The Endocannabinoid System as an Emerging Target of Pharmacotherapy

Pharmacological Reviews, Journal Year: 2006, Volume and Issue: 58(3), P. 389 - 462

Published: Sept. 1, 2006

The recent identification of cannabinoid receptors and their endogenous lipid ligands has triggered an exponential growth studies exploring the endocannabinoid system its regulatory functions in health disease. Such have been greatly facilitated by introduction selective receptor antagonists inhibitors metabolism transport, as well mice deficient or endocannabinoid-degrading enzyme fatty acid amidohydrolase. In past decade, implicated a growing number physiological functions, both central peripheral nervous systems organs. More importantly, modulating activity turned out to hold therapeutic promise wide range disparate diseases pathological conditions, ranging from mood anxiety disorders, movement disorders such Parkinson9s Huntington9s disease, neuropathic pain, multiple sclerosis spinal cord injury, cancer, atherosclerosis, myocardial infarction, stroke, hypertension, glaucoma, obesity/metabolic syndrome, osteoporosis, name just few. An impediment development medications socially unacceptable psychoactive properties plant-derived synthetic agonists, mediated CB₁ receptors. However, this problem does not arise when aim is achieved treatment with antagonist, obesity, may also be absent action endocannabinoids enhanced indirectly through blocking transport. use CB₂ which lack properties, could represent another promising avenue for certain conditions. abuse potential cannabinoids limited preparations controlled composition careful selection dose route administration. preclinical clinical trials compounds that modulate will probably result novel approaches current treatments do fully address patients9 need. Here, we provide comprehensive overview on state knowledge target pharmacotherapy.

Language: Английский

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The diverse CB₁ and CB₂ receptor pharmacology of three plant cannabinoids: Δ⁹‐tetrahydrocannabinol, cannabidiol and Δ⁹‐tetrahydrocannabivarin

British Journal of Pharmacology, Journal Year: 2007, Volume and Issue: 153(2), P. 199 - 215

Published: Sept. 10, 2007

Cannabis sativa is the source of a unique set compounds known collectively as plant cannabinoids or phytocannabinoids. This review focuses on manner with which three these compounds, (-)-trans-delta9-tetrahydrocannabinol (delta9-THC), (-)-cannabidiol (CBD) and (-)-trans-delta9-tetrahydrocannabivarin (delta9-THCV), interact cannabinoid CB1 CB2 receptors. Delta9-THC, main psychotropic constituent cannabis, receptor partial agonist in line classical pharmacology, responses it elicits appear to be strongly influenced both by expression level signalling efficiency receptors ongoing endogenous release. CBD displays unexpectedly high potency an antagonist CB1/CB2 agonists CB1- CB2-expressing cells tissues, interacts providing possible explanation for its ability inhibit evoked immune cell migration. Delta9-THCV behaves potent vitro. In contrast, antagonizes CB1-expressing tissues. does relatively that tissue ligand dependent. also when administered vivo, behaving either or, at higher doses, agonist. Brief mention made this review, first production delta9-THC pharmacodynamic tolerance, second current knowledge about extent delta9-THC, delta9-THCV pharmacological targets other than receptors, third actual potential therapeutic applications each cannabinoids.

Language: Английский

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International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid Receptors and Their Ligands: Beyond CB₁and CB₂

Pharmacological Reviews, Journal Year: 2010, Volume and Issue: 62(4), P. 588 - 631

Published: Nov. 15, 2010

There are at least two types of cannabinoid receptors (CB₁ and CB₂). Ligands activating these G protein-coupled (GPCRs) include the phytocannabinoid Δ⁹-tetrahydrocannabinol, numerous synthetic compounds, endogenous compounds known as endocannabinoids. Cannabinoid receptor antagonists have also been developed. Some ligands activate or block one type more potently than other type. This review summarizes current data indicating extent to which undergo orthosteric allosteric interactions with non-CB₁, non-CB₂ established GPCRs, deorphanized such GPR55, ligand-gated ion channels, transient potential (TRP) channels peroxisome proliferator-activated nuclear receptors. From data, it is clear that some interact similarly CB₁ and/or CB₂ likely display significantly different pharmacological profiles. The lists criteria any novel “CB₃” channel should fulfil concludes not currently met by channel. However, does identify certain targets be investigated further CB₃ channels. These TRP vanilloid 1, possibly functions an ionotropic under physiological pathological conditions, GPCRs. Also discussed 1) ability form heteromeric complexes 2) phylogenetic relationships exist between CB₁/CB₂ 3) evidence for existence several as-yet-uncharacterized receptors; 4) nomenclature.

Language: Английский

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The orphan receptor GPR55 is a novel cannabinoid receptor

British Journal of Pharmacology, Journal Year: 2007, Volume and Issue: 152(7), P. 1092 - 1101

Published: Sept. 17, 2007

The endocannabinoid system functions through two well characterized receptor systems, the CB1 and CB2 receptors. Work by a number of groups in recent years has provided evidence that is more complicated additional types should exist to explain ligand activity physiological processes.Cells transfected with human cDNA for GPR55 were tested their ability bind mediate GTPgammaS binding cannabinoid ligands. Using an antibody peptide blocking approach, nature G-protein coupling was determined further demonstrated measuring downstream signalling pathways.We demonstrate binds activated CP55940. In addition endocannabinoids including anandamide virodhamine activate via nM potencies. Ligands such as cannabidiol abnormal which exhibit no or are believed function at novel receptor, also showed GPR55. couples Galpha13 can activation rhoA, cdc42 rac1.These data suggest its profile respect described here will permit delineation function(s).

