The Experts below are selected from a list of 786 Experts worldwide ranked by ideXlab platform
Roger G Pertwee - One of the best experts on this subject based on the ideXlab platform.
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Experimental Models of Huntington’s Disease
2016Co-Authors: Roger G Pertwee, Onintza Sagredo, Maria Ruth Pazos, Hospital Universitario, Fundacion Alcorcon, Javier Fernández-ruiz, See Profile, Ruth M. Pazos, Valentina SattaAbstract:Neuroprotective effects of Phytocannabinoid-based medicines in experimental models of Huntington's disease.
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early Phytocannabinoid chemistry to endocannabinoids and beyond
Nature Reviews Neuroscience, 2014Co-Authors: Raphael Mechoulam, Roger G Pertwee, Lumir Hanus, Allyn C HowlettAbstract:Despite centuries of recreational use of cannabis, it is only relatively recently that its mechanisms of action, and the existence of endogenous cannabinoids, have been discovered. In this Timeline article, Raphael Mechoulam and colleagues discuss early research on the plant cannabinoids and speculate on the directions this research might take in the future. Isolation and structure elucidation of most of the major cannabinoid constituents — including Δ9-tetrahydrocannabinol (Δ9-THC), which is the principal psychoactive molecule in Cannabis sativa — was achieved in the 1960s and 1970s. It was followed by the identification of two cannabinoid receptors in the 1980s and the early 1990s and by the identification of the endocannabinoids shortly thereafter. There have since been considerable advances in our understanding of the endocannabinoid system and its function in the brain, which reveal potential therapeutic targets for a wide range of brain disorders.
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early Phytocannabinoid chemistry to endocannabinoids and beyond
Nature Reviews Neuroscience, 2014Co-Authors: Raphael Mechoulam, Roger G Pertwee, Lumir Hanus, Allyn C HowlettAbstract:Despite centuries of recreational use of cannabis, it is only relatively recently that its mechanisms of action, and the existence of endogenous cannabinoids, have been discovered. In this Timeline article, Raphael Mechoulam and colleagues discuss early research on the plant cannabinoids and speculate on the directions this research might take in the future.
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early Phytocannabinoid chemistry to endocannabinoids and beyond
Nature Reviews Neuroscience, 2014Co-Authors: Raphael Mechoulam, Roger G Pertwee, Lumir Hanus, Allyn C HowlettAbstract:Isolation and structure elucidation of most of the major cannabinoid constituents--including Δ(9)-tetrahydrocannabinol (Δ(9)-THC), which is the principal psychoactive molecule in Cannabis sativa--was achieved in the 1960s and 1970s. It was followed by the identification of two cannabinoid receptors in the 1980s and the early 1990s and by the identification of the endocannabinoids shortly thereafter. There have since been considerable advances in our understanding of the endocannabinoid system and its function in the brain, which reveal potential therapeutic targets for a wide range of brain disorders.
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cannabidiol for neurodegenerative disorders important new clinical applications for this Phytocannabinoid
British Journal of Clinical Pharmacology, 2013Co-Authors: Javier Fernandezruiz, Roger G Pertwee, Raphael Mechoulam, Onintza Sagredo, Ruth M. Pazos, Concepcion Garcia, Jose MartinezorgadoAbstract:Cannabidiol (CBD) is a Phytocannabinoid with therapeutic properties for numerous disorders exerted through molecular mechanisms that are yet to be completely identified. CBD acts in some experimental models as an anti-inflammatory, anticonvulsant, anti-oxidant, anti-emetic, anxiolytic and antipsychotic agent, and is therefore a potential medicine for the treatment of neuroinflammation, epilepsy, oxidative injury, vomiting and nausea, anxiety and schizophrenia, respectively. The neuroprotective potential of CBD, based on the combination of its anti-inflammatory and anti-oxidant properties, is of particular interest and is presently under intense preclinical research in numerous neurodegenerative disorders. In fact, CBD combined with Δ9-tetrahydrocannabinol is already under clinical evaluation in patients with Huntington's disease to determine its potential as a disease-modifying therapy. The neuroprotective properties of CBD do not appear to be exerted by the activation of key targets within the endocannabinoid system for plant-derived cannabinoids like Δ9-tetrahydrocannabinol, i.e. CB1 and CB2 receptors, as CBD has negligible activity at these cannabinoid receptors, although certain activity at the CB2 receptor has been documented in specific pathological conditions (i.e. damage of immature brain). Within the endocannabinoid system, CBD has been shown to have an inhibitory effect on the inactivation of endocannabinoids (i.e. inhibition of FAAH enzyme), thereby enhancing the action of these endogenous molecules on cannabinoid receptors, which is also noted in certain pathological conditions. CBD acts not only through the endocannabinoid system, but also causes direct or indirect activation of metabotropic receptors for serotonin or adenosine, and can target nuclear receptors of the PPAR family and also ion channels.
