The multidrug transporter ABCG2 (BCRP) is inhibited by plant-derived cannabinoids.

Posted on April 11, 2015 by David

“Multiple drug resistance (MDR) is one of the principal causes of chemotherapeutic treatment failure in malignant disease…

Cannabinoids are used therapeutically for the palliation of the adverse side effects associated with cancer chemotherapy. However, cannabinoids also inhibit both the activity and expression of the multidrug transporter…

Cannabinoids are novel Abcg2/ABCG2 inhibitors, reversing the Abcg2-mediated multidrug-resistant phenotype in vitro. This finding may have implications for the co-administration of cannabinoids with pharmaceuticals that are ABCG2 substrates…

Cannabis and cannabinoid preparations are used as therapeutic agents.

One of the many applications of cannabinoids is in the palliation of cancer chemotherapy-induced nausea, vomiting and anorexia. Indeed, the commercial preparations, Marinol and Cesamet, containing the synthetic Δ9-tetrahydrocannabinol (THC) analogue, dronabinol (or nabilone), are approved in some countries for this use.

Interestingly, in the future, cannabinoids might be co-administered with conventional cancer chemotherapies not only in a palliative capacity but also as primary anticancer medications. Accordingly, cannabinoids have demonstrated antiproliferative actions on cancer cells in vitro and in vivo…

To conclude, this is the first study to address the interaction of cannabinoids with the multidrug transporter ABCG2/Abcg2. The results presented here indicate that plant-derived cannabinoids are a novel class of ABCG2/Abcg2 inhibitors. Our results may have important implications for the use of cannabinoid compounds with therapeutic drugs that are substrates for ABCG2.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2190019/

The cannabis conundrum: Thinking outside the THC box.

Posted on April 10, 2015 by David

“Developing a solid evidence base regarding the health effects of cannabis is imperative given the momentum for legalization and the demand for sound regulatory practices.”

http://www.ncbi.nlm.nih.gov/pubmed/25855064

http://www.thctotalhealthcare.com/

Screening of cannabinoids in industrial-grade hemp using two-dimensional liquid chromatography coupled with acidic potassium permanganate chemiluminescence detection.

Posted on April 8, 2015 by David

Journal of Separation Science

“Widely known for its recreational use, the cannabis plant also has the potential to act as an antibacterial agent in the medicinal field.

The analysis of cannabis plants/products in both pharmacological and forensic studies often requires the separation of compounds of interest and/or accurate identification of the whole cannabinoid profile.

In order to provide a complete separation and detection of cannabinoids, a new two-dimensional liquid chromatography method has been developed using acidic potassium permanganate chemiluminescence detection, which has been shown to be selective for cannabinoids.

This was carried out using a Luna 100 Å CN column and a Poroshell 120 EC-C18 column in the first and second dimension respectively. The method has utilised a large amount of the available separation space with a spreading angle of 48.4° and a correlation of 0.66 allowing the determination of more than 120 constituents and mass spectral identification of ten cannabinoids in a single analytical run.

The method has potential to improve research involved in the characterisation of sensitive, complex matrices. ”

http://www.ncbi.nlm.nih.gov/pubmed/25845561

http://onlinelibrary.wiley.com/doi/10.1002/jssc.201500088/abstract

Major urinary protein 1 interacts with cannabinoid receptor type 1 in fatty acid-induced hepatic insulin resistance in a mouse hepatocyte model.

Posted on April 8, 2015 by David

“Hepatic insulin resistance (HIR) is a metabolic abnormality characterized by increased gluconeogenesis which usually contributes from an elevation of free fatty acids.

Cannabinoid receptor type 1 (CB1R) and major urinary protein 1 (MUP1) are thought to play pivotal roles in mitochondrial dysfunction, liver steatosis and insulin resistance.

The aim of this study was to explore the role of MUP1 in CB1R-mediated HIR through the dysregulation of mitochondrial function in AML12 mouse hepatocytes challenged with high concentration of free fatty acids (HFFA)…

Altogether, these findings suggest that the anti-HIR effect of AM251 via improvement of mitochondrial functions might occur in a MUP1-dependent manner.”

http://www.ncbi.nlm.nih.gov/pubmed/25843798

The interactive role of cannabinoid and vanilloid systems in hippocampal synaptic plasticity in rats.

