“Short overviews are presented on the historical uses of cannabis in the Middle East and on the more recent scientific and medical research on phytocannabinoids and the endocannabinoid system, with emphasis on research contributions from Israel. These are followed by examples of research projects and clinical trials with cannabinoids and by a short report on the regulation of medical marijuana in Israel, which at present is administered to over 22,000 patients.”
Author Archives: David Worrell
Protection from Radiation-Induced Pulmonary Fibrosis by Peripheral Targeting of Cannabinoid Receptor-1.
“Radiation-induced pulmonary fibrosis (RIF) is a severe complication of thoracic radiotherapy that limits its dose, intensity, and duration. The contribution of the endocannabinoid signaling system in pulmonary fibrogenesis is not known. Using a well-established mouse model of RIF, we assessed the involvement of cannabinoid receptor-1 (CB1) in the onset and progression of pulmonary fibrosis.
Our results show that CB1 signaling plays a key pathological role in the development of radiation-induced pulmonary inflammation and fibrosis, and peripherally restricted CB1 antagonists may represent a novel therapeutic approach against this devastating complication of radiotherapy/irradiation.”
http://www.ncbi.nlm.nih.gov/pubmed/26426981
“We report for the first time the involvement of cannabinoid receptor 1 (CB1)-mediated signaling in the onset and progression of radiation-induced pulmonary fibrosis (RIF). We were able to delay the onset of RIF by genetic targeting of CB1 receptors as well as by its pharmacological inhibition. Thus, pharmacological targeting of CB1 receptors with peripherally restricted CB1 antagonists void of central nervous system complications may represent a novel strategy to prevent the development of RIF.
In summary, we provide the first evidence on the key pathological role of CB1 signaling in radiation-induced pulmonary fibrogenesis and show that peripherally restricted CB1 antagonists may represent a novel therapeutic approach against this devastating and untreatable complication of radiotherapy/irradiation. Our results also suggest that targeting CB1 may provide benefits in other lung diseases associated with inflammation and fibrosis.”
Potential Therapeutical Contributions of the Endocannabinoid System towards Aging and Alzheimer’s Disease.
“Aging can lead to decline in cognition, notably due to neurodegenerative processes overwhelming the brain over time.
As people live longer, numerous concerns are rightfully raised toward long-term slowly incapacitating diseases with no cure, such as Alzheimer’s disease.
Since the early 2000’s, the role of neuroinflammation has been scrutinized for its potential role in the development of diverse neurodegenerative diseases notably because of its slow onset and chronic nature in aging.
Despite the lack of success yet, treatment of chronic neuroinflammation could help alleviate process implicated in neurodegenerative disease.
A growing number of studies including our own have aimed at the endocannabinoid system and unfolded unique effects of this system on neuroinflammation, neurogenesis and hallmarks of Alzheimer’s disease and made it a reasonable target in the context of normal and pathological brain aging.”
The Endocannabinoid System: Pivotal Orchestrator of Obesity and Metabolic Disease.
“The endocannabinoid system (ECS) functions to adjust behavior and metabolism according to environmental changes in food availability.
Its actions range from the regulation of sensory responses to the development of preference for the consumption of calorically-rich food and control of its metabolic handling.
ECS activity is beneficial when access to food is scarce or unpredictable.
However, when food is plentiful, the ECS favors obesity and metabolic disease.
We review recent advances in understanding the roles of the ECS in energy balance, and discuss newly identified mechanisms of action that, after the withdrawal of first generation cannabinoid type 1 (CB1) receptor antagonists for the treatment of obesity, have made the ECS once again an attractive target for therapy.”
Medical Cannabis Effective for Chronic Pain, Other Indications
“According to this study:
* Moderate-quality evidence supports the use of cannabinoids for the treatment of chronic pain and for the spasticity related to multiple sclerosis.
* Low-quality evidence suggests that cannabinoids may be effective for chemotherapy-induced nausea and vomiting and other indications.”
“Medical Cannabis Effective for Chronic Pain, Other Indications. According to this study.” http://www.ncbi.nlm.nih.gov/pubmed/26402288
“Cannabinoids for Medical Use: A Systematic Review and Meta-analysis” http://jama.jamanetwork.com/article.aspx?articleid=2338251
Toxic effects of cannabis and cannabinoids: Animal data.
