Targeting astrocytomas and invading immune cells with cannabinoids: a promising therapeutic avenue.

“The last quarter century has borne witness to great advances in both the detection and treatment of numerous cancers. Even so, malignancies of the central nervous system, especially high-grade astrocytomas, continue to thwart our best efforts toward effective chemotherapeutic strategies.

With prognosis remaining bleak, the time for serious consideration of alternative therapies has arrived. Various preparations of the marijuana plant, Cannabis sativa, and related synthetic and endogenous compounds, may constitute just such an alternative.

Cannabinoids, although much maligned historically for their psychotropic effects and clear abuse potential, have long been used medicinally and are now staging an impressive comeback, as recent studies have begun to explore their powerful anti-tumoral properties.

In this study, we review in vitro and in vivo evidence supporting the use of cannabinoids for treatment of brain tumors. We further propose the continued intense investigation of cannabinoid efficacies as novel anti-cancer agents, especially in models recapitulating such properties within the unique environment of the brain.”

http://www.ncbi.nlm.nih.gov/pubmed/17952648

The Expression Level of CB1 and CB2 Receptors Determines Their Efficacy at Inducing Apoptosis in Astrocytomas

“Cannabinoids represent unique compounds for treating tumors, including astrocytomas.

One of the most promising therapeutic uses of cannabinoids is linked to their ability to induce apoptosis in tumors, including in astrocytoma…

Remarkably, cannabinoids applied at high concentration induce apoptosis in all subclones independently of CB1, CB2…

…the treatment of tumors with high concentrations of cannabinoids should not be overlooked. In fact, stereotaxic injection of high concentrations of cannabinoids will eradicate a significant portion of C6 astrocytomas…”

 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2806825/

 

Dronabinol for the Treatment of Cannabis Dependence: A Randomized, Double-Blind, Placebo-Controlled Trial

“… there are no effective medications for cannabis dependence. The purpose of this study was to evaluate the safety and efficacy of dronabinol, a synthetic form of delta-9-tetrahydrocannabinol, a naturally occurring pharmacologically active component of marijuana, in treating cannabis dependence.

This is the first trial using an agonist substitution strategy for treatment of cannabis dependence. Dronabinol showed promise, it was well-tolerated, and improved treatment retention and withdrawal symptoms…

In conclusion, agonist substitution pharmacotherapy with dronabinol, a synthetic form of THC, showed promise for treatment of cannabis dependence, reducing withdrawal symptoms and improving retention in treatment…

The trial showed that among adult cannabis-dependent patients, dronabinol was well accepted, with good adherence and few adverse events.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3154755/

 

Cannabinoids inhibit peptidoglycan-induced phosphorylation of NF-κB and cell growth in U87MG human malignant glioma cells.

“Nuclear factor (NF)-κB is the key transcription factor involved in the inflammatory responses, and its activation aggravates tumors. Peptidoglycan (PGN), a main cell wall component of Gram-positive bacteria, stimulates Toll-like receptor 2 (TLR-2) and activates a number of inflammatory pathways, including NF-κB…

Cannabinoids have been reported to exert anti-inflammatory and antitumor effects…

Our finding that cannabinoids suppress the NF-κB inflammatory pathway and cell growth via CB1 receptors in glioma cells provides evidence for the therapeutic potential of targeting cannabinoid receptors for the treatment of inflammation-dependent tumor progression.”

http://www.ncbi.nlm.nih.gov/pubmed/22842590

Repositioning therapy for thyroid cancer: new insights on established medications.

“Experimental in vitro and in vivo evidence, as well as results of clinical studies, have indicated that molecular targets for medications currently available for the treatment of mood disorders, sexually transmitted diseases, metabolic disorders, and diabetes may be active and relevant in thyroid cancer.

For instance, the derivatives of cannabis and an anti-diabetic agent, metformin, are both able to inhibit extracellular signal-regulated protein kinase (ERK), which is commonly activated in thyroid cancer cells.

