delta 9-Tetrahydrocannabinol for refractory vomiting induced by cancer chemotherapy.

“Fifty-three patients receiving antineoplastic chemotherapy who had experienced severe nausea and vomiting refractory to standard antiemetic agents were treated with delta 9-tetrahydrocannabinol (THC).

These patients were given THC 8 to 12 hours before, during, and for 24 hours after chemotherapy.

Ten patients (19%) had no further nausea and vomiting; 28 (53%) had at least a 50% reduction of nausea and vomiting compared to previous courses with the same agents.

We suggest that, since THC is a useful antimetic agent in patients having refractory chemotherapy-induced vomiting, existing restrictions prohibiting its therapeutic use should promptly be eased.”

http://www.ncbi.nlm.nih.gov/pubmed/6244418

Emerging targets and therapeutic approaches for the treatment of osteoarthritis pain.

“Osteoarthritis is a complex and often painful disease that is inadequately controlled with current analgesics. This review discusses emerging targets and therapeutic approaches that may lead to the development of better analgesics…

Aberrant excitability in peripheral and central pain pathways drives osteoarthritis pain, reversing this via modulation of nerve growth factor, voltage-gated sodium channel, voltage-gated calcium channel and transient receptor potential vanilloid one activity, and increasing inhibitory mechanisms through modulation of cannabinoid and descending modulatory systems hold promise for osteoarthritis pain therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/25730180

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

 

Simultaneous inhibition of fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) shares discriminative stimulus effects with ∆9-THC in mice.

“Δ9 -tetrahydrocannabinol (∆9 -THC) is a cannabinoid CB1 /CB2 receptor agonist that produces therapeutic effects such as analgesia and anti-emetic effects…

Collectively, the current results show that pharmacological increases in endogenous AEA and 2-AG simultaneously through inhibition of FAAH and MAGL, respectively, mimics the discriminative stimulus effects of Δ9 -THC.”

http://jpet.aspetjournals.org/content/early/2015/02/24/jpet.115.222836.long

Are Cannabinoids Effective for Orofacial Pain States?

“…there is increasing attention being given in the media as well as in the biomedical sciences to the use as analgesic agents of the crude extracts of plants of the genus Cannabis (eg, marijuana) and their active ingredient delta 9-tetrahydrocannabinol (Δ9-THC).

These cannabinoid compounds have been reported in the biomedical literature to be beneficial in the treatment of some types of neuropathic pain and other pain states…

This review has found evidence indicating that they may be effective analgesic agents for neuropathic pain conditions refractory to other therapeutic approaches…

The clinical findings pointing to the usefulness of the cannabinoids for pain relief are supported by a growing body of evidence from basic science investigations addressing the possible efficacy and mechanisms of action of the cannabinoids in animal models of acute or chronic pain.

These preclinical findings add to the growing evidence that cannabinoid receptor agonists may be effective agents for the treatment of neuropathic pain and other types of pain.

They also point to their possible clinical utility in acute or chronic orofacial pain conditions, and thereby suggest an affirmative answer applies to the question posed in the title of this editorial.”

http://www.quintpub.com/journals/ofph/abstract.php?article_id=15025#.VPBsU033-iw

http://www.thctotalhealthcare.com/category/pain-2/

Cannabidiol (CBD) and its analogs: a review of their effects on inflammation.

“First isolated from Cannabis in 1940 by Roger Adams, the structure of CBD was not completely elucidated until 1963.

Subsequent studies resulted in the pronouncement that THC was the ‘active’ principle of Cannabis and research then focused primarily on it to the virtual exclusion of CBD.

This was no doubt due to the belief that activity meant psychoactivity that was shown by THC and not by CBD.

In retrospect this must be seen as unfortunate since a number of actions of CBD with potential therapeutic benefit were downplayed for many years.

In this review, attention will be focused on the effects of CBD in the broad area of inflammation where such benefits seem likely to be developed.

Topics covered in this review are; the medicinal chemistry of CBD, CBD receptor binding involved in controlling Inflammation, signaling events generated by CBD, downstream events affected by CBD (gene expression and transcription), functional effects reported for CBD and combined THC plus CBD treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/25703248

Cannabinoid signaling and liver therapeutics.

Journal of Hepatology Home

“Over the last decade, the endocannabinoid system has emerged as a pivotal mediator of acute and chronic liver injury, with the description of the role of CB1 and CB2 receptors and their endogenous lipidic ligands in various aspects of liver pathophysiology.

A large number of studies have demonstrated that CB1 receptor antagonists represent an important therapeutic target, owing to beneficial effects on lipid metabolism and in light of its antifibrogenic properties.

Unfortunately, the brain-penetrant CB1 antagonist rimonabant, initially approved for the management of overweight and related cardiometabolic risks, was withdrawn because of an alarming rate of mood adverse effects.