Claire M. Williams - One of the best experts on this subject based on the ideXlab platform.
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Molecular Pharmacology of Phytocannabinoids
Phytocannabinoids, 2017Co-Authors: Sarah E. Turner, Lars Iversen, Claire M. Williams, Benjamin J WhalleyAbstract:Cannabis sativa has been used for recreational, therapeutic and other uses for thousands of years. The plant contains more than 120 C21 terpenophenolic constituents named Phytocannabinoids. The Δ9-tetrahydrocannabinol type class of Phytocannabinoids comprises the largest proportion of the Phytocannabinoid content. Δ9-tetrahydrocannabinol was first discovered in 1971. This led to the discovery of the endocannabinoid system in mammals, including the cannabinoid receptors CB1 and CB2. Δ9-Tetrahydrocannabinol exerts its well-known psychotropic effects through the CB1 receptor but this effect of Δ9-tetrahydrocannabinol has limited the use of cannabis medicinally, despite the therapeutic benefits of this Phytocannabinoid. This has driven research into other targets outside the endocannabinoid system and has also driven research into the other non-psychotropic Phytocannabinoids present in cannabis. This chapter presents an overview of the molecular pharmacology of the seven most thoroughly investigated Phytocannabinoids, namely Δ9-tetrahydrocannabinol, Δ9-tetrahydrocannabivarin, cannabinol, cannabidiol, cannabidivarin, cannabigerol, and cannabichromene. The targets of these Phytocannabinoids are defined both within the endocannabinoid system and beyond. The pharmacological effect of each individual Phytocannabinoid is important in the overall therapeutic and recreational effect of cannabis and slight structural differences can elicit diverse and competing physiological effects. The proportion of each Phytocannabinoid can be influenced by various factors such as growing conditions and extraction methods. It is therefore important to investigate the pharmacology of these seven Phytocannabinoids further, and characterise the large number of other Phytocannabinoids in order to better understand their contributions to the therapeutic and recreational effects claimed for the whole cannabis plant and its extracts.
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Cannabigerol is a novel, well-tolerated appetite stimulant in pre-satiated rats
Psychopharmacology, 2016Co-Authors: Daniel I Brierley, James Samuels, Marnie Duncan, Benjamin J Whalley, Claire M. WilliamsAbstract:RationaleThe appetite-stimulating properties of cannabis are well documented and have been predominantly attributed to the hyperphagic activity of the psychoactive Phytocannabinoid, ∆9-tetrahydrocannabinol (∆9-THC). However, we have previously shown that a cannabis extract devoid of ∆9-THC still stimulates appetite, indicating that other Phytocannabinoids also elicit hyperphagia. One possible candidate is the non-psychoactive Phytocannabinoid cannabigerol (CBG), which has affinity for several molecular targets with known involvement in the regulation of feeding behaviour.ObjectivesThe objective of the study was to assess the effects of CBG on food intake and feeding pattern microstructure.MethodsMale Lister hooded rats were administered CBG (30–120 mg/kg, per ora (p.o.)) or placebo and assessed in open field, static beam and grip strength tests to determine a neuromotor tolerability profile for this cannabinoid. Subsequently, CBG (at 30–240 mg/kg, p.o.) or placebo was administered to a further group of pre-satiated rats, and hourly intake and meal pattern data were recorded over 2 h.ResultsCBG produced no adverse effects on any parameter in the neuromotor tolerability test battery. In the feeding assay, 120–240 mg/kg CBG more than doubled total food intake and increased the number of meals consumed, and at 240 mg/kg reduced latency to feed. However, the sizes or durations of individual meals were not significantly increased.ConclusionsHere, we demonstrate for the first time that CBG elicits hyperphagia, by reducing latency to feed and increasing meal frequency, without producing negative neuromotor side effects. Investigation of the therapeutic potential of CBG for conditions such as cachexia and other disorders of eating and body weight regulation is thus warranted.
