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Phytocannabinoid

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https://www.readbyqxmd.com/read/28799512/modulation-of-gabaa-receptors-in-the-treatment-of-epilepsy
#1
Eleonora Palma, Gabriele Ruffolo, Pierangelo Cifelli, Cristina Roseti, Erwin A van Vliet, Eleonora Aronica
BACKGROUND: A variety of evidence suggested that an imbalance in excitatory and inhibitory neurotransmission could be one of the pathophysiological mechanisms underlying the occurrence and progression of seizures. Understanding the causes of this imbalance may provide essential insight into the basic mechanisms of epilepsy and may uncover novel targets for future drug therapies. Accordingly, GABA is the most important inhibitory neurotransmitter in the CNS and its receptors (e.g., GABAARs) can still be relevant targets of new antiepileptic drugs (AEDs)...
August 9, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28750806/new-methods-for-the-synthesis-of-cannabidiol-derivatives
#2
Ana Lago-Fernandez, Vanessa Redondo, Laura Hernandez-Folgado, Laura Figuerola-Asencio, Nadine Jagerovic
Cannabidiol (CBD) is one of the most abundant components isolated from Cannabis sativa. However, CBD is a nonpsychotropic phytocannabinoid. In the last decade, there has been a growing interest in its therapeutic effects. This is why this natural product represents a lead structure for the development of new cannabinoid compounds. Even though chemistry of CBD has been explored for more than 30 years, the synthesis of only a few derivatives has been described. This chapter first reviews the synthetic methods for the preparation of CBD and derivatives...
2017: Methods in Enzymology
https://www.readbyqxmd.com/read/28738764/neuroprotection-by-endo-cannabinoids-in-glaucoma-and-retinal-neurodegenerative-diseases
#3
Cinzia Rapino, Daniel Tortolani, Lucia Scipioni, Mauro Maccarrone
Emerging neuroprotective strategies are being explored to preserve the retina from degeneration, that occurs in eye pathologies like glaucoma, diabetic retinopathy, age-related macular degeneration, and retinitis pigmentosa. Incidentally, neuroprotection of retina is a defending mechanism designed to prevent or delay neuronal cell death, and to maintain neural function following an initial insult, thus avoiding loss of vision. Numerous studies have investigated potential neuroprotective properties of plant-derived phytocannabinoids, as well as of their endogenous counterparts collectively termed endocannabinoids (eCBs), in several degenerative diseases of the retina...
July 24, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28736128/the-effect-of-pro-nanolipospheres-pnl-formulation-containing-natural-absorption-enhancers-on-the-oral-bioavailability-of-delta-9-tetrahydrocannabinol-thc-and-cannabidiol-cbd-in-a-rat-model
#4
Irina Cherniakov, Dvora Izgelov, Abraham J Domb, Amnon Hoffman
The lipophilic phytocannabinoids cannabidiol (CBD) and Δ(9)-tetrahydrocannabinol (THC) show therapeutic efficacy in various medical conditions. Both molecules are poorly water soluble and subjected to extensive first pass metabolism in the gastrointestinal tract, leading to a limited oral bioavailability of approximately 9%. We have developed an advanced lipid based Self-Emulsifying Drug Delivery System termed Advanced Pro-NanoLiposphere (PNL) pre-concentrate. The PNL is composed of lipid and emulsifying excipients of GRAS status and are known to increase solubility and reduce Phase I metabolism of lipophilic active compounds...
July 20, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28720466/antinociceptive-effects-of-huf-101-a-fluorinated-cannabidiol-derivative
#5
Nicole R Silva, Felipe V Gomes, Miriam D Fonseca, Raphael Mechoulam, Aviva Breuer, Thiago M Cunha, Francisco S Guimarães
Cannabidiol (CBD) is a phytocannabinoid with multiple pharmacological effects and several potential therapeutic properties. Its low oral bioavailability, however, can limit its clinical use. Preliminary results indicate that fluorination of the CBD molecule increases its pharmacological potency. Here, we investigated whether HUF-101 (3, 10, and 30mg/kg), a fluorinated CBD analogue, would induce antinociceptive effects. HUF-101 effects were compared to those induced by CBD (10, 30, and 90mg/kg) and the cannabinoid CB1/2 receptor agonist WIN55,212-2 (1, 3, and 5mg/kg)...
