Author Archives: David Worrell

Role of miRNA in the regulation of cannabidiol-mediated apoptosis in neuroblastoma cells.

Posted on by

Related image

“Neuroblastoma (NBL) is one of the most common childhood cancers that originate from the immature nerve cells of the sympathetic system. Studies with NBL cancers have also shown that miRNAs are dysregulated and may play a critical role in pathogenesis.

Cannabidiol (CBD) is a non-psychoactive compound found in marijuana which has been previously shown by our laboratory and others to induce apoptosis in cancer cells. However, there are no studies reported to test if CBD mediates these effects through regulation of miRNA.

In the current study, therefore, we investigated if CBD induces apoptosis in human NBL cell lines, SH SY5Y and IMR-32, and if it is regulated by miRNA.

Our data demonstrated that CBD induces apoptosis in NBL cells through activation of serotonin and vanilloid receptors. We also found that caspase-2 and -3 played an important role in the induction of apoptosis. CBD also significantly reduced NBL cell migration and invasion in vitro.

Furthermore, CBD blocked mitochondrial respiration and caused a shift in metabolism towards glycolysis. CBD altered the expression of miRNA specifically, down-regulating hsa-let-7a and upregulating hsa-mir-1972. Downregulation of let-7a increased expression of target caspase-3, and growth arrest specific-7 (GAS-7) genes. Upregulation of hsa-mir-1972 caused decreased expression of BCL2L1 and SIRT2 genes.

Together, our studies suggest that CBD-mediated apoptosis in NBL cells is regulated by miRNA.”

 https://www.ncbi.nlm.nih.gov/pubmed/30713602

Novel Approaches for Treating Pain in Children.

Posted on by

Logo SpringerLink“Good pain management in children, especially those at end of life, is a crucial component of palliative medicine. The current review assesses some of the new and/or innovative ways to manage pain in children. The article focuses on some recent medications/pharmaceutical options such as cannabinoids and also innovative ways to administer medication to children, such as intranasal and inhalation.

RECENT FINDINGS:

Current approaches to pain management now include (1) new uses of old drugs such as ketamine and lidocaine, (2) use of new drugs/medications such as cannabinoids, and (3) creative use of old technology such as atomizers, intranasal drops, and inhalation. Typically, novel approaches to care rarely start in pediatrics or palliative care. The current review has presented some new and old drugs being utilized in new and old ways.”

https://www.ncbi.nlm.nih.gov/pubmed/30714078

https://link.springer.com/article/10.1007%2Fs11912-019-0766-6

[MEDICAL CANNABIS – A SOURCE FOR A NEW TREATMENT FOR AUTOIMMUNE DISEASE?].

Posted on by

Image result for harefuah journal

“Medical uses of Cannabis sativa have been known for over 6,000 years. Nowadays, cannabis is mostly known for its psychotropic effects and its ability to relieve pain, even though there is evidence of cannabis use for autoimmune diseases like rheumatoid arthritis centuries ago. The pharmacological therapy in autoimmune diseases is mainly based on immunosuppression of diffefent axes of the immune system while many of the drugs have major side effects. In this review we set out to examine the rule of Cannabis sativa as an immunomodulator and its potential as a new treatment option. In order to examine this subject we will focus on some major autoimmune diseases such as diabetes type I and rheumatoid arthritis.”

https://www.ncbi.nlm.nih.gov/pubmed/27215114

A Comprehensive Review of Cannabis in Patients with Cancer: Availability in the USA, General Efficacy, and Safety.

Posted on by

 “As the legalization of medical cannabis continues across the USA, oncology care providers will be increasingly asked to provide recommendations regarding its use in the cancer setting.

In this article, we review recent literature that analyzes cannabis use specifically in patients with cancer and provide an accessible guide for clinicians, researchers, and patients.

We aimed to answer questions about the availability of cannabis in the USA, the trials supporting its use in the cancer setting, and the important factors to consider related to safety. Thirty states plus the District of Columbia have established comprehensive medical cannabis programs, each with different regulations and products available.

 

In June 2018, Epidiolex, a cannabis extraction product containing 99% CBD, was approved to treat refractory seizures; however, whole-plant products and non-prescription extraction products dominate the market.

 

Recent randomized, placebo-controlled studies of nabiximols (Sativex) in patients with refractory cancer-pain have largely shown no significant benefits. Conversely, large observational studies suggest patients with cancer using cannabis report significant improvement of many common symptoms.

