Cannabidiol attenuates alcohol-induced liver steatosis, metabolic dysregulation, inflammation and neutrophil-mediated injury.

“Cannabidiol (CBD) is a non-psychoactive component of marijuana, which has anti-inflammatory effects. It has also been approved by FDA for various orphan diseases for exploratory trials. Herein, we investigated the effects of CBD on liver injury induced by chronic plus binge alcohol feeding in mice. CBD may have therapeutic potential in the treatment of alcoholic liver diseases associated with inflammation, oxidative stress and steatosis, which deserves exploration in human trials.”  https://www.ncbi.nlm.nih.gov/pubmed/28935932

“Cannabidiol (CBD) is the most abundant non-psychoactive constituent of marijuana plant (Cannabis Sativa) with excellent safety profile in humans even after chronic use. In conclusion, we demonstrate that CBD treatment significantly attenuates liver injury induced by chronic plus binge alcohol in a mouse model and oxidative burst in human neutrophils. CBD ameliorates alcohol-induced liver injury by attenuating inflammatory response involving E-selectin expression and neutrophil recruitment, and consequent oxidative/nitrative stress, in addition to attenuation of the alcohol-induced hepatic metabolic dysregulation and steatosis. These beneficial effects, coupled with the proven safety of CBD in human clinical trials and its current orphan drug approval by FDA for various indications suggest that it may have therapeutic potential in liver disease associated with inflammation, oxidative stress, metabolic dysregulation and steatosis.” https://www.nature.com/articles/s41598-017-10924-8

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[Delta-9-tetrahydrocannabinol-cannabidiol in the treatment of spasticity in chronic spinal cord injury: a clinical experience].

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“Spasticity in chronic spinal cord injury is a condition that can have negative repercussions on the patient’s quality of life. Its treatment is complex and sometimes the outcome is insufficient.

Cannabinoids have recently been used in multiple sclerosis to successfully treat spasticity that is refractory to other therapies.

AIM:

To quantify the clinical response of a group of patients with spastic chronic spinal cord injury to the orally administered drug delta-9-tetrahydrocannabinol-cannabidiol (Sativex ®) as medication for use in special situations.

RESULTS:

Fifteen patients took part in this study. A significant improvement was observed on three of the scales recorded: modified Ashworth scale (z = -2.97; p = 0.003), Penn spasm frequency scale (z = -2.76; p = 0.006) and Numeric Rating Scale (z = -3.21; p = 0.001).

CONCLUSIONS:

Sativex can be considered an alternative in patients with spasticity associated with chronic spinal cord injury for whom other therapeutic measures have been insufficient. Further studies need to be conducted before the use of this drug can be recommended and so as to define a complete profile of its long-term side effects.”

https://www.ncbi.nlm.nih.gov/pubmed/28929471

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Results of a Double-Blind, Randomized, Placebo-Controlled Study of Nabiximols Oromucosal Spray as Adjunctive Therapy in Advanced Cancer Patients With Chronic Uncontrolled Pain.

Journal of Pain and Symptom Management Home

“Prior phase 2/3 studies found that cannabinoids might provide adjunctive analgesia in advanced cancer patients with uncontrolled pain.

To assess adjunctive nabiximols (Sativex®), an extract of Cannabis sativa containing two potentially therapeutic cannabinoids (Δ9-tetrahydrocannabinol and cannabidiol, in advanced cancer patients with chronic pain unalleviated by optimized opioid therapy.

Nabiximols was statistically superior to placebo on two of three quality-of-life instruments at week 3 and on all three at week 5.

The safety profile of nabiximols was consistent with earlier studies.

Although not superior to placebo on the primary efficacy endpoint, nabiximols had benefits on multiple secondary endpoints, particularly in US patients.

Nabiximols might have utility in patients with advanced cancer who receive a lower opioid dose, such as individuals with early intolerance to opioid therapy.”

https://www.ncbi.nlm.nih.gov/pubmed/28923526

http://www.jpsmjournal.com/article/S0885-3924(17)30465-7/fulltext

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Nanoparticle Drones to Target Lung Cancer with Radiosensitizers and Cannabinoids

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“Nanotechnology has opened up a new, previously unimaginable world in cancer diagnosis and therapy, leading to the emergence of cancer nanomedicine and nanoparticle-aided radiotherapy. These nanoparticle drones can be programmed to deliver therapeutic payloads to tumor sites to achieve optimal therapeutic efficacy.

In this article, we examine the state-of-the-art and potential of nanoparticle drones in targeting lung cancer. Inhalation (INH) (air) versus traditional intravenous (“sea”) routes of navigating physiological barriers using such drones is assessed. Results and analysis suggest that INH route may offer more promise for targeting tumor cells with radiosensitizers and cannabinoids from the perspective of maximizing damage to lung tumors cells while minimizing any collateral damage or side effects.

As discussed earlier, nanoparticle drones are particularly attractive because they can also be loaded with drugs payload like cannabinoids. Cannabinoids, which are the bioactive components of Cannabis sativa and their derivatives, may exert palliative effects in cancer patients by preventing nausea, vomiting, and pain and by stimulating appetite .

