Arachidonoyl-ethanolamide activates endoplasmic reticulum stress-apoptosis in tumorigenic keratinocytes: Role of cyclooxygenase-2 and novel J-series prostamides.

“Non-melanoma skin cancer and other epithelial tumors overexpress cyclooxygenase-2 (COX-2), differentiating them from normal cells…

Arachidonoyl-ethanolamide (AEA) is a cannabinoid that causes apoptosis in diverse tumor types…

These findings suggest that AEA will be selectively toxic in tumor cells that overexpress COX-2 due to the metabolism of AEA by COX-2 to J-series prostaglandin-ethanolamides (prostamides).

Hence, AEA may be an ideal topical agent for the elimination of malignancies that overexpress COX-2.”

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Activation of cannabinoid receptor 2 attenuates synovitis and joint distruction in collagen-induced arthritis.

“Recent studies have suggested immunomodulatory and anti-inflammatory effects of cannabinoid receptor 2 (CB2R) activation, which is devoid of psychoactivity. We have demonstrated the expression of CB2R in synovial tissue from patients with rheumatoid arthritis (RA), and its specific activation shows inhibitory effects on fibroblast-like synoviocytes. However, it is still unclear whether selective activation of CB2R inhibits joint inflammation or protects joint damage in RA.


Activation of CB2R by HU-308 has therapeutic potential for RA to suppress synovitis and alleviate joint destruction by inhibiting the production of autoantibodies and proinflammatory cytokines.”

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Endocannabinoids and acute pain after total knee arthroplasty.

“Osteoarthritis (OA) of the knee is a progressive disease that is associated with inflammation of the joints and lower extremity pain. Total knee arthroplasty (TKA) is a surgical procedure that aims to reduce pain and restore motor function in patients suffering from OA. The immediate postoperative period can be intensely painful leading to extended recovery times including persistent pain.

The endocannabinoid system regulates nociception, and the activation of cannabinoid receptors produces antinociceptive effects in preclinical models of OA…

Taken together, our results are the first to reveal associations between central and peripheral endocannabinoid levels and postoperative pain. This suggests that endocannabinoid metabolism may serve as a target for the development of novel analgesics both for systemic or local delivery into the joint.”

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Proapoptotic effect of endocannabinoids in prostate cancer cells.

“Recent evidence shows that derivatives of Cannabis sativa and its analogs may exert a protective effect against different types of oncologic pathologies.

The purpose of the present study was to detect the presence of cannabinoid receptors (CB1 and CB2) on cancer cells with a prostatic origin and to evaluate the effect of the in vitro use of synthetic analogs…

Based on these results, we suggest that endocannabinoids may be a beneficial option for the treatment of prostate cancer that has become nonresponsive to common therapies.”

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Role of endocannabinoid signalling in the dorsolateral periaqueductal grey in the modulation of distinct panic-like responses.

“Since the cannabinoid CB1 receptor modulates various types of aversive responses, this study tested the hypothesis that enhancement of endocannabinoid signalling in the dorsolateral periaqueductal grey inhibits panic-like reactions in rats…

The present results confirm the anti-aversive property of direct CB1 receptor activation in the dorsolateral periaqueductal grey…

Altogether, these results suggest that anandamide signalling is recruited only under certain types of aversive stimuli.”

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Cannabinoid Signaling and Neuroinflammatory Diseases: A Melting pot for the Regulation of Brain Immune Responses.

“The concept of the central nervous system (CNS) as an immune-privileged site, essentially due to the presence of the blood brain barrier, appears to be overly simplistic. Indeed, within healthy CNS immune activities are permitted and are required for neuronal function and host defense, not only due to the presence of the resident innate immune cells of the brain, but also by virtue of a complex cross-talk of the CNS with peripheral immune cells.

Nonetheless, long-standing and persisting neuroinflammatory responses are most often detrimental and characterize several neuroinflammatory diseases, including multiple sclerosis, Alzheimer’s disease and amyotrophic lateral sclerosis.

A growing body of evidence suggests that Cannabis sativa-derived phytocannabinoids, as well as synthetic cannabinoids, are endowed with significant immunoregulatory and anti-inflammatory properties, both in peripheral tissues and in the CNS, through the activation of cannabinoid receptors.

