Category Archives: Antiinflamatorio

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Is Cannabidiol a Promising Substance for New Drug Development? A Review of its Potential Therapeutic Applications.

Category : Antiinflamatorio

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Is Cannabidiol a Promising Substance for New Drug Development? A Review of its Potential Therapeutic Applications.

Crit Rev Eukaryot Gene Expr. 2018;28(1):73-86

Authors: Noreen N, Muhammad F, Akhtar B, Azam F, Anwar MI

Abstract
The pharmacological importance of cannabidiol (CBD) has been in study for several years. CBD is the major nonpsychoactive constituent of plant Cannabis sativa and its administration is associated with reduced side effects. Currently, CBD is undergoing a lot of research which suggests that it has no addictive effects, good safety profile and has exhibited powerful therapeutic potential in several vital areas. It has wide spectrum of action because it acts through endocannabinoid receptors; CB1 and CB2 and it also acts on other receptors, such as GPR18, GPR55, GPR 119, 5HT1A, and TRPV2. This indicates its therapeutic value for numerous medical conditions because of its neuroprotective and immunomodulatory properties. Potential therapeutic applications of CBD include, analgesic, anti-inflammatory, anxiolytic, anti-arthritic, anti-depressant, anti-Alzheimer disease, anti-ischemic, neuroprotective, and anti-fibrotic. More promising areas appear to include diabetes and cancer where CBD exhibits lesser side effects and more therapeutic benefits as compared to recent available medical therapies. Hence, CBD is a promising substance for the development of new drug. However further research and clinical studies are required to explore its complete potential.

PMID: 29773016 [PubMed – in process]

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Altered attentional control strategies but spared executive functioning in chronic cannabis users.

Category : Antiinflamatorio

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Altered attentional control strategies but spared executive functioning in chronic cannabis users.

Drug Alcohol Depend. 2017 Dec 01;181:116-123

Authors: Nusbaum AT, Whitney P, Cuttler C, Spradlin A, Hinson JM, McLaughlin RJ

Abstract
BACKGROUND: Cannabis use has increased rapidly in recent decades. The increase in cannabis use makes it important to understand the potential influence of chronic use on attentional control and other executive functions (EFs). Because cannabis is often used to reduce stress, and because stress can constrain attentional control and EFs, the primary goal of this study was to determine the joint effect of acute stress and chronic cannabis use on specific EFs.
METHODS: Thirty-nine cannabis users and 40 non-users were assigned to either a stress or no stress version of the Maastricht Acute Stress Test. Participants then completed two cognitive tasks that involve EFs: (1) task switching, and (2) a novel Flexible Attentional Control Task. These two tasks provided assessments of vigilant attention, inhibitory control, top-down attentional control, and cognitive flexibility. Salivary cortisol was assessed throughout the study.
RESULTS: Reaction time indices showed an interaction between stress and cannabis use on top-down attentional control (p=0.036, np2=0.059). Follow-up tests showed that cannabis users relied less on top-down attentional control than did non-users in the no stress version. Despite not relying on top-down control, the cannabis users showed no overall performance deficits on the tasks.
CONCLUSIONS: Chronic cannabis users performed cognitive tasks involving EFs as well as non-users while not employing cognitive control processes that are typical for such tasks. These results indicate alterations in cognitive processing in cannabis users, but such alterations do not necessarily lead to global performance deficits.

PMID: 29045919 [PubMed – indexed for MEDLINE]

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Illicit drugs and pharmaceuticals in swimming pool waters.

Category : Antiinflamatorio

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Illicit drugs and pharmaceuticals in swimming pool waters.

Sci Total Environ. 2018 Apr 20;635:956-963

Authors: Fantuzzi G, Aggazzotti G, Righi E, Predieri G, Castiglioni S, Riva F, Zuccato E

Abstract
The occurrence of illicit drugs (cocaine, opioids, amphetamines and cannabis derivatives), some of their metabolites and 48 pharmaceuticals, was investigated in pool and source waters in ten Italian indoor swimming pools. The samples were analyzed by highperformance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), after solid phase extraction (SPE). Cocaine and its metabolites were found in nine swimming pools, at concentrations from 0.3 to 4.2 ng/L for cocaine, 1.1 to 48.7 ng/L for norcocaine, 0.7 to 21.4 ng/L for benzoylecgonine and 0.1 to 7.3 ng/L for norbenzoylecgonine. Opioids, amphetamines and cannabis derivatives were never detected. The most frequent pharmaceuticals were anti-inflammatory drugs: ibuprofen was found in all the pool waters, with a maximum 197 ng/L and ketoprofen was detected in 9/10 samples (maximum 127 ng/L). Among anticonvulsants, carbamazepine and its metabolite, 10,11-dihydro-10,11dihydroxycarbamazepine, were frequent in swimming pool water (8/10 samples) at concentrations up to 62 ng/L. The cardiovascular drug valsartan was also found frequently (8/10 samples), but at lower concentrations (up to 9 ng/L). Other pharmaceuticals were detected occasionally and at lower concentrations (atenolol, enalapril, paracetamol, hydroclorothiazide, irbesartan and dehydro-erythromycin). Carbamazepine, irbesartan and dehydroerythromycin were detected at very low levels (up to 5 ng/L) in only one of the four source water samples. A quantitative risk assessment showed that the health risk for humans to these substance in swimming pool waters was generally negligible, even for vulnerable subpopulations such as children and adolescents.

