Category Archives: Antiinflamatorio

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Cannabis and Pediatric Inflammatory Bowel Disease: Change Blossoms a Mile High.

Category : Antiinflamatorio

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Cannabis and Pediatric Inflammatory Bowel Disease: Change Blossoms a Mile High.

J Pediatr Gastroenterol Nutr. 2017 Feb;64(2):265-271

Authors: Hoffenberg EJ, Newman H, Collins C, Tarbell S, Leinwand K

Abstract
The trend toward decriminalization of cannabis (marijuana) continues sweeping across the United States. Colorado has been a leader of legalization of medical and recreational cannabis use. The growing public interest in the medicinal properties of cannabis and its use by patients with a variety of illnesses including inflammatory bowel disease (IBD) makes it important for pediatric gastroenterologists to understand this movement and its potential effect on patients. This article describes the path to legalization and “medicalization” of cannabis in Colorado and the public perception of safety despite the known adverse health effects of use. We delineate the mammalian endocannabinoid system and our experience of caring for children and adolescents with IBD in an environment of increasing awareness and acceptance of its use. We then summarize the rationale for considering that cannabis may have beneficial and harmful effects for patients with IBD. Finally, we highlight the challenges federal laws impose on conducting research on cannabis in IBD. The intent of this article is to inform health care providers about the issues around cannabis use and research in adolescents and young adults with IBD.

PMID: 27579692 [PubMed – indexed for MEDLINE]

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Anti-inflammatory activity of cannabinoid receptor 2 ligands in primary hPDL fibroblasts.

Category : Antiinflamatorio

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Anti-inflammatory activity of cannabinoid receptor 2 ligands in primary hPDL fibroblasts.

Arch Oral Biol. 2017 Dec 06;87:79-85

Authors: Abidi AH, Presley CS, Dabbous M, Tipton DA, Mustafa SM, Moore BM

Abstract
OBJECTIVES: Approximately 65 million adults in the US have periodontitis, causing tooth loss and decreased quality of life. Cannabinoids modulate immune responses, and endocannabinoids are prevalent during oral cavity inflammation. Targets for intervention in periodontal inflammation are cannabinoid type 1 and 2 receptors (CB1R, CB2R), particularly CB2R because its levels increase during inflammation. We previously demonstrated that SMM-189 (CB2R inverse agonist) decreased pro-inflammatory cytokine production in primary microglial cells. The hypothesis of this study was that cannabinoids anandamide (AEA), HU-308 (CB2R selective agonist), and SMM-189 decrease pro-inflammatory IL-6 and MCP-1 production by primary human periodontal ligament fibroblasts (hPDLFs) stimulated with P. gingivalis LPS, TNF-α, or IL-1β.
DESIGN: Cytotoxic effects of cannabinoid compounds (10-4-10-6.5 M), LPS (1-1000 ng/ml), TNFα (10 ng/ml) and IL-1β (1 ng/ml) were assessed by measuring effects on cellular dehydrogenase activity. IL-6 and MCP-1 production were measured using Mesoscale Discovery (MSD) Human Pro-Inflammatory IL-6 and MSD Human Chemokine MCP-1 kits and analyzed using MSD Sector 2400 machine.
RESULTS: EC50 values for AEA, SMM-189, and HU-308 were 16 μM, 13 μM, and 7.3 μM respectively. LPS (1 μg/ml), TNF-α (10 ng/ml), and IL-1β (1 ng/ml) increased IL-6 and MCP-1 production, which were inhibited by AEA, SMM-189, and HU-308. AEA alone significantly increased IL-6, but not MCP-1 levels, but the other cannabinoids alone had no effect.
CONCLUSION: The effective inhibition of LPS, TNF-α, IL-1β stimulated IL-6 and MCP-1 production by CB2R ligands in hPDLFs suggests that targeting the endocannabinoid system may lead to development of novel drugs for periodontal therapy, aiding strategies to improve oral health.

PMID: 29274621 [PubMed – as supplied by publisher]

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Sex and age specific effects of delta-9-tetrahydrocannabinol during the periadolescent period in the rat: The unique susceptibility of the prepubescent animal.

