Opioid withdrawal suppression efficacy of oral dronabinol in opioid dependent humans.

:”The cannabinoid (CB) system is a rational novel target for treating opioid dependence, a significant public health problem around the world. This proof-of-concept study examined the potential efficacy of a CB1 receptor partial agonist, dronabinol, in relieving signs and symptoms of opioid withdrawal.

CONCLUSION:

CB1 receptor activation is a reasonable strategy to pursue for the treatment of opioid withdrawal; however, dronabinol is not a likely candidate given its modest withdrawal suppression effects of limited duration and previously reported tachycardia during opioid withdrawal.”

http://www.ncbi.nlm.nih.gov/pubmed/27234658

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

“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 different 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.”

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

New therapeutic strategies for the treatment of male lower urinary tract symptoms.

“Male lower urinary tract symptoms (LUTS) are prevalent in the general population, especially in those of advanced age, and are characterized by notable diversity in etiology and presentation, and have been proven to cause various degrees of impairment on quality of life.

The prostate has traditionally been regarded as the core cause of male LUTS. As a result, medical treatment aims to provide symptomatic relief and effective management of progression of male LUTS due to benign prostatic enlargement.

Anti-inflammatory agents, vitamin D3-receptor analogs, and cannabinoids represent treatment modalities currently under investigation for use in LUTS patients.

Furthermore, luteinizing hormone-releasing hormone antagonists, transient receptor-potential channel blockers, purinergic neurotransmission antagonists, Rho-kinase inhibitors, and inhibitors of endothelin-converting enzymes could have therapeutic potential in LUTS management, but still remain in the experimental setting.

This article reviews new strategies for the medical treatment of male LUTS, which are dictated by the potential role of the bladder and the risk of benign prostatic hyperplasia progression. Moreover, combination treatments and therapies currently under investigation are also presented.”

http://www.ncbi.nlm.nih.gov/pubmed/27218069

[MEDICAL CANNABIS].

“The cannabis plant has been known to humanity for centuries as a remedy for pain, diarrhea and inflammation.

Current research is inspecting the use of cannabis for many diseases, including multiple sclerosis, epilepsy, dystonia, and chronic pain.

In inflammatory conditions cannabinoids improve pain in rheumatoid arthritis and: pain and diarrhea in Crohn’s disease.

Despite their therapeutic potential, cannabinoids are not free of side effects including psychosis, anxiety, paranoia, dependence and abuse.

Controlled clinical studies investigating the therapeutic potential of cannabis are few and small, whereas pressure for expanding cannabis use is increasing.

Currently, as long as cannabis is classified as an illicit drug and until further controlled studies are performed, the use of medical cannabis should be limited to patients who failed conventional better established treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/27215115

The synthetic cannabinoid WIN55,212-2 mesylate decreases the production of inflammatory mediators in rheumatoid arthritis synovial fibroblasts by activating CB2, TRPV1, TRPA1 and yet unidentified receptor targets

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“Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by joint inflammation and cartilage destruction.

In this study we assessed the ability of WIN to modulate cytokine and MMP-3 production in SFs over a wide concentration range and identified specific receptor targets that mediate the effects of this synthetic cannabinoid.

The synthetic cannabinoid WIN in low concentrations exhibits anti-inflammatory effects in synovial fibroblasts independent of CB1 and CB2 while CB2 and yet unidentified receptor targets are responsible for WIN effects in micromolar concentrations.

Our results indicate a TRPV1/TRPA1 dependent mechanism of SF regulation that might be coupled to cellular energy status and calcium content.

In this report we demonstrated anti-inflammatory effects of the synthetic cannabinoid WIN in low and high concentrations.

Furthermore, this study demonstrated anti-inflammatory effects via modulation of TRP channels by WIN. Together, inactivation of TRPs and activation of cannabinoid receptors might also reduce the sensation of pain, which further underlines the potential of WIN in the treatment of chronic inflammation.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4858820/

Difference and Influence of Inactive and Active States of Cannabinoid Receptor Subtype CB2: From Conformation to Drug Discovery.

“Cannabinoid receptor 2 (CB2), a G protein-coupled receptor (GPCR), is a promising target for the treatment of neuropathic pain, osteoporosis, immune system, cancer, and drug abuse.”

http://www.ncbi.nlm.nih.gov/pubmed/27186994

Does cannabis use moderate smoking cessation outcomes in treatment-seeking tobacco smokers? Analysis from a large multi-center trial.

