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Research Roundup: Feb 21, 2022




Best of the Week...


A review of natural plant compounds for COVID-19 highlights CBD & PEA

Phytocompounds and COVID-19: Two years of knowledge

https://onlinelibrary.wiley.com/doi/10.1002/ptr.7420

A review of CBD in cancer management

Cannabidiol (CBD) in Cancer Management

https://www.mdpi.com/2072-6694/14/4/885

In female mice with early life stress, CBD reverses their anxiety & depression behaviors via a modulation of brain energy metabolism

Early-life stress induces emotional and molecular alterations in female mice that are partially reversed by cannabidiol

https://pubmed.ncbi.nlm.nih.gov/34973413/

In mice with liver fibrosis (scarring), CBD protected the liver tissue via the clearing of free radicals & inhibiting the degradation of lipids

Antioxidant effect of cannabidiol in mice with liver fibrosis

http://zgggws.xml-journal.net/en/article/doi/10.11847/zgggws1135692

This company is looking to use a combination of PEA & honokiol for treating pain as well as neurodegenerative diseases

Chronic pain : two tested natural compounds may break pain cycle : could they be useful in neurodegenerative disease?

https://cme30.eu/chronic-pain-two-tested-natural-compounds-may-break-pain-cycle-could-they-be-useful-in-neurodegenerative-disease/

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

A survey of multiple sclerosis patients found that a third used cannabis to alleviate symptoms

A Survey of Cannabis Use in a Large US-Based Cohort of People with Multiple Sclerosis

https://pubmed.ncbi.nlm.nih.gov/35035295/

A longitudinal study looks at the levels of AEA & 2-AG in those with PTSD

Circulating endocannabinoids and genetic polymorphisms as predictors of posttraumatic stress disorder symptom severity: heterogeneity in a community-based cohort

https://pubmed.ncbi.nlm.nih.gov/35105857/

Teens more sensitive to the effects of THC than adults

Adolescents are more sensitive than adults to acute behavioral and cognitive effects of THC

https://pubmed.ncbi.nlm.nih.gov/35110688

The anti-inflammatory effects of THC may be mediated by the user’s body mass index

Does Body Mass Index Explain The Apparent Anti-inflammatory Effects of Cannabis Use? Results From A Cohort Study Of Sexual and Gender Minority Youth

https://www.sciencedirect.com/science/article/abs/pii/S0376871622000813

These two human studies look at the effects of ayahuasca on the ECS

Effects of ayahuasca on the endocannabinoid system of healthy volunteers and in volunteers with social anxiety disorder: Results from two pilot, proof-of-concept, randomized, placebo-controlled trials

https://pubmed.ncbi.nlm.nih.gov/35107855/



Recent Reviews


A review of using cannabinoids for diseases of skin inflammation

Cannabis-Based Products for the Treatment of Skin Inflammatory Diseases: A Timely Review

https://www.mdpi.com/1424-8247/15/2/210

This review looks at CBD for tuberous sclerosis (a disease of benign tumor growth that often leads to seizures)

A scoping review on cannabidiol therapy in tuberous sclerosis: Current evidence and perspectives for future development

https://pubmed.ncbi.nlm.nih.gov/35151190/

On treating bone diseases via the ECS

Components of the Endocannabinoid System and Effects of Cannabinoids Against Bone Diseases: A Mini-Review

https://pubmed.ncbi.nlm.nih.gov/35126132/

This review looks at the link between the gut microbiome & the endocannabinoidome, especially in companion animals

Mutual Links between the Endocannabinoidome and the Gut Microbiome, with Special Reference to Companion Animals: A Nutritional Viewpoint

https://www.mdpi.com/2076-2615/12/3/348

A review of the medical potential of cannabis & the cannabinoids

Cannabis and cannabinoids: pharmacology and therapeutic potential

https://pubmed.ncbi.nlm.nih.gov/35133644/



Pain


This review confirms the efficacy of cannabis for back pain in this review of 4 studies covering 110 patients

