Thu, 21 Aug 2008 10:20:22 BST CiteULike: xico treatment http://www.citeulike.org/user/xico/tag/treatment CiteULike.org en-gb Copyright © 2004-2008 citeulike.org http://www.citeulike.org/user/xico/article/1366123 <i>Neuropharmacology, Vol. 47 Suppl 1 (2004), pp. 3-13.</i><br /><br />Imaging studies have provided evidence of how the human brain changes as an individual becomes addicted. Here, we integrate the findings from imaging studies to propose a model of drug addiction. The process of addiction is initiated in part by the fast and high increases in DA induced by drugs of abuse. We hypothesize that this supraphysiological effect of drugs trigger a series of adaptations in neuronal circuits involved in saliency/reward, motivation/drive, memory/conditioning, and control/disinhibition, resulting in an enhanced (and long lasting) saliency value for the drug and its associated cues at the expense of decreased sensitivity for salient events of everyday life (including natural reinforcers). Although acute drug intake increases DA neurotransmission, chronic drug consumption results in a marked decrease in DA activity, associated with, among others, dysregulation of the orbitofrontal cortex (region involved with salience attribution) and cingulate gyrus (region involved with inhibitory control). The ensuing increase in motivational drive for the drug, strengthened by conditioned responses and the decrease in inhibitory control favors emergence of compulsive drug taking. This view of how drugs of abuse affect the brain suggests strategies for intervention, which might include: (a) those that will decrease the reward value of the drug of choice; (b) interventions to increase the saliency value of non-drug reinforcers; (c) approaches to weaken conditioned drug behaviors; and (d) methods to strengthen frontal inhibitory and executive control. Though this model focuses mostly on findings from PET studies of the brain DA system it is evident that other neurotransmitters are involved and that a better understanding of their roles in addiction would expand the options for therapeutic targets. The addicted human brain viewed in the light of imaging studies: brain circuits and treatment strategies. ND Volkow JS Fowler GJ Wang doi:10.1016/j.neuropharm.2004.07.019 Neuropharmacology, Vol. 47 Suppl 1 (2004), pp. 3-13. 2007-06-05T19:52:37-00:00 2004 Neuropharmacology 0028-3908 47 Suppl 1 3 13 addiction brain circuit damage ddicted drug imaging mri neuroimaging pet review treatment http://www.citeulike.org/user/xico/article/963656 <i>Pharmacol Rev, Vol. 58, No. 3. (1 September 2006), pp. 389-462.</i><br /><br />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 The Endocannabinoid System as an Emerging Target of Pharmacotherapy Pal Pacher Sandor Batkai George Kunos Pharmacol Rev, Vol. 58, No. 3. (1 September 2006), pp. 389-462. 2006-11-27T18:19:49-00:00 2006 Pharmacol Rev 58 3 389 462 cannabinoid cannabis endocannabinoid marijuana pharmacology pharmacotherapy system treatment http://www.citeulike.org/user/xico/article/563229 <i>Br J Psychiatry, Vol. 182 (February 2003), pp. 97-100.</i> Neurobiology of addiction and implications for treatment. A Lingford-Hughes D Nutt Br J Psychiatry, Vol. 182 (February 2003), pp. 97-100. 2006-03-25T21:25:58-00:00 2003 Br J Psychiatry 0007-1250 182 97 100 addiction mechanism molecular neurobiology pathway review treatment