“Expansion of medical marijuana (MM) laws in the United States may offer oncology new therapeutic options. This study qualitatively explored professional opinion around the role of MM in cancer care. Expert opinion was divided between conviction in marijuana’s medicinal potential to guardedness in this assertion, with no participant refuting MM’s utility outright. Emergent themes included: that MM ameliorates cancer-related pain and nausea and is safer than certain conventional medications. Participants called for enhanced purity and production standards, and further research on MM’s utility.” https://www.ncbi.nlm.nih.gov/pubmed/28040884]]>
Tag Archives: therapeutic
Experts’ Perspectives on the Role of Medical Marijuana in Oncology: a semi-structured interview study.
“Expansion of medical marijuana (MM) laws in the United States may offer oncology new therapeutic options.
This study qualitatively explored professional opinion around the role of MM in cancer care.
Expert opinion was divided between conviction in marijuana’s medicinal potential to guardedness in this assertion, with no participant refuting MM’s utility outright.
Emergent themes included: that MM ameliorates cancer-related pain and nausea and is safer than certain conventional medications.
Participants called for enhanced purity and production standards, and further research on MM’s utility.”
Cannabidiol Modulates the Expression of Alzheimer’s Disease-Related Genes in Mesenchymal Stem Cells.
“Mesenchymal stem cells (MSCs) have emerged as a promising tool for the treatment of several neurodegenerative disorders, including Alzheimer’s disease (AD). The main neuropathological hallmarks of AD are senile plaques, composed of amyloid beta (Aβ), and neurofibrillary tangles, formed by hyperphosphorylated tau. However, current therapies for AD have shown limited efficacy.
In this study, we evaluated whether pre-treatment with cannabidiol (CBD), at 5 μM concentration, modulated the transcriptional profile of MSCs derived from gingiva (GMSCs) in order to improve their therapeutic potential, by performing a transcriptomic analysis by the next-generation sequencing (NGS) platform.
By comparing the expression profiles between GMSCs treated with CBD (CBD-GMSCs) and control GMSCs (CTR-GMSCs), we found that CBD led to the downregulation of genes linked to AD, including genes coding for the kinases responsible of tau phosphorylation and for the secretases involved in Aβ generation. In parallel, immunocytochemistry analysis has shown that CBD inhibited the expression of GSK3β, a central player in AD pathogenesis, by promoting PI3K/Akt signalling.
In order to understand through which receptor CBD exerted these effects, we have performed pre-treatments with receptor antagonists for the cannabinoid receptors (SR141716A and AM630) or for the vanilloid receptor 1 (TRPVI). Here, we have proved that TRPV1 was able to mediate the modulatory effect of CBD on the PI3K/Akt/GSK3β axis.
In conclusion, we have found that pre-treatment with CBD prevented the expression of proteins potentially involved in tau phosphorylation and Aβ production in GMSCs. Therefore, we suggested that GMSCs preconditioned with CBD possess a molecular profile that might be more beneficial for the treatment of AD.”
Bidirectional Effects of Cannabidiol on Contextual Fear Memory Extinction
“Cannabidiol (CBD) is the major non-psychotropic constituent of the Cannabis plant and has anxiolytic therapeutic potential.
Cannabidiol (CBD) has been established to have both acute and long-lasting effects to reduce fear memory expression.
We showed that under conditions of strong fear conditioning, CBD reduced contextual fear memory expression both acutely during the extinction session as well as later at a fear retention test.
This pattern of results is consistent with CBD enhancing contextual fear memory extinction when the initial conditioning is strong, but impairing extinction when conditioning is weak. This bidirectional effect of CBD may be related to stress levels induced by conditioning and evoked at retrieval during extinction, rather than the strength of the memory per se.
In summary, CBD had bidirectional effects on the extinction of contextual fear conditioning, depending on the nature of the initial fear conditioning. Nevertheless, in the more translationally-relevant stronger conditioning setting, CBD both acutely inhibited fear expression and enhanced extinction to produce longer lasting reductions in fear.
These observations provide further support for the potential translational use of CBD in conditions such as posttraumatic stress disorder and specific phobias.”
Cannabinoid 2 Receptor Agonist Improves Systemic Sensitivity to Insulin in High-Fat Diet/Streptozotocin-Induced Diabetic Mice.
“The endocannabinoid signalling (ECS) system has been known to regulate glucose homeostasis.
Previous studies have suggested that the cannabinoid 2 (CB2) receptor may play a regulatory role on insulin secretion, immune modulation and insulin resistance.