Posted on April 7, 2015 by David

“Long-term potentiation (LTP) has been most thoroughly studied in the hippocampus, which has a key role in learning and memory. Endocannabinoids are one of the endogenous systems that modulate this kind of synaptic plasticity. The activation of the vanillioid system has also been shown to mediate synaptic plasticity in the hippocampus. In addition, immunohistochemical studies have shown that cannabinoid receptor type 1 (CB1) and vanilloid receptor 1 (TRPV1) are closely located in the hippocampus.

It seems that agonists of the vanilloid system modulate cannabinoid outputs that cause an increase in synaptic plastisity, while in contemporary consumption of two agonist, TRPV1 agonist can change production of endocannabinoid, which in turn result to enhancement of LTP induction. These findings suggest that the two systems may interact or share certain common signaling pathways in the hippocampus.”

http://www.ncbi.nlm.nih.gov/pubmed/25843413

Localization and production of peptide endocannabinoids in the rodent CNS and adrenal medulla.

Posted on April 4, 2015 by David

“The endocannabinoid system (ECS) comprises the cannabinoid receptors CB1 and CB2 and their endogenous arachidonic acid-derived agonists 2-arachidonoyl glycerol and anandamide, which play important neuromodulatory roles.

Recently, a novel class of negative allosteric CB1 receptor peptide ligands, hemopressin-like peptides derived from alpha hemoglobin, has been described, with yet unknown origin and function in the CNS. Using monoclonal antibodies we now identified the localization of RVD-hemopressin (pepcan-12) and N-terminally extended peptide endocannabinoids (pepcans) in the CNS and determined their neuronal origin…

These data uncover important areas of peptide endocannabinoid occurrence with exclusive noradrenergic immunohistochemical staining, opening new doors to investigate their potential physiological function in the ECS.”

http://www.ncbi.nlm.nih.gov/pubmed/25839900

What is Pinene and What Are the Benefits of this Cannabis Terpene?

Posted on April 3, 2015 by David

“Pinene (or α-pinene) is an aromatic compound commonly found in cannabis that smells a lot like – you guessed it – a forest of pine trees.” http://www.leafly.com/news/cannabis-101/what-is-pinene-and-what-are-the-benefits-of-this-cannabis-terpene

“Anti-inflammatory and chondroprotective activity of (+)-α-pinene: structural and enantiomeric selectivity. Previous studies have suggested that α-pinene, a common volatile plant metabolite, may have anti-inflammatory effects in human chondrocytes, thus exhibiting potential antiosteoarthritic activity… The data obtained show isomer- and enantiomer-selective anti-inflammatory and anticatabolic effects of α-pinene in human chondrocytes, (+)-α-pinene being the most promising for further studies to determine its potential value as an antiosteoarthritic drug.” http://www.ncbi.nlm.nih.gov/pubmed/24455984

“The therapeutic efficacy of α-pinene in an experimental mouse model of allergic rhinitis. In the present study, the therapeutic effect and underlying mechanism of α-pinene (α-PN) in the ovalbumin (OVA)-sensitized allergic rhinitis (AR) model were investigated… Taken together, we suggest that α-PN is a promising anti-allergic agent and may be useful in the clinical management of AR.” http://www.ncbi.nlm.nih.gov/pubmed/25242385

“Structural and Thermodynamic Basis of (+)-α-Pinene Binding to Human Cytochrome P450 2B6… (+)-α-Pinene is a monoterpene hydrocarbon that is widely distributed in the environment and a potent P450 2B inhibitor. “ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3754432/

“Inhibitory effects of α-pinene on hepatoma carcinoma cell proliferation… Taken together, these findings indicate that α-pinene may be useful as a potential anti-tumor drug.” http://www.ncbi.nlm.nih.gov/pubmed/24815485

“Synergistic Antitumor Effect of α-pinene and β-pinene with Paclitaxel against Non-small-cell Lung Carcinoma (NSCLC).” http://www.ncbi.nlm.nih.gov/pubmed/25188609