Category : Antiinflamatorio

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Sex and age specific effects of delta-9-tetrahydrocannabinol during the periadolescent period in the rat: The unique susceptibility of the prepubescent animal.

Neurotoxicol Teratol. 2016 Nov – Dec;58:88-100

Authors: Silva L, Black R, Michaelides M, Hurd YL, Dow-Edwards D

Abstract
Adolescents who use marijuana are more likely to exhibit anxiety, depression, and other mood disorders, including psychotic-like symptoms. Additionally, the age at onset of use and the stress history of the individual can affect responses to cannabis. To examine the effect of early life experience on adolescent Δ-9-tetrahydrocannabinol (THC) exposure, we exposed adolescent (postnatal day (P) 29-38) male and female rats, either shipped from a supplier or born in our vivarium, to once daily injections of 3mg/kg THC. Our findings suggest that males are more sensitive to the anxiolytic and antidepressant effects of THC, as measured by the elevated plus maze (EPM) and forced swim test (FST), respectively, than females. Exposure to the FST increased plasma corticosterone levels, regardless of drug treatment or origin and females had higher levels than males overall. Shipping increased THC responses in females (acoustic startle habituation) and in males (latency to immobility in FST). No significant effects of THC or shipping on pre-pulse inhibition were observed. Due to differences in timing of puberty in males and females during the P29-38 period of THC treatment, we also dosed female rats between P21-30 (pre-puberty) and male rats between P39-48 (puberty). Pre-pubertal animals showed reductions in anxiety on the EPM, an effect that was not seen in animals treated during puberty. These results suggest that both sexes are more susceptible to changes in emotional behavior when THC exposure occurs just prior to the onset of puberty. Within the animals dosed from P29-38, THC increased cannabinoid receptor 1 (CB1R) mRNA expression and tended to decrease CP55,940 stimulated [35S]GTPγS binding in the central amygdala only of females. Therefore, early stress enhances THC responses in males (in FST) and females (ASR habituation), THC alters CB1R expression and function in females only and prepubescent rats are generally more responsive to THC than pubertal rats. In summary, THC and stress interact with the developing endocannabinoid system in a sex specific manner during the peri-pubertal period.

PMID: 26898326 [PubMed – indexed for MEDLINE]

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Cannabidiol restores intestinal barrier dysfunction and inhibits the apoptotic process induced by Clostridium difficile toxin A in Caco-2 cells.

Category : Antiinflamatorio

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Cannabidiol restores intestinal barrier dysfunction and inhibits the apoptotic process induced by Clostridium difficile toxin A in Caco-2 cells.

United European Gastroenterol J. 2017 Dec;5(8):1108-1115

Authors: Gigli S, Seguella L, Pesce M, Bruzzese E, D’Alessandro A, Cuomo R, Steardo L, Sarnelli G, Esposito G

Abstract
Background: Clostridium difficile toxin A is responsible for colonic damage observed in infected patients. Drugs able to restore Clostridium difficile toxin A-induced toxicity have the potential to improve the recovery of infected patients. Cannabidiol is a non-psychotropic component of Cannabis sativa, which has been demonstrated to protect enterocytes against chemical and/or inflammatory damage and to restore intestinal mucosa integrity.
Objective: The purpose of this study was to evaluate (a) the anti-apoptotic effect and (b) the mechanisms by which cannabidiol protects mucosal integrity in Caco-2 cells exposed to Clostridium difficile toxin A.
Methods: Caco-2 cells were exposed to Clostridium difficile toxin A (30 ng/ml), with or without cannabidiol (10-7-10-9 M), in the presence of the specific antagonist AM251 (10-7 M). Cytotoxicity assay, transepithelial electrical resistence measurements, immunofluorescence analysis and immunoblot analysis were performed in the different experimental conditions.
Results: Clostridium difficile toxin A significantly decreased Caco-2 cells’ viability and reduced transepithelial electrical resistence values and RhoA guanosine triphosphate (GTP), bax, zonula occludens-1 and occludin protein expression, respectively. All these effects were significantly and concentration-dependently inhibited by cannabidiol, whose effects were completely abolished in the presence of the cannabinoid receptor type 1 (CB1) antagonist, AM251.
Conclusions: Cannabidiol improved Clostridium difficile toxin A-induced damage in Caco-2 cells, by inhibiting the apoptotic process and restoring the intestinal barrier integrity, through the involvement of the CB1 receptor.

