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?
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
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