We present here several examples of well-known medications that have the potential to become new therapeutics for patients with thyroid cancer. Repositioning of established medications for the treatment of thyroid cancer could broaden the scope of current therapeutic strategies. These diverse treatment choices could allow physicians to provide an individualized approach to optimize treatment for patients with thyroid cancer.”

http://www.ncbi.nlm.nih.gov/pubmed/24446492

Beyond radio-displacement techniques for Identification of CB1 Ligands: The First Application of a Fluorescence-quenching Assay.

“Cannabinoid type 1 Receptor (CB1) belongs to the GPCR family and it has been targeted, so far, for the discovery of drugs aimed at the treatment of neuropathic pain, nausea, vomit, and food intake disorders. Here, we present the development of the first fluorescent assay enabling the measurement of kinetic binding constants for CB1orthosteric ligands…

…a sustainable valid alternative to the expensive and environmental impacting radiodisplacement techniques and paves the way for an easy, fast and cheap high-throughput drug screening toward CB1 for identification of new orthosteric and allosteric modulators.”

http://www.ncbi.nlm.nih.gov/pubmed/24441508

Cannabinoid modulation of predator fear: involvement of the dorsolateral periaqueductal gray.

“The present study investigated the effects of systemic or intra-dorsolateral periaqueductal gray (dlPAG) administration of CB1 agonists on behavioural changes induced in rats by predator (a live cat) exposure, a model of panic responses…

These results suggest that modulation of the cannabinoid system could be a target in the treatment of panic disorders…”

http://www.ncbi.nlm.nih.gov/pubmed/24438603

Nabiximols as an Agonist Replacement Therapy During Cannabis Withdrawal: A Randomized Clinical Trial.

“The cannabis extract nabiximols (Sativex), developed as a multiple sclerosis treatment, offers a potential agonist medication for cannabis withdrawal…

Nabiximols treatment significantly reduced the overall severity of cannabis withdrawal…

The data support further evaluation of nabiximols for management of cannabis dependence and withdrawal in treatment-seeking populations.”

http://www.ncbi.nlm.nih.gov/pubmed/24430917

A double-blind, randomized, placebo-controlled, parallel group study of THC/CBD spray in peripheral neuropathic pain treatment.

“Peripheral neuropathic pain (PNP) associated with allodynia poses a significant clinical challenge. The efficacy of Δ9 -tetrahydrocannabinol/cannabidiol (THC/CBD) oromucosal spray, a novel cannabinoid formulation, was investigated in this 15-week randomized, double-blind, placebo-controlled parallel group study…

These findings demonstrate that, in a meaningful proportion of otherwise treatment-resistant patients, clinically important improvements in pain, sleep quality and SGIC of the severity of their condition are obtained with THC/CBD spray. THC/CBD spray was well tolerated and no new safety concerns were identified.”

http://www.ncbi.nlm.nih.gov/pubmed/24420962

Modulation of Gut-Specific Mechanisms by Chronic Δ9-THC Administration in Male Rhesus Macaques Infected with Simian Immunodeficiency Virus: A Systems Biology Analysis.

“Our studies have demonstrated that chronic Δ9-tetrahydrocannabinol (THC) administration results in a generalized attenuation of viral load and tissue inflammation in simian immunodeficiency virus (SIV)-infected male rhesus macaques…

Our results indicate that chronic THC treatment modulated duodenal T cell populations, favored a pro-Th2 cytokine balance, and decreased intestinal apoptosis.

These findings reveal novel mechanisms that may potentially contribute to cannabinoid-mediated disease modulation.”

http://www.ncbi.nlm.nih.gov/pubmed/24400995

“Previous studies from our laboratory have shown that chronic THC administration ameliorates SIV disease progression and significantly reduces the morbidity and mortality of male SIV-infected macaques… In summary, using a systems biology approach to understanding the impact of chronic cannabinoid treatment on gut-associated immunopathology, we identified relevant mechanisms that can potentially modulate disease progression. Our results suggest that gut immunomodulation through changes in gene expression, cytokine profiles, and immune cell populations could potentially contribute to chronic THC modulation of SIV disease progression. Moreover, they reveal novel mechanisms that may potentially contribute to decreased morbidity and mortality.”  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4046212/