PMID: 29238589 [PubMed]

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Hypothalamic-pituitary-adrenal axis measures and cognitive abilities in early psychosis: Are there sex differences?

Category : Antiinflamatorio

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Hypothalamic-pituitary-adrenal axis measures and cognitive abilities in early psychosis: Are there sex differences?

Psychoneuroendocrinology. 2016 Oct;72:54-62

Authors: Labad J, Gutiérrez-Zotes A, Creus M, Montalvo I, Cabezas Á, Solé M, Ortega L, Algora MJ, Sánchez-Gistau V, Vilella E

Abstract
INTRODUCTION: Measures of hypothalamic-pituitary-adrenal (HPA) axis activity such as increased diurnal cortisol levels or a blunted cortisol awakening response (CAR) have been associated with cognitive impairments in people with psychotic disorders. We aimed to explore whether there are sex differences in the relationship between HPA axis measures and cognition in early psychosis (EP).
METHODS: 60 EP outpatients and 50 healthy subjects (HS) were assessed with the MATRICS Consensus Cognitive Battery. Saliva cortisol levels were determined at the neuropsychological assessment and on another day at 6 sampling times: awakening; 30′ and 60′ post-awakening; and 10:00h, 23:00h and 10:00h the day after the administration of 0.25mg of dexamethasone, which occurred at 23:00h. Three HPA axis measures were calculated: CAR, cortisol diurnal slope and cortisol suppression ratio of the dexamethasone suppression test (DST). Multiple linear regression analyses were conducted to explore the relationship between HPA axis measures and cognitive tasks while adjusting for covariates (education level, smoking, cannabis use, and cortisol levels at the cognitive assessment). Interactions between female sex, EP diagnosis and HPA axis measures were examined.
RESULTS: An increased CAR was associated with a poorer cognitive performance in EP women in processing speed and verbal memory. In contrast, a more flattened diurnal cortisol slope was associated with poorer functioning in the spatial working memory of EP women. DST suppression ratio was associated with better visual memory, without sex differences.
CONCLUSIONS: Our study suggests that there are sex differences in the relationship between HPA axis measures and cognitive abilities in EP.

PMID: 27344379 [PubMed – indexed for MEDLINE]

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Systematic review: interventions for abdominal pain management in inflammatory bowel disease.

Category : Antiinflamatorio

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Systematic review: interventions for abdominal pain management in inflammatory bowel disease.

Aliment Pharmacol Ther. 2017 Jul;46(2):115-125

Authors: Norton C, Czuber-Dochan W, Artom M, Sweeney L, Hart A

Abstract
BACKGROUND: Abdominal pain is frequently reported by people with inflammatory bowel disease (IBD), including in remission. Pain is an under-treated symptom.
AIM: To systematically review evidence on interventions (excluding disease-modifying interventions) for abdominal pain management in IBD.
METHODS: Databases (MEDLINE, EMBASE, PsycInfo, CINAHL, Scopus, Cochrane Library) were searched (February 2016). Two researchers independently screened references and extracted data.
RESULTS: Fifteen papers were included: 13 intervention studies and two cross-sectional surveys. A variety of psychological, dietary and pharmacological interventions were reported. Four of six studies reported pain reduction with psychological intervention including individualised and group-based relaxation, disease anxiety-related Cognitive Behavioural Therapy and stress management. Both psychologist-led and self-directed stress management in inactive Crohn’s disease reduced pain compared with controls (symptom frequency reduction index=-26.7, -11.3 and 17.2 at 6-month follow-up, respectively). Two dietary interventions (alcoholic drinks with high sugar content and fermentable carbohydrate with prebiotic properties) had an effect on abdominal pain. Antibiotics (for patients with bacterial overgrowth) and transdermal nicotine patches reduced abdominal pain. Current and past cannabis users report it relieves pain. One controlled trial of cannabis reduced SF-36 and EQ-5D pain scores (1.84 and 0.7, respectively). These results must be treated with caution: data were derived from predominantly small uncontrolled studies of moderate to low quality.
CONCLUSIONS: Few interventions have been tested for IBD abdominal pain. The limited evidence suggests that relaxation and changing cognitions are promising, possibly with individualised dietary changes. There is a need to develop interventions for abdominal pain management in IBD.