The Efficacy of Cannabis in Reducing Back Pain: A Systematic Review

https://pubmed.ncbi.nlm.nih.gov/35128969/

& this review looks at cannabinoids for treating spinal disorders

Analyzing the Impact of Cannabinoids on the Treatment of Spinal Disorders

https://pubmed.ncbi.nlm.nih.gov/35132567/

A review of how clinicians are using cannabis for pain

Chronic Pain Clinical and Prescriptive Practices in the Cannabis Era

https://pubmed.ncbi.nlm.nih.gov/34973920/

& a thematic analysis the experience of patients using cannabis for pain

What are the experiences of patients using cannabis for pain? A systematic review of qualitative studies

https://www.sciencedirect.com/science/article/abs/pii/S1876382021008167

An analysis of real-world patient data about cannabis for chronic refractory pain

Medicinal Cannabis for the Treatment of Chronic Refractory Pain: An Investigation of the Adverse Event Profile and Health-Related Quality of Life Impact of an Oral Formulation

https://www.karger.com/Article/PDF/521492

A mixed-method analysis shows how people are using cannabis for pain management

A mixed methods analysis of cannabis use routines for chronic pain management

https://agris.fao.org/agris-search/search.do?recordID=DJ2022074947

A look at novel FAAH inhibitors for the treatment of chronic pain

Identifying FAAH Inhibitors as New Therapeutic Options for the Treatment of Chronic Pain through Drug Repurposing

https://pubmed.ncbi.nlm.nih.gov/35056095/

In mice with neuropathic pain, CBD combined well with THCV to lessen pair via the CB1 receptor & a serotonin receptor

Role of Cannabidiol and Tetrahydrocannabivarin on Paclitaxel-Induced Neuropathic Pain in Rodents

https://europepmc.org/article/ppr/ppr437461



Neuroprotection & Neural Diseases


A review about treating central nervous system diseases by inhibiting the breakdown of endocannabinoids

Polypharmacological Approaches for CNS Diseases: Focus on Endocannabinoid Degradation Inhibition

https://www.mdpi.com/2073-4409/11/3/471

Includes a nice chart of the biochemistry.

A review on using the cannabinoids to treat Alzheimer’s

Impact of the cannabinoid system in Alzheimer's diseases

https://pubmed.ncbi.nlm.nih.gov/35105293/

& a review on the metabolism of endocannabinoids & their relation to Alzheimer’s disease

Endocannabinoid metabolism and Alzheimer’s disease

https://www.nrronline.org/article.asp?issn=1673-5374;year=2022;volume=17;issue=9;spage=1987;epage=1988;aulast=Chen

In a rat model of Parkinson’s disease, a combination of a CB1 blocker along with the standard treatment of L-DOPA helped to protect the dopamine neurons as well as alleviating motor symptoms

L-DOPA/Capsazepine or L-DOPA/Rimonabant Co-Administration in an Experimental Parkinson Disease Model: Behavioral and Cellular Consequences

https://stm.bookpi.org/IDMMR-V5/article/view/5580

In a mouse model of traumatic brain injury, increasing the endocannabinoid signaling caused greater resilience to injury, lessened neuropathology & protected from cognitive declines

Enhancing endocannabinoid signalling in astrocytes promotes recovery from traumatic brain injury

https://pubmed.ncbi.nlm.nih.gov/35136958/

In a rat model of stroke, the ability of acetaminophen (aka paracetamol) to protect the brain seems to be mediated by the endocannabinoid system

Role of PI3K/Akt axis in mitigating hippocampal ischemia-reperfusion injury via CB1 receptor stimulation by paracetamol and FAAH inhibitor in rat

https://pubmed.ncbi.nlm.nih.gov/34968475/

In a rat model of epilepsy, a look at how AEA causes its anticonvulsant effects

The Role of the Possible Receptors and Intracellular Pathways in Protective Effect of Exogenous Anandamide in Kindling Model of Epilepsy

https://pubmed.ncbi.nlm.nih.gov/35112235/

On treating neuroinflammation via targeting of the CB2 receptor

CB2 receptor activation inhibits the phagocytic function of microglia through activating ERK/AKT-Nurr1 signal pathways

https://pubmed.ncbi.nlm.nih.gov/35132190/

In a mouse model of memory, the ability of certain serotonin receptors to regulate spatial memory is dependent on a pathway using CB1 & GABA

5-HT3A receptors maintain hippocampal LTP in a CB1 and GABAA receptor- dependent manner for spatial memory

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.15793

In rats with neural problems from HIV, activating the CB2 receptor prevented neurological injury & cognitive dysfunction

