The Endocannabinoid System as an Emerging Target of Pharmacotherapy Export

@article{citeulike:963656, abstract = {The recent identification of cannabinoid receptors and their endogenous lipid ligands has triggered an exponential growth of studies exploring the endocannabinoid system and its regulatory functions in health and disease. Such studies have been greatly facilitated by the introduction of selective cannabinoid receptor antagonists and inhibitors of endocannabinoid metabolism and transport, as well as mice deficient in cannabinoid receptors or the endocannabinoid-degrading enzyme fatty acid amidohydrolase. In the past decade, the endocannabinoid system has been implicated in a growing number of physiological functions, both in the central and peripheral nervous systems and in peripheral organs. More importantly, modulating the activity of the endocannabinoid system turned out to hold therapeutic promise in a wide range of disparate diseases and pathological conditions, ranging from mood and anxiety disorders, movement disorders such as Parkinson's and Huntington's disease, neuropathic pain, multiple sclerosis and spinal cord injury, to cancer, atherosclerosis, myocardial infarction, stroke, hypertension, glaucoma, obesity/metabolic syndrome, and osteoporosis, to name just a few. An impediment to the development of cannabinoid medications has been the socially unacceptable psychoactive properties of plant-derived or synthetic agonists, mediated by CB1 receptors. However, this problem does not arise when the therapeutic aim is achieved by treatment with a CB1 receptor antagonist, such as in obesity, and may also be absent when the action of endocannabinoids is enhanced indirectly through blocking their metabolism or transport. The use of selective CB2 receptor agonists, which lack psychoactive properties, could represent another promising avenue for certain conditions. The abuse potential of plant-derived cannabinoids may also be limited through the use of preparations with controlled composition and the careful selection of dose and route of administration. The growing number of preclinical studies and clinical trials with compounds that modulate the endocannabinoid system will probably result in novel therapeutic approaches in a number of diseases for which current treatments do not fully address the patients' need. Here, we provide a comprehensive overview on the current state of knowledge of the endocannabinoid system as a target of pharmacotherapy. 10.1124/pr.58.3.2}, author = {Pacher, Pal and Batkai, Sandor and Kunos, George}, citeulike-article-id = {963656}, citeulike-linkout-0 = {http://pharmrev.aspetjournals.org/cgi/content/abstract/58/3/389}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/16968947}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=16968947}, journal = {Pharmacol Rev}, keywords = {cannabinoid, cannabis, endocannabinoid, marijuana, pharmacology, pharmacotherapy, system, treatment}, month = {September}, number = {3}, pages = {389--462}, posted-at = {2006-11-27 18:20:44}, priority = {4}, title = {The Endocannabinoid System as an Emerging Target of Pharmacotherapy}, url = {http://pharmrev.aspetjournals.org/cgi/content/abstract/58/3/389}, volume = {58}, year = {2006} }

TY - JOUR ID - citeulike:963656 L3 - citeulike-article-id:963656 N2 - The recent identification of cannabinoid receptors and their endogenous lipid ligands has triggered an exponential growth of studies exploring the endocannabinoid system and its regulatory functions in health and disease. Such studies have been greatly facilitated by the introduction of selective cannabinoid receptor antagonists and inhibitors of endocannabinoid metabolism and transport, as well as mice deficient in cannabinoid receptors or the endocannabinoid-degrading enzyme fatty acid amidohydrolase. In the past decade, the endocannabinoid system has been implicated in a growing number of physiological functions, both in the central and peripheral nervous systems and in peripheral organs. More importantly, modulating the activity of the endocannabinoid system turned out to hold therapeutic promise in a wide range of disparate diseases and pathological conditions, ranging from mood and anxiety disorders, movement disorders such as Parkinson's and Huntington's disease, neuropathic pain, multiple sclerosis and spinal cord injury, to cancer, atherosclerosis, myocardial infarction, stroke, hypertension, glaucoma, obesity/metabolic syndrome, and osteoporosis, to name just a few. An impediment to the development of cannabinoid medications has been the socially unacceptable psychoactive properties of plant-derived or synthetic agonists, mediated by CB1 receptors. However, this problem does not arise when the therapeutic aim is achieved by treatment with a CB1 receptor antagonist, such as in obesity, and may also be absent when the action of endocannabinoids is enhanced indirectly through blocking their metabolism or transport. The use of selective CB2 receptor agonists, which lack psychoactive properties, could represent another promising avenue for certain conditions. The abuse potential of plant-derived cannabinoids may also be limited through the use of preparations with controlled composition and the careful selection of dose and route of administration. The growing number of preclinical studies and clinical trials with compounds that modulate the endocannabinoid system will probably result in novel therapeutic approaches in a number of diseases for which current treatments do not fully address the patients' need. Here, we provide a comprehensive overview on the current state of knowledge of the endocannabinoid system as a target of pharmacotherapy. 10.1124/pr.58.3.2 IS - 3 JF - Pharmacol Rev EP - 462 TI - The Endocannabinoid System as an Emerging Target of Pharmacotherapy VL - 58 SP - 389 KW - cannabinoid KW - cannabis KW - endocannabinoid KW - marijuana KW - pharmacology KW - pharmacotherapy KW - system KW - treatment AU - Pacher, Pal AU - Batkai, Sandor AU - Kunos, George PY - 2006/09/01/ UR - http://pharmrev.aspetjournals.org/cgi/content/abstract/58/3/389 ER -