PMID: 28470846 [PubMed – indexed for MEDLINE]

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HIV-infected cannabis users have lower circulating CD16+ monocytes and IP-10 levels compared to non-using HIV patients.

Category : Antiinflamatorio

HIV-infected cannabis users have lower circulating CD16+ monocytes and IP-10 levels compared to non-using HIV patients.

AIDS. 2017 Nov 30;:

Authors: Rizzo MD, Crawford RB, Henriquez JE, Aldhamen Y, Gulick P, Amalfitano A, Kaminski NE

Abstract
OBJECTIVE: Chronic immune activation and elevated numbers of circulating activated monocytes (CD16) are implicated in HIV-associated neuroinflammation. The objective was to compare the level of circulating CD16 monocytes and interferon-γ-inducible protein 10 (IP-10) between HIV-infected cannabis users (HIV+MJ+) and non-cannabis users (HIV+MJ-), and determine whether in vitro Δ-Tetrahydrocannabinol (THC), a constituent of cannabis, affected CD16 expression as well as IP-10 production by monocytes.
DESIGN: The levels of circulating CD16 monocytes and IP-10 from HIV+MJ- and HIV+MJ+ donors were examined. In vitro experimentation using THC was performed on primary leukocytes isolated from HIV-MJ-, HIV+MJ- and HIV+MJ+ donors to determine if THC has an impact on CD16 monocyte and IP-10 levels.
METHODS: Flow cytometry was used to measure the number of blood CD16 monocytes and serum IP-10 from HIV+MJ- and HIV+MJ+ donors. Peripheral blood mononuclear cells (PBMC) were isolated from HIV-MJ- and HIV+ (MJ- and MJ+) donors for in vitro THC and IFNα treatment, and CD16 monocytes and supernatant IP-10 were quantified.
RESULTS: HIV+MJ+ donors possessed a lower level of circulating CD16 monocytes and serum IP-10, compared to HIV+MJ- donors. Further, monocytes from HIV+MJ+ donors were unable to induce CD16 expression when treated with in vitro IFNα, while HIV-MJ- and HIV+MJ- donors displayed pronounced CD16 induction, suggesting anti-inflammatory effects by cannabis. Lastly, in vitro THC treatment impaired CD16 monocyte transition to CD16 and monocyte-derived IP-10.
CONCLUSIONS: Components of cannabis, including THC, may decelerate peripheral monocyte processes that are implicated in HIV-associated neuroinflammation.

PMID: 29194121 [PubMed – as supplied by publisher]

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Pharmacological Foundations of Cannabis Chemovars.

Category : Antiinflamatorio

Pharmacological Foundations of Cannabis Chemovars.

Planta Med. 2017 Nov 21;:

Authors: Lewis MA, Russo EB, Smith KM

Abstract
An advanced Mendelian Cannabis breeding program has been developed utilizing chemical markers to maximize the yield of phytocannabinoids and terpenoids with the aim to improve therapeutic efficacy and safety. Cannabis is often divided into several categories based on cannabinoid content. Type I, Δ(9)-tetrahydrocannabinol-predominant, is the prevalent offering in both medical and recreational marketplaces. In recent years, the therapeutic benefits of cannabidiol have been better recognized, leading to the promotion of additional chemovars: Type II, Cannabis that contains both Δ(9)-tetrahydrocannabinol and cannabidiol, and cannabidiol-predominant Type III Cannabis. While high-Δ(9)-tetrahydrocannabinol and high-myrcene chemovars dominate markets, these may not be optimal for patients who require distinct chemical profiles to achieve symptomatic relief. Type II Cannabis chemovars that display cannabidiol- and terpenoid-rich profiles have the potential to improve both efficacy and minimize adverse events associated with Δ(9)-tetrahydrocannabinol exposure. Cannabis samples were analyzed for cannabinoid and terpenoid content, and analytical results are presented via PhytoFacts, a patent-pending method of graphically displaying phytocannabinoid and terpenoid content, as well as scent, taste, and subjective therapeutic effect data. Examples from the breeding program are highlighted and include Type I, II, and III Cannabis chemovars, those highly potent in terpenoids in general, or single components, for example, limonene, pinene, terpinolene, and linalool. Additionally, it is demonstrated how Type I - III chemovars have been developed with conserved terpenoid proportions. Specific chemovars may produce enhanced analgesia, anti-inflammatory, anticonvulsant, antidepressant, and anti-anxiety effects, while simultaneously reducing sequelae of Δ(9)-tetrahydrocannabinol such as panic, toxic psychosis, and short-term memory impairment.

