Cannabidiol, unlike synthetic cannabinoids, triggers activation of RBL-2H3 mast cells

“Plant-derived cannabinoids, such as Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), the main psychoactive and nonpsychoactive components of cannabis, respectively, possess myriad pharmacological properties…

Cannabidiol (CBD), a prominent psychoinactive component of cannabis with negligible affinity for known cannabinoid receptors, exerts numerous pharmacological actions, including anti-inflammatory and immunosuppressive effects…

Together, these results support existence of yet-to-be identified sites of interaction, i.e., receptors and/or ion channels associated with Ca2+ influx of natural cannabinoids such as CBD and THC, the identification of which has the potential to provide for novel strategies and agents of therapeutic interest.”

Full text: http://www.jleukbio.org/content/81/6/1512.long

Therapeutic potential of cannabinoid medicines.

Drug Testing and Analysis

“Cannabis was extensively used as a medicine throughout the developed world in the nineteenth century but went into decline early in the twentieth century ahead of its emergence as the most widely used illicit recreational drug later that century. Recent advances in cannabinoid pharmacology alongside the discovery of the endocannabinoid system (ECS) have re-ignited interest in cannabis-based medicines.

The ECS has emerged as an important physiological system and plausible target for new medicines. Its receptors and endogenous ligands play a vital modulatory role in diverse functions including immune response, food intake, cognition, emotion, perception, behavioural reinforcement, motor co-ordination, body temperature, wake/sleep cycle, bone formation and resorption, and various aspects of hormonal control. In disease it may act as part of the physiological response or as a component of the underlying pathology.

In the forefront of clinical research are the cannabinoids delta-9-tetrahydrocannabinol and cannabidiol, and their contrasting pharmacology will be briefly outlined. The therapeutic potential and possible risks of drugs that inhibit the ECS will also be considered. This paper will then go on to review clinical research exploring the potential of cannabinoid medicines in the following indications: symptomatic relief in multiple sclerosis, chronic neuropathic pain, intractable nausea and vomiting, loss of appetite and weight in the context of cancer or AIDS, psychosis, epilepsy, addiction, and metabolic disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/24006213

http://onlinelibrary.wiley.com/doi/10.1002/dta.1529/abstract

Cannabinoid receptors as a target for therapy of ovarian cancer

“Ovarian cancer represents one of the leading cause of cancer-relateddeaths for women and is the most common gynecologic malignancy.In spite of relative low morbidity, ovarian cancer has a highfatality ratio, with overall 5-year survival of less than 30%.At present, there are inadequate treatment options for the managementof advanced ovarian cancer, and therefore development of novelapproaches for treatment of this disease are needed.

Cannabinoids,the active components of Cannabis sativa linnaeous and their derivatives have received considerable attention in recent yearsdue to their diverse pharmacological activities such as cell growth inhibition and tumor regression. To date, two differentcannabinoid receptors have been characterized and cloned frommammalian tissues: the “central” CB1 receptor and the “peripheral”CB2 receptor…

These results support a new therapeutic approach for the treatmentof ovarian cancer. It is also conceivable that with available cannabinoids as lead compounds, non-habit forming agents that have higher biological effects could be developed.”

http://www.aacrmeetingabstracts.org/cgi/content/abstract/2006/1/1084

http://cancerres.aacrjournals.org/content/66/8_Supplement/1084.1

Cannabinoids may be a target for new strategies in cancer treatment

“Cannabis-like substances that are produced by the body have both therapeutic and harmful properties, besides their well-known intoxicating effects, and the body’s cannabinoid system may be a target for new strategies in cancer treatment…

Cannabinoids have moreover been shown to affect the fate of cells. Cannabinoids protect some brain cells, whereas cells in certain types of brain tumors, such as glioma, are stimulated to commit controlled cell suicide (apoptosis)…

In summary, the findings of Sofia Gustafsson’s studies show that cannabinoids can be toxic for cancer cells… These findings are important for our knowledge both of the potential of the cannabinoid system as a target system for new strategies in cancer treatment…”

More: http://www.news-medical.net/news/20120229/Cannabinoids-may-be-a-target-for-new-strategies-in-cancer-treatment.aspx

The endocannabinoid system as a possible target to treat both the cognitive and emotional features of post-traumatic stress disorder (PTSD).

“Post-traumatic stress disorder (PTSD) is a psychiatric disorder of significant prevalence and morbidity, whose pathogenesis relies on paradoxical changes of emotional memory processing. An ideal treatment would be a drug able to block the pathological over-consolidation and continuous retrieval of the traumatic event, while enhancing its extinction and reducing the anxiety symptoms. While the latter benefit from antidepressant medications, no drug is available to control the cognitive symptomatology. Endocannabinoids regulate affective states and participate in memory consolidation, retrieval, and extinction. Clinical findings showing a relationship between Cannabis use and PTSD, as well as changes in endocannabinoid activity in PTSD patients, further suggest the existence of a link between endocannabinoids and maladaptive brain changes after trauma exposure. Along these lines, we suggest that endocannabinoid degradation inhibitors may be an ideal therapeutic approach to simultaneously treat the emotional and cognitive features of PTSD, avoiding the unwanted psychotropic effects of compounds directly binding cannabinoid receptors.”

http://www.ncbi.nlm.nih.gov/pubmed/23950739

Evaluation of the potential of the phytocannabinoids, cannabidivarin (CBDV) and Δ9 -tetrahydrocannabivarin (THCV), to produce CB1 receptor inverse agonism symptoms of nausea in rats.