Given that diabetes and insulin resistance are attributable to elevated inflammatory tone, we investigated the role of CB2 receptor on glucose tolerance and insulin sensitivity in high-fat diet (HFD)/streptozotocin (STZ)-induced mice.
Our data suggest a lipolytic role of SER601 in HFD/STZ-induced diabetic mice, which results in significant improvement of systemic insulin sensitivity.
Thus, the CB2 receptor may be considered a promising target for therapeutic development against insulin resistance and obesity-related diabetes.”
Compensatory activation of cannabinoid CB2 receptor inhibition of GABA release in the rostral ventromedial medulla (RVM) in inflammatory pain.
“The rostral ventromedial medulla (RVM) is a relay in the descending pain modulatory system and an important site of endocannabinoid modulation of pain.
These studies demonstrate that endocannabinoid signaling to CB1- and CB2-receptors in adult RVM is altered in persistent inflammation.
The emergence of CB2 receptor function in the RVM provides additional rationale for the development of CB2 receptor-selective agonists as useful therapeutics for chronic inflammatory pain.”
Tamoxifen Isomers and Metabolites Exhibit Distinct Affinity and Activity at Cannabinoid Receptors: Potential Scaffold for Drug Development.
“Tamoxifen (Tam) is a selective estrogen receptor (ER) modulator (SERM) that is an essential drug to treat ER-positive breast cancer. Aside from known actions at ERs, recent studies have suggested that some SERMs like Tam also exhibit novel activity at cannabinoidsubtype 1 and 2 receptors (CB1R and CB2Rs).
Collectively, these results suggest that the SERMs Tam, 4OHT and End elicit ER-independent actions via CBRs in an isomer-specific manner.
As such, this novel structural scaffold might be used to develop therapeutically useful drugs for treatment of a variety of diseases mediated via CBRs.”
AM251 Suppresses Epithelial-Mesenchymal Transition of Renal Tubular Epithelial Cells.
“Epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells is one of the causative mechanisms of kidney fibrosis.
In our study, we screened lipophilic compounds using a lipid library including approximately 200 lipids to identify those that suppressed EMT induced by a transforming growth factor (TGF)-β1 stimulus.
Our findings regarding the effects of AM251 on the TGF-β signaling pathway may inform development of a novel therapeutic agent suppressing EMT, thus preventing kidney fibrosis.”
Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells.
“Human Gingival Mesenchymal Stem Cells (hGMSCs) are multipotential cells that can expand and differentiate in culture under specific and standardized conditions.
In the present study, we have investigated whether in vitro pre-treatment of hGMSCs with Cannabidiol(CBD) can influence their expression profile, improving the therapeutic potential of this cell culture.
In conclusion, the present study will provide a new simple and reproducible method for preconditioning hGMSCs with CBD, before transplantation, as an interesting strategy for improving the hGMSCs molecular phenotype, reducing the risk of immune or inflammatory reactions in the host, and in parallel, for increasing their survival and thus, their long-term therapeutic efficacy.”
Cannabidiol Regulation of Learned Fear: Implications for Treating Anxiety-Related Disorders.
“Anxiety and trauma-related disorders are psychiatric diseases with a lifetime prevalence of up to 25%. Phobias and post-traumatic stress disorder (PTSD) are characterized by abnormal and persistent memories of fear-related contexts and cues. The effects of psychological treatments such as exposure therapy are often only temporary and medications can be ineffective and have adverse side effects.
Growing evidence from human and animal studies indicates that cannabidiol, the main non-psychotomimetic phytocannabinoid present in Cannabis sativa, alleviates anxiety in paradigms assessing innate fear.
More recently, the effects of cannabidiol on learned fear have been investigated in preclinical studies with translational relevance for phobias and PTSD.
Here we review the findings from these studies, with an emphasis on cannabidiol regulation of contextual fear.
The evidence indicates that cannabidiol reduces learned fear in different ways: (1) cannabidiol decreases fear expression acutely, (2) cannabidiol disrupts memory reconsolidation, leading to sustained fear attenuation upon memory retrieval, and (3) cannabidiol enhances extinction, the psychological process by which exposure therapy inhibits learned fear.
We also present novel data on cannabidiol regulation of learned fear related to explicit cues, which indicates that auditory fear expression is also reduced acutely by cannabidiol.
We conclude by outlining future directions for research to elucidate the neural circuit, psychological, cellular, and molecular mechanisms underlying the regulation of fear memory processing by cannabidiol.
This line of investigation may lead to the development of cannabidiol as a novel therapeutic approach for treating anxiety and trauma-related disorders such as phobias and PTSD in the future.”