July 15, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28682102/the-effects-of-cannabidiol-cbd-on-%C3%AE-%C3%A2-tetrahydrocannabinol-thc-self-administration-in-male-and-female-long-evans-rats
#6
Alison G P Wakeford, Bradley B Wetzell, Rebecca L Pomfrey, Matthew M Clasen, William W Taylor, Briana J Hempel, Anthony L Riley
Despite widespread cannabis use in humans, few rodent models exist demonstrating significant Δ⁹-tetrahydrocannabinol (THC) self-administration, possibly due to THC's co-occurring aversive effects, which impact drug reinforcement. Cannabis contains a number of phytocannabinoids in addition to THC, one of which, cannabidiol (CBD), has been reported to antagonize some of the aversive effects of THC. Given such effects of CBD, it is possible that it might influence THC intravenous self-administration in rodents...
August 2017: Experimental and Clinical Psychopharmacology
https://www.readbyqxmd.com/read/28680401/cannabidiol-is-a-potential-therapeutic-for-the-affective-motivational-dimension-of-incision-pain-in-rats
#7
Karina Genaro, Débora Fabris, Ana L F Arantes, Antônio W Zuardi, José A S Crippa, Wiliam A Prado
Background: Pain involves different brain regions and is critically determined by emotional processing. Among other areas, the rostral anterior cingulate cortex (rACC) is implicated in the processing of affective pain. Drugs that interfere with the endocannabinoid system are alternatives for the management of clinical pain. Cannabidiol (CBD), a phytocannabinoid found in Cannabis sativa, has been utilized in preclinical and clinical studies for the treatment of pain. Herein, we evaluate the effects of CBD, injected either systemically or locally into the rACC, on mechanical allodynia in a postoperative pain model and on the negative reinforcement produced by relief of spontaneous incision pain...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28655644/pregnenolone-does-not-interfere-with-the-effects-of-cannabinoids-on-synaptic-transmission-in-the-cerebellum-and-the-nucleus-accumbens
#8
Anna Krohmer, Martin Brehm, Volker Auwärter, Bela Szabo
The steroid hormone pregnenolone attenuates several in vivo behavioural and somatic effects of the phytocannabinoid Δ(9)-tetrahydrocannabinol, and it was suggested that pregnenolone can protect the brain from cannabis intoxication. The primary neuronal cannabinoid action behind most of the behavioural and somatic effects of cannabinoids is presynaptic inhibition of synaptic transmission. Therefore, the hypothesis of the present study was that pregnenolone attenuates the inhibition of synaptic transmission elicited by cannabinoids...
June 24, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28624721/assessing-the-role-of-serotonergic-receptors-in-cannabidiol-s-anticonvulsant-efficacy
#9
Madeline C Pelz, Kathleen D Schoolcraft, Chloe Larson, Mitchell G Spring, Hassan H López
Cannabidiol (CBD) is a phytocannabinoid that has demonstrated anticonvulsant efficacy in several animal models of seizure. The current experiment validated CBD's anticonvulsant effect using the acute pentylenetetrazol (PTZ) model. Furthermore, it tested whether CBD reduces seizure activity by interacting with either the serotonergic 5HT1A or 5HT2A receptor. 120 male adolescent Wistar-Kyoto rats were randomly assigned to 8 treatment groups in two consecutive experiments. In both experiments, subjects received either CBD (100mg/kg) or vehicle 60min prior to seizure testing...
June 15, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28614793/a-single-dose-of-cannabidiol-reduces-blood-pressure-in-healthy-volunteers-in-a-randomized-crossover-study
#10
Khalid A Jadoon, Garry D Tan, Saoirse E O'Sullivan
BACKGROUND: Cannabidiol (CBD) is a nonpsychoactive phytocannabinoid used in multiple sclerosis and intractable epilepsies. Preclinical studies show CBD has numerous cardiovascular benefits, including a reduced blood pressure (BP) response to stress. The aim of this study was to investigate if CBD reduces BP in humans. METHODS: Nine healthy male volunteers were given 600 mg of CBD or placebo in a randomized, placebo-controlled, double-blind, crossover study. Cardiovascular parameters were monitored using a finometer and laser Doppler...