“Acute toxicity studies show that it is virtually impossible to die from acute administration of marijuana or tetrahydrocannabinol, the main psychoactive component of cannabis.”
Endocannabinoids and Cancer.
“A large body of evidence shows that cannabinoids, in addition to their well-known palliative effects on some cancer-associated symptoms, can reduce tumour growth in animal models of cancer.
They do so by modulating key cell signalling pathways involved in the control of cancer cell proliferation and survival.
In addition, cannabinoids inhibit angiogenesis and cell proliferation in different types of tumours in laboratory animals.
By contrast, little is known about the biological role of the endocannabinoid system in cancer physio-pathology, and several studies suggest that it may be over-activated in cancer.
In this review, we discuss our current understanding of cannabinoids as antitumour agents, focusing on recent advances in the molecular mechanisms of action, including resistance mechanisms and opportunities for combination therapy approaches.”
Endocannabinoids and the Digestive Tract and Bladder in Health and Disease.
“Components of the so-called endocannabinoid system, i.e., cannabinoid receptors, endocannabinoids, as well as enzymes involved in endocannabinoid synthesis and degradation, have been identified both in the gastrointestinal and in the urinary tract.
Evidence suggests that the endocannabinoid system is implicated in many gastrointestinal and urinary physiological and pathophysiological processes, including epithelial cell growth, inflammation, analgesia, and motor function.
A pharmacological modulation of the endocannabinoid system might be beneficial for widespread diseases such as gastrointestinal reflux disease, irritable bowel syndrome, inflammatory bowel disease, colon cancer, cystitis, and hyperactive bladder.
Drugs that inhibit endocannabinoid degradation and raise the level of endocannabinoids, non-psychotropic cannabinoids (notably cannabidiol), and palmitoylethanolamide, an acylethanolamide co-released with the endocannabinoid anandamide, are promising candidates for gastrointestinal and urinary diseases.”
Endocannabinoids and the Cardiovascular System in Health and Disease.
“The endocannabinoid system is widely distributed throughout the cardiovascular system.
Endocannabinoids play a minimal role in the regulation of cardiovascular function in normal conditions, but are altered in most cardiovascular disorders.
In shock, endocannabinoids released within blood mediate the associated hypotension through CB1 activation. In hypertension, there is evidence for changes in the expression of CB1, and CB1 antagonism reduces blood pressure in obese hypertensive and diabetic patients.
The endocannabinoid system is also upregulated in cardiac pathologies.
This is likely to be cardioprotective, via CB2 and CB1 (lesser extent).
In the vasculature, endocannabinoids cause vasorelaxation through activation of multiple target sites, inhibition of calcium channels, activation of potassium channels, NO production and the release of vasoactive substances. Changes in the expression or function of any of these pathways alter the vascular effect of endocannabinoids.
Endocannabinoids have positive (CB2) and negative effects (CB1) on the progression of atherosclerosis. However, any negative effects of CB1 may not be consequential, as chronic CB1 antagonism in large scale human trials was not associated with significant reductions in atheroma.
In neurovascular disorders such as stroke, endocannabinoids are upregulated and protective, involving activation of CB1, CB2, TRPV1 and PPARα.
Although most of this evidence is from preclinical studies, it seems likely that cannabinoid-based therapies could be beneficial in a range of cardiovascular disorders.”
Endocannabinoids and Metabolic Disorders.
“The endocannabinoid system (ECS) is known to exert regulatory control on essentially every aspect related to the search for, and the intake, metabolism and storage of calories, and consequently it represents a potential pharmacotherapeutic target for obesity, diabetes and eating disorders.
While the clinical use of the first generation of cannabinoid type 1 (CB1) receptor blockers has been halted due to the psychiatric side effects that their use occasioned, recent research in animals and humans has provided new knowledge on the mechanisms of actions of the ECS in the regulation of eating behavior, energy balance, and metabolism.
In this review, we discuss these recent advances and how they may allow targeting the ECS in a more specific and selective manner for the future development of therapies against obesity, metabolic syndrome, and eating disorders.”