Win55,212-2 Improves Neural Injury induced by HIV-1 Glycoprotein 120 in Rats by Exciting CB2R

https://pubmed.ncbi.nlm.nih.gov/35157986/

More on how the CB1 receptor modulates synaptic plasticity

SGIP1 modulates kinetics and interactions of the cannabinoid receptor 1 and G protein-coupled receptor kinase 3 signalosome

https://pubmed.ncbi.nlm.nih.gov/34970999/


Addiction


In a mouse model of heroin addiction & withdrawal, CBD reduced behavioral impairments & normalized the associated gene expression changes

CBD-mediated regulation of heroin withdrawal-induced behavioural and molecular changes in mice

https://onlinelibrary.wiley.com/doi/abs/10.1111/adb.13150

In a mouse model of cocaine addiction, CBD helped them to not pick up the habit but did not affect abstinence or cravings

Cannabidiol decreases motivation for cocaine in a behavioral economics paradigm but does not prevent incubation of craving in mice

https://pubmed.ncbi.nlm.nih.gov/35168076/

In rats, CBD blocks the dopamine release of methamphetamine

Cannabidiol inhibits methamphetamine-induced dopamine release via modulation of the DRD1-MeCP2-BDNF-TrkB signaling pathway

https://pubmed.ncbi.nlm.nih.gov/34997862/

On endocannabinoids & addition to meth or morphine

Endocannabinoids and addiction memory: Relevance to Methamphetamine/Morphine Abuse

https://www.tandfonline.com/doi/abs/10.1080/15622975.2022.2039408?journalCode=iwbp20

& on treating substance use disorders by targeting the CB2 receptor

CB2 Receptor Involvement in the Treatment of Substance Use Disorders

https://pubmed.ncbi.nlm.nih.gov/34827554/

In a mouse model of pain & opioid addiction, a look at the effects of CBD & a novel CBD derivative (CBD-val-HS)

Differential Effects of Cannabidiol and a Novel Cannabidiol Analog on Oxycodone Place Preference and Analgesia in Mice: an Opioid Abuse Deterrent with Analgesic Properties

https://pubmed.ncbi.nlm.nih.gov/34962133/



Antimicrobial


In kidney cells, CBD increased the effects of the antibiotic protein gramicidin

Cannabidiol increases gramicidin current in human embryonic kidney cells: An observational study

https://europepmc.org/article/ppr/ppr446159

Essential oil from hemp causes antimicrobial & antioxidant activity

In vitro antioxidant and antimicrobial activity of Cannabis sativa L. cv 'Futura 75' essential oil

https://pubmed.ncbi.nlm.nih.gov/32865042/

In mice, cannabis extract helped to prevent malaria infection, especially the cannabinoid THCV

Evaluation of anti-malarial activity and GC–MS finger printing of cannabis: An in-vivo and in silico approach

https://www.sciencedirect.com/science/article/pii/S2468227622000175

A review of the antimicrobial effects of the cannabinoids

ANTIMICROBIAL EFFECT OF CANNABIS SATIVA L

http://revroum.lew.ro/wp-content/uploads/2021/05/Art%2004.pdf



Channels


In heart cells stressed by high levels of glucose (a model of diabetes), CBD protected them from arrythmia & cytotoxicity via inhibition of the sodium channels

Cannabidiol protects against high glucose-induced oxidative stress and cytotoxicity in cardiac voltage-gated sodium channels

https://pubmed.ncbi.nlm.nih.gov/32077098/

CBD modulates potassium channels to control neuronal excitability

Human kV7 channel subtypes are differentially modulated by cannabidiol

https://www.cell.com/biophysj/pdf/S0006-3495(21)02519-4.pdf

& CBD's modulation of potassium channel phenotypes

Cannabidiol differentially modulates Kv7 channelopathy-related phenotypes

https://www.cell.com/biophysj/pdf/S0006-3495(21)01791-4.pdf

How CBD modulates the TRPV2 channels

TRPV2 modulation by endogenous lipid and exogenous ligand (CBD)

https://www.cell.com/biophysj/pdf/S0006-3495(21)03185-4.pdf

Endocannabinoids modulate important potassium channels for maintaining the resting membrane potential of a cell

