A randomised controlled trial of vaporised Δ9-tetrahydrocannabinol and cannabidiol alone and in combination in frequent and infrequent cannabis users: acute intoxication effects

Abstract

Access to cannabis and cannabinoid products is increasing worldwide for recreational and medicinal use. Two primary compounds within cannabis plant matter, Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD), are both psychoactive, but only THC is considered intoxicating. There is significant interest in potential therapeutic properties of these cannabinoids and of CBD in particular. Some research has suggested that CBD may ameliorate adverse effects of THC, but this may be dose dependent as other evidence suggests possible potentiating effects of THC by low doses of CBD. We conducted a randomised placebo controlled trial to examine the acute effects of these compounds alone and in combination when administered by vaporisation to frequent and infrequent cannabis users. Participants (n = 36; 31 male) completed 5 drug conditions spaced one week apart, with the following planned contrasts: placebo vs CBD alone (400 mg); THC alone (8 mg) vs THC combined with low (4 mg) or high (400 mg) doses of CBD. Objective (blind observer ratings) and subjective (self-rated) measures of intoxication were the primary outcomes, with additional indices of intoxication examined. CBD showed some intoxicating properties relative to placebo. Low doses of CBD when combined with THC enhanced, while high doses of CBD reduced the intoxicating effects of THC. The enhancement of intoxication by low-dose CBD was particularly prominent in infrequent cannabis users and was consistent across objective and subjective measures. Most effects were significant at p < .0001. These findings are important to consider in terms of recommended proportions of THC and CBD in cannabis plant matter whether used medicinally or recreationally and have implications for novice or less experienced cannabis users.

Trial registration: ISRCTN Registry Identifier: ISRCTN24109245.

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Acknowledgements

The study was funded by the National Health and Medical Research Council of Australia (NHMRC Project Grant 1007593). NS was supported by the Australian Research Council (ARC Future Fellowship FT110100752). The authors are grateful to Professor Antonio Zuardi and Dr Arno Hazekamp for advice around dosing and drug administration at the commencement of the study; to Clare Bate, Camilla Beale, Andrew Bonney, Gary Chan, Francesca Fernandez, Sarah Gallagher, David Garne, Madeleine Godber, Stuart Johnstone, Lisa Lole, Elke Macdonald, Philip McGuire, Jelena Novakovic, Nagesh Pai, Gabrielle Puckett, Karina Rovere, Beth Shaw and Lara Tramazzo for assistance with participant, trial and data management and logistics; and to Storz & Bickel, Tuttlingen, Germany for supplying a Volcano® Vaporiser used in this study. Cannabinoid compounds were purchased from STI Pharmaceuticals, UK.

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Correspondence to Nadia Solowij.

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This study was approved by the University of Wollongong and Illawarra Shoalhaven Local Health District Health and Medical Human Research Ethics Committee and registered as a clinical trial (ISRCTN24109245 [89]). Participants provided written informed consent prior to participating in the study and at the start of each drug session.

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The authors declare that they have no conflict of interest.

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Solowij, N., Broyd, S., Greenwood, L. et al. A randomised controlled trial of vaporised Δ9-tetrahydrocannabinol and cannabidiol alone and in combination in frequent and infrequent cannabis users: acute intoxication effects. Eur Arch Psychiatry Clin Neurosci 269, 17–35 (2019). https://doi.org/10.1007/s00406-019-00978-2

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Keywords

  • Δ9-Tetrahydrocannabinol (THC)
  • Cannabidiol (CBD)
  • Cannabis
  • Cannabinoids
  • Intoxication
  • Synergistic effects