Language: Английский

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Endocannabinoid-Mediated Control of Synaptic Transmission

Physiological Reviews, Journal Year: 2009, Volume and Issue: 89(1), P. 309 - 380

Published: Jan. 1, 2009

The discovery of cannabinoid receptors and subsequent identification their endogenous ligands (endocannabinoids) in early 1990s have greatly accelerated research on actions the brain. Then, 2001 that endocannabinoids mediate retrograde synaptic signaling has opened up a new era for also established concept how diffusible messengers modulate efficacy neural activity. last 7 years witnessed remarkable advances our understanding endocannabinoid system. It is now well accepted are released from postsynaptic neurons, activate presynaptic CB(1) receptors, cause transient long-lasting reduction neurotransmitter release. In this review, we aim to integrate current functions system, especially focusing control transmission We summarize recent electrophysiological studies carried out synapses various brain regions discuss regulated by signaling. Then refer anatomical subcellular distribution molecules involved these arranged around synapses. addition, make brief overview intracellular signaling, biochemical metabolism, behavioral roles system aspects functions.

Language: Английский

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An Introduction to the Endogenous Cannabinoid System

Biological Psychiatry, Journal Year: 2015, Volume and Issue: 79(7), P. 516 - 525

Published: Nov. 3, 2015

Language: Английский

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Endocannabinoid Signaling and Synaptic Function

Neuron, Journal Year: 2012, Volume and Issue: 76(1), P. 70 - 81

Published: Oct. 1, 2012

Language: Английский

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The Endocannabinoid System and the Brain

Annual Review of Psychology, Journal Year: 2012, Volume and Issue: 64(1), P. 21 - 47

Published: July 19, 2012

The psychoactive constituent in cannabis, Δ(9)-tetrahydrocannabinol (THC), was isolated the mid-1960s, but cannabinoid receptors, CB1 and CB2, major endogenous cannabinoids (anandamide 2-arachidonoyl glycerol) were identified only 20 to 25 years later. system affects both central nervous (CNS) peripheral processes. In this review, we have tried summarize research--with an emphasis on recent publications--on actions of endocannabinoid anxiety, depression, neurogenesis, reward, cognition, learning, memory. effects are at times biphasic--lower doses causing opposite those seen high doses. Recently, numerous endocannabinoid-like compounds been brain. Only a few investigated for their CNS activity, future investigations action may throw light wide spectrum brain functions.

Language: Английский

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Effects of cannabinoids and cannabinoid‐enriched Cannabis extracts on TRP channels and endocannabinoid metabolic enzymes

British Journal of Pharmacology, Journal Year: 2010, Volume and Issue: 163(7), P. 1479 - 1494

Published: Dec. 22, 2010

BACKGROUND AND PURPOSE Cannabidiol (CBD) and Δ 9 ‐tetrahydrocannabinol (THC) interact with transient receptor potential (TRP) channels enzymes of the endocannabinoid system. EXPERIMENTAL APPROACH The effects 11 pure cannabinoids botanical extracts [botanical drug substance (BDS)] from Cannabis varieties selected to contain a more abundant cannabinoid, on TRPV1, TRPV2, TRPM8, TRPA1, human recombinant diacylglycerol lipase α (DAGLα), rat brain fatty acid amide hydrolase (FAAH), COS cell monoacylglycerol (MAGL), N‐acylethanolamine (NAAA) anandamide cellular uptake (ACU) by RBL‐2H3 cells, were studied using fluorescence‐based calcium assays in transfected cells radiolabelled substrate‐based enzymatic assays. Cannabinol (CBN), cannabichromene (CBC), acids (CBDA, CBGA, THCA) propyl homologues (CBDV, CBGV, THCV) CBD, cannabigerol (CBG) THC, tetrahydrocannabivarin (THCVA) also tested. KEY RESULTS CBG, CBGV THCV stimulated desensitized TRPV1. CBC, CBD CBN potent TRPA1 agonists desensitizers, but THCV‐BDS was most compound at this target. CBG‐BDS TRPM8 antagonists. All non‐acid cannabinoids, except CBC CBN, potently activated TRPV2. CBDV all inhibited DAGLα. Some BDS, not compounds, MAGL. only inhibit FAAH, whereas BDS > CBG NAAA. = ACU, as did THCVA, CBDA THCA, latter inhibitors. CONCLUSIONS IMPLICATIONS These results are relevant analgesic, anti‐inflammatory anti‐cancer extracts. LINKED ARTICLES This article is part themed issue Cannabinoids Biology Medicine. To view other articles visit http://dx.doi.org/10.1111/bph.2011.163.issue‐7

Language: Английский

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Cannabinoid CB2 receptors: Immunohistochemical localization in rat brain

Brain Research, Journal Year: 2006, Volume and Issue: 1071(1), P. 10 - 23

Published: Feb. 1, 2006

Language: Английский

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