and possibly modifying malignancy by virtue of direct effects and in improving compliance or adherence with disease-modulating treatments such as chemotherapy and radiation therapy.” https://www.ncbi.nlm.nih.gov/pubmed/28050136

“The Cannabis plant has a long and colourful history that spans more than 5000 years of world history and human usage. In contemporary times, the term “cannabis” has commonly been supplanted by the more colloquial term “marijuana” (also spelled “marihuana”). An extremely versatile and easily cultivatable plant, Cannabis was used by ancient cultures for food, fibre, and medicinal purposes. The integration and broader utilization of cannabinoid therapies within the domain of oncology (including palliation) carries the potential not only for improved health care outcomes for patients but also for economic savings and greater safety for society. Patient reports of improvement in quality of life, especially for those undergoing intensive treatment regimens, could be key to patients continuing with lifesaving or life-prolonging therapies.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5176373/

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A user’s guide to cannabinoid therapies in oncology.

Posted on January 5, 2017 by David Worrell

“”Cannabinoid” is the collective term for a group of chemical compounds that either are derived from the Cannabis plant, are synthetic analogues, or occur endogenously.

Although cannabinoids interact mostly at the level of the currently recognized cannabinoid receptors, they might have cross reactivity, such as at opioid receptors.

Patients with malignant disease represent a cohort within health care that have some of the greatest unmet needs despite the availability of a plethora of guideline-driven disease-modulating treatments and pain and symptom management options.

Cannabinoid therapies are varied and versatile, and can be offered as pharmaceuticals (nabilone, dronabinol, and nabiximols), dried botanical material, and edible organic oils infused with cannabis extracts. Cannabinoid therapy regimens can be creative, involving combinations of all of the aforementioned modalities.

Patients with malignant disease, at all points of their disease trajectory, could be candidates for cannabinoid therapies whether as monotherapies or as adjuvants.

The most studied and established roles for cannabinoid therapies include pain, chemotherapy-induced nausea and vomiting, and anorexia.

Moreover, given their breadth of activity, cannabinoids could be used to concurrently optimize the management of multiple symptoms, thereby reducing overall polypharmacy.

The use of cannabinoid therapies could be effective in improving quality of life and possibly modifying malignancy by virtue of direct effects and in improving compliance or adherence with disease-modulating treatments such as chemotherapy and radiation therapy.” https://www.ncbi.nlm.nih.gov/pubmed/28050136

Cannabinoid CB2 receptor ligand profiling reveals biased signalling and off-target activity.

Posted on January 4, 2017 by David Worrell

“The cannabinoid CB₂ receptor (CB₂R) represents a promising therapeutic target for various forms of tissue injury and inflammatory diseases. Although numerous compounds have been developed and widely used to target CB₂R, their selectivity, molecular mode of action and pharmacokinetic properties have been poorly characterized. Here we report the most extensive characterization of the molecular pharmacology of the most widely used CB₂R ligands to date. In a collaborative effort between multiple academic and industry laboratories, we identify marked differences in the ability of certain agonists to activate distinct signalling pathways and to cause off-target effects. We reach a consensus that HU910, HU308 and JWH133 are the recommended selective CB₂R agonists to study the role of CB₂R in biological and disease processes. We believe that our unique approach would be highly suitable for the characterization of other therapeutic targets in drug discovery research.”

https://www.ncbi.nlm.nih.gov/pubmed/28045021

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Potent immunomodulatory activity of a highly selective cannabinoid CB2 agonist on immune cells from healthy subjects and patients with multiple sclerosis.

Posted on January 4, 2017 by David Worrell

“COR167, a novel CB2-selective high affinity agonist, was found to significantly inhibit, in a dose-dependent manner, the proliferation of both peripheral blood mononuclear cells and myelin basic protein-reactive T cell lines from normal healthy subjects and patients with relapsing-remitting multiple sclerosis (MS). In MS, a significantly higher inhibition was observed in patients on treatment with disease modifying drugs compared to those naive to treatment. The inhibitory activity of COR167 was exerted through a mixed mechanism involving atypical and incomplete shift of Th1 phenotype towards Th2 phenotype associated with slight reduction of IL-4 and IL-5 as well as strongly reduced levels of Th17-related cytokines. COR167 was also able to reduce in vitro migration of stimulated immunocompetent cells through human brain endothelium associated with a significant reduction of levels of several chemokines. These findings demonstrate that COR167 exerts potent immunomodulatory effects and confirm the cannabinoid CB2 receptor as a novel pharmacological target to counteract neuroinflammation.” https://www.ncbi.nlm.nih.gov/pubmed/28041663]]>