However, the efficacy of peripherally-restricted CB1 antagonists with limited brain penetrance has now been validated in preclinical models of NAFLD, and beneficial effects on fibrosis and its complications are anticipated.

CB2 receptor is currently considered as a promising anti-inflammatory and antifibrogenic target, although clinical development of CB2 agonists is still awaited.

In this review, we highlight the latest advances on the impact of the endocannabinoid system on the key steps of chronic liver disease progression and discuss the therapeutic potential of molecules targeting cannabinoid receptors…

Overwhelming evidence supports the therapeutic potential of peripherally-restricted CB1 antagonists and CB2 agonists in the management of chronic liver diseases.”

http://www.journal-of-hepatology.eu/article/S0168-8278(13)00212-2/fulltext

http://www.thctotalhealthcare.com/category/liver-disease/

Cannabinoid CB2 receptors protect against alcoholic liver disease by regulating Kupffer cell polarization in mice.

“Activation of Kupffer cells plays a central role in the pathogenesis of alcoholic liver disease.

Because cannabinoid CB2 receptors (CB2) display potent anti-inflammatory properties, we investigated their role in the pathogenesis of alcoholic liver disease, focusing on the impact of CB2 on Kupffer cell polarization and the consequences on liver steatosis.

Altogether, these findings demonstrate that CB2 receptors display beneficial effects on alcohol-induced inflammation by regulating M1/M2 balance in Kupffer cells, thereby reducing hepatocyte steatosis via paracrine interactions between Kupffer cells and hepatocytes.

These data identify CB2 agonists as potential therapeutic agents for the management of alcoholic liver disease.”

http://www.ncbi.nlm.nih.gov/pubmed/21735467

http://www.thctotalhealthcare.com/category/liver-disease/

Emerging role of cannabinoids in gastrointestinal and liver diseases: basic and clinical aspects.

“A multitude of physiological effects and putative pathophysiological roles have been proposed for the endogenous cannabinoid system in the gastrointestinal tract, liver and pancreas.

These range from effects on epithelial growth and regeneration, immune function, motor function, appetite control, fibrogenesis and secretion.

Cannabinoids have the potential for therapeutic application in gut and liver diseases.

Two exciting therapeutic applications in the area of reversing hepatic fibrosis as well as antineoplastic effects may have a significant impact in these diseases.

This review critically appraises the experimental and clinical evidence supporting the clinical application of cannabinoid receptor-based drugs in gastrointestinal, liver and pancreatic diseases.

Application of modern pharmacological principles will most probably expand the selective modulation of the cannabinoid system peripherally in humans.

We anticipate that, in addition to the approval in several countries of the CB(1) antagonist, rimonabant, for the treatment of obesity and associated metabolic dysfunctions, other cannabinoid modulators are likely to have an impact on human disease in the future, including hepatic fibrosis and neoplasia.”

http://www.ncbi.nlm.nih.gov/pubmed/18397936

http://www.thctotalhealthcare.com/category/liver-disease/

Components of the endocannabinoid and dopamine systems are dysregulated in Huntington’s disease: analysis of publicly available microarray datasets.

“The endocannabinoid system (ECS) and the dopaminergic system (DAS) are two major regulators of basal ganglia function. During Huntington’s disease (HD) pathogenesis, the expression of genes in both the ECS and DAS is dysregulated…

The resulting data confirm gene expression changes observed using different approaches and provide novel insights into the consistency between changes observed in human tissue and various models, as well as disease stage- and tissue-specific transcriptional dysregulation in HD.

The major implication of the systems-wide data presented here is that therapeutic strategies targeting the ECS or DAS must consider the dynamic changes in gene expression over time and in different body areas, which occur during HD progression and the interconnectedness of the two systems.”

http://www.ncbi.nlm.nih.gov/pubmed/25692022

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

Protective and therapeutic effects of cannabis plant extract on liver cancer induced by dimethylnitrosamine in mice

Cover image

“Hepatocellular carcinomas will emerge as a major form of malignancy in the coming decades.

When these tumors are in advanced stages, few therapeutic options are available.

Therefore, it is essential to search for new treatment modalities to fight this disease.

Aim

Evaluate the possible protective and therapeutic effects of Cannabis extract on dimethylnitrosamine (DMNA)-induced hepatocarcinogenicity in mice.

Conclusion

The protective effect of cannabis extract is more pronounced in group taking cannabis before DMNA.

Cannabinoids might exert their anti-tumor effects by the direct induction of apoptosis and can decrease telomerase activity by inhibiting the expression of the TERT gene…”

http://www.sciencedirect.com/science/article/pii/S209050681400027X

 http://www.thctotalhealthcare.com/category/liver-cancer-2/