Author Archives: David Worrell

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

Posted on by

View details for Cannabis and Cannabinoid Research cover image“Literature 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.

Posted on by

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.

Posted on by

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.

Posted on by

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

Cannabinoids in epilepsy: Clinical efficacy and pharmacological considerations.

Posted on by

Neurología“Advances in the development of drugs with novel mechanisms of action have not been sufficient to significantly reduce the percentage of patients presenting drug-resistant epilepsy. This lack of satisfactory clinical results has led to the search for more effective treatment alternatives with new mechanisms of action.

The aim of this study is to examine epidemiological aspects of the use of cannabis-based products for the treatment of epilepsy, with particular emphasis on the main mechanisms of action, indications for use, clinical efficacy, and safety.

In recent years there has been growing interest in the use of cannabis-based products for the treatment of a wide range of diseases, including epilepsy. The cannabis plant is currently known to contain more than 100 terpenophenolic compounds, known as cannabinoids. The 2 most abundant are delta-9-tetrahydrocannabinol and cannabidiol.

Studies of preclinical models of epilepsy have shown that these cannabinoids have anticonvulsant properties, and 100% purified cannabidiol and cannabidiol-enriched cannabis extracts are now being used to treat epilepsy in humans. Several open-label studies and randomised controlled clinical trials have demonstrated the efficacy and safety of these products.”

https://www.ncbi.nlm.nih.gov/pubmed/32317123

https://www.sciencedirect.com/science/article/pii/S0213485320300402?via%3Dihub

In Search of Preventative Strategies: Novel Anti-Inflammatory High-CBD Cannabis Sativa Extracts Modulate ACE2 Expression in COVID-19 Gateway Tissues

Posted on by
Preprints.org (@Preprints_org) | Twitter
“With the rapidly growing pandemic of COVID-19 caused by the new and challenging to treat zoonotic SARS-CoV2 coronavirus, there is an urgent need for new therapies and prevention strategies that can help curtail disease spread and reduce mortality. Inhibition of viral entry and thereby spread constitute plausible therapeutic avenues. Similar to other respiratory pathogens, SARS-CoV2 is transmitted through respiratory droplets, with potential for aerosol and contact spread. It uses receptor-mediated entry into the human host via angiotensin-converting enzyme II (ACE2) that is expressed in lung tissue, as well as oral and nasal mucosa, kidney, testes, and the gastrointestinal tract. Modulation of ACE2 levels in these gateway tissues may prove a plausible strategy for decreasing disease susceptibility.
Cannabis sativa, especially one high in the anti-inflammatory cannabinoid cannabidiol (CBD), has been proposed to modulate gene expression and inflammation and harbour anti-cancer and anti-inflammatory properties. Working under the Health Canada research license, we have developed over 800 new Cannabis sativa lines and extracts and hypothesized that high-CBD C. sativa extracts may be used to modulate ACE2 expression in COVID-19 target tissues. Screening C. sativa extracts using artificial human 3D models of oral, airway, and intestinal tissues, we identified 13 high CBD C. sativa extracts that modulate ACE2 gene expression and ACE2 protein levels. Our initial data suggest that some C. sativa extract down-regulate serine protease TMPRSS2, another critical protein required for SARS-CoV2 entry into host cells. While our most effective extracts require further large-scale validation, our study is crucial for the future analysis of the effects of medical cannabis on COVID-19.
The extracts of our most successful and novel high CBD C. sativa lines, pending further investigation, may become a useful and safe addition to the treatment of COVID-19 as an adjunct therapy. They can be used to develop easy-to-use preventative treatments in the form of mouthwash and throat gargle products for both clinical and at-home use. Such products ought to be tested for their potential to decrease viral entry via the oral mucosa. Given the current dire and rapidly evolving epidemiological situation, every possible therapeutic opportunity and avenue must be considered.”

Cannabinoids as therapeutics for PTSD.

Posted on by

Pharmacology & Therapeutics“Post-traumatic stress disorder (PTSD) is a complex disorder that involves dysregulation of multiple neurobiological systems. The traumatic stressor plays a causal role in producing psychological dysfunction and the pattern of findings suggests that the hypothalamic-pituitary-adrenal (HPA) axis, which is instrumental for stress adaptation, is critically dysfunctional in PTSD. Given the lack of understanding of the basic mechanisms and underlying pathways that cause the disorder and its heterogeneity, PTSD poses challenges for treatment.

Targeting the endocannabinoid (ECB) system to treat mental disorders, and PTSD in particular, has been the focus of research and interest in recent years. The ECB system modulates multiple functions, and drugs enhancing ECB signaling have shown promise as potential therapeutic agents in stress effects and other psychiatric and medical conditions.