Medical Cannabis in the Palliation of Malignant Wounds—A Case Report

Posted on January 1, 2017 by David Worrell

“Anecdotal accounts of the use of topical extracts from the cannabis plant being used on open wounds date back to antiquity. In modern times, cannabinoid therapies have demonstrated efficacy as analgesic agents in both pharmaceutical and botanical formats. Medical cannabis (MC), also known as medical marijuana,… The endogenous cannabinoid system, consisting of cannabinoid receptors and their endogenous ligands, is ubiquitous throughout the human body. Available research shows that cancer cells express higher levels of the cannabinoid receptors, CB1 and CB2, relative to their noncancer counterparts, while also demonstrating an overall state of upregulation. Human in vitro studies, using nonmelanoma skin lines, have demonstrated direct induction of tumor cell apoptosis and inhibition of tumor-related angiogenesis, both by way of activation of cannabinoid receptors.

The analgesic outcomes observed in this case are supported by the results of a recent systematic review and meta-analysis of cannabinoids for medical use. Unlike intact skin, which is polar and hydrophilic, wounds lack epithelial coverage and are nonpolar and lipophilic. Therefore, lipophilic compounds such as the THC and CBD cannabinoids may be readily absorbed through cutaneous wounds.

Before the use of topical MC oil, the patient’s wound was growing rapidly. Yet, after a few weeks, a modest regression of his malignant wound was observed while the patient used topical MC. This secondary outcome suggests that topical MC may promote antineoplastic activity as per the findings of Casanova et al.

In summary, this is the first case report to demonstrate the potential for MC to provide effective pain and symptom management in the setting of malignant wounds. The rapid onset of analgesia after topical placement suggests that the effects were mediated through absorption of the THC and CBD cannabinoids that subsequently interacted with peripheral nociceptors, immune cells, and cancer cells. The postapplication analgesia may be because of the gastrointestinal absorption of ingested residual MC oil. This case suggests that MC delivered in vaporized and topical oil formats warrants further investigation in human malignancy, including randomized controlled trials capable of establishing long-term efficacy, optimal dosage, schedules of administration, mixture composition, and safety.”

http://www.jpsmjournal.com/article/S0885-3924(16)30328-1/fulltext “Can Cannabis Oil Help Heal Wounds?” http://www.livescience.com/57500-can-medical-cannabis-help-heal-wounds.html “Oral cancer patient, 44, claims cannabis oil helped to shrink a hole in his cheek that was caused by the disease” http://www.dailymail.co.uk/health/article-4124752/Oral-cancer-patient-44-claims-cannabis-oil-helped-shrink-hole-cheek-caused-disease.html

“Miracle plant: Can medical marijuana heal wounds?” http://www.nydailynews.com/life-style/medical-marijuana-heal-wounds-article-1.3384572

“Cannabis Oil Shows Potential To Heal Cancer Wounds Fast” http://www.healthaim.com/cannabis-oil-shows-potential-heal-cancer-wounds-fast/71395]]>

Extravirgin olive oil up-regulates CB₁ tumor suppressor gene in human colon cancer cells and in rat colon via epigenetic mechanisms.

Posted on December 31, 2016 by David Worrell

“Extravirgin olive oil (EVOO) represents the typical lipid source of the Mediterranean diet, an eating habit pattern that has been associated with a significant reduction of cancer risk. Diet is the more studied environmental factor in epigenetics, and many evidences suggest dysregulation of epigenetic pathways in cancer.

The aim of our study was to investigate the effects of EVOO and its phenolic compounds on endocannabinoid system (ECS) gene expression via epigenetic regulation in both human colon cancer cells (Caco-2) and rats exposed to short- and long-term dietary EVOO.

Taken together, our findings demonstrating CB₁ gene expression modulation by EVOO or its phenolic compounds via epigenetic mechanism, both in vitro and in vivo, may provide a new therapeutic avenue for treatment and/or prevention of colon cancer.”

https://www.ncbi.nlm.nih.gov/pubmed/25533906