Endocannabinoid-Mediated Neuromodulation in the Olfactory Bulb: Functional and Therapeutic Significance.

ijms-logo “Endocannabinoid synthesis in the human body is naturally occurring and on-demand.

It occurs in response to physiological and environmental stimuli, such as stress, anxiety, hunger, other factors negatively disrupting homeostasis, as well as the therapeutic use of the phytocannabinoid cannabidiol and recreational use of exogenous cannabis.

Together with their specific receptors CB1R and CB2R, endocannabinoids are major components of endocannabinoid-mediated neuromodulation in a rapid and sustained manner. Extensive research on endocannabinoid function and expression includes studies in limbic system structures such as the hippocampus and amygdala.

The wide distribution of endocannabinoids, their on-demand synthesis at widely different sites, their co-existence in specific regions of the body, their quantitative differences in tissue type, and different pathological conditions indicate their diverse biological functions that utilize specific and overlapping pathways in multiple organ systems.

Here, we review emerging evidence of these pathways with a special emphasis on the role of endocannabinoids in decelerating neurodegenerative pathology through neural networks initiated by cells in the main olfactory bulb.”

https://www.ncbi.nlm.nih.gov/pubmed/32325875

https://www.mdpi.com/1422-0067/21/8/2850

Endocannabinoids and Stroke Prevention: Review of Clinical Studies.

View details for Cannabis and Cannabinoid Research cover image“The societal burden of ischemic stroke suggests a need for additional therapeutic categories in stroke prevention.

Modulation of the endocannabinoid system (ECS) is a rational target for stroke prevention because of its effects on inflammation, vascular tone, and metabolic balance, all well-described stroke risk factors.

In this article, we summarize the existing ECS clinical studies in human subjects’ research as they relate to conventional vascular risk factors associated with ischemic stroke.”

https://www.ncbi.nlm.nih.gov/pubmed/32322672

https://www.liebertpub.com/doi/10.1089/can.2018.0066

“The endocannabinoid system and stroke: A focused review. This review seeks to summarize the recent evidence for the role of the endocannabinoid signaling system in stroke pathophysiology, as well as the evidence from preclinical studies regarding the efficacy of cannabinoids as neuroprotective therapies in the treatment of stroke.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6458776/

A Comprehensive Patient and Public Involvement Program Evaluating Perception of Cannabis-Derived Medicinal Products in the Treatment of Acute Postoperative Pain, Nausea, and Vomiting Using a Qualitative Thematic Framework.

View details for Cannabis and Cannabinoid Research cover image“Cannabis-derived medicinal products (CDMPs) have antiemetic properties and in combination with opioids have synergistic analgesic effects in part signaling through the delta and kappa opioid receptors.

The objective of this patient and public involvement program was to determine perception of perioperative CDMPs in our local population to inform design of a clinical trial.

Consensus was that potential benefits of CDMPs were attractive compared with the known risk profile of opioid use. Decrease in opioid dependence was agreed to be an appropriate clinical end-point for a randomized controlled clinical trial and there was concurrence of positive opinion of a therapeutic schedule of 5 days.

The perception of postoperative CDMP therapy was overwhelmingly positive in this West London population. The data from this thematic analysis will inform protocol development of clinical trials to determine analgesic and antiemetic efficacy of CDMPs.”

https://www.ncbi.nlm.nih.gov/pubmed/32322678

https://www.liebertpub.com/doi/10.1089/can.2019.0020

Chronic Psychosocial Stress Causes Increased Anxiety-Like Behavior and Alters Endocannabinoid Levels in the Brain of C57Bl/6J Mice.

View details for Cannabis and Cannabinoid Research cover image“Chronic stress causes a variety of physiological and behavioral alterations, including social impairments, altered endocrine function, and an increased risk for psychiatric disorders. Thereby, social stress is one of the most effective stressful stimuli among mammals and considered to be one of the major risk factors for the onset and progression of neuropsychiatric diseases.

Although the chronic social defeat stress model has been extensively studied, little is known about the effects of repeated or chronic social defeat stress on the endocannabinoid system (ECS).

The present study aimed to understand the effects of chronic social stress on anxiety behavior and the levels of endocannabinoids (ECs) and two N-acylethanolamines (NAEs) in different brain regions of mice.

 

The current study confirms that the ECS plays an essential role in stress responses, whereby its modulation seems to be brain region dependent.”

https://www.ncbi.nlm.nih.gov/pubmed/32322676

https://www.liebertpub.com/doi/10.1089/can.2019.0041

“Deficiency in endocannabinoid signaling in the nucleus accumbens induced by chronic unpredictable stress.” https://www.ncbi.nlm.nih.gov/pubmed/20664582

“Cannabinoids ameliorate impairments induced by chronic stress to synaptic plasticity and short-term memory.” https://www.ncbi.nlm.nih.gov/pubmed/23426383

“Blunted stress reactivity in chronic cannabis users.”  https://link.springer.com/article/10.1007/s00213-017-4648-z?no-access=true

A preliminary study of the effects of cannabidiol (CBD) on brain structure in patients with epilepsy.

Epilepsy & Behavior Reports“This preliminary study examines whether daily CBD dose of 15-25 mg/kg produces cerebral macrostructure changes and, if present, how they relate to changes in seizure frequency.

In conclusion, short-term exposure to highly purified CBD may not affect cortical macrostructure.”

https://www.ncbi.nlm.nih.gov/pubmed/32322816

“We document no effect of CBD on gray matter volume and cortical thickness.”

https://www.sciencedirect.com/science/article/pii/S258998641930111X?via%3Dihub

Cannabis Indica speeds up Recovery from Coronavirus

ResearchGate“Cannabis Indica Speeds up Recovery from Coronavirus Severe acute respiratory syndrome (SARS) is a viral respiratory disease caused by the SARS coronavirus (SARS-CoV).