In this review, we focus on the interaction between the ECB-HPA systems in animal models for PTSD and in patients with PTSD. We summarize evidence supporting the use of cannabinoids in preventing and treating PTSD in preclinical and clinical studies. As the HPA system plays a key role in the mediation of the stress response and the pathophysiology of PTSD, we describe preclinical studies suggesting that enhancing ECB signaling is consistent with decreasing PTSD symptoms and dysfunction of the HPA axis.

Overall, we suggest that a pharmacological treatment targeted at one system (e.g., HPA) may not be very effective because of the heterogeneity of the disorder. There are abnormalities across different neurotransmitter systems in the pathophysiology of PTSD and none of these systems function uniformly among all patients with PTSD. Hence, conceptually, enhancing ECB signaling may be a more effective avenue for pharmacological treatment.”

https://www.ncbi.nlm.nih.gov/pubmed/32311373

https://www.sciencedirect.com/science/article/abs/pii/S0163725820300796?via%3Dihub

Cannabinoids.

Posted on by

Cover of StatPearls“Cannabinoids, broadly speaking, are a class of biological compounds that bind to cannabinoid receptors. They are most frequently sourced from and associated with the plants of the Cannabis genus, including Cannabis sativa, Cannabis indica, and Cannabis ruderalis.

The earliest known use of cannabinoids dates back 5,000 years ago in modern Romania, while the documentation of the earliest medical dates back to around 400 AD. However, formal extraction, isolation, and structural elucidation of cannabinoids have taken place rather recently in the late 19th and early 20th centuries. Since then, numerous advancements have been made in further isolating naturally occurring cannabinoids, synthesizing artificial equivalents, and discovering the endogenous the endocannabinoid system in mammals, reptiles, fish, and birds.”

https://www.ncbi.nlm.nih.gov/pubmed/32310522

https://www.ncbi.nlm.nih.gov/books/NBK556062/

The Therapeutic Potential and Usage Patterns of Cannabinoids in People with Spinal Cord.

Posted on by

“People with spinal cord injuries (SCI) commonly experience pain and spasticity, but limitations of current treatments have generated interest in cannabis as a possible therapy.

We conducted this systematic review to: 1) examine usage patterns and reasons for cannabinoid use, and 2) determine the treatment efficacy and safety of cannabinoid use, in people with SCI.

Though 26 studies addressed cannabinoid usage, only 8 investigated its therapeutic potential on outcomes such as pain and spasticity.

The most common usage method was smoking. Relief of pain, spasticity and pleasure were the most common reasons for use. Statistically significant reduction of pain and spasticity was observed with cannabinoid use in 80% and 90% of experimental studies, respectively.

 

CONCLUSIONS:

Current evidence suggests cannabinoids may reduce pain and spasticity in people with SCI, but its effect magnitude and clinical significance is unclear. Existing information is lacking on optimal dosage, method of use, composition and concentration of compounds. Longterm, double-blind, RCTs, assessing a wider range of outcomes should be conducted to further understanding of the effects of cannabinoid use in people with SCI.”

https://www.ncbi.nlm.nih.gov/pubmed/32310048

http://www.eurekaselect.com/181078/article

“Cannabis cures the spine” https://www.jtcvs.org/article/S0022-5223(18)32080-4/fulltext

Promising in vitro antioxidant, anti-acetylcholinesterase and neuroactive effects of essential oil from two non-psychotropic Cannabis sativa L. biotypes.

Posted on by

Phytotherapy Research“The aim of this study was to compare the micro-morphological features of two different non-drug Cannabis sativa L. biotypes (Chinese accession G-309 and one fibrante variety) and to evaluate the phytochemical profile as well as some biological properties of the essential oils (EOs) obtained by hydrodistillation of dried flowering tops. After a micro-morphological evaluation by scanning electron microscopy, the phytochemical composition was analysed by GC-FID and GC-MS analyses.

Antioxidant and anti-acetylcholinesterase properties were investigated by several in vitro cell-free assays, while neuroactive effects were evaluated on mouse cortical neuronal as well as human iPS cell-derived central nervous system cells grown on MEA chips. Both EOs showed strong antioxidant properties mainly attributable to the high content of hydroxylated compounds as well as significant anti-acetylcholinesterase activities (IC50 74.64 and 57.31 μg/ml for Chinese accession and fibrante variety, respectively).

Furthermore, they showed a concentration-dependent inhibition of spontaneous electrical activity of human and mouse neuronal networks, with the fibrante variety, which showed the best activity (MFR, IC50 0.71 and 10.60 μg/ml, respectively). The observed biological activities could be due to a synergic effect between terpenes and phytocannabinoids, although in vivo studies, which clarify the molecular mechanism, are still lacking.”

https://www.ncbi.nlm.nih.gov/pubmed/32309898

https://onlinelibrary.wiley.com/doi/abs/10.1002/ptr.6678