Acute effects of Δ⁹-tetrahydrocannabinol and cannabidiol on auditory mismatch negativity

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dc.contributor.authorGreenwood, L.M.
dc.contributor.authorBroyd, S.J.
dc.contributor.authorvan Hell, H.H.
dc.contributor.authorTodd, J.
dc.contributor.authorJones, A.
dc.contributor.authorMurray, R.M.
dc.contributor.authorCroft, R.J.
dc.contributor.authorMichie, P.T.
dc.contributor.authorSolowij, N.
dc.date.issued2022
dc.description.abstractRationale: Mismatch negativity (MMN) is a candidate endophenotype for schizophrenia subserved by N-methyl-D-aspartate receptor (NMDAR) function and there is increasing evidence that prolonged cannabis use adversely affects MMN generation. Few human studies have investigated the acute effects of cannabinoids on brain-based biomarkers of NMDAR function and synaptic plasticity. Objectives: The current study investigated the acute effects of Δ⁹-tetrahydrocannabinol (THC) and cannabidiol (CBD) alone and in combination on the mismatch negativity (MMN). Methods: In a randomised, double-blind, crossover placebo-controlled study, 18 frequent and 18 less-frequent cannabis users underwent 5 randomised drug sessions administered via vaporiser: (1) placebo; (2) THC 8 mg; (3) CBD 400 mg; (4) THC 8 mg + CBD 4 mg [THC + CBD low]; (5) THC 12 mg + CBD 400 mg [THC + CBDhigh]. Participants completed a multifeature MMN auditory oddball paradigm with duration, frequency and intensity deviants (6% each). Results: Relative to placebo, both THC and CBD were observed to increase duration and intensity MMN amplitude in less-frequent users, and THC also increased frequency MMN in this group. The addition of low-dose CBD added to THC attenuated the effect of THC on duration and intensity MMN amplitude in less-frequent users. The same pattern of effects was observed following high-dose CBD added to THC on duration and frequency MMN in frequent users.<h4>Conclusions</h4>The pattern of effects following CBD combined with THC on MMN may be subserved by different underlying neurobiological interactions within the endocannabinoid system that vary as a function of prior cannabis exposure. These results highlight the complex interplay between the acute effects of exogenous cannabinoids and NMDAR function. Further research is needed to determine how this process normalises after the acute effects dissipate and following repeated acute exposure.
dc.description.statementofresponsibilityLisa-Marie Greenwood, Samantha J. Broyd, Hendrika H. van Hell, Juanita Todd, Alison Jones, Robin M. Murray, Rodney J. Croft, Patricia T. Michie, Nadia Solowij
dc.identifier.citationPsychopharmacology, 2022; 239(5):1409-1424
dc.identifier.doi10.1007/s00213-021-05997-3
dc.identifier.issn0033-3158
dc.identifier.issn1432-2072
dc.identifier.orcidJones, A. [0000-0002-1105-6195]
dc.identifier.urihttps://hdl.handle.net/2440/139173
dc.language.isoen
dc.publisherSpringer Science and Business Media LLC
dc.relation.granthttp://purl.org/au-research/grants/nhmrc/1007593
dc.relation.granthttp://purl.org/au-research/grants/arc/FT110100752
dc.rights© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021
dc.source.urihttps://doi.org/10.1007/s00213-021-05997-3
dc.subjectΔ9 -Tetrahydrocannabinol (THC); Cannabidiol (CBD); Cannabis; Mismatch negativity (MMN) · Brain electrophysiology
dc.subject.meshHumans
dc.subject.meshCannabis
dc.subject.meshCannabinoids
dc.subject.meshCannabidiol
dc.subject.meshHallucinogens
dc.subject.meshDronabinol
dc.titleAcute effects of Δ⁹-tetrahydrocannabinol and cannabidiol on auditory mismatch negativity
dc.title.alternativeAcute effects of Δ9-tetrahydrocannabinol and cannabidiol on auditory mismatch negativity
dc.typeJournal article
pubs.publication-statusPublished

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