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      Psychopharmacological advances in eating disorders

      1 , 1
      Expert Review of Clinical Pharmacology
      Informa UK Limited

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          Abstract

          Anorexia nervosa (AN), bulimia nervosa (BN) and binge eating disorder (BED) are the primary eating disorders (EDs). The only psychopharmacological treatment options for EDs with approval in some countries include fluoxetine for BN and lisdexamfetamine for BED. Given the high comorbidity and genetic correlations with other psychiatric disorders, it seems possible that novel medications for these conditions might also be effective in EDs. Areas covered: The current scientific literature has increased our understanding of how medication could be beneficial for patients with EDs on a molecular, functional and behavioral level. On the basis of theoretical considerations about neurotransmitters, hormones and neural circuits, possible drug targets for the treatment of EDs may include signal molecules and receptors of the self-regulatory system such as serotonin, norepinephrine and glutamate, the hedonic system including opioids, cannabinoids and dopamine and the hypothalamic homeostatic system including histamine, ghrelin, leptin, insulin, and glucagon-like peptide-1. Expert commentary: The latest research points to an involvement of both the immune and the metabolic systems in the pathophysiology of EDs and highlights the importance of the microbiome. Therefore, the next few years may unveil drug targets for EDs not just inside and outside of the brain, but possibly even outside of the human body.

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          Most cited references141

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          Pharmacokinetics and pharmacodynamics of cannabinoids.

          Delta(9)-Tetrahydrocannabinol (THC) is the main source of the pharmacological effects caused by the consumption of cannabis, both the marijuana-like action and the medicinal benefits of the plant. However, its acid metabolite THC-COOH, the non-psychotropic cannabidiol (CBD), several cannabinoid analogues and newly discovered modulators of the endogenous cannabinoid system are also promising candidates for clinical research and therapeutic uses. Cannabinoids exert many effects through activation of G-protein-coupled cannabinoid receptors in the brain and peripheral tissues. Additionally, there is evidence for non-receptor-dependent mechanisms. Natural cannabis products and single cannabinoids are usually inhaled or taken orally; the rectal route, sublingual administration, transdermal delivery, eye drops and aerosols have only been used in a few studies and are of little relevance in practice today. The pharmacokinetics of THC vary as a function of its route of administration. Pulmonary assimilation of inhaled THC causes a maximum plasma concentration within minutes, psychotropic effects start within seconds to a few minutes, reach a maximum after 15-30 minutes, and taper off within 2-3 hours. Following oral ingestion, psychotropic effects set in with a delay of 30-90 minutes, reach their maximum after 2-3 hours and last for about 4-12 hours, depending on dose and specific effect. At doses exceeding the psychotropic threshold, ingestion of cannabis usually causes enhanced well-being and relaxation with an intensification of ordinary sensory experiences. The most important acute adverse effects caused by overdosing are anxiety and panic attacks, and with regard to somatic effects increased heart rate and changes in blood pressure. Regular use of cannabis may lead to dependency and to a mild withdrawal syndrome. The existence and the intensity of possible long-term adverse effects on psyche and cognition, immune system, fertility and pregnancy remain controversial. They are reported to be low in humans and do not preclude legitimate therapeutic use of cannabis-based drugs. Properties of cannabis that might be of therapeutic use include analgesia, muscle relaxation, immunosuppression, sedation, improvement of mood, stimulation of appetite, antiemesis, lowering of intraocular pressure, bronchodilation, neuroprotection and induction of apoptosis in cancer cells.
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            Dopamine reward circuitry: two projection systems from the ventral midbrain to the nucleus accumbens-olfactory tubercle complex.

            Anatomical and functional refinements of the meso-limbic dopamine system of the rat are discussed. Present experiments suggest that dopaminergic neurons localized in the posteromedial ventral tegmental area (VTA) and central linear nucleus raphe selectively project to the ventromedial striatum (medial olfactory tubercle and medial nucleus accumbens shell), whereas the anteromedial VTA has few if any projections to the ventral striatum, and the lateral VTA largely projects to the ventrolateral striatum (accumbens core, lateral shell and lateral tubercle). These findings complement the recent behavioral findings that cocaine and amphetamine are more rewarding when administered into the ventromedial striatum than into the ventrolateral striatum. Drugs such as nicotine and opiates are more rewarding when administered into the posterior VTA or the central linear nucleus than into the anterior VTA. A review of the literature suggests that (1) the midbrain has corresponding zones for the accumbens core and medial shell; (2) the striatal portion of the olfactory tubercle is a ventral extension of the nucleus accumbens shell; and (3) a model of two dopamine projection systems from the ventral midbrain to the ventral striatum is useful for understanding reward function. The medial projection system is important in the regulation of arousal characterized by affect and drive and plays a different role in goal-directed learning than the lateral projection system, as described in the variation-selection hypothesis of striatal functional organization.
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              The assessment of binge eating severity among obese persons

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                Author and article information

                Journal
                Expert Review of Clinical Pharmacology
                Expert Review of Clinical Pharmacology
                Informa UK Limited
                1751-2433
                1751-2441
                October 23 2017
                January 02 2018
                October 05 2017
                January 02 2018
                : 11
                : 1
                : 95-108
                Affiliations
                [1 ] Department of Psychological Medicine, King’s College London, London, UK
                Article
                10.1080/17512433.2018.1383895
                28933969
                369059c9-8bfd-4212-881f-024d58f05a8e
                © 2018
                History

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