Marijuana is not associated with progression of hepatic fibrosis in liver disease: a systematic review and meta-analysis.

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“An estimated 22 million adults use marijuana in the USA. The role of marijuana in the progression of hepatic fibrosis remains unclear.

AIMS:

We carried out a systematic review and meta-analysis to evaluate the impact of marijuana on prevalence and progression of hepatic fibrosis in chronic liver disease.

PATIENTS AND METHODS:

We searched several databases from inception through 10 November 2017 to identify studies evaluating the role of marijuana in chronic liver disease. Our main outcome of interest was prevalence/progression of hepatic fibrosis. Adjusted odds ratios (ORs) and hazards ratios (HRs) were pooled and analyzed using random-effects model.

RESULTS:

Nine studies with 5 976 026 patients were included in this meta-analysis. Prevalence of hepatic fibrosis was evaluated in nonalcoholic fatty liver disease (NAFLD), hepatitis C virus (HCV), and hepatitis C and HIV coinfection by two, four, and one studies. Progression of hepatic fibrosis was evaluated by two studies. Pooled OR for prevalence of fibrosis was 0.91 (0.72-1.15), I=75%. On subgroup analysis, pooled OR among NAFLD patients was 0.80 (0.75-0.86), I=0% and pooled OR among HCV patients was 1.96 (0.78-4.92), I=77%. Among studies evaluating HR, pooled HR for progression of fibrosis in HCV-HIV co-infected patients was 1.03 (0.96-1.11), I=0%.

CONCLUSION:

Marijuana use did not increase the prevalence or progression of hepatic fibrosis in HCV and HCV-HIV-coinfected patients. On the contrary, we noted a reduction in the prevalence of NAFLD in marijuana users. Future studies are needed to further understand the therapeutic impact of cannabidiol-based formulations in the management of NAFLD.”

https://www.ncbi.nlm.nih.gov/pubmed/30234644

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Care After Chemotherapy: Peripheral Neuropathy, Cannabis for Symptom Control, and Mindfulness.

ASCO Educational Book

“As cancer therapies improve, patients are living longer. With these improvements in therapy comes a responsibility to optimize patients’ quality of life during cancer therapy and beyond. This report reviews three timely and important topics.

The first section reviews the mechanism underlying chemotherapy-induced peripheral neuropathy and evaluates the evidence for interventions to prevent and treat peripheral neuropathy. It also provides a framework for approaching the diagnosis and management of this common and bothersome side effect.

The second section addresses the controversial but effective use of cannabinoids for cancer and chemotherapy symptoms. Although clinical trials are difficult to conduct because of the political and social stigma of this class of drugs, this review provides evidence of the efficacy of cannabinoids for treatment of pain and nausea.

The last section addresses the mind-body connection, with a focus on the negative emotions patients with cancer often experience. This section assesses the literature regarding mindfulness-based programs to improve cancer-related stress. These three topics may appear unrelated, but all address one common goal: treating the body and the mind to optimize quality of life during and after cancer therapy.”

“Although commercially available dronabinol is not superior to other antiemetics and oromucosal nabiximols is not very effective for treating cancer pain, cannabis has been shown to be effective for treating pain and may help patients reduce opioid intake.”
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Inflammation and CB2 signaling drive novel changes in the ocular lipidome and regulate immune cell activity in the eye.

Prostaglandins & Other Lipid Mediators

“Uveitis is inflammation of the uvea which consists of the iris, ciliary body and the choroid of the eye. Uveitis can lead to impaired vision and is responsible for 10% of all cases of blindness globally.

Using an endotoxin-induced uveitis (EIU) rodent model, our previous data implicated the endogenous cannabinoid system (ECS) in the amelioration of many of the components of the inflammatory response.

Here, we test the hypothesis that the reduction in inflammatory mediators in the EIU model by the CB2 agonist, HU308, is associated with changes in ECS endogenous ligands as well as related lipids, prostaglandins (PGs), 2-acyl glycerols, and lipoamines.

