Author Archives: adminoacido

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The current state and future perspectives of cannabinoids in cancer biology.

Category : Cancer

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The current state and future perspectives of cannabinoids in cancer biology.

Cancer Med. 2018 Feb 23;:

Authors: Śledziński P, Zeyland J, Słomski R, Nowak A

Abstract
To date, cannabinoids have been allowed in the palliative medicine due to their analgesic and antiemetic effects, but increasing number of preclinical studies indicates their anticancer properties. Cannabinoids exhibit their action by a modulation of the signaling pathways crucial in the control of cell proliferation and survival. Many in vitro and in vivo experiments have shown that cannabinoids inhibit proliferation of cancer cells, stimulate autophagy and apoptosis, and have also a potential to inhibit angiogenesis and metastasis. In this review, we present an actual state of knowledge regarding molecular mechanisms of cannabinoids’ anticancer action, but we discuss also aspects that are still not fully understood such as the role of the endocannabinoid system in a carcinogenesis, the impact of cannabinoids on the immune system in the context of cancer development, or the cases of a stimulation of cancer cells’ proliferation by cannabinoids. The review includes also a summary of currently ongoing clinical trials evaluating the safety and efficacy of cannabinoids as anticancer agents.

PMID: 29473338 [PubMed – as supplied by publisher]

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Cannabidiol Regulates Long Term Potentiation Following Status Epilepticus: Mediation by Calcium Stores and Serotonin.

Category : Epilepsia

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Cannabidiol Regulates Long Term Potentiation Following Status Epilepticus: Mediation by Calcium Stores and Serotonin.

Front Mol Neurosci. 2018;11:32

Authors: Maggio N, Shavit Stein E, Segal M

Abstract
Epilepsy is a devastating disease, with cognitive and emotional consequences that are not curable. In recent years, it became apparent that cannabinoids help patients to cope with epilepsy. We have studied the effects of cannabidiol (CBD) on the ability to produce long term potentiation (LTP) in stratum radiatum of CA1 region of the mouse hippocampus. Exposure to seizure-producing pilocarpine reduced the ability to generate LTP in the slice. Pre-exposure to CBD prevented this effect of pilocarpine. Furthermore, CBD caused a marked increase in ability to generate LTP, an effect that was blocked by calcium store antagonists as well as by a reduction in serotonin tone. Serotonin, possibly acting at a 5HT1A receptor, or fenfluramine (FFA), which causes release of serotonin from its native terminals, mimicked the effect of CBD. It is proposed that CBD enhances non-NMDA LTP in the slice by facilitating release of serotonin from terminals, consequently ameliorating the detrimental effects of pilocarpine.

PMID: 29467619 [PubMed]

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Species-specific susceptibility to cannabis-induced convulsions.

Category : Epilepsia

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Species-specific susceptibility to cannabis-induced convulsions.

Br J Pharmacol. 2018 Feb 19;:

Authors: Whalley BJ, Lin H, Bell L, Hill T, Patel A, Gray RA, Elizabeth Roberts C, Devinsky O, Bazelot M, Williams CM, Stephens GJ

Abstract
BACKGROUND AND PURPOSE: Numerous claims are made for cannabis’ therapeutic utility upon human seizures, but concerns persist about risks. A potential confounder is the presence of both Δ9 -tetrahydrocannabinol (Δ9 -THC), variously reported to be pro- and anti-convulsant, and cannabidiol (CBD), widely confirmed as anticonvulsant. Therefore, we investigated effects of prolonged exposure to different Δ9 -THC/CBD cannabis extracts on seizure activity and associated measures of endocannabinoid (eCB) system signalling.
EXPERIMENTAL APPROACH: Cannabis extract effects on in vivo neurological and behavioural responses, and on bioanalyte levels, were measured in rats and dogs. Extract effects on seizure activity were measured using electroencephalography-telemetry in rats. eCB signalling was also investigated using radioligand binding in cannabis extract-treated rats, and treatment-naïve rat, mouse, chicken, dog and human tissue.
KEY RESULTS: Prolonged exposure to cannabis extracts caused spontaneous, generalised seizures, subserved by epileptiform discharges in rats, but not dogs, and produced higher Δ9 -THC, but lower 11-hydroxy-THC (11-OH-THC) and CBD, plasma concentrations in rats versus dogs. In the same rats, prolonged exposure to cannabis also impaired cannabinoid type 1 receptor (CB1 R)-mediated signalling. Profiling CB1 R expression, basal activity, extent of activation and sensitivity to Δ9 -THC suggested interspecies differences in eCB signalling, being more pronounced in a species that exhibited cannabis extract-induced seizures (rat) than a species that did not (dog).
CONCLUSION AND IMPLICATIONS: Sustained cannabis extract treatment caused differential seizure, behavioural and bioanalyte levels between rats and dogs. Supporting radioligand binding data suggest species differences in eCB signalling. Interspecies variations may have important implications for predicting cannabis-induced convulsions from animal models.

