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Research Roundup: Nov 1, 2021



Nobel Prize news:

We often mention here that anandamide is both an endocannabinoid & an endovanilloid. It activates the TRPV1 receptor (transient receptor potential cation channel subfamily V member 1) – and if you’re a fan of biochemical diagrams, you see the TRPV1 receptor pop up a lot when talking about the benefits of endocannabinoids.


But this vanilloid receptor wasn’t even discovered until 1997 when Dr. Davis Julius & his team went searching for heat-sensitive ion channels that could be activated by capsaicin (which makes hot foods hot). They found the first ever TRPV receptor – and just this week, Dr. Julius was co-awarded a Nobel Prize in Medicine for this work because it changed our understanding of sensory biology & how we experience sensations like heat.


For practical applications, TRPV1 is now a target for the development of pain reducers as well as treatments for anxiety. CBD, CBDA, CBDV & PEA all bind to the TRPV1 receptors & if you go searching for it on this site, you find it as an underlying mechanism in almost every organ of the body, especially the brain. And in fact, a review came out just this week about TRPV channels & osteoporosis.


How CBD works can often be a mystery, but often, it seems that the answer lies in the vanilloids. And the Nobel Prize committee concurs.



Best of the Week...


A review of patient charts suggest benefits for Parkinson’s disease & Lewy body dementia from the use of CBD or CBD/CBG extracts

Standardized extracts enriched in cannabidiol and cannabigerol: Real-world experience of cases series of Parkinson's disease and dementia with Lewy bodies

https://www.researchgate.net/profile/Flavio-Henrique-Costa/publication/355440483_Standardized_extracts_enriched_in_cannabidiol_and_cannabigerol_Real-world_experience_of_cases_series_of_Parkinson's_disease_and_dementia_with_Lewy_bodies/links/6170a5a0c10b387664c87790/Standardized-extracts-enriched-in-cannabidiol-and-cannabigerol-Real-world-experience-of-cases-series-of-Parkinsons-disease-and-dementia-with-Lewy-bodies.pdf

A literature review that included 41 articles looking at CBD for opioid withdrawal suggests that it can be a safe & effective treatment for many of the relevant symptoms

Adjunctive Management of Opioid Withdrawal with the Nonopioid Medication Cannabidiol

https://pubmed.ncbi.nlm.nih.gov/34678050/

This review suggests the use of cannabis for tissue fibrosis (scarring) with a focus on CBD & THC

The Potential Use of Cannabis in Tissue Fibrosis

https://pubmed.ncbi.nlm.nih.gov/34708034/


Clinical Studies & Reviews of CBD & the Endocannabinoid System (ECS)

In children with drug-resistant epilepsy, CBD reduced their brain’s electrical discharges as well as improving their sleep microstructure

Effect of Cannabidiol on Interictal Epileptiform Activity and Sleep Architecture in Children with Intractable Epilepsy: A Prospective Open-Label Study

https://pubmed.ncbi.nlm.nih.gov/34687005/

With an exciting new technique, these researchers visualized MAGL levels in a human brain

First-In-Human in Vivo Imaging and Quantification of Monoacylglycerol Lipase in The Brain: A PET Study With 18F-T-401

https://assets.researchsquare.com/files/rs-986766/v1/bb99393b-23e5-41e3-a73b-03cfa2e69ffb.pdf

MAGL is the enzyme that breaks down 2-AG, so knowing where it is & what it is doing in a living brain is an important step in learning more about our endocannabinoid system.

A retrospective study in humans with endometriosis-associated pelvic pain found medical cannabis helpful for pain & GI symptoms

Effects of cannabis ingestion on endometriosis-associated pelvic pain and related symptoms

https://pubmed.ncbi.nlm.nih.gov/34699540/

A survey of pediatric oncologists found that most recognize a potential role for cannabis in symptom control

Perspectives of pediatric oncologists and palliative care physicians on the therapeutic use of cannabis in children with cancer

https://pubmed.ncbi.nlm.nih.gov/34672127/

In the hair of chronic cocaine users, they contained higher levels of the steroid cortisone (which becomes the stress hormone cortisol) & lower levels of the endocannabinoids OEA & PEA

Alterations of stress-related glucocorticoids and endocannabinoids in hair of chronic cocaine users

https://pubmed.ncbi.nlm.nih.gov/34676867/



Preclinical Research & Cannabinoid Chemistry

In cells, these researchers looked at extracts from male & female hemp plants & found that female plants rich in CBD showed the greatest anti-inflammatory activity & the most improved function of the mitochondria (powerhouse of the cell)

Immune Responses Are Differentially Regulated by Root, Stem, Leaf, and Flower Extracts of Female and Male CBD Hemp (Cannabis sativa L.) Plants

https://www.mdpi.com/2673-5601/1/4/25/htm

In a mouse model of cocaine addiction, CBD & blocking the CB1 receptor had an array of effects on drug seeking behavior

CB1 receptor antagonist AM4113 reverts the effects of cannabidiol on cue and stress-induced reinstatement of cocaine-seeking behaviour in mice

https://pubmed.ncbi.nlm.nih.gov/34688811/

In a rat model of depression, males & females showed differential antidepressant effects from CBD

Strain, Sex, and Time Dependent Antidepressant-like Effects of Cannabidiol

https://www.preprints.org/manuscript/202110.0347/v1

In rat heart tissue, THC protected the heart from the negative effects of a toxic gas

Inhibition of Mitochondria Permeability Transition Pore and Antioxidant Effect of Delta-9-Tetrahydrocannabinol Reduces Aluminum Phosphide-Induced Mitochondrial Dysfunction and Cytotoxicity

https://assets.researchsquare.com/files/rs-998530/v1/aaffbd8f-32b0-4606-a7c7-26530d81c600.pdf?c=1635174312

In obese mice, alterations to their orexin system & to their 2-AG/CB1 signaling led to problems with episodic memory

Orexin-A and endocannabinoids are involved in obesity-associated alteration of hippocampal neurogenesis, plasticity, and episodic memory in mice

https://pubmed.ncbi.nlm.nih.gov/34675233/

Orexin is an important neurotransmitter for food, arousal, the sleep/wake cycle & in the motivation and reward processes involved in addiction. And as we mentioned, Dr. Di Marzo & his team recently figured out that CBD is an antagonist at an orexin receptor.

In rats, the ability of the coffee terpene kahweol to lessen pain is mediated by the endocannabinoid system

Kahweol, a natural diterpene from coffee, induces peripheral antinociception by endocannabinoid system activation

https://www.bjournal.org/wp-content/uploads/articles_xml/1414-431X-bjmbr-54-12-e11071/1414-431X-bjmbr-54-12-e11071.pdf

In mice with no CB1 receptors in their neurons that release stress hormones, they were more likely to be started by sudden loud sounds

CB1 receptors in corticotropin-releasing factor neurons selectively control the acoustic startle response in male mice

https://pubmed.ncbi.nlm.nih.gov/34672092/