 

Cannabis use appears well tolerated, with few serious adverse effects reported. Though prospective clinical trials are needed to provide the robust data required to establish the proper role of cannabinoid and cannabis-based therapy in cancer patients, physicians can draw upon the knowledge currently available to have informed discussions with their patients.”

https://www.ncbi.nlm.nih.gov/pubmed/30707319

https://link.springer.com/article/10.1007%2Fs11912-019-0757-7

Synthetic Cannabinoids Influence the Invasion of Glioblastoma Cell Lines in a Cell- and Receptor-Dependent Manner.

Posted on by

cancers-logo

“The current treatment of glioblastoma is not sufficient, since they are heterogeneous and often resistant to chemotherapy.

Earlier studies demonstrated effects of specific cannabinoid receptor (CB) agonists on the invasiveness of glioblastoma cell lines, but the exact mechanism remained unclear.

Three human glioblastoma cell lines were treated with synthetic CB ligands. The effect of cannabinoids on microRNAs (miRs), Akt, and on the expression of proliferation and apoptosis markers were analyzed.

Furthermore, in a model of organotypic hippocampal slice cultures cannabinoid mediated changes in the invasiveness were assessed. MicroRNAs and the activation of Akt which are related to cell migration, apoptosis, and proliferation were evaluated and found not to be associated with changes in the invasiveness after treatment with CB ligands.

Also proliferation and/or apoptosis were not altered after treatment. The effects of cannabinoids on invasiveness could be blocked by the application of receptor antagonists and are likely mediated via CB₁/CB₂.

In conclusion, our results suggest that cannabinoids can influence glioblastoma cell invasion in a receptor and cell type specific manner that is independent of proliferation and apoptosis. Thus, cannabinoids can potentially be used in the future as an addition to current therapy.”

https://www.ncbi.nlm.nih.gov/pubmed/30709059
https://www.mdpi.com/2072-6694/11/2/161

Opposite effects of cannabinoid CB1 and CB2 receptors on antipsychotic clozapine-induced cardiotoxicity.

Posted on by

Publication cover image

“Clozapine is an atypical antipsychotic drug that is very efficacious in treating psychosis but the risk of severe cardiotoxicity limits its clinical use.

The present study investigated the myocardial injury effects of clozapine and assessed the involvement of cannabinoid receptors in clozapine cardiotoxicity.

Our data provided evidence that cannabinoid CB1 and CB2 receptors had opposite effects and selective antagonists of CB1R or agonists of CB2R might confer protective effects against clozapine.”

https://www.ncbi.nlm.nih.gov/pubmed/30707759

https://bpspubs.onlinelibrary.wiley.com/doi/abs/10.1111/bph.14591

Activation of the cannabinoid CB2 receptor increases renal perfusion.

Posted on by

Physiological Genomics 0 0 cover image

“Acute kidney injury (AKI) is an increasing problem clinically and is associated with chronic kidney disease progression.

Cannabinoid type 2 receptor activation has been shown to mitigate some of the deleterious tubular effects due to AKI, but its role on the renal vasculature has not been fully described.

In this study, we investigated the effects of our novel cannabinoid CB2 receptor agonist, SMM-295, on renal vasculature by assessing cortical perfusion using laser Doppler flowmetry and changes in luminal diameter using isolated afferent arterioles.

These data provide new insight into the potential benefit of SMM-295 by activating vascular and non-vascular CB2 receptors to promote renal vasodilation, and provide a new therapeutic target to treat renal injuries that impact renal blood flow dynamics.”

 https://www.ncbi.nlm.nih.gov/pubmed/30707046
https://www.physiology.org/doi/abs/10.1152/physiolgenomics.00001.2019

Is cannabidiol the ideal drug to treat non-motor Parkinson’s disease symptoms?

Posted on by

 “Parkinson’s disease (PD) is a chronic neurodegenerative disorder characterized by motor symptoms such as bradykinesia, rest tremor, postural disturbances, and rigidity. PD is also characterized by non-motor symptoms such as sleep disturbances, cognitive deficits, and psychiatric disorders such as psychosis, depression, and anxiety. The pharmacological treatment for these symptoms is limited in efficacy and induce significant adverse reactions, highlighting the need for better treatment options.