PMID: 29161743 [PubMed – as supplied by publisher]

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[Cannabis and lung. What we know and everything we don’t know yet].

Category : Antiinflamatorio

[Cannabis and lung. What we know and everything we don’t know yet].

Rev Pneumol Clin. 2017 Nov 07;:

Authors: Urban T, Hureaux J

Abstract
Cannabis use increased sharply from 2010 to 2014 in France. Cannabis is often consumed with tobacco, although the use of marijuana is developing. Tobacco and cannabis smoke have many common characteristics in terms of irritants, carcinogens and carbon monoxide. They also differentiate by their dependence mechanisms, with nicotine and its receptors for tobacco and tetra-hydro-cannabinol (THC) and its specific receptors for cannabis. Chronic inhalation (700,000 daily users in France) over a long period most likely increases the relative risk of bronchial cancer. But long-term cohort studies targeting this group of strong cannabis users, especially over time, are lacking. Inhalation of cannabis smoke, despite an acute bronchodilator effect, is associated with the risk of chronic bronchitis in the case of regular use. However, the risk of developing COPD in the exclusive marijuana smoker group with no associated tobacco is not yet clear, with studies yielding discordant results. There is also a lack of long-term follow-up studies of respiratory investigations in large cannabis users. Finally, cannabis smoke contains various cannabinoids, for example cannabidiol which also have anti-inflammatory and antifibrotic properties, with the unconfirmed hypothesis that these properties can partially modulate the deleterious action of cannabis smoke.

PMID: 29126755 [PubMed – as supplied by publisher]

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Single-Dose Pharmacokinetics of Oral Cannabidiol Following Administration of PTL101: A New Formulation Based on Gelatin Matrix Pellets Technology.

Category : Antiinflamatorio

Single-Dose Pharmacokinetics of Oral Cannabidiol Following Administration of PTL101: A New Formulation Based on Gelatin Matrix Pellets Technology.

Clin Pharmacol Drug Dev. 2017 Nov 10;:

Authors: Atsmon J, Heffetz D, Deutsch L, Deutsch F, Sacks H

Abstract
Cannabidiol (CBD) is the main nonpsychoactive component of the cannabis plant. It has been associated with antiseizure, antioxidant, neuroprotective, anxiolytic, anti-inflammatory, antidepressant, and antipsychotic effects. PTL101 is an oral gelatin matrix pellets technology-based formulation containing highly purified CBD embedded in seamless gelatin matrix beadlets. Study objectives were to evaluate the safety and tolerability of PTL101 containing 10 and 100 mg CBD, following single administrations to healthy volunteers and to compare the pharmacokinetic profiles and relative bioavailability of CBD with Sativex oromucosal spray (the reference product) in a randomized, crossover study design. Administration of PTL101 containing 10 CBD, led to a 1.7-fold higher Cmax and 1.3-fold higher AUC compared with the oromucosal spray. Tmax following both modes of delivery was 3-3.5 hours postdosing. CBD exhibited about a 1-hour lag in absorption when delivered via PTL101. A 10-fold increase in the dose resulted in an ∼15-fold increase in Cmax and AUC. Bioavailability of CBD in the 10-mg PTL101 dose was 134% relative to the reference spray. PTL101 is a pharmaceutical-grade, user-friendly oral formulation that demonstrated safe and efficient delivery of CBD and therefore could be an attractive candidate for therapeutic indications.

PMID: 29125702 [PubMed – as supplied by publisher]

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