Endocannabinoid system: a promising therapeutic target for the treatment of haematological malignancies?

“The therapeutic properties of cannabinoids are well-known since ancient years.

Growing evidence exist on endocannabinoid system (ECS) modulation related with human tumorigenesis.

Taking into account the substantial role of ECS on immune cell regulation, the present review is aimed to summarize the emerging evidence concerning cannabinoid receptor (CBR) expression and cannabinoid ligand effects on haematological malignancies.

CONCLUSIONS:

Most of cannabinoid actions, mainly CB2R-mediated against haematopoietic malignant cells, seems promising, as inhibition of cell proliferation and apoptosis and paraptosis induction have been documented.

Cannabinoid ligands appear to activate rudimentary pathways for cell survival, such as ERK, JNK, p38 MAPK, and to induce caspase synthesis, in vitro. Such data are strongly recommended to be confirmed by in vivo experiments with emphasis on cannabinoid ligands’ bioavailability and phytocannabinoid psychotropic properties.

The preliminary antitumoral ECS effects and their relative lack of important side effects render ECS a promising therapeutic target for the treatment of haematological malignancies.”

http://www.ncbi.nlm.nih.gov/pubmed/27237820

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Endocannabinoid Modulation of Orbitostriatal Circuits Gates Habit Formation.

“Everyday function demands efficient and flexible decision-making that allows for habitual and goal-directed action control. An inability to shift has been implicated in disorders with impaired decision-making, including obsessive-compulsive disorder and addiction. Despite this, our understanding of the specific molecular mechanisms and circuitry involved in shifting action control remains limited. Here we identify an endogenous molecular mechanism in a specific cortical-striatal pathway that mediates the transition between goal-directed and habitual action strategies. Deletion of cannabinoid type 1 (CB1) receptors from cortical projections originating in the orbital frontal cortex (OFC) prevents mice from shifting from goal-directed to habitual instrumental lever pressing. Activity of OFC neurons projecting to dorsal striatum (OFC-DS) and, specifically, activity of OFC-DS terminals is necessary for goal-directed action control. Lastly, CB1 deletion from OFC-DS neurons prevents the shift from goal-directed to habitual action control. These data suggest that the emergence of habits depends on endocannabinoid-mediated attenuation of a competing circuit controlling goal-directed behaviors.”

http://www.ncbi.nlm.nih.gov/pubmed/27238866

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Cannabinoid receptor type-1: breaking the dogmas.

“The endocannabinoid system (ECS) is abundantly expressed in the brain. This system regulates a plethora of physiological functions and is composed of cannabinoid receptors, their endogenous ligands (endocannabinoids), and the enzymes involved in the metabolism of endocannabinoids. In this review, we highlight the new advances in cannabinoid signaling, focusing on a key component of the ECS, the type-1cannabinoid receptor (CB 1). In recent years, the development of new imaging and molecular tools has demonstrated that this receptor can be distributed in many cell types (e.g., neuronal or glial cells) and intracellular compartments (e.g., mitochondria). Interestingly, cellular and molecular effects are differentially mediated by CB 1 receptors according to their specific localization (e.g., glutamatergic or GABAergic neurons). Moreover, this receptor is expressed in the periphery, where it can modulate periphery-brain connections. Finally, the better understanding of the CB 1 receptor structure led researchers to propose interesting and new allosteric modulators. Thus, the advances and the new directions of the CB 1 receptor field will provide new insights and better approaches to profit from its interesting therapeutic profile.”

http://www.ncbi.nlm.nih.gov/pubmed/27239293

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β-Caryophyllene attenuates palmitate-induced lipid accumulation through AMPK signaling by activating CB2 receptor in human HepG2 hepatocytes.

“Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic liver disease worldwide, characterized by excessive hepatic lipid accumulation without significant ethanol consumption.

We have performed a screening for medicinal foods that inhibit hepatocytic lipid accumulation through activation of AMP-activated protein kinase (AMPK), which is a critical regulator of the hepatic lipid metabolism.

CONCLUSION:

Our results suggest that β-caryophyllene has the potential efficacy in preventing and ameliorating NAFLD and its associated metabolic disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/27234712

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”  http://www.ncbi.nlm.nih.gov/pubmed/23138934

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Opioid withdrawal suppression efficacy of oral dronabinol in opioid dependent humans.

:”The cannabinoid (CB) system is a rational novel target for treating opioid dependence, a significant public health problem around the world. This proof-of-concept study examined the potential efficacy of a CB1 receptor partial agonist, dronabinol, in relieving signs and symptoms of opioid withdrawal.

CONCLUSION:

CB1 receptor activation is a reasonable strategy to pursue for the treatment of opioid withdrawal; however, dronabinol is not a likely candidate given its modest withdrawal suppression effects of limited duration and previously reported tachycardia during opioid withdrawal.”

http://www.ncbi.nlm.nih.gov/pubmed/27234658

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Activation of endocannabinoid system in the rat basolateral amygdala improved scopolamine-induced memory consolidation impairment.

“The current study was designed to examine the involvement of cannabinoid CB1 receptors in the basolateral amygdala (BLA) in scopolamine-induced memory impairment in adult male Wistar rats.

In view of the known actions of the drugs used, the present data pointed to the involvement of the BLA CB1 receptors in scopolamine-induced memory consolidation impairment.