Cannabidiol (CBD) is a phytocannabinoid devoid of the euphoriant and cognitive effects of tetrahydrocannabinol, and preclinical and preliminary clinical studies suggest that this compound has therapeutic effect in non-motor symptoms of PD.

In the present text, we review the clinical studies of cannabinoids in PD and the preclinical and clinical studies specifically on CBD.

We found four randomized controlled trials (RCTs) involving the administration of agonists/antagonists of the cannabinoid 1 receptor, showing that these compounds were well tolerated, but only one study found positive results (reductions on levodopa-induced dyskinesia).

We found seven preclinical models of PD using CBD, with six studies showing a neuroprotective effect of CBD.

We found three trials involving CBD and PD: an open-label study, a case series, and an RCT. CBD was well tolerated, and all three studies reported significant therapeutic effects in non-motor symptoms (psychosis, rapid eye movement sleep behaviour disorder, daily activities, and stigma). However, sample sizes were small and CBD treatment was short (up to 6 weeks). Large-scale RCTs are needed to try to replicate these results and to assess the long-term safety of CBD.”

https://www.ncbi.nlm.nih.gov/pubmed/30706171

https://link.springer.com/article/10.1007%2Fs00406-019-00982-6

How effective and safe is medical cannabis as a treatment of mental disorders? A systematic review.

Posted on by

“We conducted a review of systematic reviews (SRs) and randomized-controlled trials (RCTs) to analyze efficacy and safety of cannabis-based medication in patients with mental disorders.

Five data bases were systematically searched (2006-August 2018); 4 SRs (of 11 RCTs) and 14 RCTs (1629 participants) were included. Diagnoses were: dementia, cannabis and opioid dependence, psychoses/schizophrenia, general social anxiety, posttraumatic stress disorder, anorexia nervosa, attention-deficit hyperactivity disorder, and Tourette`s disorder. Outcome variables were too heterogeneous to conduct a  meta-analysis. A narrative synthesis method was applied. The study quality was assessed using the risk-of-bias tool and SIGN-checklists.

THC- and CBD-based medicines, given as adjunct to pharmaco- and psychotherapy, were associated with improvements of several symptoms of mental disorders, but not with remission. Side effects occurred, but severe adverse effects were mentioned in single cases only. In order to provide reliable treatment recommendations, more and larger RCTs with follow-up assessments, consistent outcome measures and active comparisons are needed.”

https://www.ncbi.nlm.nih.gov/pubmed/30706168

https://link.springer.com/article/10.1007%2Fs00406-019-00984-4

Potential Use of Cannabinoids for the Treatment of Pancreatic Cancer.

Posted on by

Image result for Journal Pancreatic Cancer

“Cannabinoid extracts may have anticancer properties, which can improve cancer treatment outcomes.

The aim of this review is to determine the potentially utility of cannabinoids in the treatment of pancreatic cancer.

Results: Cannabinol receptors have been identified in pancreatic cancer with several studies showing in vitroantiproliferative and proapoptotic effects. The main active substances found in cannabis plants are cannabidiol (CBD) and tetrahydrocannabinol (THC). There effects are predominately mediated through, but not limited to cannabinoid receptor-1, cannabinoid receptor-2, and G-protein-coupled receptor 55 pathways. In vitro studies consistently demonstrated tumor growth-inhibiting effects with CBD, THC, and synthetic derivatives. Synergistic treatment effects have been shown in two studies with the combination of CBD/synthetic cannabinoid receptor ligands and chemotherapy in xenograft and genetically modified spontaneous pancreatic cancer models. There are, however, no clinical studies to date showing treatment benefits in patients with pancreatic cancer.

Conclusions: Cannabinoids may be an effective adjunct for the treatment of pancreatic cancer. Data on the anticancer effectiveness of various cannabinoid formulations, treatment dosing, precise mode of action, and clinical studies are lacking.”

 https://www.ncbi.nlm.nih.gov/pubmed/30706048
“Endogenous cannabinoids, synthetic or cannabis extracted from plants, can reduce tumor invasion and growth, induce tumor cell death, and inhibit tumor angiogenesis via cannabinoid receptor or receptor-independent pathways. Cannabinoid receptors appear to be highly expressed in pancreatic cancer compared with normal pancreatic tissue. CBD and THC appear to have antiproliferative and proapoptotic effects.”
https://www.liebertpub.com/doi/10.1089/pancan.2018.0019