Cannabinoid Receptors Are Overexpressed in CLL but of Limited Potential for Therapeutic Exploitation.

Posted on June 2, 2016 by David

“The cannabinoid receptors 1 and 2 (CNR1&2) are overexpressed in a variety of malignant diseases and cannabinoids can have noteworthy impact on tumor cell viability and tumor growth.

Patients diagnosed with chronic lymphocytic leukemia (CLL) present with very heterogeneous disease characteristics translating into highly differential risk properties.

To meet the urgent need for refinement in risk stratification at diagnosis and the search for novel therapies we studied CNR expression and response to cannabinoid treatment in CLL.

Expression levels of CNR1&2 were determined in 107 CLL patients by real-time PCR and analyzed with regard to prognostic markers and survival.

In contrast to other tumor entities, our data suggest a limited usability of cannabinoids for CLL therapy. Nonetheless, we could define CNR1 mRNA expression as novel prognostic marker.”

http://www.ncbi.nlm.nih.gov/pubmed/27248492

The effect of cannabinoids on dinitrofluorobenzene-induced experimental asthma in mice.

Posted on May 25, 2016 by David

“Cannabinoids have anti-inflammatory effects and can produce bronchodilation in the airways.

We have investigated the effects of cannabinoids on tracheal hyperreactivity and airway inflammation in dinitrofluorobenzene (DNFB)-induced experimental non-atopic asthma in mice.

These results show that cannabinoid CB₁ receptor agonist can prevent tracheal hyperreactivity to 5-HT in DNFB-induced non-atopic asthma in mice.”

http://www.ncbi.nlm.nih.gov/pubmed/27216000

Anti-inflammatory and antioxidant effects of a combination of cannabidiol and moringin in LPS-stimulated macrophages.

Posted on May 25, 2016 by David

“Inflammatory response plays an important role in the activation and progress of many debilitating diseases. Natural products, like cannabidiol, a constituent of Cannabis sativa, and moringin, an isothiocyanate obtained from myrosinase-mediated hydrolysis of the glucosinolate precursor glucomoringin present in Moringa oleifera seeds, are well known antioxidants also endowed with anti-inflammatory activity.

This is due to a covalent-based mechanism for ITC, while non-covalent interactions underlie the activity of CBD. Since these two mechanisms are distinct, and the molecular endpoints are potentially complementary, we investigated in a comparative way the protective effect of these compounds alone or in combination on lipopolysaccharide-stimulated murine macrophages.

Our results show that the cannabidiol (5μM) and moringin (5μM) combination outperformed the single constituents that, at this dosage had only a moderate efficacy on inflammatory (Tumor necrosis factor-α, Interleukin-10) and oxidative markers (inducible nitric oxide synthase, nuclear factor erythroid 2-related factor 2, nitrotyrosine). Significant upregulation of Bcl-2 and downregulation of Bax and cleaved caspase-3 was observed in cells treated with cannabidiol-moringin combination.

Treatment with the transient receptor potential vanilloid receptor 1 antagonist was detrimental for the efficacy of cannabidiol, while no effect was elicited by cannabinoid receptor 1 and cannabinoid receptor 2 antagonists. None of these receptors was involved in the activity of moringin.

Taken together, our in vitro results testify the anti-inflammatory, antioxidative, and anti-apoptotic effects of the combination of cannabidiol and moringin.”

http://www.ncbi.nlm.nih.gov/pubmed/27215129

MicroRNA let-7d is a target of cannabinoid CB1 receptor and controls cannabinoid signaling.

Posted on May 19, 2016 by David

“Cannabinoid CB₁ receptor, the molecular target of endocannabinoids and cannabis active components, is one of the most abundant metabotropic receptors in the brain. Cannabis is widely used for both recreational and medicinal purposes.

Despite the ever-growing fundamental roles of microRNAs in the brain, the possible molecular connections between the CB₁ receptor and microRNAs are surprisingly unknown. Here, by using reporter gene constructs that express interaction sequences for microRNAs in human SH-SY5Y neuroblastoma cells, we show that CB₁ receptor activation enhances the expression of several microRNAs, including let-7d.

Taken together, these findings provide the first evidence for a bidirectional link between the CB₁ receptor and a microRNA, namely let-7d, and thus unveil a new player in the complex process of cannabinoid action.”

http://www.ncbi.nlm.nih.gov/pubmed/27179908

Efficacy and safety of cannabinoid oromucosal spray for multiple sclerosis spasticity.

Posted on May 11, 2016 by David

“The approval of 9-δ-tetrahydocannabinol and cannabidiol (THC:CBD) oromucosal spray (Sativex) for the management of treatment-resistant multiple sclerosis (MS) spasticity opened a new opportunity for many patients.

The aim of our study was to describe Sativex effectiveness and adverse events profile in a large population of Italian patients with MS in the daily practice setting.

CONCLUSIONS:

Sativex can be a useful and safe option for patients with MS with moderate to severe spasticity resistant to common antispastic drugs.”

http://www.ncbi.nlm.nih.gov/pubmed/27160523

Evidences for the anti-panic actions of Cannabidiol.

Posted on May 10, 2016 by David

“Panic disorder (PD) is a disabling psychiatry condition that affects approximately 5% of the worldwide population. Currently, long-term selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for PD; however, the common side-effect profiles and drug interactions may provoke patients to abandon the treatment, leading to PD symptoms relapse.

Cannabidiol (CBD) is the major non-psychotomimetic constituent of the Cannabis sativa plant with anti-anxiety properties that has been suggested as an alternative for treating anxiety disorders.

