Emerging Class of Omega-3 Fatty Acid Endocannabinoids & Their Derivatives.

Prostaglandins & Other Lipid Mediators

“Cannabinoid receptor activation is involved in homeostatic regulation of the body. These receptors are activated by cannabinoids, that include the active constituents of Cannabis sativa as well as endocannabinoids (eCBs). The eCBs are endogenously synthesized from the omega-6 and omega-3 polyunsaturated fatty acids (PUFAs). In summary, we outline the novel findings regarding a growing class of signaling molecules, omega-3 eCBs, that can control the physiological and pathophysiological processes in the body.” https://www.ncbi.nlm.nih.gov/pubmed/31085370

“Anti-inflammatory ω-3 endocannabinoid epoxides.”  https://www.ncbi.nlm.nih.gov/pubmed/28687674

“Antitumorigenic Properties of Omega-3 Endocannabinoid Epoxides.” https://www.ncbi.nlm.nih.gov/pubmed/29856219

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Cannabinoid interactions with ion channels and receptors.

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“Cannabidiol (CBD), the non-psychoactive component of Cannabis sativa, acts on a diverse selection of membrane proteins with promising therapeutic potential in epilepsy and chronic pain. In this review, we will outline the studies that report reproducible results of CBD and other cannabinoids changing membrane channel function, with particular interest on Nav. Nav are implicated in fatal forms of epilepsy and are also associated with chronic pain. This makes Nav potential targets for CBD interaction since it has been reported to reduce pain and seizures. This discovery will not only prompt further research towards CBD’s characterization, but also promotes the application of cannabinoids as potentially therapeutic compounds for diseases like epilepsy and pain.” https://www.ncbi.nlm.nih.gov/pubmed/31088312
https://www.tandfonline.com/doi/full/10.1080/19336950.2019.1615824

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Tetrahydrocannabinol Reduces Hapten-Driven Mast Cell Accumulation and Persistent Tactile Sensitivity in Mouse Model of Allergen-Provoked Localized Vulvodynia.

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“Vulvodynia is a remarkably prevalent chronic pain condition of unknown etiology.

Therapeutic intra-vaginal administration of Δ9-tetrahydrocannabinol (THC) reduced mast cell accumulation and tactile sensitivity.

Mast cell-targeted therapeutic strategies may therefore provide new ways to manage and treat vulvar pain potentially instigated by repeated allergenic exposures.”

https://www.ncbi.nlm.nih.gov/pubmed/31052404

https://www.mdpi.com/1422-0067/20/9/2163

“Marijuana Relieves Chronic Pain, Research Shows”  https://www.webmd.com/pain-management/news/20100830/marijuana-relieves-chronic-pain-research-show#1

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The effects of delta-9-tetrahydrocannabinol on Krüppel-like factor-4 expression, redox homeostasis, and inflammation in the kidney of diabetic rat.

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“Diabetes mellitus is a complex, multifactorial disorder that is attributed to pancreatic β cell dysfunction. Pancreatic β cell dysfunction results in declining utilization of glucose by peripheral tissues as kidney and it leads to nephropathy. Excessive production and accumulation of free radicals and incapable antioxidant defense system lead to impaired redox status. Macromolecular damage may occur due to impaired redox status and also immune imbalance.

Δ9-Tetrahydrocannabinol (THC) is the main active ingredient in cannabis. THC acts as an immunomodulator and an antioxidant agent.

Our aim was to evaluate the effects of THC in the diabetic kidney.

According to our data, THC has ameliorative effects on the impaired redox status of diabetic kidney and also it acts as an immunomodulator. Therefore, THC might be used as a therapeutic agent for diabetic kidneys but its usage in the healthy kidney may show adverse effects.”

https://www.ncbi.nlm.nih.gov/pubmed/31081965

https://onlinelibrary.wiley.com/doi/abs/10.1002/jcb.28903

“Marijuana Doesn’t Seem to Harm the Kidneys” https://www.webmd.com/mental-health/addiction/news/20180306/marijuana-doesnt-seem-to-harm-the-kidneys

“Pot Won’t Harm Healthy Young People’s Kidneys, Study Suggests”   https://www.medicinenet.com/script/main/art.asp?articlekey=206375

“Marijuana doesn’t appear to harm kidneys”   https://www.hsph.harvard.edu/news/hsph-in-the-news/marijuana-kidneys/

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Medical Cannabis Use in Glioma Patients Treated at a Comprehensive Cancer Center in Florida.

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“Glioma is a devastating primary tumor of the central nervous system with difficult-to-manage symptoms.

Cannabis products have been postulated to potentially benefit glioma patients. Recent state legalization allowed investigators an opportunity to study glioma patients’ adoption of medical marijuana (MM).

Objective: Our goals were to: (1) determine the prevalence of marijuana use, both through physician recommendation and self-medication, and (2) evaluate its perceived risks and benefits in glioma patients.

Results: A total of 73 patients were surveyed. The majority of participants were aware that MM was legal in the state, and most reported learning of this through the media. Over 70% of participants reported having considered using MM, and a third reported using marijuana products after their diagnosis. Most received recommendations from friends/family rather than a medical provider, and only half of the users had obtained a physician’s recommendation. Users generally reported benefits.

Conclusions: With the increasing national conversation that accompanies legalization, glioma patients are pursuing marijuana for the treatment for their symptoms. More research and education is needed to bring health care providers into the conversation.”

