The Endocannabinoid System in the Retina: From Physiology to Practical and Therapeutic Applications.

“Cannabis is one of the most prevalent drugs used in industrialized countries.

The main effects of Cannabis are mediated by two major exogenouscannabinoids: ∆9-tetrahydroxycannabinol and cannabidiol. They act on specific endocannabinoid receptors, especially types 1 and 2.

Mammals are endowed with a functional cannabinoid system including cannabinoid receptors, ligands, and enzymes.

This endocannabinoid signaling pathway is involved in both physiological and pathophysiological conditions with a main role in the biology of the central nervous system.

As the retina is a part of the central nervous system due to its embryonic origin, we aim at providing the relevance of studying the endocannabinoid system in the retina. Here, we review the distribution of the cannabinoid receptors, ligands, and enzymes in the retina and focus on the role of the cannabinoid system in retinal neurobiology.

This review describes the presence of the cannabinoid system in critical stages of retinal processing and its broad involvement in retinal neurotransmission, neuroplasticity, and neuroprotection.

Accordingly, we support the use of synthetic cannabinoids as new neuroprotective drugs to prevent and treat retinal diseases.

Finally, we argue for the relevance of functional retinal measures in cannabis users to evaluate the impact of cannabis use on human retinal processing.”

http://www.ncbi.nlm.nih.gov/pubmed/26881099

Functions of the CB1 and CB 2 receptors in neuroprotection at the level of the blood-brain barrier.

“The cannabinoid (CB) receptors are the main targets of the cannabinoids, which include plant cannabinoids, endocannabinoids and synthetic cannabinoids. Over the last few years, accumulated evidence has suggested a role of the CB receptors in neuroprotection.

The blood-brain barrier (BBB) is an important brain structure that is essential for neuroprotection. A link between the CB receptors and the BBB is thus likely, but this possible connection has only recently gained attention.

Cannabinoids and the BBB share the same mechanisms of neuroprotection and both protect against excitotoxicity (CB1), cell death (CB1), inflammation (CB2) and oxidative stress (possibly CB independent)-all processes that also damage the BBB.

Several examples of CB-mediated protection of the BBB have been found, such as inhibition of leukocyte influx and induction of amyloid beta efflux across the BBB.

Moreover, the CB receptors were shown to improve BBB integrity, particularly by restoring the tightness of the tight junctions. This review demonstrated that both CB receptors are able to restore the BBB and neuroprotection, but much uncertainty about the underlying signaling cascades still exists and further investigation is needed.”

http://www.ncbi.nlm.nih.gov/pubmed/24929655

Cannabinoids Promote Oligodendrocyte Progenitor Survival: Involvement of Cannabinoid Receptors and Phosphatidylinositol-3 Kinase/Akt Signaling

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“Cannabinoids exert pleiotropic actions in the CNS, including the inhibition of inflammatory responses and the enhancement of neuronal survival after injury… cannabinoid receptors are distributed widely in brain… Cannabinoids Promote Oligodendrocyte Progenitor Survival: Involvement of Cannabinoid Receptors and Phosphatidylinositol-3 Kinase/Akt Signaling.

Limited clinical studies have suggested that cannabis might ameliorate the symptomatology in multiple sclerosis patients, and beneficial effects of synthetic cannabinoids have been reported in vivoin rodent models of multiple sclerosis.

Apart from their actions on motor and pain pathways, cannabinoids regulate the immune response by reducing the production of inflammatory mediators by leukocytes, astrocytes, and microglia, which may contribute to their beneficial effects.

The results of the present study also point to a direct role of cannabinoids in promoting the survival of oligodendrocyte progenitors, particularly in unfavorable conditions, as would be the case in demyelinating diseases. Studies in progress are aimed to evaluate the function of cannabinoids in other models affecting oligodendroglial survival.

http://www.jneurosci.org/content/22/22/9742.long

Smoking marijuana reduces cancer risk

“Marijuana reduces cancer risk and kills existing tumors”

People smoke a joint during a demonstration organised by the CIRC (research and information center) and entitled 'L'appel du 18 juin' (the call of June 18) to claim for the legalization of the use of marijuana and hashish, on June 18, 2011 at the Parc de la Villette in Paris. The 'Appel du 18 Joint' uses a play on words to make their point, coming on the same day as France celebrates the 'Appel du 18 Juin' or Call of 18 June, when Charles de Gaulle called for resistance against collaborationist Vichy government in 1940. AFP PHOTO / FRED DUFOUR

“This may be hard to believe — as we’re fairly accustomed to the notion that inhaling smoke is always bad for your health — but research shows smoking marijuana actually decreases the risk for developing lung cancer.

