Cannabinoid receptors in brain: pharmacogenetics, neuropharmacology, neurotoxicology, and potential therapeutic applications.

“Much progress has been achieved in cannabinoid research. A major breakthrough in marijuana-cannabinoid research has been the discovery of a previously unknown but elaborate endogenous endocannabinoid system (ECS), complete with endocannabinoids and enzymes for their biosynthesis and degradation with genes encoding two distinct cannabinoid (CB1 and CB2) receptors (CBRs) that are activated by endocannabinoids, cannabinoids, and marijuana use.

Physical and genetic localization of the CBR genes CNR1 and CNR2 have been mapped to chromosome 6 and 1, respectively. A number of variations in CBR genes have been associated with human disorders including osteoporosis, attention deficit hyperactivity disorder (ADHD), posttraumatic stress disorder (PTSD), drug dependency, obesity, and depression. Other family of lipid receptors including vanilloid (VR1) and lysophosphatidic acid (LPA) receptors appear to be related to the CBRs at the phylogenetic level. The ubiquitous abundance and differential distribution of the ECS in the human body and brain along with the coupling to many signal transduction pathways may explain the effects in most biological system and the myriad behavioral effects associated with smoking marijuana. The neuropharmacological and neuroprotective features of phytocannabinoids and endocannabinoid associated neurogenesis have revealed roles for the use of cannabinoids in neurodegenerative pathologies with less neurotoxicity. The remarkable progress in understanding the biological actions of marijuana and cannabinoids have provided much richer results than previously appreciated cannabinoid genomics and raised a number of critical issues on the molecular mechanisms of cannabinoid induced behavioral and biochemical alterations. These advances will allow specific therapeutic targeting of the different components of the ECS in health and disease.

 This review focuses on these recent advances in cannabinoid genomics and the surprising new fundamental roles that the ECS plays in the retrograde signaling associated with cannabinoid inhibition of neurotransmitter release to the genetic basis of the effects of marijuana use and pharmacotherpeutic applications and limitations. Much evidence is provided for the complex CNR1 and CNR2 gene structures and their associated regulatory elements. Thus, understanding the ECS in the human body and brain will contribute to elucidating this natural regulatory mechanism in health and disease.”

http://www.ncbi.nlm.nih.gov/pubmed/19897083

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The Endocannabinoid System and the Brain.

Abstract

“The psychoactive constituent in cannabis, Δ(9)-tetrahydrocannabinol (THC), was isolated in the mid-1960s, but the cannabinoid receptors, CB1 and CB2, and the major endogenous cannabinoids (anandamide and 2-arachidonoyl glycerol) were identified only 20 to 25 years later. The cannabinoid system affects both central nervous system (CNS) and peripheral processes. In this review, we have tried to summarize research-with an emphasis on recent publications-on the actions of the endocannabinoid system on anxiety, depression, neurogenesis, reward, cognition, learning, and memory. The effects are at times biphasic-lower doses causing effects opposite to those seen at high doses. Recently, numerous endocannabinoid-like compounds have been identified in the brain. Only a few have been investigated for their CNS activity, and future investigations on their action may throw light on a wide spectrum of brain functions. Expected final online publication date for the Annual Review of Psychology Volume 64 is November 30, 2012. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.”

http://www.ncbi.nlm.nih.gov/pubmed/22804774

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Marijuana May Fight Lung Tumors – CBSNews

“the active ingredient in marijuana may help combat lung cancer, new research suggests.

Moreover, other early research suggests the cannabis compound could help fight brain, prostate, and skin cancers as well, Preet says.

The finding builds on the recent discovery of the body’s own cannabinoid system, Preet says. Known as endocannabinoids, the natural cannabinoids stimulate appetite and control pain and inflammation.

THC seeks out, attaches to, and activates two specific endocannabinoids that are present in high amounts on lung cancer cells, Preet says. This revs up their natural anti-inflammatory properties. Inflammation can promote the growth and spread of cancer.

In the new study, the researchers first demonstrated that THC inhibited the growth and spread of cells from two different lung cancer cell lines and from patient lung tumors. Then, they injected THC into mice that had been implanted with human lung cancer cells. After three weeks, tumors shrank by about 50 percent, compared with tumors in untreated mice.”

 http://www.cbsnews.com/2100-500368_162-2696726.html

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Marijuana Fights Cancer

“Marijuana Fights Cancer, Cristina Sanchez, a young biologist at Complutense University in Madrid, was studying cell metabolism when she noticed something peculiar. She had been screening brain cancer cells because they grow faster than normal cell lines and thus are useful for research purposes. But the cancer cells died each time they were exposed to tetrahydrocannabinol (THC), the principal psychoactive ingredient of marijuana.”

Source: http://todaynewsgazette.com/marijuana-fights-cancer/

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Anti-tumoral Action of Cannabinoids

“Delta9-Tetrahydrocannabinol, the main active component of marijuana… Here, we show that intratumoral administration of Delta9-tetrahydrocannabinol… induced a considerable regression of malignant gliomas… Cannabinoid treatment did not produce any substantial neurotoxic effect… cannabinoids signal apoptosis (cell death/suicide) by a pathway involving cannabinoid receptors… These results may provide the basis for a new therapeutic approach for the treatment of malignant gliomas.”

‎”Remarkably, cannabinoids kill glioma cells selectively and can protect non-transformed glial cells from death…”

http://www.ncbi.nlm.nih.gov/pubmed/10700234

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Cannabis Science Publishes List of Over 800 Peer-Reviewed Cannabis and Cancer References From Scientists Around the World

“This list of peer-reviewed manuscripts, provides support for the anecdotal observations of an increasing number of patients claiming successful cancer treatment using medical cannabis extracts.”

“The scientific documentation of the anti-cancer and anti-metastatic properties of cannabinoids is a driving force behind behind our long-term goal, to make high quality, effective, reliable and safe cannabis extracts available to the public beyond the borders of current medical marijuana states.”

http://www.drugs.com/clinical_trials/cannabis-science-publishes-list-over-800-peer-reviewed-cannabis-cancer-references-scientists-around-12716.html

https://www.cannabisscience.com/index.php/news-media/news-archive/215-cannabis-science-publishes-list-of-over-800-peer-reviewed-cannabis-and-cancer-references-from-scientists-around-the-world

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Cannabis and amyotrophic lateral sclerosis: hypothetical and practical applications, and a call for clinical trials

“Cannabis and amyotrophic lateral sclerosis… Significant advances have increased our understanding of the molecular mechanisms of amyotrophic lateral sclerosis (ALS)… It appears that a number of abnormal physiological processes occur simultaneously in this devastating disease. Ideally, a multidrug regimen… would be required to comprehensively address the known pathophysiology of ALS.REMARKABLY, CANNABIS APPEARS to have activity in all of those areas. Preclinical data indicate that cannabis has POWERFUL antioxidative, anti-inflammatory, and neuroprotective effects… Based on the currently available scientific data, it is reasonable to think that cannabis might significantly slow the progression of ALS, potentially extending LIFE expectancy and substantially reducing the overall burden of the disease.”

http://www.ncbi.nlm.nih.gov/pubmed/20439484

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