title: Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders.
abstract: Cannabidiol (CBD) is a major phytocannabinoid present in the Cannabis sativa plant. It lacks the psychotomimetic and other psychotropic effects that the main plant compound Δ(9)-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 in vitro studies, the mechanisms responsible for its therapeutic potential are still not clear. Here, we review recent in vivo 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, PPARγ receptors agonism, intracellular (Ca(2+)) increase, etc.), on CBD behavioural effects.
authors.affiliation: Group of Neuroimmunology, Laboratory of Immunopharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Alline Cristina
authors.initials: AC
authors.lastname: Campos
authors.forename: Fabricio Araújo
authors.initials: FA
authors.lastname: Moreira
authors.forename: Felipe Villela
authors.initials: FV
authors.lastname: Gomes
authors.forename: Elaine Aparecida
authors.initials: EA
authors.lastname: Del Bel
authors.forename: Francisco Silveira
authors.initials: FS
authors.lastname: Guimarães
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D000928:Antidepressive Agents / Q000494:pharmacology; D001008:Anxiety Disorders / Q000188:drug therapy / Q000378:metabolism; D001095:Arachidonic Acids / Q000378:metabolism; D002185:Cannabidiol / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D003863:Depression / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids / Q000378:metabolism; D006801:Humans; D055495:Neurogenesis; D008517:Phytotherapy; D053284:Polyunsaturated Alkamides / Q000378:metabolism; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism; D009435:Synaptic Transmission; D050916:TRPV Cation Channels / Q000378:metabolism
chemical_list: D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D001095:Arachidonic Acids; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D043884:Receptor, Cannabinoid, CB1; D050916:TRPV Cation Channels; C494482:TRPV1 protein, human; D044282:Receptor, Serotonin, 5-HT1A; D002185:Cannabidiol; C078814:anandamide