title: The CB1 Neutral Antagonist Tetrahydrocannabivarin Reduces Default Mode Network and Increases Executive Control Network Resting State Functional Connectivity in Healthy Volunteers.
abstract: BACKGROUND
  The cannabinoid cannabinoid type 1 (CB1) neutral antagonist tetrahydrocannabivarin (THCv) has been suggested as a possible treatment for obesity, but without the depressogenic side-effects of inverse antagonists such as Rimonabant. However, how THCv might affect the resting state functional connectivity of the human brain is as yet unknown.
  
  
  METHODS
  We examined the effects of a single 10mg oral dose of THCv and placebo in 20 healthy volunteers in a randomized, within-subject, double-blind design. Using resting state functional magnetic resonance imaging and seed-based connectivity analyses, we selected the amygdala, insula, orbitofrontal cortex, and dorsal medial prefrontal cortex (dmPFC) as regions of interest. Mood and subjective experience were also measured before and after drug administration using self-report scales.
  
  
  RESULTS
  Our results revealed, as expected, no significant differences in the subjective experience with a single dose of THCv. However, we found reduced resting state functional connectivity between the amygdala seed region and the default mode network and increased resting state functional connectivity between the amygdala seed region and the dorsal anterior cingulate cortex and between the dmPFC seed region and the inferior frontal gyrus/medial frontal gyrus. We also found a positive correlation under placebo for the amygdala-precuneus connectivity with the body mass index, although this correlation was not apparent under THCv.
  
  
  CONCLUSIONS
  Our findings are the first to show that treatment with the CB1 neutral antagonist THCv decreases resting state functional connectivity in the default mode network and increases connectivity in the cognitive control network and dorsal visual stream network. This effect profile suggests possible therapeutic activity of THCv for obesity, where functional connectivity has been found to be altered in these regions.
authors.affiliation: School of Psychology and Clinical Language Sciences, University of Reading, UK (Ms Rzepa, Mr Tudge, and Dr McCabe); Department of Psychiatry, Warneford Hospital, University of Oxford, UK (Dr McCabe).
authors.forename: Ewelina
authors.initials: E
authors.lastname: Rzepa
authors.affiliation: School of Psychology and Clinical Language Sciences, University of Reading, UK (Ms Rzepa, Mr Tudge, and Dr McCabe); Department of Psychiatry, Warneford Hospital, University of Oxford, UK (Dr McCabe).
authors.forename: Luke
authors.initials: L
authors.lastname: Tudge
authors.affiliation: School of Psychology and Clinical Language Sciences, University of Reading, UK (Ms Rzepa, Mr Tudge, and Dr McCabe); Department of Psychiatry, Warneford Hospital, University of Oxford, UK (Dr McCabe). c.mccabe@reading.ac.uk.
authors.forename: Ciara
authors.initials: C
authors.lastname: McCabe
mesh_terms: D000328:Adult; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D056344:Executive Function / Q000187:drug effects / Q000502:physiology*; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D009415:Nerve Net / Q000187:drug effects / Q000378:metabolism*; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors*; D012146:Rest / Q000502:physiology; D055815:Young Adult
chemical_list: D043884:Receptor, Cannabinoid, CB1; C003403:tetrahydrocannabivarin 9; D013759:Dronabinol
keywords: Cannabinoids; default mode; fMRI; obesity; resting state; reward