Furthermore, studies indicate that cannabinoids can inhibit cancer cell growth in in vitro and in vivo. A Nature Reviews Cancer article and other recently published work highlight the potential of cannabinoids for treating cancer, working in synergy with radiotherapy and serving as radiosensitzers to enhance damage to lung tumor cells in particular. Consistent with this, our own experiments have confirmed the potential of cannabinoids in treating lung cancer, with results confirming that cannabinoids can enhance damage to cancer cells.

Overall, the use of nanoparticle drones administered via INH to enhance NRT, as highlighted in this article, may provide a good strategy for maximizing therapeutic efficacy in external beam NRT for lung cancer. Also there is growing evidence that cannabinoids can serve as radiosensitizers, enhance damage to tumor cells, slow tumor growth, and work synergistically with radiotherapy in cancer treatment.”

http://journal.frontiersin.org/article/10.3389/fonc.2017.00208/full

“Cannabis Science Announces Publication of Initial Research Results Using Nanoparticle Drones to Target Lung Cancer With Radiosensitizers and Cannabinoids in the Renowned Journal Frontiers in Oncology” https://ca.finance.yahoo.com/news/cannabis-science-announces-publication-initial-120522920.html

“Cannabis Science “Nanoparticle Drones to Target Lung Cancer with Radiosensitizers and Cannabinoids” Full Publication Released Today In Frontiers In Oncology” http://www.marketwired.com/press-release/cannabis-science-nanoparticle-drones-target-lung-cancer-with-radiosensitizers-cannabinoids-2234167.htm

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Re-visiting the Endocannabinoid System and Its Therapeutic Potential in Obesity and Associated Diseases.

 Current Diabetes Reports

“The purpose of the review was to revisit the possibility of the endocannabinoid system being a therapeutic target for the treatment of obesity by focusing on the peripheral roles in regulating appetite and energy metabolism.

Previous studies with the global cannabinoid receptor blocker rimonabant, which has both central and peripheral properties, showed that this drug has beneficial effects on cardiometabolic function but severe adverse psychiatric side effects. Consequently, focus has shifted to peripherally restricted cannabinoid 1 (CB1) receptor blockers as possible therapeutic agents that mitigate or eliminate the untoward effects in the central nervous system.

Targeting the endocannabinoid system using novel peripheral CB1 receptor blockers with negligible penetrance across the blood-brain barrier may prove to be effective therapy for obesity and its co-morbidities.

Perhaps the future of blockers targeting CB1 receptors will be tissue-specific neutral antagonists (e.g., skeletal muscle specific to treat peripheral insulin resistance, adipocyte-specific to treat fat excess, liver-specific to treat fatty liver and hepatic insulin resistance).”

https://www.ncbi.nlm.nih.gov/pubmed/28913816

https://link.springer.com/article/10.1007%2Fs11892-017-0924-x

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Inhibition of Wnt/β-Catenin pathway and Histone acetyltransferase activity by Rimonabant: a therapeutic target for colon cancer.

 

“In a high percentage (≥85%) of both sporadic and familial adenomatous polyposis forms of colorectal cancer (CRC), the inactivation of the APC tumor suppressor gene initiates tumor formation and modulates the Wnt/β-Catenin transduction pathways involved in the control of cell proliferation, adhesion and metastasis.

Increasing evidence showed that the endocannabinoids control tumor growth and progression, both in vitro and in vivo.

We evaluated the effect of Rimonabant, a Cannabinoid Receptor 1 (CB1) inverse agonist, on the Wnt/β-Catenin pathway in HCT116 and SW48 cell lines carrying the genetic profile of metastatic CRC poorly responsive to chemotherapies.

Obtained data heavily supported the rationale for the use of cannabinoids in combined therapies for metastatic CRC harbouring activating mutations of β-Catenin.”

https://www.ncbi.nlm.nih.gov/pubmed/28916833

https://www.nature.com/articles/s41598-017-11688-x

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The role of cannabinoid receptors in renal diseases.

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“Chronic kidney disease (CKD) remains a major challenge for Public Health systems and corresponds to the replacement of renal functional tissue by extra-cellular matrix proteins such as collagens and fibronectin. There is no efficient treatment to date for CKD except nephroprotective strategies.

The cannabinoid system and more specifically the cannabinoid receptors 1 (CB1) and 2 (CB2) may represent a new therapeutic target in CKD.

Our review will first focus on the current state of knowledge regarding the cannabinoid system in normal renal physiology and in various experimental nephropathies, especially diabetes.  We will review the data obtained in models of diabetes and obesity as well as in nonmetabolic models of renal fibrosis and emphasizes the promising role of CB1 blockers and CB2 agonists in the development of renal disease and fibrosis. Next, we will review the current state of knowledge regarding the cellular pathways involved in renal fibrogenesis and renal injury.

Overall, this review will highlight the therapeutic potential of targeting the cannabinoid receptors in CKD and diabetes.”

https://www.ncbi.nlm.nih.gov/pubmed/28901271

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Piperine-pro-nanolipospheres as a novel oral delivery system of cannabinoids: Pharmacokinetic evaluation in healthy volunteers in comparison to buccal spray administration.