June 15, 2017: JCI Insight
https://www.readbyqxmd.com/read/28571738/gpr3-and-gpr6-novel-molecular-targets-for-cannabidiol
#11
Alyssa S Laun, Zhao-Hui Song
GPR3 and GPR6 are members of a family of constitutively active, Gs protein-coupled receptors. Previously, it has been reported that GPR3 is involved in Alzheimer's disease whereas GPR6 plays potential roles in Parkinson's disease. GPR3 and GPR6 are considered orphan receptors because there are no confirmed endogenous agonists for them. However, GPR3 and GPR6 are phylogenetically related to the cannabinoid receptors. In this study, the activities of endocannabinoids and phytocannabinoids were tested on GPR3 and GPR6 using a β-arrestin2 recruitment assay...
August 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28560402/anticancer-effects-of-phytocannabinoids-used-with-chemotherapy-in-leukaemia-cells-can-be-improved-by-altering-the-sequence-of-their-administration
#12
Katherine A Scott, Angus G Dalgleish, Wai M Liu
Phytocannabinoids possess anticancer activity when used alone, and a number have also been shown to combine favourably with each other in vitro in leukaemia cells to generate improved activity. We have investigated the effect of pairing cannabinoids and assessed their anticancer activity in cell line models. Those most effective were then used with the common anti-leukaemia drugs cytarabine and vincristine, and the effects of this combination therapy on cell death studied in vitro. Results show a number of cannabinoids could be paired together to generate an effect superior to that achieved if the components were used individually...
May 29, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28548225/single-and-combined-effects-of-%C3%AE-9-tetrahydrocannabinol-and-cannabidiol-in-a-mouse-model-of-chemotherapy-induced-neuropathic-pain
#13
Kirsten M King, Alyssa M Myers, Ariele J Soroka-Monzo, Ronald F Tuma, Ronald J Tallarida, Ellen A Walker, Sara Jane Ward
BACKGROUND AND PURPOSE: The non-psychoactive phytocannabinoid cannabidiol (CBD) can affect the pharmacological effects of Δ(9) -tetrahydrocannabinol (THC). We tested the possible synergy between CBD and THC in decreasing mechanical sensitivity in a mouse model of paclitaxel-induced neuropathic pain. We also tested the effects of CBD on oxaliplatin- and vincristine-induced mechanical sensitivity. EXPERIMENTAL APPROACH: Paclitaxel-treated mice (8.0 mg·kg(-1) i...
September 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28501518/cannabidiol-in-medical-marijuana-research-vistas-and-potential-opportunities
#14
REVIEW
Carola Rong, Yena Lee, Nicole E Carmona, Danielle S Cha, Renee-Marie Ragguett, Joshua D Rosenblat, Rodrigo B Mansur, Roger C Ho, Roger S McIntyre
The high and increasing prevalence of medical marijuana consumption in the general population invites the need for quality evidence regarding its safety and efficacy. Herein, we synthesize extant literature pertaining to the phytocannabinoid cannabidiol (CBD) and its brain effects. The principle phytocannabinoid Δ(9)-tetrahydrocannabinol (Δ(9)-THC) and CBD are the major pharmacologically active cannabinoids. The effect of CBD on brain systems as well as on phenomenological measures (e.g. cognitive function) are distinct and in many cases opposite to that of Δ(9)-THC...
July 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28440188/trp-channels-as-novel-targets-for-endogenous-ligands-focus-on-endocannabinoids-and-nociceptive-signalling
#15
Maksim V Storozhuk, Alexander V Zholos
The endocannabinoid system is gaining steadily increasing research interest as its important role in the regulation of many fundamental physiological processes becomes more and more evident. One area which received particularly significant attention concerns targeting the endocannabinoid system as a useful strategy in pain control, especially in refractory, difficult to treat cases of chronic pain. Apart from the classical targets of cannabinoids, the CB1 and CB2 receptors, several members of the large TRP family of Ca2+-permeable cation channels have been designated as "ionotropic cannabinoid receptors" to highlight their role in cannabinoid signalling...