PMID: 29710617 [PubMed – as supplied by publisher]

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The relationship between cannabis use and cortisol levels in youth at ultra high-risk for psychosis.

Category : Antiinflamatorio

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The relationship between cannabis use and cortisol levels in youth at ultra high-risk for psychosis.

Psychoneuroendocrinology. 2017 Sep;83:58-64

Authors: Carol EE, Spencer RL, Mittal VA

Abstract
Recent studies have posited a relationship between cannabis use and the biological stress system, but this critical relationship has not been evaluated during the ultra high-risk (UHR) period immediately preceding the onset of psychotic disorders. Salivary cortisol samples were collected on 46 UHR and 29 control adolescents; these individuals were assessed for current cannabis use with a urine panel and self-report. UHR participants where separated into two groups: Current Cannabis Use (UHR-CU) and No Current Cannabis Use (UHR-NC). Healthy Control participants (HC) were free of cannabis use. Consistent with the literature, results indicate UHR individuals showed elevated cortisol levels when compared to HC participants. Further, we also observed that UHR-CU participants exhibited elevated levels when compared to both the non-using UHR and HC groups. Findings suggest that cannabis use may interact with underlying biological vulnerability associated with the hypothalamic-pituitary-adrenal (HPA) axis system.

PMID: 28595088 [PubMed – indexed for MEDLINE]

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Antiepileptogenic Effect of Subchronic Palmitoylethanolamide Treatment in a Mouse Model of Acute Epilepsy.

Category : Antiinflamatorio

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Antiepileptogenic Effect of Subchronic Palmitoylethanolamide Treatment in a Mouse Model of Acute Epilepsy.

Front Mol Neurosci. 2018;11:67

Authors: Post JM, Loch S, Lerner R, Remmers F, Lomazzo E, Lutz B, Bindila L

Abstract
Research on the antiepileptic effects of (endo-)cannabinoids has remarkably progressed in the years following the discovery of fundamental role of the endocannabinoid (eCB) system in controlling neural excitability. Moreover, an increasing number of well-documented cases of epilepsy patients exhibiting multi-drug resistance report beneficial effects of cannabis use. Pre-clinical and clinical research has increasingly focused on the antiepileptic effectiveness of exogenous administration of cannabinoids and/or pharmacologically induced increase of eCBs such as anandamide (also known as arachidonoylethanolamide [AEA]). Concomitant research has uncovered the contribution of neuroinflammatory processes and peripheral immunity to the onset and progression of epilepsy. Accordingly, modulation of inflammatory pathways such as cyclooxygenase-2 (COX-2) was pursued as alternative therapeutic strategy for epilepsy. Palmitoylethanolamide (PEA) is an endogenous fatty acid amide related to the centrally and peripherally present eCB AEA, and is a naturally occurring nutrient that has long been recognized for its analgesic and anti-inflammatory properties. Neuroprotective and anti-hyperalgesic properties of PEA were evidenced in neurodegenerative diseases, and antiepileptic effects in pentylenetetrazol (PTZ), maximal electroshock (MES) and amygdaloid kindling models of epileptic seizures. Moreover, numerous clinical trials in chronic pain revealed that PEA treatment is devoid of addiction potential, dose limiting side effects and psychoactive effects, rendering PEA an appealing candidate as antiepileptic compound or adjuvant. In the present study, we aimed at assessing antiepileptic properties of PEA in a mouse model of acute epileptic seizures induced by systemic administration of kainic acid (KA). KA-induced epilepsy in rodents is assumed to resemble to different extents human temporal lobe epilepsy (TLE) depending on the route of KA administration; intracerebral (i.c.) injection was recently shown to most closely mimic human TLE, while systemic KA administration causes more widespread pathological damage, both in brain and periphery. To explore the potential of PEA to exert therapeutic effects both in brain and periphery, acute and subchronic administration of PEA by intraperitoneal (i.p.) injection was assessed on mice with systemically administered KA. Specifically, we investigated: (i) neuroprotective and anticonvulsant properties of acute and subchronic PEA treatment in KA-induced seizure models, and (ii) temporal dynamics of eCB and eicosanoid (eiC) levels in hippocampus and plasma over 180 min post seizure induction in PEA-treated and non-treated KA-injected mice vs. vehicle injected mice. Finally, we compared the systemic PEA treatment with, and in combination with, pharmacological blockade of fatty acid amide hydrolase (FAAH) in brain and periphery, in terms of anticonvulsant properties and modulation of eCBs and eiCs. Here, we demonstrate that subchronic administration of PEA significantly alleviates seizure intensity, promotes neuroprotection and induces modulation of the plasma and hippocampal eCB and eiC levels in systemic KA-injected mice.