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cannabigerol is a novel well tolerated appetite stimulant in pre satiated rats
Psychopharmacology, 2016Co-Authors: Daniel I Brierley, James Samuels, Marnie Duncan, Benjamin J Whalley, Claire M. WilliamsAbstract:Rationale The appetite-stimulating properties of cannabis are well documented and have been predominantly attributed to the hyperphagic activity of the psychoactive Phytocannabinoid, ∆9-tetrahydrocannabinol (∆9-THC). However, we have previously shown that a cannabis extract devoid of ∆9-THC still stimulates appetite, indicating that other Phytocannabinoids also elicit hyperphagia. One possible candidate is the non-psychoactive Phytocannabinoid cannabigerol (CBG), which has affinity for several molecular targets with known involvement in the regulation of feeding behaviour.
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cannabinol and cannabidiol exert opposing effects on rat feeding patterns
Psychopharmacology, 2012Co-Authors: Jonathan A Farrimond, Benjamin J Whalley, Claire M. WilliamsAbstract:Increased food consumption following ∆9-tetrahydrocannabinol-induced cannabinoid type 1 receptor agonism is well documented. However, possible non-∆9-tetrahydrocannabinol Phytocannabinoid-induced feeding effects have yet to be fully investigated. Therefore, we have assessed the effects of the individual Phytocannabinoids, cannabigerol, cannabidiol and cannabinol, upon feeding behaviors. Adult male rats were treated (p.o.) with cannabigerol, cannabidiol, cannabinol or cannabinol plus the CB1R antagonist, SR141716A. Prior to treatment, rats were satiated and food intake recorded following drug administration. Data were analyzed for hourly intake and meal microstructure. Cannabinol induced a CB1R-mediated increase in appetitive behaviors via significant reductions in the latency to feed and increases in consummatory behaviors via increases in meal 1 size and duration. Cannabinol also significantly increased the intake during hour 1 and total chow consumed during the test. Conversely, cannabidiol significantly reduced total chow consumption over the test period. Cannabigerol administration induced no changes to feeding behavior. This is the first time cannabinol has been shown to increase feeding. Therefore, cannabinol could, in the future, provide an alternative to the currently used and psychotropic ∆9-tetrahydrocannabinol-based medicines since cannabinol is currently considered to be non-psychotropic. Furthermore, cannabidiol reduced food intake in line with some existing reports, supporting the need for further mechanistic and behavioral work examining possible anti-obesity effects of cannabidiol.
Maria Grazia Cascio - One of the best experts on this subject based on the ideXlab platform.
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evidence that the plant cannabinoid cannabigerol is a highly potent α2 adrenoceptor agonist and moderately potent 5ht1a receptor antagonist
British Journal of Pharmacology, 2010Co-Authors: Maria Grazia Cascio, Lisa Anne Gauson, Lesley A Stevenson, R. A. Ross, Roger G PertweeAbstract:Background and purpose: Cannabis is the source of at least seventy Phytocannabinoids. The pharmacology of most of these has been little investigated, three notable exceptions being Δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin. This investigation addressed the question of whether the little-studied Phytocannabinoid, cannabigerol, can activate or block any G protein-coupled receptor. Experimental approach: The [35S]GTPγS binding assay, performed with mouse brain membranes, was used to test the ability of cannabigerol to produce G protein-coupled receptor activation or blockade. Its ability to displace [3H]CP55940 from mouse CB1 and human CB2 cannabinoid receptors and to inhibit electrically evoked contractions of the mouse isolated vas deferens was also investigated. Key results: In the brain membrane experiments, cannabigerol behaved as a potent α2-adrenoceptor agonist (EC50= 0.2 nM) and antagonized the 5-HT1A receptor agonist, R-(+)-8-hydroxy-2-(di-n-propylamino)tetralin (apparent KB= 51.9 nM). At 10 µM, it also behaved as a CB1 receptor competitive antagonist. Additionally, cannabigerol inhibited evoked contractions of the vas deferens in a manner that appeared to be α2-adrenoceptor-mediated (EC50= 72.8 nM) and displayed significant affinity for mouse CB1 and human CB2 receptors. Conclusions and implications: This investigation has provided the first evidence that cannabigerol can activate α2-adrenoceptors, bind to cannabinoid CB1 and CB2 receptors and block CB1 and 5-HT1A receptors. It will now be important to investigate why cannabigerol produced signs of agonism more potently in the [35S]GTPγS binding assay than in the vas deferens and also whether it can inhibit noradrenaline uptake in this isolated tissue and in the brain.