PMID: 29457829 [PubMed – as supplied by publisher]

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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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Cannabinoid-induced cell death in endometrial cancer cells: involvement of TRPV1 receptors in apoptosis.

Category : Cancer

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Cannabinoid-induced cell death in endometrial cancer cells: involvement of TRPV1 receptors in apoptosis.

J Physiol Biochem. 2018 Feb 13;:

Authors: Fonseca BM, Correia-da-Silva G, Teixeira NA

Abstract
Among a variety of phytocannabinoids, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are the most promising therapeutic compounds. Besides the well-known palliative effects in cancer patients, cannabinoids have been shown to inhibit in vitro growth of tumor cells. Likewise, the major endocannabinoids (eCBs), anandamide (AEA) and 2-arachidonoylglycerol (2-AG), induce tumor cell death. The purpose of the present study was to characterize cannabinoid elements and evaluate the effect of cannabinoids in endometrial cancer cell viability. The presence of cannabinoid receptors, transient receptor potential vanilloid 1 (TRPV1), and endocannabinoid-metabolizing enzymes were determined by qRT-PCR and Western blot. We also examined the effects and the underlying mechanisms induced by eCBs and phytocannabinoids in endometrial cancer cell viability. Besides TRPV1, both EC cell lines express all the constituents of the endocannabinoid system. We observed that at concentrations higher than 5 μM, eCBs and CBD induced a significant reduction in cell viability in both Ishikawa and Hec50co cells, whereas THC did not cause any effect. In Ishikawa cells, contrary to Hec50co, treatment with AEA and CBD resulted in an increase in the levels of activated caspase -3/-7, in cleaved PARP, and in reactive oxygen species generation, confirming that the reduction in cell viability observed in the MTT assay was caused by the activation of the apoptotic pathway. Finally, these effects were dependent on TRPV1 activation and intracellular calcium levels. These data indicate that cannabinoids modulate endometrial cancer cell death. Selective targeting of TPRV1 by AEA, CBD, or other stable analogues may be an attractive research area for the treatment of estrogen-dependent endometrial carcinoma. Our data further support the evaluation of CBD and CBD-rich extracts for the potential treatment of endometrial cancer, particularly, that has become non-responsive to common therapies.

PMID: 29441458 [PubMed – as supplied by publisher]

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Cannabis for paediatric epilepsy: challenges and conundrums.

Category : Epilepsia

Cannabis for paediatric epilepsy: challenges and conundrums.

Med J Aust. 2018 Feb 19;208(3):132-136

Authors: Chen KA, Farrar MA, Cardamone M, Lawson JA

Abstract
Research is expanding for the use of cannabidiol as an anticonvulsant drug. The mechanism of cannabidiol in paediatric epilepsy is unclear but is thought to play a role in modulation of synaptic transmission. Evidence for its efficacy in treating epilepsy is limited but growing, with a single pharmaceutical company-funded randomised double-blind controlled trial in children with Dravet syndrome. Progress towards the use of medicinal cannabinoids incorporates a complex interplay of social influences and political and legal reform. Access to unregistered but available cannabidiol in Australia outside of clinical trials and compassionate access schemes is state dependent and will require Therapeutic Goods Administration approval, although the cost may be prohibitive. Further clinical trials are needed to clearly define efficacy and safety, particularly long term.

PMID: 29438649 [PubMed – in process]

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Efficacy of artisanal preparations of cannabidiol for the treatment of epilepsy: Practical experiences in a tertiary medical center.

Category : Epilepsia

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Efficacy of artisanal preparations of cannabidiol for the treatment of epilepsy: Practical experiences in a tertiary medical center.