In the present chapter, we included both experimental laboratory animal and human studies that have investigated the putative anti-panic properties of CBD.

Taken together, the studies assessed in the present chapter clearly suggest an anxiolytic-like effect of CBD in both animal models and healthy volunteers.

Novel clinical trials involving patients with the PD diagnosis, however, are clearly needed to clarify the specific mechanism of action of CBD and the safe and ideal therapeutic doses of this compound.”

http://www.ncbi.nlm.nih.gov/pubmed/27157263

Cannabidiol Counteracts Amphetamine-Induced Neuronal and Behavioral Sensitization of the Mesolimbic Dopamine Pathway through a Novel mTOR/p70S6 Kinase Signaling Pathway.

Posted on May 6, 2016 by David

“Schizophrenia-related psychosis is associated with disturbances in mesolimbic dopamine (DA) transmission, characterized by hyperdopaminergic activity in the mesolimbic pathway. Currently, the only clinically effective treatment for schizophrenia involves the use of antipsychotic medications that block DA receptor transmission. However, these medications produce serious side effects leading to poor compliance and treatment outcomes.

Emerging evidence points to the involvement of a specific phytochemical component of marijuana called cannabidiol (CBD), which possesses promising therapeutic properties for the treatment of schizophrenia-related psychoses.

Our findings demonstrate a novel mechanism for the putative antipsychotic-like properties of CBD in the mesolimbic circuitry. We identify the molecular signaling pathways through which CBD may functionally reduce schizophrenia-like neuropsychopathology.

SIGNIFICANCE STATEMENT:

The cannabis-derived phytochemical, cannabidiol (CBD), has been shown to have pharmacotherapeutic efficacy for the treatment of schizophrenia.

However, the mechanisms by which CBD may produce antipsychotic effects are entirely unknown. Using preclinical behavioral procedures combined with molecular analyses and in vivo neuronal electrophysiology, our findings identify a functional role for the nucleus accumbens as a critical brain region whereby CBD can produce effects similar to antipsychotic medications by triggering molecular signaling pathways associated with the effects of classic antipsychotic medications.

Specifically, we report that CBD can attenuate both behavioral and dopaminergic neuronal correlates of mesolimbic dopaminergic sensitization, via a direct interaction with mTOR/p70S6 kinase signaling within the mesolimbic pathway.”

http://www.ncbi.nlm.nih.gov/pubmed/27147666

http://www.thctotalhealthcare.com/category/schizophrenia/

Synthetic Cannabinoids versus Natural Marijuana: A Comparison of Expectations

Posted on May 3, 2016 by David

“A new study evaluated the expected outcomes of both synthetic and natural marijuana.

An article entitled “Comparison of Outcome Expectancies for Synthetic Cannabinoids and Botanical Marijuana,” from The American Journal of Drug and Alcohol Abuse, studied the expected outcomes of both synthetic and natural marijuana.

186 adults who had previously used both synthetic and natural marijuana, as well as 181 who had previously used only botanical marijuana, were surveyed about their expected outcomes of using either type of cannabinoid.

The results showed that the expected negative effects were significantly higher for synthetic marijuana than for natural marijuana across both categories of use history.

Despite the more commonly expected negative effects of synthetic cannabinoids, the most cited reasons for using these compounds were wider availability, avoiding a positive drug test, curiosity, perceived legality, and cost.

Authors concluded, “Given growing public acceptance of recreational and medical marijuana, coupled with negative perceptions and increasing regulation of synthetic cannabinoid compounds, botanical marijuana is likely to remain more available and more popular than synthetic cannabinoids.”

https://www.sciencedaily.com/releases/2016/04/160427081800.htm

“Comparison of outcome expectancies for synthetic cannabinoids and botanical marijuana.” http://www.ncbi.nlm.nih.gov/pubmed/26910181

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Cannabidiol attenuates catalepsy induced by distinct pharmacological mechanisms via 5-HT1A receptor activation in mice.

Posted on May 2, 2016 by David

“Cannabidiol (CBD) is a non-psychotomimetic compound from Cannabis sativa plant that produces antipsychotic effects in rodents and humans.

It also reverses L-dopa-induced psychotic symptoms and improves motor function in Parkinson’s patients. This latter effect raised the possibility that CBD could have beneficial effects on motor related striatal disorders.

To investigate this possibility we evaluated if CBD would prevent catalepsy induced by drugs with distinct pharmacological mechanisms.

These findings indicate that CBD can attenuate catalepsy caused by different mechanisms (D2 blockade, NOS inhibition and CB1 agonism) via 5-HT1A receptor activation, suggesting that it could be useful in the treatment of striatal disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/23791616

Cannabidiol attenuates haloperidol-induced catalepsy and c-Fos protein expression in the dorsolateral striatum via 5-HT1A receptors in mice.

Posted on May 2, 2016 by David

“Cannabidiol (CBD) is a major non-psychoactive compound from Cannabis sativa plant.

Given that CBD reduces psychotic symptoms without inducing extrapyramidal motor side-effects in animal models and schizophrenia patients, it has been proposed to act as an atypical antipsychotic.

In addition, CBD reduced catalepsy induced by drugs with distinct pharmacological mechanisms, including the typical antipsychotic haloperidol.

Altogether, these results suggest that CBD acts in the dorsal striatum to improve haloperidol-induced catalepsy via postsynaptic 5-HT_1A receptors.”

http://www.ncbi.nlm.nih.gov/pubmed/27131780