Cannabidiol does not attenuate acute delta-9-tetrahydrocannabinol-induced attentional bias in healthy volunteers: A randomised, double-blind, cross-over study

Dominic Oliver, Amir Englund, Edward Chesney, Lucy Chester, Jack Wilson, Simina Sovi, Stina Wigroth, John Hodsoll, John Strang, Robin M. Murray, Tom P. Freeman, Paolo Fusar-Poli, Philip McGuire

Research output: Contribution to journalArticlepeer-review

Abstract

Aims: To test how attentional bias and explicit liking are influenced by delta-9-tetrahydrocannabinol (THC) and whether these effects are moderated by cannabidiol (CBD). 

Design: Double-blind, randomised, within-subjects cross-over study. 

Setting: NIHR Wellcome Trust Clinical Research Facility at King's College Hospital, London, United Kingdom. 

Participants/Cases: Forty-six infrequent cannabis users (cannabis use <1 per week). 

Intervention(s): Across four sessions, participants inhaled vaporised cannabis containing 10 mg of THC and either 0 mg (0:1 CBD:THC), 10 mg (1:1), 20 mg (2:1) or 30 mg (3:1) of CBD, administered in a randomised order and counter-balanced across participants (a total of 24 order groups). 

Measurements: Participants completed two tasks: (1) Attentional Bias (AB), comparing reaction times toward visual probes presented behind 28 target stimuli (cannabis/food) compared with probes behind corresponding non-target (neutral) stimuli. Participants responding more quickly to probes behind target than non-target stimuli would indicate greater attentional bias to cannabis/food; (2) Picture Rating (PR), where all AB stimuli were rated on a 7-point pleasantness scale, measuring explicit liking. 

Findings: During the AB task, participants were more biased toward cannabis stimuli in the 0:1 condition compared with baseline (mean difference = 12.2, 95% confidence intervals [CIs] = 1.20–23.3, d = 0.41, P = 0.03). No other significant AB or PR differences were found between cannabis and food stimuli between baseline and 0:1 condition (P > 0.05). No significant CBD effect was found on AB or PR task performance at any dose (P > 0.05). There was additionally no cumulative effect of THC exposure on AB or PR outcomes (P > 0.05). 

Conclusions: A double-blind, randomised, cross-over study among infrequent cannabis users found that inhaled delta-9-tetrahydrocannabinol increased attentional bias toward cannabis in the absence of explicit liking, a marker of liability toward cannabis use disorder. At the concentrations normally found in legal and illegal cannabis, cannabidiol had no influence on this effect.

Original languageEnglish
Number of pages12
JournalAddiction
Early online date11 Oct 2023
DOIs
Publication statusPublished - 31 Dec 2023

Bibliographical note

ACKNOWLEDGEMENTS:
We thank all the participants who took part in this study, both those who completed as well as those who withdrew. A.E., L.C., J.H., R.M.M. and J.S. are part-funded or supported by the NIHR Maudsley Biomedical Research Centre at South London and Maudsley National Health Service (NHS) Foundation Trust and King's College London. We thank George Brown, John Villajin, Louisa Green, Asha Mathews, Chifundo Stubbs, Olabisi Awogbemila, Noah Yogo, Elka Giemza, Stephanie David, Adebukola Shopade and Herman Rocha of the NIHR Wellcome Trust Clinical Research Facility for supporting this study. We also thank Storz-Bickel GmbH for generously providing us with the cannabis vaporisers and related equipment for this study. We thank Bedrocan BV for their support and advice in supplying the study drug, as well as the Maudsley Pharmacy for their support in receiving, storing, preparing and dispensing of the study drug. We thank GW Pharmaceuticals for kindly providing us with reference standards for plasma analysis of cannabinoid metabolites, and thanks as well to the Mass Spectrometry Facility at King's for analysing the samples. We thank the following physicians who assisted us with medical screening of participants: Giulia Spada, Victoria Rodriguez, Graham Blackman, Robert McCutcheon, Matthew Nour and Marco Colizzi. As well as a special thanks to Cathy Davies for helping in the early stages of the study. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.

Keywords

  • attentional bias
  • cannabidiol
  • cannabis
  • cannabis use disorder
  • CBD
  • delta-9-tetrahydrocannabinol
  • THC

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Psychiatry and Mental health

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