Cannabis indica speeds up recovery.

Recovered individuals do not infect others.

Cannabis indica resin is antiviral and inhibits cell proliferation.

It has a higher efficacy than any single compound like THC or CBD”

https://www.researchgate.net/publication/339746853_Cannabis_Indica_speeds_up_Recovery_from_Coronavirus

Bidirectional Longitudinal Associations Between Cannabis Use and Body Mass Index Among Adolescents.

View details for Cannabis and Cannabinoid Research cover imageLiterature on the association between cannabis use and body mass index (BMI) among adults suggests that greater cannabis use is associated with a lower BMI. However, results are mixed among adolescents, with both cross-sectional and longitudinal studies finding positive, negative, and nonsignificant associations between cannabis use and BMI.

This longitudinal study aims to shed light on these associations by prospectively examining the associations between cannabis use and BMI across a 2-year window in a large sample of adolescent cannabis users.

Results: Results showed that baseline BMI predicted a positive and significant association with cannabis use slope. In addition, there was a significant and negative correlation between the cannabis use slope and the BMI slope. These significant associations remained after controlling for relevant covariates.

Conclusions: Results are consistent with the adult literature that reports a negative association between cannabis use and BMI. Future research should focus on uncovering the mechanisms that may drive the association between cannabis use and BMI.”

https://www.ncbi.nlm.nih.gov/pubmed/32322679

https://www.liebertpub.com/doi/10.1089/can.2019.0091

Oral Cannabidiol Does Not Convert to Δ8-THC or Δ9-THC in Humans: A Pharmacokinetic Study in Healthy Subjects.

View details for Cannabis and Cannabinoid Research cover image“Recent studies have suggested that cannabidiol (CBD) could interconvert into Delta-8- and Delta-9- tetrahydrocannabinol. Thus, we tested the plasma samples of 120 healthy human subjects (60 male and 60 female), 60 in fasting and the other 60 under normal feeding conditions after acute administration of an oral solution containing CBD 300 mg.

The results showed that THC was not detected in plasma after the administration of CBD, and those study participants did not present psychotomimetic effects.

The findings presented here are consistent with previous evidence suggesting that the oral administration of CBD in a corn oil formulation is a safe route for the administration of the active substance without bioconversion to THC in humans.”

https://www.ncbi.nlm.nih.gov/pubmed/32322680

https://www.liebertpub.com/doi/10.1089/can.2019.0024

A Guide to Targeting the Endocannabinoid System in Drug Design.

ijms-logo “The endocannabinoid system (ECS) is one of the most crucial systems in the human organism, exhibiting multi-purpose regulatory character. It is engaged in a vast array of physiological processes, including nociception, mood regulation, cognitive functions, neurogenesis and neuroprotection, appetite, lipid metabolism, as well as cell growth and proliferation. Thus, ECS proteins, including cannabinoid receptors and their endogenous ligands’ synthesizing and degrading enzymes, are promising therapeutic targets. Their modulation has been employed in or extensively studied as a treatment of multiple diseases. However, due to a complex nature of ECS and its crosstalk with other biological systems, the development of novel drugs turned out to be a challenging task. In this review, we summarize potential therapeutic applications for ECS-targeting drugs, especially focusing on promising synthetic compounds and preclinical studies. We put emphasis on modulation of specific proteins of ECS in different pathophysiological areas. In addition, we stress possible difficulties and risks and highlight proposed solutions. By presenting this review, we point out information pivotal in the spotlight of ECS-targeting drug design, as well as provide an overview of the current state of knowledge on ECS-related pharmacodynamics and show possible directions for needed research.”

https://www.ncbi.nlm.nih.gov/pubmed/32316328

https://www.mdpi.com/1422-0067/21/8/2778

Cannabidiol improves survival and behavioural co-morbidities of Dravet syndrome in mice.

British Journal of Pharmacology“Dravet syndrome is a severe, genetic form of paediatric epilepsy associated with premature mortality and co-morbidities such as anxiety, depression, autism, motor dysfunction and memory deficits. Cannabidiol is an approved anticonvulsive drug in the United States and Europe for seizures associated with Dravet syndrome in patients 2 years of age and older. We investigated its potential to prevent premature mortality and improve associated co-morbidities.

EXPERIMENTAL APPROACH:

The efficacy of sub-chronic cannabidiol administration in two mouse models of Dravet syndrome was investigated. The effect of cannabidiol on neonatal welfare and survival was studied using Scn1a-/- mice. We then used a hybrid, heterozygote Scn1a+/- mouse model to study the effect of cannabidiol on survival and behavioural co-morbidities: motor deficits (rotarod and static-beam test), gait abnormality (gait test), social anxiety (social interaction test), anxiety-like (elevated plus maze) and depressive-like behaviours (sucrose preference test) and cognitive impairment (radial arm maze test).

KEY RESULTS:

In Scn1a-/- mice, cannabidiol increased survival and delayed worsening of neonatal welfare. In Scn1a+/- mice, chronic cannabidiol administration did not show any adverse effect on motor function and gait, reduced premature mortality, improved social behaviour and memory function, and reduced anxiety-like and depressive-like behaviours.

CONCLUSION AND IMPLICATIONS:

We are the first to demonstrate a potential disease-modifying effect of cannabidiol in animal models of Dravet syndrome. Cannabidiol treatment reduced premature mortality and improved several behavioural co-morbidities in Dravet syndrome mice. These crucial findings may be translated into human therapy to address behavioural co-morbidities associated with Dravet syndrome.”

https://www.ncbi.nlm.nih.gov/pubmed/32321192

https://bpspubs.onlinelibrary.wiley.com/doi/full/10.1111/bph.15003