PMID: 29593494 [PubMed]

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Blunted stress reactivity in chronic cannabis users.

Category : Antiinflamatorio

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Blunted stress reactivity in chronic cannabis users.

Psychopharmacology (Berl). 2017 Aug;234(15):2299-2309

Authors: Cuttler C, Spradlin A, Nusbaum AT, Whitney P, Hinson JM, McLaughlin RJ

Abstract
RATIONALE: One of the most commonly cited reasons for chronic cannabis use is to cope with stress. Consistent with this, cannabis users have shown reduced emotional arousal and dampened stress reactivity in response to negative imagery.
OBJECTIVES: To our knowledge, the present study represents the first to examine the effects of an acute stress manipulation on subjective stress and salivary cortisol in chronic cannabis users compared to non-users.
METHODS: Forty cannabis users and 42 non-users were randomly assigned to complete either the stress or no stress conditions of the Maastricht Acute Stress Test (MAST). The stress condition of the MAST manipulates both physiological (placing hand in ice bath) and psychosocial stress (performing math under conditions of social evaluation). Participants gave baseline subjective stress ratings before, during, and after the stress manipulation. Cortisol was measured from saliva samples obtained before and after the stress manipulation. Further, cannabis cravings and symptoms of withdrawal were measured.
RESULTS: Subjective stress ratings and cortisol levels were significantly higher in non-users in the stress condition relative to non-users in the no stress condition. In contrast, cannabis users demonstrated blunted stress reactivity; specifically, they showed no increase in cortisol and a significantly smaller increase in subjective stress ratings. The stress manipulation had no impact on cannabis users’ self-reported cravings or withdrawal symptoms.
CONCLUSION: Chronic cannabis use is associated with blunted stress reactivity. Future research is needed to determine whether this helps to confer resiliency or vulnerability to stress-related psychopathology as well as the mechanisms underlying this effect.

PMID: 28567696 [PubMed – indexed for MEDLINE]

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The Cannabinoids Δ8THC, CBD, and HU-308 Act via Distinct Receptors to Reduce Corneal Pain and Inflammation.

Category : Antiinflamatorio

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The Cannabinoids Δ8THC, CBD, and HU-308 Act via Distinct Receptors to Reduce Corneal Pain and Inflammation.

Cannabis Cannabinoid Res. 2018;3(1):11-20

Authors: Thapa D, Cairns EA, Szczesniak AM, Toguri JT, Caldwell MD, Kelly MEM

Abstract
Background and Purpose: Corneal injury can result in dysfunction of corneal nociceptive signaling and corneal sensitization. Activation of the endocannabinoid system has been reported to be analgesic and anti-inflammatory. The purpose of this research was to investigate the antinociceptive and anti-inflammatory effects of cannabinoids with reported actions at cannabinoid 1 (CB1R) and cannabinoid 2 (CB2R) receptors and/or noncannabinoid receptors in an experimental model of corneal hyperalgesia. Methods: Corneal hyperalgesia (increased pain response) was generated using chemical cauterization of the corneal epithelium in wild-type (WT) and CB2R knockout (CB2R-/-) mice. Cauterized eyes were treated topically with the phytocannabinoids Δ8-tetrahydrocannabinol (Δ8THC) or cannabidiol (CBD), or the CBD derivative HU-308, in the presence or absence of the CB1R antagonist AM251 (2.0 mg/kg i.p.), or the 5-HT1A receptor antagonist WAY100635 (1 mg/kg i.p.). Behavioral pain responses to a topical capsaicin challenge at 6 h postinjury were quantified from video recordings. Mice were euthanized at 6 and 12 h postcorneal injury for immunohistochemical analysis to quantify corneal neutrophil infiltration. Results: Corneal cauterization resulted in hyperalgesia to capsaicin at 6 h postinjury compared to sham control eyes. Neutrophil infiltration, indicative of inflammation, was apparent at 6 and 12 h postinjury in WT mice. Application of Δ8THC, CBD, and HU-308 reduced the pain score and neutrophil infiltration in WT mice. The antinociceptive and anti-inflammatory actions of Δ8THC, but not CBD, were blocked by the CB1R antagonist AM251, but were still apparent, for both cannabinoids, in CB2R-/- mice. However, the antinociceptive and anti-inflammatory actions of HU-308 were absent in the CB2R-/- mice. The antinociceptive and anti-inflammatory effects of CBD were blocked by the 5-HT1A antagonist WAY100635. Conclusion: Topical cannabinoids reduce corneal hyperalgesia and inflammation. The antinociceptive and anti-inflammatory effects of Δ8THC are mediated primarily via CB1R, whereas that of the cannabinoids CBD and HU-308, involve activation of 5-HT1A receptors and CB2Rs, respectively. Cannabinoids could be a novel clinical therapy for corneal pain and inflammation resulting from ocular surface injury.