According to multiple study findings published on Cancer.gov, “Cannabinoids appear to kill tumor cells but do not affect their nontransformed counterparts and may even protect them from cell death.”

Dr. Donald Tashkin, professor emeritus of medicine at UCLA, also recently revealed to LA Weekly that after 30 years of studying the effects of marijuana smoke on lung function, he did not find any association between lung cancer and smoking weed.

Smoking marijuana doesn’t lead to impaired lung function either

Tashkin also found smoking marijuana does not lead to impaired lung function even after years of habitual use.”

More: http://extract.suntimes.com/information-resources/10/153/892/smoking-marijuana-reduces-cancer-risk

“Cannabis has been shown to kill cancer cells in the laboratory. Cannabinoids appear to kill tumor cells but do not affect their nontransformed counterparts and may even protect them from cell death.” http://www.cancer.gov/about-cancer/treatment/cam/patient/cannabis-pdq#section/all

http://www.thctotalhealthcare.com/category/cancer/

Cannabis sativa: The Plant of the Thousand and One Molecules.

“Cannabis sativa L. is an important herbaceous species originating from Central Asia, which has been used in folk medicine and as a source of textile fiber since the dawn of times.

This fast-growing plant has recently seen a resurgence of interest because of its multi-purpose applications: it is indeed a treasure trove of phytochemicals and a rich source of both cellulosic and woody fibers.

Equally highly interested in this plant are the pharmaceutical and construction sectors, since its metabolites show potent bioactivities on human health and its outer and inner stem tissues can be used to make bioplastics and concrete-like material, respectively.

In this review, the rich spectrum of hemp phytochemicals is discussed by putting a special emphasis on molecules of industrial interest, including cannabinoids, terpenes and phenolic compounds, and their biosynthetic routes.

Cannabinoids represent the most studied group of compounds, mainly due to their wide range of pharmaceutical effects in humans, including psychotropic activities.

The therapeutic and commercial interests of some terpenes and phenolic compounds, and in particular stilbenoids and lignans, are also highlighted in view of the most recent literature data.

Biotechnological avenues to enhance the production and bioactivity of hemp secondary metabolites are proposed by discussing the power of plant genetic engineering and tissue culture. In particular two systems are reviewed, i.e., cell suspension and hairy root cultures.

Additionally, an entire section is devoted to hemp trichomes, in the light of their importance as phytochemical factories.

Ultimately, prospects on the benefits linked to the use of the -omics technologies, such as metabolomics and transcriptomics to speed up the identification and the large-scale production of lead agents from bioengineered Cannabis cell culture, are presented.”

http://www.ncbi.nlm.nih.gov/pubmed/26870049

“Known since the ancient times for its medicinal and textile uses, hemp is currently witnessing a revival, because of its rich repertoire of phytochemicals, its fibers and its agricultural features, namely quite good resistance to drought and pests, well-developed root system preventing soil erosion, lower water requirement with respect to other crops, e.g., cotton.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4740396/

Review of Various Herbal Supplements as Complementary Treatments for Oral Cancer.

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“In the United States, nearly 44,000 people are diagnosed with oral or pharyngeal cancer annually. The life expectancy for those who are diagnosed have a survival rate of 57% after five years. Among them, oral cancer can be classified as benign or malignant tumors and is diagnosed at several stages in the development: premalignant conditions, premalignant lesions, and malignant cancer. The early signs of oral cancer often go unnoticed by the individual and are often discovered during routine dental examinations. Early detection and treatment may help to increase patient survival rates. The most widely used treatments for oral cancer include surgery, radiation, and chemotherapy-alone or in combination.

Preclinical and clinical evidence for the use of green tea, raspberry, asparagus, and cannabis extracts is discussed in this review. Diet changes, supplementation with antioxidants, high-dose vitamin C therapy, and cannabinoid use have been suggested to decrease cancer cell replication and increase chance of remission.

Early detection and lifestyle changes, including the use of dietary supplements in at-risk populations, are critical steps in preventing and successfully treating oral cancer. The main evidence for supplement use is currently in cancer prevention rather than treatment.