April 24, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28432556/enzymes-that-hydrolyze-adenine-nucleotides-in-a-model-of-hypercholesterolemia-induced-by-triton-wr-1339-protective-effects-of-%C3%AE-caryophyllene
#16
Matheus D Baldissera, Carine F Souza, Pedro H Doleski, Daniela B R Leal, Lenita M Stefani, Aline A Boligon, Silvia G Monteiro
Purinergic system has been proven to play a critical role in the inflammatory process and to represent an important therapeutic target to improve the immune response during hypercholesterolemia. β-caryophyllene, a phytocannabinoid compound, has a powerful hypolipidemic and anti-inflammatory actions. However, the effects of β-caryophyllene on seric enzymes of purinergic system have not been evaluated. The purpose of this study was to investigate whether β-caryophyllene is able to ameliorate the seric activities of NTPDase and adenosine deaminase (ADA) in a model of hypercholesterolemia induced by Triton WR-1339...
April 21, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28425013/cannabinoids-as-modulators-of-cell-death-clinical-applications-and-future-directions
#17
B M Fonseca, N A Teixeira, G Correia-da-Silva
Endocannabinoids are bioactive lipids that modulate various physiological processes through G-protein-coupled receptors (CB1 and CB2) and other putative targets. By sharing the activation of the same receptors, some phytocannabinoids and a multitude of synthetic cannabinoids mimic the effects of endocannabinoids. In recent years, a growing interest has been dedicated to the study of cannabinoids properties for their analgesic, antioxidant, anti-inflammatory and neuroprotective effects. In addition to these well-recognized effects, various studies suggest that cannabinoids may affect cell survival, cell proliferation or cell death...
April 20, 2017: Reviews of Physiology, Biochemistry and Pharmacology
https://www.readbyqxmd.com/read/28411027/%C3%AE-caryophyllene-reduces-atherogenic-index-and-coronary-risk-index-in-hypercholesterolemic-rats-the-involvement-of-cardiac-oxidative-damage
#18
Matheus D Baldissera, Carine F Souza, Thirssa H Grando, Lenita M Stefani, Silvia G Monteiro
Hypercholesterolemia and cardiac oxidative damage have been implicated in the pathophysiology of atherosclerosis. In earlier studies, treatment using natural phytocannabinoid β-caryophyllene caused a hypolipemic effect, as well as ameliorated hepatic oxidative damage. In this regard, the present study aimed to investigate whether β-caryophyllene treatment was able to protect the cardiac tissue against hypercholesterolemic atherosclerosis, and to investigate the involvement of antioxidant mechanisms in this effect using a model of hypercholesterolemia induced by Triton WR-1339...
May 25, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28392266/cannabinoids-as-hippocampal-network-administrators
#19
REVIEW
Carl R Lupica, Yuhan Hu, Orrin Devinsky, Alexander F Hoffman
Extensive pioneering studies performed in the hippocampus have greatly contributed to our knowledge of an endogenous cannabinoid system comprised of the molecular machinery necessary to process endocannabinoid lipid messengers and their associated cannabinoid receptors. Moreover, a foundation of knowledge regarding the function of hippocampal circuits, and its role in supporting synaptic plasticity has facilitated our understanding of the roles cannabinoids play in the diverse behaviors in which the hippocampus participates, in both normal and pathological states...
April 6, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28377876/cannabinoid-type-1-receptor-containing-axons-innervate-npy-agrp-neurons-in-the-mouse-arcuate-nucleus
#20
Yury M Morozov, Marco Koch, Pasko Rakic, Tamas L Horvath
OBJECTIVES: Phytocannabinoids, such as THC and endocannabinoids, are well known to promote feeding behavior and to control energy metabolism through cannabinoid type 1 receptors (CB1R). However, the underlying mechanisms are not fully understood. Generally, cannabinoid-conducted retrograde dis-inhibition of hunger-promoting neurons has been suggested to promote food intake, but so far it has not been demonstrated due to technical limitations. METHODS: We applied immunohistochemical labeling of CB1R for light microscopy and electron microscopy combined with three-dimensional reconstruction from serial sections in CB1R-expressing and CB1R-null mice, which served as a negative control...
April 2017: Molecular Metabolism
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