Endocannabinoid regulation of Kir2.1 inward rectifier potassium channels

https://www.cell.com/biophysj/pdf/S0006-3495(21)02529-7.pdf

In neurons, CBG helps to lower excitability via control of the sodium channels

Cannabigerol inhibits sodium conductance to reduce neuronal dorsal root ganglion excitability

https://www.cell.com/biophysj/pdf/S0006-3495(21)03215-X.pdf



Preclinical Research & Cannabinoid Chemistry


In mice, a combination of diet & exercise improved their ECS & their metabolic function

Effect of diet and physical exercise on endocannabinoid system and energy homeostasis in obese mice

https://e-century.us/files/ijcem/14/3/ijcem0118169.pdf

Endocannabinoids & endovanilloids balance each other’s actions in the release of stress hormones

Cannabinoid and vanilloid pathways mediate opposing forms of synaptic plasticity in corticotropin-releasing hormone neurons

https://pubmed.ncbi.nlm.nih.gov/35034400/

In this rat model of PTSD, they look at how THC & CBD might affect the stress responses

Cannabinoid use is enhanced by stress and changes conditioned stress responses

https://pubmed.ncbi.nlm.nih.gov/35145212/

In mice who are suckling, adding extra oleamide to the milk increases hippocampus growth & neuronal plasticity

Neonatal Supplementation of Oleamide During Suckling Promotes Learning Ability and Memory in Adolescent Mice

https://pubmed.ncbi.nlm.nih.gov/34967906/

Two medicinal Japanese plants for inflammation work at least partially via downregulation of the C2 receptor

Curcumae Longae Rhizoma and Saussureae Radix Inhibit Nitric Oxide Production and Cannabinoid Receptor 2 Down-regulation

https://pubmed.ncbi.nlm.nih.gov/34972719/

In mice with ocular blast injury, a CB2 receptor inverse agonist protected their eyes from visual deficits via the microglial cells

Raloxifene, a cannabinoid type-2 receptor inverse agonist, mitigates visual deficits and pathology and modulates microglia after ocular blast

https://pubmed.ncbi.nlm.nih.gov/35143834/

In tadpoles, CB1 regulates the growth of their optic neurons

Cannabinoid Receptor Type 1 regulates growth cone filopodia and axon dispersion in the optic tract of Xenopus laevis tadpoles

https://pubmed.ncbi.nlm.nih.gov/35060216/

In dairy calves, they have a similar pharmacokinetic response to CBD

Plasma Pharmacokinetics of Cannabidiol Following Oral Administration of Cannabidiol Oil to Dairy Calves

https://pubmed.ncbi.nlm.nih.gov/35141311/

In a mouse model of Down’s syndrome, the CB1 levels are upregulated on the GABA neurons (the inhibitory neurotransmitter) & downregulated on the glutamate neurons (the excitatory neurotransmitter)

Differential expression of the neuronal CB1 cannabinoid receptor in the hippocampus of male Ts65Dn Down syndrome mouse model

https://pubmed.ncbi.nlm.nih.gov/35158060/

On using antibodies to learn more about the CB1 receptors

Fit-for-purpose based testing and validation of antibodies to amino- and carboxy-terminal domains of cannabinoid receptor 1

https://pubmed.ncbi.nlm.nih.gov/34453219/

A biophysical look at the activation of the CB1 & CB2 receptors

Mechanistic understanding of cannabinoid receptors' activation to decipher ligand selectivity

https://www.cell.com/biophysj/pdf/S0006-3495(21)02732-6.pdf

A new series of drugs focused on the FAAH enzymes (that break down endocannabinoids) & the PPAR receptors (which live on the nuclear membrane & regulate genetic transcription

A New Series of Aryloxyacetic Acids Endowed with Multi-Target Activity towards Peroxisome Proliferator-Activated Receptors (PPARs), Fatty Acid Amide Hydrolase (FAAH), and Acetylcholinesterase (AChE)

https://www.mdpi.com/1420-3049/27/3/958

CBD also binds to these targets.

A look at the differences between 2-AG & its stereoisomers 1-AG & 3-AG

1-, 2- and 3-AG as substrates of the endocannabinoid enzymes and endogenous ligands of the cannabinoid receptor 1

https://pubmed.ncbi.nlm.nih.gov/34995983/

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