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Research Roundup: Aug 2, 2021



CV Sciences win Immune Support Product of the year from NutraIngredients

https://www.nutraingredients-usa.com/Article/2021/07/26/NutraIngredients-USA-Awards-Meet-the-Products-of-the-Year



Best of the Week...


This review of clinical studies of cannabinoids in older adults found CBD to have a low incidence of adverse events & no serious adverse advents

Safety and Tolerability of Natural and Synthetic Cannabinoids in Older Adults: A Systematic Review and Meta-Analysis of Open-Label Trials and Observational Studies

https://pubmed.ncbi.nlm.nih.gov/34235645/


A review of the complex, extensive & controversial relationship between your serotonin, your cannabinoids & your sleep-wake cycle

Cannabinoids and sleep-wake cycle: The potential role of serotonin

https://pubmed.ncbi.nlm.nih.gov/34216647/

For any nerds of the dorsal raphe, you’ll be in heaven.


Case study of PEA for the neuropathic pain of shingles

Palmitoylethanolamide (PEA) in the treatment of neuropathic pain: a case study

https://pubmed.ncbi.nlm.nih.gov/34289728/


In mice, in a study supportive of ‘the entourage effect’, delivering CBDA in a cannabis extract versus as an isolated molecule caused its levels in the blood plasma to be 14x higher

Cannabis constituents interact at the drug efflux pump BCRP to markedly increase plasma cannabidiolic acid concentrations

https://pubmed.ncbi.nlm.nih.gov/34294753/


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

A review of the potential of CBD & THC in sports medicine

Therapeutic Potential for Cannabinoids in Sports Medicine: Current Literature Review

https://pubmed.ncbi.nlm.nih.gov/34234089/


In humans, a new analysis method for looking at your metabolites of CBD produced from using it to treat epilepsy

UHPLC-MS/MS Analysis of Cannabidiol and Its Metabolites in Serum of Patients with Resistant Epilepsy Treated with CBD Formulations

https://pubmed.ncbi.nlm.nih.gov/34209666/


In humans, their circulating levels of AEA altered connectivity in the brain between regions linked to reward & salience (noticing of stimuli)

Endocannabinoid signaling of homeostatic status modulates functional connectivity in reward and salience networks

https://pubmed.ncbi.nlm.nih.gov/34212205/


This review discusses targeting the ECS for treatment of PTSD

Targeting the endocannabinoid system in the treatment of PTSD: A promising case of preclinical-clinical translation?

https://www.sciencedirect.com/science/article/pii/S0006322321014724


This review looks at CB2 as a target for epilepsy treatment

The CB2 Receptor as a Novel Therapeutic Target for Epilepsy Treatment

https://www.preprints.org/manuscript/202107.0163/v1


This study looked at how various nutraceuticals bound to the CB2 receptor

CB2 Receptor Binding Affinity of Various Nutraceutical Ingredients and Their Combinations

https://www.longdom.org/abstract/cb2-receptor-binding-affinity-of-various-nutraceutical-ingredientsrnand-their-combinations-75852.html


This review looks at targeting FAAH & MAGL to treat Alzheimer’s disease

The role of endocannabinoid pathway in the neuropathology of Alzheimer's disease: Can the inhibitors of MAGL and FAAH prove to be potential therapeutic targets against the cognitive impairment associated with Alzheimer's disease?

https://pubmed.ncbi.nlm.nih.gov/34217798/


This review examines what we know about modulating the endocannabinoid system from birth through adolescence

Early Consumption of Cannabinoids: From Adult Neurogenesis to Behavior

https://pubmed.ncbi.nlm.nih.gov/34299069/


In the breast milk of human mothers, the endocannabinoid 2-AG is highest during the day

Human Milk Endocannabinoid Levels as a Function of Obesity and Diurnal Rhythm

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8308542/


In a patient with severe pain after a stroke, a 1:1 ratio of THC & CBD gave relief after 3 years of other therapies did not

Tetrahydrocannabinol and cannabidiol as an oromucosal spray in a 1:1 ratio: a therapeutic option for patients with central post-stroke pain syndrome?

https://casereports.bmj.com/content/14/7/e243072.abstract

Preclinical Research & Cannabinoid Chemistry

In rats exposed to UV radiation, topical CBD protected the skin & also absorbed into the bloodstream where it proceeded to the liver & caused many changes

