title: Δ9-Tetrahydrocannabinol decreases willingness to exert cognitive effort in male rats.
abstract: Acceptance of cannabis use is growing. However, prolonged use is associated with diminished psychosocial outcomes, potentially mediated by drug-induced cognitive impairments. Δ9-Tetrahydrocannabinol (THC) is the main psychoactive ingredient in cannabis, yet other phytocannabinoids in the plant, such as cannabidiol (CBD), have unique properties. Given that CBD can modulate the undesirable effects of THC, therapeutic agents, such as nabiximols, contain higher CBD:THC ratios than illicit marijuana. We tested the hypothesis that THC impairs a relevant cognitive function for long-term success, namely willingness to exert cognitive effort for greater rewards, and that CBD could attenuate such decision-making impairments.
  
  
  
  Male Long-Evans rats (n= 29) performing the rat cognitive effort task (rCET) received acute THC and CBD, independently and concurrently, in addition to other cannabinoids. Rats chose between 2 options differing in reward magnitude, but also in the cognitive effort (attentional load) required to obtain them.
  
  
  
  We found that THC decreased choice of hard trials without impairing the animals' ability to accurately complete them. Strikingly, this impairment was correlated with CB1 receptor density in the medial prefrontal cortex - an area previously implicated in effortful decision-making. In contrast, CBD did not affect choice. Coadministration of 1:1 CBD:THC matching that in nabiximols modestly attenuated the deleterious effects of THC in "slacker" rats.
  
  
  
  Only male rats were investigated, and the THC/CBD coadministration experiment was carried out in a subset of individuals.
  
  
  
  These findings confirm that THC, but not CBD, selectively impairs decision-making involving cognitive effort costs. However, coadministration of CBD only partially ameliorates such THC-induced dysfunction.
authors.affiliation: From the Department of Psychology, University of British Columbia, Vancouver, B.C. (Silveira, Adams, Winstanley); the Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, B.C. (Silveira, Adams, Winstanley); and the Hotchkiss Brain Institute, Departments of Cell Biology and Anatomy & Psychiatry, University of Calgary, Calgary, Alta. (Hill).
authors.forename: Mason M
authors.initials: MM
authors.lastname: Silveira
authors.affiliation: From the Department of Psychology, University of British Columbia, Vancouver, B.C. (Silveira, Adams, Winstanley); the Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, B.C. (Silveira, Adams, Winstanley); and the Hotchkiss Brain Institute, Departments of Cell Biology and Anatomy & Psychiatry, University of Calgary, Calgary, Alta. (Hill).
authors.forename: Wendy K
authors.initials: WK
authors.lastname: Adams
authors.affiliation: From the Department of Psychology, University of British Columbia, Vancouver, B.C. (Silveira, Adams, Winstanley); the Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, B.C. (Silveira, Adams, Winstanley); and the Hotchkiss Brain Institute, Departments of Cell Biology and Anatomy & Psychiatry, University of Calgary, Calgary, Alta. (Hill).
authors.forename: Maria
authors.initials: M
authors.lastname: Morena
authors.affiliation: From the Department of Psychology, University of British Columbia, Vancouver, B.C. (Silveira, Adams, Winstanley); the Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, B.C. (Silveira, Adams, Winstanley); and the Hotchkiss Brain Institute, Departments of Cell Biology and Anatomy & Psychiatry, University of Calgary, Calgary, Alta. (Hill).
authors.forename: Matthew N
authors.initials: MN
authors.lastname: Hill
authors.affiliation: From the Department of Psychology, University of British Columbia, Vancouver, B.C. (Silveira, Adams, Winstanley); the Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, B.C. (Silveira, Adams, Winstanley); and the Hotchkiss Brain Institute, Departments of Cell Biology and Anatomy & Psychiatry, University of Calgary, Calgary, Alta. (Hill).
authors.forename: Catharine A
authors.initials: CA
authors.lastname: Winstanley
mesh_terms: D000818:Animals; D001288:Attention / Q000187:drug effects* / Q000502:physiology; D002185:Cannabidiol / Q000494:pharmacology; D063385:Cannabinoid Receptor Modulators / Q000494:pharmacology; D003071:Cognition / Q000187:drug effects* / Q000502:physiology; D003657:Decision Making / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D008297:Male; D009042:Motivation / Q000187:drug effects* / Q000502:physiology; D009483:Neuropsychological Tests; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D011619:Psychotropic Drugs / Q000494:pharmacology*; D020318:Rats, Long-Evans; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists / Q000037:antagonists & inhibitors; D012201:Reward
chemical_list: D063385:Cannabinoid Receptor Modulators; C543264:Cnr1 protein, rat; C469526:Cnr2 protein, rat; D011619:Psychotropic Drugs; D043884:Receptor, Cannabinoid, CB1; D043885:Receptor, Cannabinoid, CB2; D002185:Cannabidiol; D013759:Dronabinol