Author Archives: David Worrell
Anti-Tumorigenic Properties of Omega-3 Endocannabinoid Epoxides.
“Accumulating studies have linked inflammation to tumor progression.
Dietary omega-3 fatty acids including docosahexaenoic acid (DHA) have been shown to suppress tumor growth through their conversion to epoxide metabolites. Alternatively, DHA is converted enzymatically into docosahexaenoylethanolamide (DHEA), an endocannabinoid with anti-proliferative activity.
Recently, we reported a novel class of anti-inflammatory DHEA-epoxides (EDP-EAs) that contain both ethanolamide and epoxide moieties. Herein we evaluate the anti-tumorigenic properties of EDP-EAs in an osteosarcoma model.
First, we show ~80% increase in EDP-EAs in metastatic lungs versus normal mouse lungs. We found significant differences in the apoptotic and anti-migratory potency of the different EDP-EA regioisomers, which are partly mediated through cannabinoid receptor 1 (CB1).
Furthermore, we synthesized derivatives of the most pro-apoptotic regioisomer. These derivatives had reduced hydrolytic susceptibility to fatty acid-amide hydrolase and increased CB1 binding.
Collectively, we report a novel class of EDP-EAs that exhibit anti-angiogenic, anti-tumorigenic and anti-migratory properties in osteosarcoma.”
https://www.ncbi.nlm.nih.gov/pubmed/29856219
https://pubs.acs.org/doi/10.1021/acs.jmedchem.8b00243
“Omega-3 Fatty Byproducts May Have Anticancer Effects.” https://scienceblog.com/502227/omega-3-fatty-byproducts-may-have-anticancer-effects/
“Omega 3 fatty acids hold the key to stop cancer” http://www.thehansindia.com/posts/index/Health/2018-07-14/Omega-3-fatty-acids-hold-the-key-stop-cancer/398130
“Products of omega-3 fatty acid metabolism may have anticancer effects, study shows” https://medicalxpress.com/news/2018-07-products-omega-fatty-acid-metabolism.html
“Omega-3-derived cannabinoid may stop cancer. New research suggests that the body’s natural pain-killer, the “endocannabinoid system,” may also have cancer-fighting properties when “activated” by omega-3 fatty acids.” https://www.medicalnewstoday.com/articles/322482.php
“Omega-3 diet can do more than protecting your heart, it may keep cancer away” https://economictimes.indiatimes.com/magazines/panache/omega-3-diet-can-do-more-than-protecting-your-heart-it-may-keep-cancer-away/articleshow/64988681.cms
“Products of omega-3 fatty acid metabolism may have anticancer effects” https://www.sciencedaily.com/releases/2018/07/180713220137.htm
The biomedical challenge of neurodegenerative disorders: an opportunity for cannabinoid-based therapies to improve on the poor current therapeutic outcomes.
“At the beginning of the 21st century, the therapeutic management of neurodegenerative disorders remains a major biomedical challenge, particularly given the worldwide aging of the population over the past 50 years that is expected to continue in the forthcoming years.
This review will focus on the promise of cannabinoid based therapies to address this challenge.
Such promise is based on the broad neuroprotective profile of cannabinoids, which may cooperate to combat excitotoxicity, oxidative stress, glia-driven inflammation and protein aggregation.
Such effects may be produced by the activity of cannabinoids through their canonical targets (e.g. cannabinoid receptors, endocannabinoid enzymes) but also, via non-canonical elements and activities in distinct cell types critical for cell survival or neuronal replacement (e.g. neurons, glia, neural precursor cells).
Ultimately, the therapeutic events driven by endocannabinoid signalling reflect the activity of an endogenous system that regulates the preservation, rescue, repair and replacement of neurons and glia.”
https://www.ncbi.nlm.nih.gov/pubmed/29856067
https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.14382
“G protein-coupled receptors (GPCRs) interact with multiple intracellular effector proteins such that different ligands may preferentially activate one signal pathway over others, a phenomenon known as signaling bias. Signaling bias can be quantified to optimize drug selection for preclinical research.
Here, we describe moderate-throughput methods to quantify signaling bias of known and novel compounds. In the example provided, we describe a method to define 
“Maintenance of body weight is fundamental to maintain one’s health and to promote longevity. Nevertheless, it appears that the global obesity epidemic is still constantly increasing.
Endocannabinoids (eCBs) are lipid messengers that are involved in overall body weight control by interfering with manifold central and peripheral regulatory circuits that orchestrate energy homeostasis.
Initially, blocking of eCB signaling by first generation 
“Nonalcoholic fatty liver disease (NAFLD) is comprised of nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). It is defined by histologic or radiographic evidence of steatosis in the absence of alternative etiologies, including significant alcohol consumption, steatogenic medication use, or hereditary disorders.
NAFLD is now the most common liver disease, and when NASH is present it can progress to fibrosis and hepatocellular carcinoma. Different mechanisms have been identified as contributors to the physiology of NAFLD; insulin resistance and related metabolic derangements have been the hallmark of physiology associated with NAFLD.
The mainstay of treatment has classically involved lifestyle modifications focused on the reduction of insulin resistance. However, emerging evidence suggests that the endocannabinoid system and its associated 
“The anticonvulsant activity of