“Biological activities of α-pinene and β-pinene enantiomers. The antimicrobial activities of the isomers and enantiomers of pinene were evaluated against bacterial and fungal cells.” http://www.ncbi.nlm.nih.gov/pubmed/23442885

“Microbial Synthesis of Pinene” http://pubs.acs.org/doi/abs/10.1021/sb4001382

“Effect of alpha-pinene on nuclear translocation of NF-kappa B in THP-1 cells.” http://www.ncbi.nlm.nih.gov/pubmed/15066217

“Protective effects of alpha-pinene in mice with cerulein-induced acute pancreatitis. Acute pancreatitis (AP) is a complicated inflammatory disease that has an unknown underlying pathogenesis. Because alpha-pinene can modulate inflammation, we examined whether alpha-pinene plays a role in AP… These findings suggest that alpha-pinene has an anti-inflammatory effect during cerulein-induced AP.” http://www.ncbi.nlm.nih.gov/pubmed/22982349

Clearing the Smokescreen: The Current Evidence on Cannabis Use

Posted on April 3, 2015 by David

“The therapeutic potential of cannabis is one of the factors driving the push for legalization of cannabis use…

Decisions regarding the legal status of cannabis have long been framed (for the public at least) with reference to the perceived health risks and harms associated with use. Yet, drug policy and legislation relating to the use of cannabis are rarely based on the scientific evidence of the known risks and harms.

There are many reasons for this discrepancy, with the politicization of cannabis use, where ideology and moralizing are given precedence over the science, being one.

Thus, we begin this research topic with Aggarwal discussion of how such politicization has contributed to the current smokescreen that is obscuring our understanding of cannabis, including the impact it has on the ability of researchers to collect and disseminate accurate information about the effects of cannabis use.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358058/

Increased Cerebral Cannabinoid-1 Receptor Availability Is a Stable Feature of Functional Dyspepsia: A [F]MK-9470 PET Study.

Posted on April 3, 2015 by David

“Functional dyspepsia (FD) is a prevalent functional gastrointestinal disorder (FGID) defined by chronic epigastric symptoms in the absence of organic abnormalities likely to explain them. Comorbidity with mood and anxiety disorders as well as with other FGIDs and functional somatic syndrome (FSS) is high. FD is characterized by abnormal regional cerebral activity in cognitive/affective pain modulatory circuits, but it is unknown which neurotransmitter systems are involved.

The authors aimed to assess and compare in vivo cerebral cannabinoid-1 (CB1) receptor availability between FD patients and age-, gender- and BMI-matched healthy controls (HC).

FD patients had significantly higher CB1 receptor availability in the cerebral regions involved in (visceral) nociception (brainstem, insula, anterior cingulate cortex) as well as in the homeostatic and hedonic regulation of food intake [hypothalamus, (ventral) striatum]….

Although these findings need replication in larger samples, they suggest that the abnormal brain activity in several of these regions, previously demonstrated in FD, may be due to a sustained endocannabinoid system dysfunction, identifying it as a potential novel target for treatment and warranting further studies to elucidate whether it is also a feature of other FGIDs or FSSs.”

http://www.ncbi.nlm.nih.gov/pubmed/25833408

Minocycline Attenuates Neonatal Germinal-Matrix-Hemorrhage-Induced Neuroinflammation and Brain Edema by Activating Cannabinoid Receptor 2.

Posted on April 3, 2015 by David

“Germinal matrix hemorrhage (GMH) is the most common neurological disease of premature newborns leading to detrimental neurological sequelae.

Minocycline has been reported to play a key role in neurological inflammatory diseases by controlling some mechanisms that involve cannabinoid receptor 2 (CB2R). The current study investigated whether minocycline reduces neuroinflammation and protects the brain from injury in a rat model of collagenase-induced GMH by regulating CB2R activity…

Our study demonstrates, for the first time, that minocycline attenuates neuroinflammation and brain injury in a rat model of GMH, and activation of CBR2 was partially involved in these processes.”

http://www.ncbi.nlm.nih.gov/pubmed/25833102