“Tobacco and cannabis are frequently used in combination and cannabis co-use may lead to poor tobacco cessation outcomes. Therefore, it is important to explore if cannabis co-use is associated with a reduced likelihood of achieving successful tobacco abstinence among treatment-seeking tobacco smokers.

The present study examined whether current cannabis use moderated tobacco cessation outcomes after 12 weeks of pharmacological treatment with adjunctive behavioral counseling.

 RESULTS:

Controlling for rate of nicotine metabolism, treatment arm, age, sex, alcohol, and level of nicotine dependence, cannabis users were as successful at achieving biochemically verified 7-day point prevalence abstinence compared to tobacco-only smokers.

CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE:

Findings suggest that cannabis use does not hinder the ability to quit tobacco smoking.”

http://www.ncbi.nlm.nih.gov/pubmed/27187893

Cannabis in Pain Treatment: Clinical and Research Considerations

“Cannabinoids show promise as therapeutic agents, particularly as analgesics, but their development and clinical use has been complicated by recognition of their botanical source, cannabis, as a substance of misuse.

Although research into endogenous cannabinoid systems and potential cannabinoid pharmaceuticals is slowly increasing, there has been intense societal interest in making herbal (plant) cannabis available for medicinal use; 23 U.S. States and all Canadian provinces currently permit use in some clinical contexts.

Whether or not individual professionals support the clinical use of herbal cannabis, all clinicians will encounter patients who elect to use it and therefore need to be prepared to advise them on cannabis-related clinical issues despite limited evidence to guide care.

Expanded research on cannabis is needed to better determine the individual and public health effects of increasing use of herbal cannabis and to advance understanding of the pharmaceutical potential of cannabinoids as medications.

This article reviews clinical, research, and policy issues related to herbal cannabis to support clinicians in thoughtfully advising and caring for patients who use cannabis, and it examines obstacles and opportunities to expand research on the health effects of herbal cannabis and cannabinoids.

Perspective

Herbal cannabis is increasingly available for clinical use in the United States despite continuing controversies over its efficacy and safety. This article explores important considerations in the use of plant Cannabis to better prepare clinicians to care for patients who use it, and identifies needed directions for research.”

http://www.jpain.org/article/S1526-5900%2816%2900543-5/fulltext

“APS Issues New Guidance on Medical Marijuana for Pain”  http://www.medscape.com/viewarticle/863396

Potentiation of cannabinoid-induced cytotoxicity in Mantle Cell Lymphoma through modulation of ceramide metabolism

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“Ceramide accumulation is a widely described event in cancers after various treatments.

Ceramide levels are elevated in Mantle Cell Lymphoma (MCL) cells following treatment with cannabinoids.

In previous publications we and others observed that induction of ceramide accumulation by cannabinoids leads to apoptosis in MCL, glioma and pancreatic cancer.

Here, we investigated the pathways of ceramide accumulation in the MCL cell line Rec-1 using the stable endocannabinoid analogue R(+)-methanandamide (R-MA).

Our findings suggest that R-MA induces cell death in MCL via CB1-mediated upregulation of the de novo ceramide synthesis pathway.

This is the first study showing that the cytotoxic effect of a cannabinoid can be enhanced by modulation of ceramide metabolism.

The results suggest that interference with ceramide conversion may provide a tool to enhance the targeted cell death-promoting effects of cannabinoids in MCL and other malignant lymphomas overexpressing the CB1 receptor.

Cannabinoids have been suggested as a new non-toxic therapeutic option for cancer treatment.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3077284/

Cannabinoid receptor-mediated apoptosis induced by R(+)-methanandamide and Win55,212-2 is associated with ceramide accumulation and p38 activation in mantle cell lymphoma.

“We have recently shown that cannabinoids induce growth inhibition and apoptosis in mantle cell lymphoma (MCL), a malignant B-cell lymphoma that expresses high levels of cannabinoid receptor types 1 and 2 (CB(1) and CB(2)).

In the current study, the role of each receptor and the signal transduction triggered by receptor ligation were investigated.

The present data suggest that targeting CB(1)/CB(2) may have therapeutic potential for the treatment of mantle cell lymphoma.”

http://www.ncbi.nlm.nih.gov/pubmed/16936228