These data implicate ocular CB2 as a key component of lipid signaling in the eye and part of the regulatory processes of inflammation.”

https://www.ncbi.nlm.nih.gov/pubmed/30232034

https://www.sciencedirect.com/science/article/pii/S109888231830025X?via%3Dihub

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Cannabinoids and spinal cord stimulation for the treatment of failed back surgery syndrome refractory pain

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“This study aimed to evaluate pain and its symptoms in patients with failed back surgery syndrome (FBSS) refractory to other therapies, treated with a combination of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), in association with spinal cord stimulation (SCS).

Results: Effective pain management as compared to baseline result was achieved in all the cases studied. The positive effect of cannabinoid agonists on refractory pain was maintained during the entire duration of treatment with minimal dosage titration. Pain perception, evaluated through numeric rating scale, decreased from a baseline mean value of 8.18±1.07–4.72±0.9 by the end of the study duration (12 months) (P<0.001).

Conclusion: The results indicate that cannabinoid agonists (THC/CBD) can have remarkable analgesic capabilities, as adjuvant of SCS, for the treatment of chronic refractory pain of FBSS patients.”

https://www.ncbi.nlm.nih.gov/pubmed/30233233

https://www.dovepress.com/cannabinoids-and-spinal-cord-stimulation-for-the-treatment-of-failed-b-peer-reviewed-article-JPR

“Outcomes indicate remarkable analgesic capabilities of cannabinoid agonists (THC/CBD) as an adjuvant to SCS for treating chronic refractory pain in FBSS patients, since all the cases studied achieved effective pain management compared to baseline.”

https://www.mdlinx.com/journal-summaries/cannabinoids-delta-9-tetrahydrocannabinol-thc-cannabidiol/2018/09/13/7544234/

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Effect of cannabidiolic acid and ∆9-tetrahydrocannabinol on carrageenan-induced hyperalgesia and edema in a rodent model of inflammatory pain.

“Cannabidiol (CBD), a non-intoxicating component of cannabis, or the psychoactive Δ9-tetrahydrocannabiol (THC), shows anti-hyperalgesia and anti-inflammatory properties.

OBJECTIVES:

The present study evaluates the anti-inflammatory and anti-hyperalgesia effects of CBD’s potent acidic precursor, cannabidiolic acid (CBDA), in a rodent model of carrageenan-induced acute inflammation in the rat hind paw, when administered systemically (intraperitoneal, i.p.) or orally before and/or after carrageenan. In addition, we assess the effects of oral administration of THC or CBDA, their mechanism of action, and the efficacy of combined ineffective doses of THC and CBDA in this model. Finally, we compare the efficacy of CBD and CBDA.

RESULTS:

CBDA given i.p. 60 min prior to carrageenan (but not 60 min after carrageenan) produced dose-dependent anti-hyperalgesia and anti-inflammatory effects. In addition, THC or CBDA given by oral gavage 60 min prior to carrageenan produced anti-hyperalgesia effects, and THC reduced inflammation. The anti-hyperalgesia effects of THC were blocked by SR141716 (a cannabinoid 1 receptor antagonist), while CBDA’s effects were blocked by AMG9810 (a transient receptor potential cation channel subfamily V member 1 antagonist). In comparison to CBDA, an equivalent low dose of CBD did not reduce hyperalgesia, suggesting that CBDA is more potent than CBD for this indication. Interestingly, when ineffective doses of CBDA or THC alone were combined, this combination produced an anti-hyperalgesia effect and reduced inflammation.

CONCLUSION:

CBDA or THC alone, as well as very low doses of combined CBDA and THC, has anti-inflammatory and anti-hyperalgesia effects in this animal model of acute inflammation.”

https://www.ncbi.nlm.nih.gov/pubmed/30225659

https://link.springer.com/article/10.1007%2Fs00213-018-5034-1

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Adolescent cannabinoid exposure induces irritability-like behavior and cocaine cross-sensitization without affecting the escalation of cocaine self-administration in adulthood.

