Stimulation of the midkine/ALK axis renders glioma cells resistant to cannabinoid antitumoral action

“Δ9-Tetrahydrocannabinol (THC), the major active ingredient of marijuana, and other cannabinoids inhibit tumor growth in animal models of cancer, including glioma, an effect that relies, at least in part, on the stimulation of autophagy-mediated apoptosis in tumor cells. 

…Altogether, our findings identify Mdk as a pivotal factor involved in the resistance of glioma cells to THC pro-autophagic and antitumoral action, and suggest that selective targeting of the Mdk/ALK axis could help to improve the efficacy of antitumoral therapies for gliomas.”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3131933/

Stimulation of ALK by the growth factor midkine renders glioma cells resistant to autophagy-mediated cell death

“Δ9-tetrahydrocannabinol (THC), the main active component of marijuana, promotes cancer cell death via autophagy stimulation.

We find that activation of the tyrosine kinase receptor ALK by its ligand midkine interferes with the signaling mechanism by which THC promotes autophagy-mediated glioma cell death.”

 http://www.ncbi.nlm.nih.gov/pubmed/21593591

Marijuana Chemical May Fight Brain Cancer – CBSNews

“The active chemical in marijuana promotes the death of brain cancer cells by essentially helping them feed upon themselves, researchers in Spain report.

Guillermo Velasco and colleagues at Complutense University in Spain have found that the active ingredient in marijuana, THC, causes brain cancer cells to undergo a process called autophagy. Autophagy is the breakdown of a cell that occurs when the cell essentially self-digests.

The team discovered that cannabinoids such as THC had anticancer effects in mice with human brain cancer cells and people with brain tumors . When mice with the human brain cancer cells received the THC, the tumor growth shrank.

Two patients enrolled in a clinical trial received THC directly to the brain as an experimental treatment for recurrent glioblastoma multiforme , a highly aggressive brain tumor. Biopsies taken before and after treatment helped track their progress. After receiving the THC, there was evidence of increased autophagy activity.

The findings appear in the April 1 issue of the Journal of Clinical Investigation.

The patients did not have any toxic effects from the treatment. Previous studies of THC for the treatment of cancer have also found the therapy to be well tolerated, according to background information in journal article.

Study authors say their findings could lead to new strategies for preventing tumor growth.”

http://www.cbsnews.com/2100-500368_162-4913095.html

“Cannabinoid action induces autophagy-mediated cell death through stimulation of ER stress in human glioma cells…These findings describe a mechanism by which THC can promote the autophagic death of human and mouse cancer cells and provide evidence that cannabinoid administration may be an effective therapeutic strategy for targeting human cancers.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2673842/

 

Cannabinoid receptor 1 deficiency in a mouse model of Alzheimer’s disease leads to enhanced cognitive impairment despite of a reduction in amyloid deposition.

“Alzheimer’s disease (AD) is characterized by amyloid-β deposition in amyloid plaques, neurofibrillary tangles, inflammation, neuronal loss, and cognitive deficits. Cannabinoids display neuromodulatory and neuroprotective effects and affect memory acquisition. Here, we studied the impact of cannabinoid receptor type 1 (CB1) deficiency on the development of AD pathology…

…the findings indicate that CB1 deficiency can worsen AD-related cognitive deficits and support a potential role of CB1 as a pharmacologic target.”

http://www.ncbi.nlm.nih.gov/pubmed/23838176

Structure-dependent inhibitory effects of synthetic cannabinoids against 12-O-tetradecanoylphorbol-13-acetate-induced inflammation and skin tumour promotion in mice.

“Whether and how synthetic cannabinoids affect inflammation and carcinogenesis has not been well studied. The present study was thus conducted to assess effects of synthetic cannabinoids on inflammation and carcinogenesis in vivo in mice…

The present results suggest that synthetic cannabinoids, such as JWH-018, -122 and -210, may be used as cancer chemopreventive agents in the future.”

http://www.ncbi.nlm.nih.gov/pubmed/23837590

Biochemical and immunohistochemical changes in delta-9-tetrahydrocannabinol-treated type 2 diabetic rats.

“The regulation of glucose, lipid metabolism and immunoreactivities of insulin and glucagon peptides by delta-9-tetrahydrocannabinol (Δ9-THC) in diabetes were examined in an experimental rat model… 

These results indicate that Δ9-THC may serve a protective role against hyperlipidemia and hyperglycemia in diabetic rats.”

http://www.ncbi.nlm.nih.gov/pubmed/23845579

CB1 Cannabinoid Receptor Agonist Prevents NGF-Induced Sensitization of TRPV1 in Sensory Neurons.

“The transient receptor potential vanilloid type 1 channel (TRPV1) and nerve growth factor (NGF) are important mediators of inflammatory pain…

Cannabinoids, by activating CB1 G protein-coupled receptors, produce analgesia in a variety of pain models, though the exact mechanisms are not known. We tested the hypothesis that activation of the CB1 receptor by cannabinoids attenuates NGF-induced TRPV1 sensitization….

These results support the hypothesis that cannabinoids, acting through CB1 receptors, may produce analgesia in part by preventing NGF-induced sensitization of TRPV1 in afferent nociceptor nerve endings.”

http://www.ncbi.nlm.nih.gov/pubmed/23850608

Cannabidiol provides long-lasting protection against the deleterious effects of inflammation in a viral model of multiple sclerosis: A role for A2A receptors.

“Inflammation in the central nervous system (CNS) is a complex process that involves a multitude of molecules and effectors, and it requires the transmigration of blood leukocytes across the blood-brain barrier (BBB) and the activation of resident immune cells. Cannabidiol (CBD), a non-psychotropic cannabinoid constituent of Cannabis sativa, has potent anti-inflammatory and immunosuppressive properties.

 …Moreover, CBD administration at the time of viral infection exerts long-lasting effects, ameliorating motor deficits in the chronic phase of the disease in conjunction with reduced microglial activation and pro-inflammatory cytokine production. Adenosine A2A receptors participate in some of the anti-inflammatory effects of CBD…

Together, our findings highlight the anti-inflammatory effects of CBD in this viral model of MS, and demonstrate the significant therapeutic potential of this compound for the treatment of pathologies with an inflammatory component.”

http://www.ncbi.nlm.nih.gov/pubmed/23851307

Cannabinoid receptor subtypes 1 and 2 mediate long-lasting neuroprotection and improve motor behavior deficits after transient focal cerebral ischemia.

“The endocannabinoid system is crucially involved in the regulation of brain activity and inflammation… we show that the endocannabinoid system assembles a comprehensive machinery to defend the brain against the devastating consequences of cerebral ischemia.

 In summary, this study underlines the therapeutic potential of CB1 and/or CB2 receptor agonists against neurodegenerative diseases or injuries involving acute or chronic imbalances of cerebral blood flow and energy consumption.”

http://www.ncbi.nlm.nih.gov/pubmed/23069763

Role of cannabinoid CB2 receptor in the reinforcing actions of ethanol.

“This study examines the role of the cannabinoid CB2 receptor (CB2 r) on the vulnerability to ethanol consumption… These results suggest that deletion of the CB2 r gene increased preference for and vulnerability to ethanol consumption…

Future studies will determine the role of CB2 r as a target for the treatment of problems related with alcohol consumption.”

http://www.ncbi.nlm.nih.gov/pubmed/23855434