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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. 2019 Feb; 269(1):17-35.EA

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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Authors+Show Affiliations

Solowij N
School of Psychology and Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW, Australia. nadia@uow.edu.au. The Australian Centre for Cannabinoid Clinical and Research Excellence (ACRE), New Lambton Heights, NSW, Australia. nadia@uow.edu.au.
Broyd S
School of Psychology and Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW, Australia.
Greenwood LM
School of Psychology and Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW, Australia.
van Hell H
School of Psychology and Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW, Australia.
Martelozzo D
School of Psychology and Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW, Australia.
Rueb K
School of Psychology and Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW, Australia.
Todd J
School of Psychology, University of Newcastle, University Drive, Callaghan, NSW, Australia.
Liu Z
School of Medicine and Public Health, Hunter Medical Research Institute, University of Newcastle, New Lambton Heights, NSW, Australia. Clinical Pharmacology, Department of Medicine, The Royal Children's Hospital, Melbourne, VIC, Australia.
Galettis P
The Australian Centre for Cannabinoid Clinical and Research Excellence (ACRE), New Lambton Heights, NSW, Australia. School of Medicine and Public Health, Hunter Medical Research Institute, University of Newcastle, New Lambton Heights, NSW, Australia.
Martin J
The Australian Centre for Cannabinoid Clinical and Research Excellence (ACRE), New Lambton Heights, NSW, Australia. School of Medicine and Public Health, Hunter Medical Research Institute, University of Newcastle, New Lambton Heights, NSW, Australia.
Murray R
Institute of Psychiatry, Kings College London, London, UK.
Jones A
Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW, Australia.
Michie PT
School of Psychology, University of Newcastle, University Drive, Callaghan, NSW, Australia.
Croft R
School of Psychology and Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW, Australia.

MeSH

AdolescentAdultBlood PressureCannabidiolCannabinoid Receptor ModulatorsCannabisDissociative DisordersDronabinolDrug InteractionsDrug-Related Side Effects and Adverse ReactionsFemaleHeart RateHumansMaleMiddle AgedPerceptual DisordersSelf ReportYoung Adult

Pub Type(s)

Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

30661105

Citation

Solowij, Nadia, 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." European Archives of Psychiatry and Clinical Neuroscience, vol. 269, no. 1, 2019, pp. 17-35.
Solowij N, Broyd S, Greenwood LM, 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. 2019;269(1):17-35.
Solowij, N., Broyd, S., Greenwood, L. M., van Hell, H., Martelozzo, D., Rueb, K., Todd, J., Liu, Z., Galettis, P., Martin, J., Murray, R., Jones, A., Michie, P. T., & Croft, R. (2019). A randomised controlled trial of vaporised Δ9-tetrahydrocannabinol and cannabidiol alone and in combination in frequent and infrequent cannabis users: acute intoxication effects. European Archives of Psychiatry and Clinical Neuroscience, 269(1), 17-35. https://doi.org/10.1007/s00406-019-00978-2
Solowij N, 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. 2019;269(1):17-35. PubMed PMID: 30661105.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A randomised controlled trial of vaporised Δ9-tetrahydrocannabinol and cannabidiol alone and in combination in frequent and infrequent cannabis users: acute intoxication effects. AU - Solowij,Nadia, AU - Broyd,Samantha, AU - Greenwood,Lisa-Marie, AU - van Hell,Hendrika, AU - Martelozzo,Dave, AU - Rueb,Kuna, AU - Todd,Juanita, AU - Liu,Zheng, AU - Galettis,Peter, AU - Martin,Jennifer, AU - Murray,Robin, AU - Jones,Alison, AU - Michie,Patricia T, AU - Croft,Rodney, Y1 - 2019/01/19/ PY - 2018/12/13/received PY - 2019/01/03/accepted PY - 2019/1/21/pubmed PY - 2019/6/6/medline PY - 2019/1/21/entrez KW - Cannabidiol (CBD) KW - Cannabinoids KW - Cannabis KW - Intoxication KW - Synergistic effects KW - Δ9-Tetrahydrocannabinol (THC) SP - 17 EP - 35 JF - European archives of psychiatry and clinical neuroscience JO - Eur Arch Psychiatry Clin Neurosci VL - 269 IS - 1 N2 - 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. SN - 1433-8491 UR - https://www.unboundmedicine.com/medline/citation/30661105/A_randomised_controlled_trial_of_vaporised_Δ9_tetrahydrocannabinol_and_cannabidiol_alone_and_in_combination_in_frequent_and_infrequent_cannabis_users:_acute_intoxication_effects_ DB - PRIME DP - Unbound Medicine ER -