Scientific Reports

“In summary, these results suggest that psychoactive cannabinoid exposure during adolescence is unlikely to have a major effect on the escalation of cocaine intake or the development of compulsive-like responding per se in adulthood in a rat model of cocaine self-administration.”

https://www.ncbi.nlm.nih.gov/pubmed/30224774

https://www.nature.com/articles/s41598-018-31921-5

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Benefits and Risks of Therapeutic Cannabinoids for Neurologic Disorders

Clinical Therapeutics Home

“The Cannabis genus originated in Central Asia and is probably one of the most ancient nonfood crops to be cultivated by humans. Its medicinal properties have been recognized for centuries. Isolation of the psychoactive compound, Δ9-tetrahydrocannabinol, followed by the identification of cannabidiol, led to increased focus on the therapeutic potential of the plant. One of the prominent species, Cannabis sativa, may produce more than 100 different cannabinoids.”

https://www.ncbi.nlm.nih.gov/pubmed/30224192

https://www.clinicaltherapeutics.com/article/S0149-2918(18)30331-X/fulltext

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Exploring the Ligand Efficacy of Cannabinoid Receptor 1 (CB1) using Molecular Dynamics Simulations.

Scientific Reports

“Cannabinoid receptor 1 (CB1) is a promising therapeutic target for a variety of disorders. Distinct efficacy profiles showed different therapeutic effects on CB1 dependent on three classes of ligands: agonists, antagonists, and inverse agonists. To discriminate the distinct efficacy profiles of the ligands, we carried out molecular dynamics (MD) simulations to identify the dynamic behaviors of inactive and active conformations of CB1 structures with the ligands. In addition, the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method was applied to analyze the binding free energy decompositions of the CB1-ligand complexes. With these two methods, we found the possibility that the three classes of ligands can be discriminated. Our findings shed light on the understanding of different efficacy profiles of ligands by analyzing the structural behaviors of intact CB1 structures and the binding energies of ligands, thereby yielding insights that are useful for the design of new potent CB1 drugs.”

https://www.ncbi.nlm.nih.gov/pubmed/30213978

https://www.nature.com/articles/s41598-018-31749-z

“Chemical structure of the partial agonist THC, antagonist THCV, and inverse agonist Taranabant.”

Figure 1

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Role of the endocannabinoid system in drug addiction.

Biochemical Pharmacology

“Drug addiction is a chronic relapsing disorder that produces a dramaticglobal health burden worldwide. Not effective treatment of drug addiction is currently available probably due to the difficulties to find an appropriate target to manage this complex disease raising the needs for further identification of novel therapeutic approaches.

The endocannabinoid system has been found to play a crucial role in the neurobiological substrate underlying drug addiction.

Endocannabinoids and cannabinoid receptors are widely expressed in the main areas of the mesocorticolimbic system that participate in the initiation and maintenance of drug consumption and in the development of compulsion and loss of behavioral control occurring during drug addiction.

The identification of the important role played by CB1 cannabinoid receptors in drug addiction encouraged the possible used of an early commercialized CB1 receptor antagonist for treating drug addiction.

However, the incidence of serious psychiatric adverse events leaded to the sudden withdrawal from the market of this CB1 antagonist and all the research programs developed by pharmaceutical companies to obtain new CB1 antagonists were stopped.

Currently, new research strategies are under development to target the endocannabinoid system for drug addiction avoiding these side effects, which include allosteric negative modulators of CB1 receptors and compounds targeting CB2 receptors.

Recent studies showing the potential role of CB2 receptors in the addictive properties of different drugs of abuse have open a promising research opportunity to develop novel possible therapeutic approaches.”

https://www.ncbi.nlm.nih.gov/pubmed/30217570

https://www.sciencedirect.com/science/article/abs/pii/S0006295218303952

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False-positive cannabinoid screens in adult cystic fibrosis patients treated with lumacaftor/ivacaftor

Journal of Cystic Fibrosis

“Cystic fibrosis (CF) is caused by gene mutations resulting in defective cystic fibrosis transmembrane conductance regulator (CFTR) protein activity. CFTR modulators have been developed to improve CFTR protein function. The combination of ivacaftor (IVA) and lumacaftor (LUM) partially restores CFTR protein function of F508del, the most common CF mutation.”

https://www.ncbi.nlm.nih.gov/pubmed/30217546

“False-positive cannabinoid screens in adult cystic fibrosis patients treated with lumacaftor/ivacaftor”

https://www.cysticfibrosisjournal.com/article/S1569-1993(18)30754-9/fulltext

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