PMID: 29450258 [PubMed]

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Complementary and Alternative Medicine.

Category : Antiinflamatorio

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Complementary and Alternative Medicine.

Inflamm Bowel Dis. 2016 Jun;22(6):1523-30

Authors: Quezada SM, Briscoe J, Cross RK

Abstract
Inflammatory bowel disease is a complex, chronic, multifactorial inflammatory disorder of the digestive tract. Standard therapies include immunosuppressive and biological treatments, but there is increasing interest in the potential benefit of complementary and alternative medicine for the treatment of inflammatory bowel disease. Given the high prevalence of use of complementary and alternative medicine among inflammatory bowel disease patients, gastroenterologists must remain knowledgeable regarding the risks and benefits of these treatment options. This article reviews the updated scientific data on the use of biologically based complementary and alternative therapies for the treatment of inflammatory bowel disease.

PMID: 27057686 [PubMed – indexed for MEDLINE]

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Individual prolactin reactivity modulates response of nucleus accumbens to erotic stimuli during acute cannabis intoxication: an fMRI pilot study.

Category : Antiinflamatorio

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Individual prolactin reactivity modulates response of nucleus accumbens to erotic stimuli during acute cannabis intoxication: an fMRI pilot study.

Psychopharmacology (Berl). 2017 Jul;234(13):1933-1943

Authors: Androvicova R, Horacek J, Tintera J, Hlinka J, Rydlo J, Jezova D, Balikova M, Hlozek T, Miksatkova P, Kuchar M, Roman M, Tomicek P, Tyls F, Viktorinova M, Palenicek T

Abstract
RATIONALE: Self-report studies indicate that cannabis could increase sexual desire in some users. We hypothesized that intoxication increases activation of brain areas responsive to visual erotica, which could be useful in the treatment of hypoactive sexual desire disorder, a condition marked by a lack of sexual desire.
OBJECTIVES: The aim of this study is to assess the aphrodisiacal properties of cannabis.
METHODS: We conducted an open-randomized study with 21 heterosexual casual cannabis users. A 3T MRI was used to measure brain activation in response to erotic pictures. Blood samples were collected to determine the serum levels of cannabinoids, cortisol and prolactin. Participants were grouped according to whether they had ever experienced any aphrodisiacal effects during intoxication (Group A) or not (Group non-A).
RESULTS: Intoxication was found to significantly increase activation in the right nucleus accumbens in the Group A while significantly decreasing activation in the Group non-A. There was also a significant interaction between the group and intoxication, with elevated prolactin in the Group non-A during intoxication. No intoxication-related differences in subjective picture evaluations were found.
CONCLUSION: Cannabis intoxication increases activation of the right nucleus accumbens to erotic stimuli. This effect is limited to users whose prolactin is not elevated in response to intoxication. This effect may be useful in the treatment of low sexual desire.

PMID: 28401285 [PubMed – indexed for MEDLINE]

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Use of N-Acetylcysteine in Psychiatric Conditions among Children and Adolescents: A Scoping Review.

Category : Antiinflamatorio

Use of N-Acetylcysteine in Psychiatric Conditions among Children and Adolescents: A Scoping Review.

Cureus. 2017 Nov 29;9(11):e1888

Authors: Naveed S, Amray A, Waqas A, Chaudhary AM, Azeem MW

Abstract
N-acetylcysteine (NAC) is a well-known antidote for acetaminophen toxicity and is easily available over the counter. It has antioxidant and anti-inflammatory properties and an established tolerance and safety profile. Owing to its neuroprotective effects, its clinical use has recently expanded to include the treatment of different psychiatric and non-psychiatric disorders. Although a number of randomized controlled trials have documented the clinical evidence for NAC, there are no reviews that summarize the evidence. The present scoping review summarizes the study designs, the patient characteristics, the evidence and the limitations in randomized controlled trials designed to explore the efficacy of NAC for psychiatric conditions in the pediatric population.

PMID: 29392100 [PubMed]

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