The non-euphoric phytocannabinoid cannabidivarin counteracts intestinal inflammation in mice and cytokine expression in biopsies from UC pediatric patients.

Pharmacological Research“Patients with ulcerative colitis (UC) using marijuana have been reported to experience symptomatic benefit.

Cannabidivarin (CBDV) is a safe non-psychoactive phytocannabinoid able to activate TRPA1, a member of TRP channels superfamily, which plays a pivotal role in intestinal inflammation.

Here, we have investigated the potential intestinal anti-inflammatory effect of CBDV in mice and in biopsies from pediatric patients with active UC.

Our preclinical study shows that CBDV exerts intestinal anti-inflammatory effects in mice via TRPA1, and in children with active UC.

Since CBDV has a favorable safety profile in humans, it may be considered for possible clinical trials in patients with UC.”

https://www.ncbi.nlm.nih.gov/pubmed/31553934

https://linkinghub.elsevier.com/retrieve/pii/S1043661819311077

Cannabidiol Is a Novel Modulator of Bacterial Membrane Vesicles.

 Image result for frontiers in cellular and infection microbiology“Membrane vesicles (MVs) released from bacteria participate in cell communication and host-pathogen interactions.

Roles for MVs in antibiotic resistance are gaining increased attention and in this study we investigated if known anti-bacterial effects of cannabidiol (CBD), a phytocannabinoid from Cannabis sativa, could be in part attributed to effects on bacterial MV profile and MV release.

We found that CBD is a strong inhibitor of MV release from Gram-negative bacteria (E. coli VCS257), while inhibitory effect on MV release from Gram-positive bacteria (S. aureus subsp. aureus Rosenbach) was negligible. When used in combination with selected antibiotics, CBD significantly increased the bactericidal action of several antibiotics in the Gram-negative bacteria.

In addition, CBD increased antibiotic effects of kanamycin in the Gram-positive bacteria, without affecting MV release. CBD furthermore changed protein profiles of MVs released from E. coli after 1 h CBD treatment.

Our findings indicate that CBD may pose as a putative adjuvant agent for tailored co-application with selected antibiotics, depending on bacterial species, to increase antibiotic activity, including via MV inhibition, and help reduce antibiotic resistance.”

https://www.ncbi.nlm.nih.gov/pubmed/31552202

https://www.frontiersin.org/articles/10.3389/fcimb.2019.00324/full 

Δ9-Tetrahydrocannabinol During Adolescence Attenuates Disruption of Dopamine Function Induced in Rats by Maternal Immune Activation.

Image result for frontiers in behavioral neuroscience“Here, we hypothesized that adolescent Δ9-tetrahydrocannabinol (THC) worsens the impact of prenatal maternal immune activation (MIA) on ventral tegmental area (VTA) dopamine cells in rat offspring.

Adolescent THC attenuated several MIA-induced effects.

Contrary to our expectations, adolescent THC did not worsen MIA-induced deficits.”

https://www.ncbi.nlm.nih.gov/pubmed/31551729

https://www.frontiersin.org/articles/10.3389/fnbeh.2019.00202/full

Cannabis use in cancer: a survey of the current state at BC Cancer before recreational legalization in Canada.

Image result for Curr Oncol.“Cancer patients experience multiple symptoms throughout their illness, and some report benefit from the use of cannabis. There are concerns that many patients are accessing products inappropriate for their situation and potentially putting themselves at risk.

In the present study, we aimed to capture the prevalence of cannabis use among cancer patients at BC Cancer before recreational legalization in Canada and to identify the reasons that patients take cannabis, the various routes of administration they use, and the reasons that prior users stopped.

RESULTS:

Of surveys sent to 2998 patients, 821 (27.4%) were returned and included in analysis. Of those respondents, 23% were currently using cannabis-based products, almost exclusively for medical purposes, and an additional 28% had been users in the past (most often recreationally). Of the patients currently using cannabis, 31% had medical authorization. The most common symptoms that the current users were targeting were pain, insomnia, nausea, and anxiety; many were also hoping for anticancer effects.

CONCLUSIONS:

More than half the respondents had tried cannabis at some time, and almost one quarter of respondents were currently taking cannabis to help manage their symptoms or treat their cancer, or both. Many more patients would consider use with appropriate guidance from a health care professional. More research is needed to inform physicians and patients about safe uses and doses and about the potential adverse effects of cannabis use.”

https://www.ncbi.nlm.nih.gov/pubmed/31548810

A National Survey of Marijuana Use Among US Adults With Medical Conditions, 2016-2017.

Image result for JAMA network“This study found that marijuana use was more common among adults with medical conditions than those without such conditions.”

https://www.ncbi.nlm.nih.gov/pubmed/31539078/

https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2751558

Medical cannabis for chronic pain: can it make a difference in pain management?

 “Globally, chronic pain is a major therapeutic challenge and affects more than 15% of the population. As patients with painful terminal diseases may face unbearable pain, there is a need for more potent analgesics.

Although opioid-based therapeutic agents received attention to manage severe pain, their adverse drug effects and mortality rate associated with opioids overdose are the major concerns.

Evidences from clinical trials showed therapeutic benefits of cannabis, especially delta-9-tetrahydrocannabinol and cannabinoids reduced neuropathic pain intensity in various conditions. Also, there are reports on using combination cannabinoid therapies for chronic pain management.

The association of cannabis dependence and addiction has been discussed much and the reports mentioned that it can be comparatively lower than other substances such as nicotine and alcohol.

More countries have decided to legalise the medicinal use of cannabis and marijuana.

