“Aberrant proliferation and migration of vascular smooth muscle cells (VSMC) have been closely linked to the development and progression of cardiovascular and cancer diseases. The cytoprotective enzyme heme oxygenase-1 (HO-1) has been shown to mediate anti-proliferative and anti-migratory effects in VSMC. This study investigates the effect of cannabidiol (CBD), a non-psychoactive cannabinoid, on HO-1 expression and disease-associated functions of human umbilical artery smooth muscle cells (HUASMC). HO-1 protein and mRNA were significantly increased by CBD in a time- and concentration-dependent manner. Although the expression of several cannabinoid-activated receptors (CB1, CB2, G protein-coupled receptor 55, transient receptor potential vanilloid 1) was verified in HUASMC, CBD was shown to induce HO-1 via none of these targets. Instead, the CBD-mediated increase in HO-1 protein was reversed by the glutathione precursor N-acetylcysteine, indicating the participation of reactive oxygen species (ROS) signaling; this was confirmed by flow cytometry-based ROS detection. CBD-induced HO-1 expression was accompanied by inhibition of growth factor-mediated proliferation and migration of HUASMC. However, neither inhibition of HO-1 activity nor knockdown of HO-1 protein attenuated CBD-mediated anti-proliferative and anti-migratory effects. Indeed, inhibition or depletion of HO-1 resulted in induction of apoptosis and intensified CBD-mediated effects on proliferation and migration. Collectively, this work provides the first indication of CBD-mediated enhancement of HO-1 in VSMC and potential protective effects against aberrant VSMC proliferation and migration. On the other hand, our data argue against a role of HO-1 in CBD-mediated inhibition of proliferation and migration while substantiating its anti-apoptotic role in oxidative stress-mediated cell fate.” https://www.ncbi.nlm.nih.gov/pubmed/30349652 http://www.oncotarget.com/index.php?journal=oncotarget&page=article&op=view&path[]=26191&path[]=81658]]>
Reduced Incidence and Better Liver Disease Outcomes among Chronic HCV Infected Patients Who Consume Cannabis.
“The effect of cannabis use on chronic liver disease (CLD) from Hepatitis C Virus (HCV) infection, the most common cause of CLD, has been controversial. Here, we investigated the impact of cannabis use on the prevalence of CLD among HCV infected individuals. Our study revealed that cannabis users (CUs) had decreased prevalence of liver cirrhosis, unfavorable discharge disposition, and lower total health care cost versus, compared to noncannabis users (NCUs). Among CUs, dependent cannabis use was associated with lower prevalence of liver cirrhosis, compared to nondependent use.
CONCLUSIONS:
Our findings suggest that cannabis use is associated with decreased incidence of liver cirrhosis, but no change in mortality nor LOS among HCV patients. These novel observations warrant further molecular mechanistic studies.” https://www.ncbi.nlm.nih.gov/pubmed/30345261]]>Combined THC and CBD to treat pain in epidermolysis bullosa: a report of three cases.
“Epidermolysis bullosa (EB) is a genetic blistering disorder characterized by intense pain related to disease pathology and care-based interventions. Opioid-based therapies underpin pain-care in EB however are unable to provide adequate analgesia in a significant proportion of patients. Cannabinoid-based medicines (CBMs) have been increasingly studied for pain conditions of various etiologies and pose as a novel dimension for pain-care in EB. We present three cases of EB who were prescribed pharmaceutical-grade sublingually administered CBMs comprising tetrahydrocannabinol (THC) and cannabidiol (CBD). All three patients reported improved pain scores, reduced pruritus and reduction in overall analgesic drug intake. ” https://www.ncbi.nlm.nih.gov/pubmed/30347109 https://onlinelibrary.wiley.com/doi/abs/10.1111/bjd.17341]]>
Light-activatable cannabinoid prodrug for combined and target-specific photodynamic and cannabinoid therapy.
“Cannabinoids are emerging as promising antitumor drugs. However, complete tumor eradication solely by cannabinoid therapy remains challenging. In this study, we developed a far-red light activatable cannabinoid prodrug, which allows for tumor-specific and combinatory cannabinoid and photodynamic therapy. This prodrug consists of a phthalocyanine photosensitizer (PS), reactive oxygen species (ROS)-sensitive linker, and cannabinoid. It targets the type-2 cannabinoid receptor (CB2R) overexpressed in various types of cancers. Upon the 690-nm light irradiation, the PS produces cytotoxic ROS, which simultaneously cleaves the ROS-sensitive linker and subsequently releases the cannabinoid drug. We found that this unique multifunctional prodrug design offered dramatically improved therapeutic efficacy, and therefore provided a new strategy for targeted, controlled, and effective antitumor cannabinoid therapy.”
Anandamide Effects in a Streptozotocin-Induced Alzheimer's Disease-Like Sporadic Dementia in Rats.
“Alzheimer’s disease (AD) is characterized by multiple cognitive deficits including memory and sensorimotor gating impairments as a result of neuronal and synaptic loss.
The endocannabinoid system plays an important role in these deficits but little is known about its influence on the molecular mechanism regarding phosphorylated tau (p-tau) protein accumulation – one of the hallmarks of AD -, and on the density of synaptic proteins.
Thus, the aim of this study was to investigate the preventive effects of anandamide (N-arachidonoylethanolamine, AEA) on multiple cognitive deficits and on the levels of synaptic proteins (syntaxin 1, synaptophysin and synaptosomal-associated protein, SNAP-25), cannabinoid receptor type 1 (CB1) and molecules related to p-tau degradation machinery (heat shock protein 70, HSP70), and Bcl2-associated athanogene (BAG2) in an AD-like sporadic dementia model in rats using intracerebroventricular (icv) injection of streptozotocin (STZ).
This study showed, for the first time, that the administration of an endocannabinoid can prevent AD-like effects induced by STZ, boosting further investigations about the modulation of endocannabinoid levels as a therapeutic approach for AD.”
“The
“Hodgkin lymphoma (HL) is one of the most curable malignancies. Despite its effectiveness, chemotherapy is often associated with adverse events (AEs) such as nausea, anorexia, and impairment of general well-being.
Our objective was to assess the extent of medical cannabis use among HL patients and evaluate its efficacy in controlling chemotherapy-related AEs.
Cannabis users reported improvement in pain, general well-being, appetite, and nausea in 94, 87, 82, and 79% of cases, respectively. Importantly, 81.5% reported a high overall efficacy of cannabis in relieving symptoms. AEs related to cannabis use itself were mild.
Thus, medical cannabis use is prevalent in this HL cohort, and appears to be effective in ameliorating chemotherapy-related AEs.”