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It lacks the psychotomimetic and other psychotropic effects that the main plant compound\n                    <jats:italic>\u0394<\/jats:italic>\n                    <jats:sup>9<\/jats:sup>\n                    -tetrahydrocannabinol (THC) being able, on the contrary, to antagonize these effects. This property, together with its safety profile, was an initial stimulus for the investigation of CBD pharmacological properties. It is now clear that CBD has therapeutic potential over a wide range of non-psychiatric and psychiatric disorders such as anxiety, depression and psychosis. Although the pharmacological effects of CBD in different biological systems have been extensively investigated by\n                    <jats:italic>in vitro<\/jats:italic>\n                    studies, the mechanisms responsible for its therapeutic potential are still not clear. Here, we review recent\n                    <jats:italic>in vivo<\/jats:italic>\n                    studies indicating that these mechanisms are not unitary but rather depend on the behavioural response being measured. Acute anxiolytic and antidepressant-like effects seem to rely mainly on facilitation of 5-HT1A-mediated neurotransmission in key brain areas related to defensive responses, including the dorsal periaqueductal grey, bed nucleus of the stria terminalis and medial prefrontal cortex. Other effects, such as anti-compulsive, increased extinction and impaired reconsolidation of aversive memories, and facilitation of adult hippocampal neurogenesis could depend on potentiation of anandamide-mediated neurotransmission. Finally, activation of TRPV1 channels may help us to explain the antipsychotic effect and the bell-shaped dose-response curves commonly observed with CBD. Considering its safety profile and wide range of therapeutic potential, however, further studies are needed to investigate the involvement of other possible mechanisms (e.g. inhibition of adenosine uptake, inverse agonism at CB2 receptor, CB1 receptor antagonism, GPR55 antagonism, PPAR\u03b3 receptors agonism, intracellular (Ca\n                    <jats:sup>2+<\/jats:sup>\n                    ) increase, etc.), on CBD behavioural effects.\n                  <\/jats:p>","DOI":"10.1098\/rstb.2011.0389","type":"journal-article","created":{"date-parts":[[2012,10,19]],"date-time":"2012-10-19T20:04:26Z","timestamp":1350677066000},"page":"3364-3378","update-policy":"https:\/\/doi.org\/10.1098\/crossmark-policy","source":"Crossref","is-referenced-by-count":367,"title":["Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders"],"prefix":"10.1098","volume":"367","author":[{"given":"Alline Cristina","family":"Campos","sequence":"first","affiliation":[{"name":"Group of Neuroimmunology, Laboratory of Immunopharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil"},{"name":"Infectious Diseases and Tropical Medicine Program, Medical School, Universidade Federal de Minas Gerais, Avenue Antonio Carlos 6627, 31270-901, Belo Horizonte, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabricio Ara\u00fajo","family":"Moreira","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Avenue Antonio Carlos 6627, 31270-901, Belo Horizonte, Minas Gerais, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felipe Villela","family":"Gomes","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Avenue Bandeirantes 3900, 14049-900, Ribeir\u00e3o Preto, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine Aparecida","family":"Del Bel","sequence":"additional","affiliation":[{"name":"Faculty of Odontology of Ribeir\u00e3o Preto, Department of Morphology, Physiology and Stomatology, University of S\u00e3o Paulo, Avenue Caf\u00e9 s\/n, 14040-904, Ribeir\u00e3o Preto, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco Silveira","family":"Guimar\u00e3es","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, School of Medicine of Ribeir\u00e3o Preto, University of S\u00e3o Paulo, Avenue Bandeirantes 3900, 14049-900, Ribeir\u00e3o Preto, S\u00e3o Paulo, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"175","published-online":{"date-parts":[[2012,12,5]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja01062a046"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0165-6147(94)90106-6"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2011.09.002"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2009.07.006"},{"key":"e_1_3_2_6_2","first-page":"251","article-title":"Comparative effects between cannabidiol and diazepam on neo-phobia, food intake and conflict behavior","volume":"6","author":"Silveira Filho N. 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