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“Nowadays, therapeutic indications for cannabinoids, specifically Δ9-tetrahydrocannabinol (THC) and Cannabidiol (CBD) are widening. However, the oral consumption of the molecules is very limited due to their highly lipophilic nature that leads to poor solubility at the aqueous environment. Additionally, THC and CBD are prone to extensive first pass mechanisms. These absorption obstacles render the molecules with low and variable oral bioavailability. To overcome these limitations we designed and developed the advanced pro-nanolipospheres (PNL) formulation. The PNL delivery system is comprised of a medium chain triglyceride, surfactants, a co-solvent and the unique addition of a natural absorption enhancer: piperine. Piperine was selected due to its distinctive inhibitory properties affecting both Phase I and Phase II metabolism. This constellation self emulsifies into nano particles that entrap the cannabinoids and the piperine in their core and thus improve their solubility while piperine and the other PNL excipients inhibit their intestinal metabolism. Another clear advantage of the formulation is its composition of materials approved for human consumption. The safe nature of the excipients enabled their direct evaluation in humans. In order to evaluate the pharmacokinetic profile of the THC-CBD-piperine-PNL formulation, a two-way crossover, single administration clinical study was conducted. The trial comprised of 9 healthy volunteers under fasted conditions. Each subject received a THC-CBD (1:1, 10mg) piperine (20mg)-PNL filled capsule and an equivalent dose of the oromucosal spray Sativex® with a washout period in between treatments. Single oral administration of the piperine-PNL formulation resulted in a 3-fold increase in Cmax and a 1.5-fold increase in AUC for THC when compared to Sativex®. For CBD, a 4-fold increase in Cmax and a 2.2-fold increase in AUC was observed. These findings demonstrate the potential this formulation has in serving as a standardized oral cannabinoid formulation. Moreover, the concept of improving oral bioavailability described here, can pave the way for other potential lipophilic active compounds requiring enhancement of their oral bioavailability.”

https://www.ncbi.nlm.nih.gov/pubmed/28890215

http://www.sciencedirect.com/science/article/pii/S016836591730843X

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Attenuation of early phase inflammation by cannabidiol prevents pain and nerve damage in rat osteoarthritis.

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“Osteoarthritis (OA) is a multifactorial joint disease, which includes joint degeneration, intermittent inflammation, and peripheral neuropathy. Cannabidiol (CBD) is a non-euphoria producing constituent of cannabis that has the potential to relieve pain.

The aim of this study was to determine if CBD is anti-nociceptive in OA, and whether inhibition of inflammation by CBD could prevent the development of OA pain and joint neuropathy.

The therapeutic and prophylactic effects of peripheral CBD (100-300μg) were assessed. In end stage OA, CBD dose-dependently decreased joint afferent firing rate, and increased withdrawal threshold and weight bearing (p<0.0001; n=8). Acute, transient joint inflammation was reduced by local CBD treatment (p<0.0001; n=6). Prophylactic administration of CBD prevented the development of MIA-induced joint pain at later time points (p<0.0001; n=8), and was also found to be neuroprotective (p<0.05; n=6-8).

The data presented here indicate that local administration of CBD blocked OA pain. Prophylactic CBD treatment prevented the later development of pain and nerve damage in these OA joints.

These findings suggest that CBD may be a safe, useful therapeutic for treating OA joint neuropathic pain.”

https://www.ncbi.nlm.nih.gov/pubmed/28885454             https://insights.ovid.com/crossref?an=00006396-900000000-99152

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Clinical and Pre-Clinical Evidence for Functional Interactions of Cannabidiol and Δ9-Tetrahydrocannabinol.

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“The plant Cannabis sativa, commonly called cannabis or marijuana, has been used for its psychotropic and mind-altering side effects for millennia. There has been growing attention in recent years on its potential therapeutic efficacy as municipalities and legislative bodies in the United States, Canada, and other countries grapple with enacting policy to facilitate the use of cannabis or its constituents for medical purposes. There are over 550 chemical compounds and over 100 phytocannabinoids isolated from cannabis, including Δ9-tetrahydrocannabinol (THC) and Cannabidiol (CBD). THC is thought to produce the main psychoactive effects of cannabis, while CBD does not appear to have similar effects. Studies conflict as to whether CBD attenuates or exacerbates the behavioral and cognitive effects of THC. This includes effects of CBD on THC induced anxiety, psychosis and cognitive deficits. In this article, we review the available evidence on the pharmacology and behavioral interactions of THC and CBD from pre-clinical and human studies particularly with reference to anxiety and psychosis like symptoms. Both THC and CBD, as well as other cannabinoid molecules, are currently being evaluated for medicinal purposes, separately and in combination. Future cannabis-related policy decisions should include consideration of scientific findings including the individual and interactive effects of CBD and THC.”

https://www.ncbi.nlm.nih.gov/pubmed/28875990

https://www.nature.com/npp/journal/vaop/naam/abs/npp2017209a.html

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