“The cannabinoid 1(CB1 ) receptor inverse agonists/antagonists, rimonabant (SR141716, SR) and AM251, produce nausea and potentiate toxin-induced nausea by inverse agonism (rather than antagonism) of the CB1 receptor. Here, we evaluated two phytocannabinoids, cannabidivarin (CBDV) and Δ9 -tetrahydrocannabivarin (THCV) for their ability to produce these behavioural effects characteristic of CB1 receptor inverse agonism in rats.

…we investigated the potential of THCV and CBDV to produce conditioned gaping (measure of nausea-induced behaviour),..

THC, THCV  and CBDV suppressed LiCl-induced conditioned gaping, suggesting anti-nausea potential…

The pattern of findings indicates that neither THCV nor CBDV produced a behavioural profile characteristic of CB1 receptor inverse agonists.

As well, these compounds may have therapeutic potential in reducing nausea.”

http://www.ncbi.nlm.nih.gov/pubmed/23902479

Marijuana Compounds Possess Synergistic Anti-Cancer Effects, Study Says

“Marijuana’s active compounds act synergistically to inhibit the growth of cancer cells and induce malignant cell death, according to preclinical trial data published online by the journal Molecular Cancer Therapeutics.

Investigators at the University of California, Pacific Medical Center Research Institute assessed whether the administration of the non-psychoactive cannabidiol would enhance the anti-cancer effects of THC on glioblastoma (brain cancer) cells.

Researchers reported that a combination of cannabinoids showed greater anti-cancer activity than the administration of either compound individually. “We discovered that cannabidiol enhanced the ability of THC to inhibit cell proliferation and induce cell cycle arrest and apoptosis (programmed cell death),” authors reported.

Investigators concluded: “Individually, THC and cannabidiol can activate distinct pathways in glioblastoma cells that ultimately culminate in inhibition of cancer cell growth and invasion as well as induction of cell death. We hypothesized that, if the individual agents were combined, a convergence on shared pathways may ensue, leading to an enhanced ability of the combination treatment to inhibit certain cancer cell phenotypes. We found this to be true in this investigation.”

A 2008 scientific review published in the journal Cancer Research reported that the cannabinioids inhibit cell proliferation in a wide range of cancers, including brain cancer, prostate cancer, breast cancer, lung cancer, skin cancer, pancreatic cancer, and lymphoma.”

http://norml.org/news/2010/01/21/marijuana-compounds-possess-synergistic-anti-cancer-effects-study-says

Cannabinoids can inhibit tumor cell growth in highly invasive cancers

“A new study has found that Cannabinoids, the active components in marijuana, may aid in inhibiting tumor cell growth in highly invasive cancers.”

Fig. 4

“Although, Cannabinoids are used in reducing the side effects of cancer treatment, such as pain, weight loss, and vomiting, evidences indicate that they might even help in suppressing tumor invasion.

Robert Ramer, Ph.D., and Burkhard Hinz, Ph.D., of the University of Rostock in Germany investigated whether and by what mechanism cannabinoids hold back tumor cell invasion.

It was found that Cannabinoids did suppress tumor cell invasion and stimulated TIMP-1 expression.

TIMP-1 is an inhibitor of a group of enzymes involved in tumor cell invasion.

“To our knowledge, this is the first report of TIMP-1-dependent anti-invasive effects of cannabinoids,” the authors said.

They added: “This signaling pathway may play an important role in the antimetastatic action of cannabinoids, whose potential therapeutic benefit in the treatment of highly invasive cancers should be addressed in clinical trials.”

The study was published in the Journal of the National Cancer Institute (ANI)”

“Inhibition of Cancer Cell Invasion by Cannabinoids via Increased Expression of Tissue Inhibitor of Matrix Metalloproteinases-1” http://jnci.oxfordjournals.org/content/100/1/59.long

http://www.topnews.in/health/cannabinoids-can-inhibit-tumor-cell-growth-highly-invasive-cancers-2380 

Inhibition of tumor angiogenesis by cannabinoids

“Cannabinoids, the active components of marijuana and their derivatives, inhibit tumor growth in animal models… Because the generation of a new vascular supply (angiogenesis) is causally involved in the progression of the majority of solid tumors, the aim of this study was to test whether cannabinoids inhibit tumor angiogenesis.”

Figure 1.

“PRINCIPAL FINDINGS

1. Cannabinoid administration inhibits tumor angiogenesis

2. Cannabinoid administration inhibits vascular endothelial cell migration and survival

3. Cannabinoid administration inhibits tumor expression of proangiogenic factors and improves other markers of tumor malignancy

 

 …In the context of the renaissance in the study of the therapeutic effects of cannabinoids, our findings show that these compounds may be considered promising anti-tumoral agents as they inhibit tumor angiogenesis and growth in vivo with no significant side effects.

 This report provides a mechanistic basis for the anti-tumoral action of cannabinoids and a novel pharmacological target for cannabinoid-based anti-tumoral therapies…”

Full text:  http://www.fasebj.org/content/17/3/529.full

The Hypocretin/Orexin Receptor-1 as a Novel Target to Modulate Cannabinoid Reward.

“Although there is a high prevalence of users who seek treatment for cannabis dependence, no accepted pharmacologic treatment is available to facilitate and maintain abstinence.

 The hypocretin/orexin system plays a critical role in drug addiction, but the potential participation of this system in the addictive properties of cannabinoids is unknown.

 We investigated…  studies were performed to evaluate dopamine extracellular levels in the nucleus accumbens after acute Δ9-tetrahydrocannabinol administration..

… role of Hcrtr-1 in the reinforcing and motivational properties of WIN55,212-2 (THC) was confirmed…

CONCLUSIONS:

These findings demonstrate that Hcrtr-1 modulates the reinforcing properties of cannabinoids, which could have a clear therapeutic interest.”

http://www.ncbi.nlm.nih.gov/pubmed/23896204