Healthcare professionals should keep themselves updated with the changing state of medical cannabis and its applications.”

https://www.ncbi.nlm.nih.gov/pubmed/31535218

https://link.springer.com/article/10.1007%2Fs00540-019-02680-y

Insights into the role of cannabis in the management of inflammatory bowel disease.

Image result for therapeutic advances in gastroenterology“Cannabis, a drug made up of the flowers and buds of the Cannabis sativa plant, has been used therapeutically for centuries. Ancient Chinese cultures have reported use in their medical practices, dating back as early as 2700 BC.  Although widely used recreationally during the 19th and 20th centuries, the use of medical cannabis has exploded over the last decade, as a result of mainstream cultural acceptance and legalization in several countries around the world.

Over the last decade, interest in the therapeutic potential of cannabis and its constituents (e.g. cannabidiol) in the management of inflammatory bowel diseases (IBD) has escalated. Cannabis has been increasingly approved for a variety of medical conditions in several jurisdictions around the world.

In animal models, cannabinoids have been shown to improve intestinal inflammation in experimental models of IBD through their interaction with the endocannabinoid system. However, the few randomized controlled trials of cannabis or cannabidiol in patients with IBD have not demonstrated efficacy in modulating inflammatory disease activity.

Cannabis may be effective in the symptomatic management of IBD. Given the increasing utilization and cultural acceptance of cannabis, physicians need to be aware of its safety and efficacy in order to better counsel patients. The aim of this review is to provide an overview of the role of cannabis in the management of patients with IBD.

There is emerging evidence that cannabis may play a role in the management of patients with IBD. Many patients are already using cannabis to help manage symptoms associated with the disease, and physicians cannot ignore this when taking histories and managing their patients.”

https://www.ncbi.nlm.nih.gov/pubmed/31523278

https://journals.sagepub.com/doi/10.1177/1756284819870977

Evaluation of the effects of cannabinoids CBD and CBG on human ovarian cancer cells in vitro

University of Huddersfield“Ovarian cancer, with over a 90% reoccurrence within 18 months of treatment, and approximately a 30% mortality rate after 5 years, is the leading cause of death in cases of gynaecological malignancies. Acquired resistance, and toxic side effects by clinically used agents are major challenges associated with current treatments, indicating the need for new approaches in ovarian cancer treatment.

Increased tumour cell proliferation associated with upregulation of cannabinoid (CB) receptors has been observed in ovarian cancer. As cannabinoids reported to bind to CB receptors, and can potentially modulate their downstream signalling, this raises the possibility of cannabinoids as potential anticancer drugs for ovarian cancer treatment.

Amongst the cannabinoids, non-psychoactive CBD and CBG have been shown to have anticancer activities towards prostate and colon cancer cells through multiple mechanisms of action. However, CBD and CBG have yet to be investigated in relation to ovarian cancer therapy either in vitro or in vivo.

Aim:

The aims of this study were to evaluate the potential cytotoxic effects of CBD and CBG in human ovarian cancer cells, their ability to potentiate existing clinically used agents for ovarian cancer, and to perform initial mode of action studies in vitro.

Conclusions:

Both CBD and CBG showed preferential cytotoxicity against the ovarian cancer cells analysed compared to the non-cancer cells; however, this was less than for carboplatin. Importantly, in contrast to carboplatin, CBD and CBG showed similar activity towards cisplatin sensitive and cisplatin resistant cells indicating distinctive mechanisms of action to platinum drugs.

Preferential cytotoxicity towards cancer cells in vitro and ability to potentiate carboplatin and overcome cisplatin resistance identify CBD and CBG as promising candidates that warrant further investigation, both in terms of detailed mechanism of action studies and also in vivo studies to assess whether this promising activity translates into an in vivo setting and their potential for further progression towards the clinic.”

http://eprints.hud.ac.uk/id/eprint/34866/

Cannabidiol induces antioxidant pathways in keratinocytes by targeting BACH1.

Redox Biology“Cannabidiol (CBD) is a major non-psychotropic phytocannabinoid that attracted a great attention for its therapeutic potential against different pathologies including skin diseases.

However, although the efficacy in preclinical models and the clinical benefits of CBD in humans have been extensively demonstrated, the molecular mechanism(s) and targets responsible for these effects are as yet unknown.

Herein we characterized at the molecular level the effects of CBD on primary human keratinocytes using a combination of RNA sequencing (RNA-Seq) and sequential window acquisition of all theoretical mass spectrometry (SWATH-MS).

Functional analysis revealed that CBD regulated pathways involved in keratinocyte differentiation, skin development and epidermal cell differentiation among other processes. In addition, CBD induced the expression of several NRF2 target genes, with heme oxygenase 1 (HMOX1) being the gene and the protein most upregulated by CBD. CRISPR/Cas9-mediated genome editing, RNA interference and biochemical studies demonstrated that the induction of HMOX1 mediated by CBD, involved nuclear export and proteasomal degradation of the transcriptional repressor BACH1.

Notably, we showed that the effect of BACH1 on HMOX1 expression in keratinocytes is independent of NRF2. In vivo studies showed that topical CBD increased the levels of HMOX1 and of the proliferation and wound-repair associated keratins 16 and 17 in the skin of mice.

Altogether, our study identifies BACH1 as a molecular target for CBD in keratinocytes and sets the basis for the use of topical CBD for the treatment of different skin diseases including atopic dermatitis and keratin disorders.”

https://www.ncbi.nlm.nih.gov/pubmed/31518892

https://www.sciencedirect.com/science/article/pii/S2213231719306470?via%3Dihub