Epilepsy Behav. 2018 Feb 08;:

Authors: Porcari GS, Fu C, Doll ED, Carter EG, Carson RP

Abstract
Medically refractory epilepsy continues to be a challenge worldwide, and despite an increasing number of medical therapies, approximately 1 in 3 patients continues to have seizures. Cannabidiol (CBD), one of many constituents of the Cannabis sativa or marijuana plant, has received renewed interest in the treatment of epilepsy. While highly purified CBD awaits Food and Drug Administration (FDA) approval, artisanal formulations of CBD are readily available and are seeing increased use in our patient population. Although randomized controlled trials of CBD are ongoing and promising, data regarding artisanal formulations of CBD are minimal and largely anecdotal. Here, we report a retrospective study to define the efficacy of artisanal CBD preparations in children with epilepsy. Given the known interaction between CBD and clobazam, we also conducted a subgroup comparison to determine if clobazam use was related to any beneficial effects of CBD. Additionally, we compared response rates with CBD and with clobazam alone within an overlapping patient cohort. A pediatric cohort with epilepsy of 108 patients was identified through a medical record search for patients using CBD oil. The addition of CBD resulted in 39% of patients having a >50% reduction in seizures, with 10% becoming seizure-free. The responder rate for clobazam was similar. No patients achieved CBD monotherapy, although the weaning of other antiepileptic drugs (AEDs) became possible in 22% of patients. A comparable proportion had AED additions during CBD therapy. With concomitant use of clobazam, 44% of patients had a 50% reduction in seizures upon addition of CBD compared with 33% in the population not taking clobazam; this difference was not statistically significant. The most common reported side effect of CBD was sedation in less than 4% of patients, all of whom were also taking clobazam. Increased alertness and improved verbal interactions were reported in 14% of patients in the CBD group and 8% of patients in the CBD and clobazam group. Benefits were more marked in the CBD alone group, in contrast to the CBD and clobazam group, but this difference was not statistically significant. In summary, these findings support efficacy of artisanal CBD preparations in seizure reduction with few significant side effects. The response to CBD was independent of concurrent clobazam use, although clobazam may contribute to the sedation seen with concurrent CBD use.

PMID: 29429908 [PubMed – as supplied by publisher]

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Inhibition of aldose reductase activity by Cannabis sativa chemotypes extracts with high content of cannabidiol or cannabigerol.

Category : Cancer

Inhibition of aldose reductase activity by Cannabis sativa chemotypes extracts with high content of cannabidiol or cannabigerol.

Fitoterapia. 2018 Feb 07;:

Authors: Smeriglio A, Giofrè SV, Galati EM, Monforte MT, Cicero N, D’Angelo V, Grassi G, Circosta C

Abstract
Aldose reductase (ALR2) is a key enzyme involved in diabetic complications and the search for new aldose reductase inhibitors (ARIs) is currently very important. The synthetic ARIs are often associated with deleterious side effects and medicinal and edible plants, containing compounds with aldose reductase inhibitory activity, could be useful for prevention and therapy of diabetic complications. Non-psychotropic phytocannabinoids exert multiple pharmacological effects with therapeutic potential in many diseases such as inflammation, cancer, diabetes. Here, we have investigated the inhibitory effects of extracts and their fractions from two Cannabis sativa L. chemotypes with high content of cannabidiol (CBD)/cannabidiolic acid (CBDA) and cannabigerol (CBG)/cannabigerolic acid (CBGA), respectively, on human recombinant and pig kidney aldose reductase activity in vitro. A molecular docking study was performed to evaluate the interaction of these cannabinoids with the active site of ALR2 compared to known ARIs. The extracts showed significant dose-dependent aldose reductase inhibitory activity (>70%) and higher than fractions. The inhibitory activity of the fractions was greater for acidic cannabinoid-rich fractions. Comparative molecular docking results have shown a higher stability of the ALR2-cannabinoid acids complex than the other inhibitors. The extracts of Cannabis with high content of non-psychotropic cannabinoids CBD/CBDA or CBG/CBGA significantly inhibit aldose reductase activity. These results may have some relevance for the possible use of C. sativa chemotypes based preparations as aldose reductase inhibitors.

PMID: 29427593 [PubMed – as supplied by publisher]

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