Furthermore, it seems that a functional interaction between the BLA endocannabinoid and cholinergic muscarinic systems may be critical for memory formation.”

http://www.ncbi.nlm.nih.gov/pubmed/27230394

“The most dangerous drug in the world: ‘Devil’s Breath’ chemical from Colombia can block free will, wipe memory and even kill. Scopolamine often blown into faces of victims or added to drinks. Within minutes, victims are like ‘zombies’ – coherent, but with no free will. Drug is made from borrachero tree, which is common in Colombia”  http://www.dailymail.co.uk/news/article-2143584/Scopolamine-Powerful-drug-growing-forests-Colombia-ELIMINATES-free-will.html

“Activation of endocannabinoid system in the rat basolateral amygdala improved scopolamine-induced memory consolidation impairment.”  http://www.ncbi.nlm.nih.gov/pubmed/27230394

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Cannabinoids inhibit fibrogenesis in diffuse systemic sclerosis fibroblasts.

Rheumatology

“Recently, it has also been demonstrated that the pleiotropic cannabinoid system is involved in both liver and pancreatic fibrosis. Furthermore, cannabinoids may play a pro- or anti-fibrogenic role depending on their interaction with CB1r or CB2r.

This raises the possibility that pharmacologic modulation of the endocannabinoid system could be a target to limit tissue damage in pathologic fibrosis.

It has been demonstrated that the endocannabinoid system is up-regulated in pathologic fibrosis and that modulation of the cannabinoid receptors might limit the progression of uncontrolled fibrogenesis.

Both CB1 and CB2 receptors were over-expressed in dcSSc fibroblasts compared with healthy controls.

Our preliminary findings suggest that cannabinoids are provided with an anti-fibrotic activity, thereby possibly representing a new class of agents targeting fibrosis diseases.”

http://rheumatology.oxfordjournals.org/content/48/9/1050.long

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Can Cannabinoids Modulate Fibrotic Progression in Systemic Sclerosis?

“Since ancient times, plants have been used for therapeutic purposes.

Cannabis sativa has been widely used as a medicinal herb by Ayurveda and traditional Chinese medicine for centuries.

According to our in vitro and in vivo experimental models, cannabinoids are able to modulate fibrosis.

The exact mechanism underlying this effect requires further investigation, but it seems to go beyond their anti-inflammatory and immunomodulatory properties.

Based on the above observations, we aimed to investigate the role of cannabinoids in systemic sclerosis (SSc), an autoimmune disease characterized by diffuse fibrosis.

Since preclinical data on cannabinoids show their capability to modulate fibrosis, inflammation and vasodilatation, these molecules could be ideal drugs for targeting SSc.”

http://www.ima.org.il/FilesUpload/IMAJ/0/193/96907.pdf

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Medical Cannabis Use Is Associated With Decreased Opiate Medication Use in a Retrospective Cross-Sectional Survey of Patients With Chronic Pain

“Cannabis use was associated with 64% lower opioid use in patients with chronic pain.

Cannabis use was associated with better quality of life in patients with chronic pain.

Cannabis use was associated with fewer medication side effects and medications used.”

  • Journal of Pain Home

“Opioids are commonly used to treat patients with chronic pain (CP), though there is little evidence that they are effective for long term CP treatment. Previous studies reported strong associations between passage of medical cannabis laws and decrease in opioid overdose statewide. Our aim was to examine whether using medical cannabis for CP changed individual patterns of opioid use.

Using an online questionnaire, we conducted a cross-sectional retrospective survey of 244 medical cannabis patients with CP who patronized a medical cannabis dispensary in Michigan between November 2013 and February 2015. Data collected included demographic information, changes in opioid use, quality of life, medication classes used, and medication side effects before and after initiation of cannabis usage. Among study participants, medical cannabis use was associated with a 64% decrease in opioid use (n = 118), decreased number and side effects of medications, and an improved quality of life (45%).

This study suggests that many CP patients are essentially substituting medical cannabis for opioids and other medications for CP treatment, and finding the benefit and side effect profile of cannabis to be greater than these other classes of medications. More research is needed to validate this finding.

Perspective

This article suggests that using medical cannabis for CP treatment may benefit some CP patients. The reported improvement in quality of life, better side effect profile, and decreased opioid use should be confirmed by rigorous, longitudinal studies that also assess how CP patients use medical cannabis for pain management.”

http://www.jpain.org/article/S1526-5900(16)00567-8/abstract

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Drug vaping applied to cannabis: Is “Cannavaping” a therapeutic alternative to marijuana?

“Therapeutic cannabis administration is increasingly used in Western countries due to its positive role in several pathologies. Dronabinol or tetrahydrocannabinol (THC) pills, ethanolic cannabis tinctures, oromucosal sprays or table vaporizing devices are available but other cannabinoid forms can be used.

Inspired by the illegal practice of dabbing of butane hashish oil (BHO), cannabinoids from cannabis were extracted with butane gas, and the resulting concentrate (BHO) was atomized with specific vaporizing devices. The efficiency of “cannavaping,” defined as the “vaping” of liquid refills for e-cigarettes enriched with cannabinoids, including BHO, was studied as an alternative route of administration for therapeutic cannabinoids.

The results showed that illegal cannavaping would be subjected to marginal development due to the poor solubility of BHO in commercial liquid refills (especially those with high glycerin content). This prevents the manufacture of liquid refills with high BHO concentrations adopted by most recreational users of cannabis to feel the psychoactive effects more rapidly and extensively.

Conversely, “therapeutic cannavaping” could be an efficient route for cannabinoids administration because less concentrated cannabinoids-enriched liquid refills are required. However, the electronic device marketed for therapeutic cannavaping should be carefully designed to minimize potential overheating and contaminant generation.”

http://www.ncbi.nlm.nih.gov/pubmed/27228348

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