Further research, determination, and mechanism of action for bioactive compounds such as epigallocatechin, epicatechin-3-gallate, and Bowman-Birk inhibitor concentrate, through in vitro, in vivo, and clinical trials need to be completed to support the use of natural products and their effectiveness in preventative care and supporting therapeutic approaches.” http://www.ncbi.nlm.nih.gov/pubmed/26863913

http://www.tandfonline.com/doi/abs/10.3109/19390211.2015.1122693?journalCode=ijds20

http://www.thctotalhealthcare.com/category/oral-cancer/

Cannabidiol Oil for Decreasing Addictive Use of Marijuana: A Case Report.

“This case study illustrates the use of cannabidiol (CBD) oil to decrease the addictive use of marijuana and provide anxiolytic and sleep benefits.

The second most abundant component-CBD-has been suggested to have the medicinal effects of decreasing anxiety, improving sleep, and other neuro-protective effects.

The mechanism of action for CBD has been suggested to be antagonistic to the psychoactive properties of THC in many locations within the central nervous system. Such action raises the issue of whether it might be beneficial to use CBD in isolation to facilitate withdrawal of marijuana use.

With use of the CBD oil, the patient reported being less anxious, as well as settling into a regular pattern of sleep. He also indicated that he had not used any marijuana since starting the CBD oil. With the decrease in the dosage to 18 mg, the patient was able to maintain his nonuse of marijuana.”

http://www.ncbi.nlm.nih.gov/pubmed/26807069

Cannabis use and symptoms of anxiety in adolescence and the moderating effect of the serotonin transporter gene.

“Prior studies have concluded that cannabis use alone is not sufficient for the development of long-term anxiety, and it has been suggested that cannabis is simply a risk factor that operates in conjunction with other risk factors.

One such risk factor may be an individuals’ genetic vulnerability.

The present study examines the relationship between cannabis use and symptoms of anxiety by taking a developmental molecular-genetic perspective with a focus on a polymorphism involved in the regulation of serotonin.

The findings of the present study show first evidence that the links between cannabis use and symptoms of anxiety are conditional on the individuals’ genetic make-up.”

http://www.ncbi.nlm.nih.gov/pubmed/26860734

Peripubertal treatment with cannabidiol prevents the emergence of psychosis in an animal model of schizophrenia

“Currently, the pharmacotherapy of schizophrenia is still associated with significant side effects and high rates of treatment resistance, causing a great deal of suffering to patients and their caregivers. Developing safe interventions able to prevent the emergence of full-blown psychosis would therefore represent a major advance.

Cannabidiol (CBD) is a non-psychotomimetic compound of Cannabis sativa that presents antipsychotic properties in animal models and humans.

However, despite the growing evidence of CBD’s neuroprotective effects and therapeutic application in schizophrenia, so far no study has addressed its potential as a preventive intervention.”

http://www.schres-journal.com/article/S0920-9964(16)30060-3/abstract

http://www.thctotalhealthcare.com/category/schizophrenia/

Harvesting the biosynthetic machineries that cultivate a variety of indispensable plant natural products.

“Plants are a sustainable resource for valuable natural chemicals best illustrated by large-scale farming centered on specific products. Here, we review recent discoveries of plant metabolic pathways producing natural products with unconventional biomolecular structures.

Prenylation of polyketides by aromatic prenyltransferases (aPTases) ties together two of the major groups of plant specialized chemicals, terpenoids and polyketides, providing a core modification leading to new bioactivities and downstream metabolic processing. Moreover, PTases that biosynthesize Z-terpenoid precursors for small molecules such as lycosantalene have recently been found in the tomato family.

Gaps in our understanding of how economically important compounds such as cannabinoids are produced are being identified using next-generation ‘omics’ to rapidly advance biochemical breakthroughs at an unprecedented rate. For instance, olivetolic acid cyclase, a polyketide synthase (PKS) co-factor from Cannabis sativa, directs the proper cyclization of a polyketide intermediate.

Elucidations of spatial and temporal arrangements of biosynthetic enzymes into metabolons, such as those used to control the efficient production of natural polymers such as rubber and defensive small molecules such as linamarin and lotaustralin, provide blueprints for engineering streamlined production of plant products.”

http://www.ncbi.nlm.nih.gov/pubmed/26851514