Changes in Hepatic Phospholipid Metabolism in Rats under UV Irradiation and Topically Treated with Cannabidiol

https://www.mdpi.com/2076-3921/10/8/1157/htm


In baby rats with crushed spinal cords, CBD protected the neurons in the spine & reduced the reaction of the glial cells, probably via the CB1 receptor

Short and long-term neuroprotective effects of cannabidiol after neonatal peripheral nerve axotomy

https://pubmed.ncbi.nlm.nih.gov/34303725/


In a rat model of seizures, both THC & CBD are effective at have antiseizure properties but the most effective is a small amount of THC added to a larger dose of CBD

Antiseizure effects of the cannabinoids in the amygdala-kindling model

https://pubmed.ncbi.nlm.nih.gov/34251027/


In mice addicted to cocaine, CBD helped to prevent drug motivated behavior

Cannabidiol produces distinct U-shaped dose-response effects on cocaine conditioned place preference and associated recruitment of prelimbic neurons in male rats

https://www.bpsgos.org/article/S2667-1743(21)00060-4/fulltext


In glioma cells (the fastest growing type of brain tumor), CBD caused the transcription factor NFKB to become toxic to the tumor cells

OMRT-1. Cannabidiol converts NFKB into a tumor-suppressor in glioblastoma with defined antioxidative properties

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255461/


In placental cells, CBD affects apoptotic and autophagic processes

Cannabidiol disrupts apoptosis, autophagy and invasion processes of placental trophoblasts

https://pubmed.ncbi.nlm.nih.gov/34302491/


In a mouse model of Alzheimer’s, inhibiting the FAAH enzyme (a mechanism of CBD) lowers inflammation of the microglia (brain immune cells) via several different cellular processes

Fatty Acid Amide Hydrolase (FAAH) Inhibition Modulates Amyloid-Beta-Induced Microglia Polarization

https://pubmed.ncbi.nlm.nih.gov/34299330/


In neurons of the hippocampus, activating the CB2 receptor protected them from the Aβ plaques associated with Alzheimer’s

Effects of CB2 Receptor Agonist JWH133 on Aβ42-Induced Hippocampal Neurons

https://www.ijsciences.com/pub/article/2353


In animal models of alcoholism, inhibiting the DAGL enzyme (which produces 2-AG) reduced alcohol consumption

Targeting diacylglycerol lipase reduces alcohol consumption in preclinical models

https://pubmed.ncbi.nlm.nih.gov/34292886/


In mice, augmenting endocannabinoid levels helped facilitate goal seeking via increases of dopamine

Chronic augmentation of endocannabinoid levels persistently increases dopaminergic encoding of reward cost and motivation

https://pubmed.ncbi.nlm.nih.gov/34230105/


In brain slices from rats, the ECS helps to regulate synaptic plasticity via the PPARs (nuclear receptors that control the regulation of genetic transcription)

Tonic Endocannabinoid Signaling Gates Synaptic Plasticity in Dorsal Raphe Nucleus Serotonin Neurons Through Peroxisome Proliferator-Activated Receptors

https://pubmed.ncbi.nlm.nih.gov/34262460/

CBD also targets the PPARs & in some studies, CBD has been found to turn on hundreds of different genes & turn off hundreds of other genes.

No wonder it’s often so hard to figure out exactly how CBD is helping.


In neurons, activating the endocannabinoid system protected from the damage of the potent neuroexcitatory amino acid kainic acid

Kainate-Induced Degeneration of Hippocampal Neurons. Protective Effect of Activation of the Endocannabinoid System

https://pubmed.ncbi.nlm.nih.gov/34297297/


In mice, the novel cannabinoid VSN16R is helpful for the behavioral symptoms of Fragile X Syndrome

Reversal of behavioural phenotype by the cannabinoid-like compound VSN16R in fragile X syndrome mice

https://pubmed.ncbi.nlm.nih.gov/34196695/


In a chick model of the eye, cannabinoids are involved with the control of stem cells

Cannabinoid signaling promotes the de-differentiation and proliferation of Müller glia-derived progenitor cells

https://pubmed.ncbi.nlm.nih.gov/34231253/


A fascinating doctoral thesis on cannabinoid probes that are fluorescent or photoswitchable (able to be turned on by light)

Out of the Dark, Into the Light: Fluorescent and Photoswitchable Probes for Cannabinoid Receptors

https://www.research-collection.ethz.ch/bitstream/handle/20.500.11850/492206/4/Abstract_27609.pdf

The ability to use light to switch a cannabinoid on & off is a wonderfully science-fiction type method for figuring out how the endocannabinoid system actually works.