In this review, the immunomodulatory effects of cannabinoid signaling on the most relevant brain immune cells will be discussed. In addition, the impact of cannabinoid regulation on the overall integration of the manifold brain immune responses will also be highlighted, along with the implication of these compounds as potential agents for the management of neuroinflammatory disorders.”

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Cannabis use in relation to obesity and insulin resistance in the inuit population.


To ascertain the relationship between cannabis use, obesity, and insulin resistance…

Cannabis use was highly prevalent in the study population and was statistically associated with lower body mass index (BMI)


Cannabis use was associated with lower BMI, and such an association did not occur through the glucose metabolic process or related inflammatory markers. The association between cannabis use and insulin resistance was mediated through its influence on weight.”

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Cannabidiol increases survival and promotes rescue of cognitive function in a murine model of Cerebral Malaria.


“Cerebral malaria (CM) is a severe complication resulting from Plasmodium falciparuminfection that might cause permanent neurological deficits.

Cannabidiol (CBD) is a nonpsychotomimetic compound of Cannabis sativa with neuroprotective properties.

In the present work, we evaluated the effects of CBD in a murine model of CM.

CBD treatment resulted in an increase in BDNF expression in the hippocampus and decreased levels of proinflammatory cytokines in the hippocampus (TNF-α) and prefrontal cortex (IL-6).

Our results indicate that CBD exhibits neuroprotective effects in CM model and might be useful as an adjunctive therapy to prevent neurological symptoms following this disease.”

“Cannabidiol adjuvant treatment increases survival in the murine model of CM. Cannabidiol adjuvant treatment promotes rescue of behavioral and cognitive function.”

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Selective CB2 receptor agonists.

“Selective CB2 receptor agonists. Part 1: The identification of novel ligands through computer-aided drug design (CADD) approaches. Computer-aided drug design scaffold hopping strategies were utilized to identify new classes of CB2 agonists when compounds of an established series with low nanomolar potency were challenging to optimize for good drug-like properties. Use of ligand-based design strategies through BI Builder (a tool for de novo design) and PharmShape (a virtual screening software package) approaches led to the discovery of new chemotypes. Specifically, compounds containing azetidine-, proline-, and piperidine-based cores were found to have low nanomolar and picomolar CB2 agonist activities with drug-like properties considered appropriate for early profiling.”

“Selective CB2 receptor agonists. Part 2: Structure-activity relationship studies and optimization of proline-based compounds. Through a ligand-based pharmacophore model (S)-proline based compounds were identified as potent cannabinoid receptor 2 (CB2) agonists with high selectivity over the cannabinoid receptor 1 (CB1). Structure-activity relationship investigations for this compound class lead to oxo-proline compounds 21 and 22 which combine an impressive CB1 selectivity profile with good pharmacokinetic properties. In a streptozotocin induced diabetic neuropathy model, 22 demonstrated a dose-dependent reversal of mechanical hyperalgesia.”

“Selective CB2 receptor agonists. Part 3: The optimization of a piperidine-based series that demonstrated efficacy in an in vivo neuropathic pain model. A novel class of potent cannabinoid receptor 2 (CB2) agonists based on a (S)-piperidine scaffold was identified using ligand-based pharmacophore models. Optimization of solubility and metabolic stability led to the identification of several potent CB2 agonists (e.g., 30) that displayed selectivity over cannabinoid receptor 1 (CB1) and acceptable drug like properties. In rats, compound 30 demonstrated a favorable pharmacokinetic profile and efficacy in a Streptozotocin-induced diabetic neuropathy model, with full reversal of mechanical hyperalgesia.”


Facebook Twitter Pinterest Stumbleupon Tumblr Posterous

Beneficial effects of cannabinoid receptor type 2 (CB2R) in injured skeletal muscle post-contusion.

“The aim of the current study was to investigate the effects of cannabinoid receptor type 2 (CB2R) on the repair process of injured skeletal muscle, which could potentially lay solid foundations as a novel target for curing muscular fibrosis in future…

These results revealed multiple effects of CB2R in systematically inhibiting fibrotic formation and improving muscle regeneration, alongside its potential for clinical application in patients with skeletal muscle injuries and diseases.”

Facebook Twitter Pinterest Stumbleupon Tumblr Posterous