“A glioma is a primary brain tumor that originates from the supportive cells of the brain, called glial cells.” http://neurosurgery.ucla.edu/body.cfm?id=159
“Remarkably, cannabinoids kill glioma cells selectively and can protect non-transformed glial cells from death.” https://www.ncbi.nlm.nih.gov/pubmed/15275820
“A meta-analysis of 34 in vitro and in vivo studies of cannabinoids in glioma reported that all but one study confirmed that cannabinoids selectively kill tumor cells.”  https://www.cancer.gov/about-cancer/treatment/cam/hp/cannabis-pdq#section/_7
“Since cannabinoids kill tumor cells without toxicity on their non transformed counterparts, they can represent a class of new potential anticancer drugs.”                                        http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3835116/ 
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Towards A Molecular Understanding of The Cannabinoid Related Orphan Receptor GPR18: A Focus on Its Constitutive Activity.

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“The orphan G-protein coupled receptor (GPCR), GPR18, has been recently proposed as a potential member of the cannabinoid family as it recognizes several endogenous, phytogenic, and synthetic cannabinoids. Potential therapeutic applications for GPR18 include intraocular pressure, metabolic disorders, and cancer. GPR18 has been reported to have high constitutive activity, i.e., activation/signaling occurs in the absence of an agonist. This activity can be reduced significantly by the A3.39N mutation. At the intracellular (IC) ends of (transmembrane helices) TMH3 and TMH6 in GPCRs, typically, a pair of oppositely charged amino acids form a salt bridge called the “ionic lock”. Breaking of this salt bridge creates an IC opening for coupling with G protein. The GPR18 “ionic lock” residues (R3.50/S6.33) can form only a hydrogen bond. In this paper, we test the hypothesis that the high constitutive activity of GPR18 is due to the weakness of its “ionic lock” and that the A3.39N mutation strengthens this lock. To this end, we report molecular dynamics simulations of wild-type (WT) GPR18 and the A3.39N mutant in fully hydrated (POPC) phophatidylcholine lipid bilayers. Results suggest that in the A3.39N mutant, TMH6 rotates and brings R3.50 and S6.33 closer together, thus strengthening the GPR18 “ionic lock”.”

https://www.ncbi.nlm.nih.gov/pubmed/31075933

https://www.mdpi.com/1422-0067/20/9/2300

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Cannabidiol Enhances the Therapeutic Effects of TRAIL by Upregulating DR5 in Colorectal Cancer.

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“Cannabidiol, a major non-psychotomimetic compound derived from Cannabis sativa, is a potential therapeutic agent for a variety of diseases such as inflammatory diseases, chronic neurodegenerative diseases, and cancers.

Here, we found that the combination of cannabidiol and TNF-related apoptosis-inducing ligand (TRAIL) produces synergistic antitumor effects in vitro. However, this synergistic effect was not observed in normal colonic cells. The levels of ER stress-related proteins, including C/EBP homologous protein (CHOP) and phosphorylated protein kinase RNA-like ER kinase (PERK) were increased in treatment of cannabidiol.

Cannabidiol enhanced significantly DR5 expression by ER stress. Knockdown of DR5 decreased the combined effect of cannabidioland TRAIL. Additionally, the combination of TRAIL and cannabidiol decreased tumor growth in xenograft models.

Our studies demonstrate that cannabidiol enhances TRAIL-induced apoptosis by upregulating DR5 and suggests that cannabidiol is a novel agent for increasing sensitivity to TRAIL.”

https://www.ncbi.nlm.nih.gov/pubmed/31075907

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Tetrahydrocannabinol – friend or foe? – Debate.

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“Medical THC is beneficial for various conditions (especially pain relief).”

https://www.ncbi.nlm.nih.gov/pubmed/31062643

https://www.tandfonline.com/doi/abs/10.1080/15563650.2019.1610567?journalCode=ictx20

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Cannabis Use Does Not Affect Outcomes After Total Knee Arthroplasty.

Journal of Arthroplasty Home

“The self-reported use of cannabis has increased since its recent legalization in several states. The primary purpose of this study is to report total knee arthroplasty (TKA) outcomes in patients using cannabis.

RESULTS:

No difference in length of stay was noted between the users (46.9 hours ± 15.7) and nonusers (49.3 hours ± 20.4) (P = .464). In-hospital total morphine equivalents did not differ between the 2 groups (user = 137 ± 104 mg, nonuser = 146 ± 117 mg, P = .634). Postoperative range of motion did not differ between users (128.4° ± 10.4°) and nonusers (126.9° ± 7.5°) (P = .346). No mean differences in follow-up KSS (user = 180.1 ± 24.9, nonuser = 172.0 ± 33.9, P = .106) or total change (user = 61.7 ± 32.8, nonuser = 62.7 ± 30.7, P = .852) in KSS were noted. Likewise, no significant mean differences in Veterans RAND-12 (mental component scores: user = 54.8 ± 9.3, nonuser = 55.9 ± 8.79, P = .472; physical component scores: user = 48.3 ± 9.9, nonuser = 45.8 ± 10.1, P = .145) scores were demonstrated. There were no differences in readmissions (user = 5, nonuser = 4, P = .730) or reoperations (user = 5, nonuser = 2, P = .238).

CONCLUSION:

Cannabis use does not appear to influence (adverse or beneficial) short-term outcomes in patients undergoing a primary TKA. Further studies are warranted to determine the efficacy and safety of cannabis as a constituent of multimodal pain management following TKA before endorsements can be made by orthopedic surgeons.”

https://www.ncbi.nlm.nih.gov/pubmed/31072746

https://www.arthroplastyjournal.org/article/S0883-5403(19)30347-X/fulltext

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Effect of Cannabis Use on HIV DNA during Suppressive ART.

Infectious Diseases Society of America

“Cannabis use is frequent among people living with HIV and is associated with reduced systemic inflammation. We observed a faster HIV DNA decay during antiretroviral therapy among cannabis users, compared to no drug use. No cannabis-effect was observed on cellular HIV RNA transcription.”

https://www.ncbi.nlm.nih.gov/pubmed/31074488

 

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