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evidence that the plant cannabinoid cannabigerol is a highly potent α2 adrenoceptor agonist and moderately potent 5ht1a receptor antagonist
British Journal of Pharmacology, 2010Co-Authors: Maria Grazia Cascio, Lisa Anne Gauson, Lesley A Stevenson, Ruth A. Ross, Roger G PertweeAbstract:Background and purpose: Cannabis is the source of at least seventy Phytocannabinoids. The pharmacology of most of these has been little investigated, three notable exceptions being Δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin. This investigation addressed the question of whether the little-studied Phytocannabinoid, cannabigerol, can activate or block any G protein-coupled receptor. Experimental approach: The [35S]GTPγS binding assay, performed with mouse brain membranes, was used to test the ability of cannabigerol to produce G protein-coupled receptor activation or blockade. Its ability to displace [3H]CP55940 from mouse CB1 and human CB2 cannabinoid receptors and to inhibit electrically evoked contractions of the mouse isolated vas deferens was also investigated. Key results: In the brain membrane experiments, cannabigerol behaved as a potent α2-adrenoceptor agonist (EC50= 0.2 nM) and antagonized the 5-HT1A receptor agonist, R-(+)-8-hydroxy-2-(di-n-propylamino)tetralin (apparent KB= 51.9 nM). At 10 µM, it also behaved as a CB1 receptor competitive antagonist. Additionally, cannabigerol inhibited evoked contractions of the vas deferens in a manner that appeared to be α2-adrenoceptor-mediated (EC50= 72.8 nM) and displayed significant affinity for mouse CB1 and human CB2 receptors. Conclusions and implications: This investigation has provided the first evidence that cannabigerol can activate α2-adrenoceptors, bind to cannabinoid CB1 and CB2 receptors and block CB1 and 5-HT1A receptors. It will now be important to investigate why cannabigerol produced signs of agonism more potently in the [35S]GTPγS binding assay than in the vas deferens and also whether it can inhibit noradrenaline uptake in this isolated tissue and in the brain.
Thomas Voets - One of the best experts on this subject based on the ideXlab platform.
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delta 9 tetrahydrocannabivarin impairs epithelial calcium transport through inhibition of trpv5 and trpv6
Pharmacological Research, 2018Co-Authors: Annelies Janssens, Cristoforo Silvestri, Andrea Martella, Jo M Vanoevelen, Thomas VoetsAbstract:Abstract Compounds extracted from the cannabis plant, including the psychoactive Δ9-tetrahydrocannabinol (THC) and related Phytocannabinoids, evoke multiple diverse biological actions as ligands of the G protein-coupled cannabinoid receptors CB1 and CB2. In addition, there is increasing evidence that Phytocannabinoids also have non-CB targets, including several ion channels of the transient receptor potential superfamily. We investigated the effects of six non-THC Phytocannabinoids on the epithelial calcium channels TRPV5 and TRPV6, and found that one of them, Δ9-tetrahydrocannabivarin (THCV), exerted a strong and concentration-dependent inhibitory effect on mammalian TRPV5 and TRPV6 and on the single zebrafish orthologue drTRPV5/6. Moreover, THCV attenuated the drTRPV5/6-dependent ossification in zebrafish embryos in vivo. Oppositely, 11-hydroxy-THCV (THCV−OH), a product of THCV metabolism in mammals, stimulated drTRPV5/6-mediated Ca2+ uptake and ossification. These results identify the epithelial calcium channels TRPV5 and TRPV6 as novel targets of Phytocannabinoids, and suggest that THCV-containing products may modulate TRPV5- and TRPV6-dependent epithelial calcium transport.
Lesley A Stevenson - One of the best experts on this subject based on the ideXlab platform.
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evidence that the plant cannabinoid cannabigerol is a highly potent α2 adrenoceptor agonist and moderately potent 5ht1a receptor antagonist
British Journal of Pharmacology, 2010Co-Authors: Maria Grazia Cascio, Lisa Anne Gauson, Lesley A Stevenson, R. A. Ross, Roger G PertweeAbstract:Background and purpose: Cannabis is the source of at least seventy Phytocannabinoids. The pharmacology of most of these has been little investigated, three notable exceptions being Δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin. This investigation addressed the question of whether the little-studied Phytocannabinoid, cannabigerol, can activate or block any G protein-coupled receptor. Experimental approach: The [35S]GTPγS binding assay, performed with mouse brain membranes, was used to test the ability of cannabigerol to produce G protein-coupled receptor activation or blockade. Its ability to displace [3H]CP55940 from mouse CB1 and human CB2 cannabinoid receptors and to inhibit electrically evoked contractions of the mouse isolated vas deferens was also investigated. Key results: In the brain membrane experiments, cannabigerol behaved as a potent α2-adrenoceptor agonist (EC50= 0.2 nM) and antagonized the 5-HT1A receptor agonist, R-(+)-8-hydroxy-2-(di-n-propylamino)tetralin (apparent KB= 51.9 nM). At 10 µM, it also behaved as a CB1 receptor competitive antagonist. Additionally, cannabigerol inhibited evoked contractions of the vas deferens in a manner that appeared to be α2-adrenoceptor-mediated (EC50= 72.8 nM) and displayed significant affinity for mouse CB1 and human CB2 receptors. Conclusions and implications: This investigation has provided the first evidence that cannabigerol can activate α2-adrenoceptors, bind to cannabinoid CB1 and CB2 receptors and block CB1 and 5-HT1A receptors. It will now be important to investigate why cannabigerol produced signs of agonism more potently in the [35S]GTPγS binding assay than in the vas deferens and also whether it can inhibit noradrenaline uptake in this isolated tissue and in the brain.
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evidence that the plant cannabinoid cannabigerol is a highly potent α2 adrenoceptor agonist and moderately potent 5ht1a receptor antagonist
British Journal of Pharmacology, 2010Co-Authors: Maria Grazia Cascio, Lisa Anne Gauson, Lesley A Stevenson, Ruth A. Ross, Roger G PertweeAbstract:Background and purpose: Cannabis is the source of at least seventy Phytocannabinoids. The pharmacology of most of these has been little investigated, three notable exceptions being Δ9-tetrahydrocannabinol, cannabidiol and Δ9-tetrahydrocannabivarin. This investigation addressed the question of whether the little-studied Phytocannabinoid, cannabigerol, can activate or block any G protein-coupled receptor. Experimental approach: The [35S]GTPγS binding assay, performed with mouse brain membranes, was used to test the ability of cannabigerol to produce G protein-coupled receptor activation or blockade. Its ability to displace [3H]CP55940 from mouse CB1 and human CB2 cannabinoid receptors and to inhibit electrically evoked contractions of the mouse isolated vas deferens was also investigated. Key results: In the brain membrane experiments, cannabigerol behaved as a potent α2-adrenoceptor agonist (EC50= 0.2 nM) and antagonized the 5-HT1A receptor agonist, R-(+)-8-hydroxy-2-(di-n-propylamino)tetralin (apparent KB= 51.9 nM). At 10 µM, it also behaved as a CB1 receptor competitive antagonist. Additionally, cannabigerol inhibited evoked contractions of the vas deferens in a manner that appeared to be α2-adrenoceptor-mediated (EC50= 72.8 nM) and displayed significant affinity for mouse CB1 and human CB2 receptors. Conclusions and implications: This investigation has provided the first evidence that cannabigerol can activate α2-adrenoceptors, bind to cannabinoid CB1 and CB2 receptors and block CB1 and 5-HT1A receptors. It will now be important to investigate why cannabigerol produced signs of agonism more potently in the [35S]GTPγS binding assay than in the vas deferens and also whether it can inhibit noradrenaline uptake in this isolated tissue and in the brain.