The effects of acute cannabis with and without cannabidiol on neural reward anticipation in adults and adolescents

Martine Skumlien; H. Valerie Curran; Barbara Sahakian; Anya Borissova; Tom Freeman; Claire Mokrysz; Will Lawn

doi:10.1016/j.bpsc.2022.10.004

The effects of acute cannabis with and without cannabidiol on neural reward anticipation in adults and adolescents

Martine Skumlien^*, H. Valerie Curran, Barbara Sahakian, Anya Borissova, Tom Freeman, Claire Mokrysz, Will Lawn^*

^*Corresponding author for this work

Psychology

Research output: Contribution to journal › Article › peer-review

9 Citations (Scopus)

Abstract

Background: Adolescents may respond differently to cannabis than adults, yet no previous functional magnetic resonance imaging study has examined acute cannabis effects in this age group. In this study, we investigated the neural correlates of reward anticipation after acute exposure to cannabis in adolescents and adults. Methods: This was a double-blind, placebo-controlled, randomized, crossover experiment. Forty-seven adolescents (n = 24, 12 females, ages 16–17 years) and adults (n = 23, 11 females, ages 26–29 years) matched on cannabis use frequency (0.5–3 days/week) completed the Monetary Incentive Delay task during functional magnetic resonance imaging after inhaling cannabis with 0.107 mg/kg Δ⁹-tetrahydrocannabinol (“THC”) (8 mg THC for a 75-kg person) or with THC plus 0.320 mg/kg cannabidiol (“THC+CBD”) (24 mg CBD for a 75-kg person), or placebo cannabis. We investigated reward anticipation activity with whole-brain analyses and region of interest analyses in the right and left ventral striatum, right and left anterior cingulate cortex, and right insula. Results: THC reduced anticipation activity compared with placebo in the right (p = .005, d = 0.49) and left (p = .003, d = 0.50) ventral striatum and the right insula (p = .01, d = 0.42). THC+CBD reduced activity compared with placebo in the right ventral striatum (p = .01, d = 0.41) and right insula (p = .002, d = 0.49). There were no differences between “THC” and “THC+CBD” conditions and no significant drug by age group interaction effect, supported by Bayesian analyses. There were no significant effects in the whole-brain analyses. Conclusions: In weekly cannabis users, cannabis suppresses the brain's anticipatory reward response to money, and CBD does not modulate this effect. Furthermore, the adolescent reward circuitry is not differentially sensitive to acute effects of cannabis on reward anticipation.

Original language	English
Pages (from-to)	219-229
Number of pages	11
Journal	Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
Volume	8
Issue number	2
Early online date	6 Feb 2023
DOIs	https://doi.org/10.1016/j.bpsc.2022.10.004
Publication status	Published - Feb 2023

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@article{3db0b66ffad34567875c039d3eabe4aa,

title = "The effects of acute cannabis with and without cannabidiol on neural reward anticipation in adults and adolescents",

abstract = "Background: Adolescents may respond differently to cannabis than adults, yet no previous functional magnetic resonance imaging study has examined acute cannabis effects in this age group. In this study, we investigated the neural correlates of reward anticipation after acute exposure to cannabis in adolescents and adults. Methods: This was a double-blind, placebo-controlled, randomized, crossover experiment. Forty-seven adolescents (n = 24, 12 females, ages 16–17 years) and adults (n = 23, 11 females, ages 26–29 years) matched on cannabis use frequency (0.5–3 days/week) completed the Monetary Incentive Delay task during functional magnetic resonance imaging after inhaling cannabis with 0.107 mg/kg Δ⁹-tetrahydrocannabinol (“THC”) (8 mg THC for a 75-kg person) or with THC plus 0.320 mg/kg cannabidiol (“THC+CBD”) (24 mg CBD for a 75-kg person), or placebo cannabis. We investigated reward anticipation activity with whole-brain analyses and region of interest analyses in the right and left ventral striatum, right and left anterior cingulate cortex, and right insula. Results: THC reduced anticipation activity compared with placebo in the right (p = .005, d = 0.49) and left (p = .003, d = 0.50) ventral striatum and the right insula (p = .01, d = 0.42). THC+CBD reduced activity compared with placebo in the right ventral striatum (p = .01, d = 0.41) and right insula (p = .002, d = 0.49). There were no differences between “THC” and “THC+CBD” conditions and no significant drug by age group interaction effect, supported by Bayesian analyses. There were no significant effects in the whole-brain analyses. Conclusions: In weekly cannabis users, cannabis suppresses the brain's anticipatory reward response to money, and CBD does not modulate this effect. Furthermore, the adolescent reward circuitry is not differentially sensitive to acute effects of cannabis on reward anticipation.",

author = "Martine Skumlien and Curran, {H. Valerie} and Barbara Sahakian and Anya Borissova and Tom Freeman and Claire Mokrysz and Will Lawn",

note = "Funding Information: This study was funded by the Medical Research Council (Grant No. MR/P012728/1 [to HVC and TPF]); an Aker Scholarship from the Aker Foundation (to MS); a fellowship from the National Institute for Health Research (NIHR) UCLH Biomedical Research Centre (to AB) and a NIHR Academic Clinical Fellowship (to AB); the Lundbeck Foundation and the Leverhulme Trust (to BJS); the UK MRC (Grant No. MR/P012728/1), UK Department of Health, and the NIHR UCLH Biomedical Research Centre [to HVC]; and a Wellcome Trust Collaborative Award (Grant No. 200181/Z//15/Z [to CL]). BJS's and CL's research is conducted within the NIHR Cambridge Biomedical Research Centre (Mental-Health Theme and Neurodegeneration Theme) and the NIHR MedTech in vitro diagnostics Co-operative. Funding Information: This study was funded by the Medical Research Council (Grant No. MR/P012728/1 [to HVC and TPF]); an Aker Scholarship from the Aker Foundation (to MS); a fellowship from the National Institute for Health Research (NIHR) UCLH Biomedical Research Centre (to AB) and a NIHR Academic Clinical Fellowship (to AB); the Lundbeck Foundation and the Leverhulme Trust (to BJS); the UK MRC (Grant No. MR/P012728/1), UK Department of Health, and the NIHR UCLH Biomedical Research Centre [to HVC]; and a Wellcome Trust Collaborative Award (Grant No. 200181/Z//15/Z [to CL]). BJS's and CL's research is conducted within the NIHR Cambridge Biomedical Research Centre (Mental-Health Theme and Neurodegeneration Theme) and the NIHR MedTech in vitro diagnostics Co-operative. The funding sources had no role in the design or conduct of the study; the collection, management, analysis, or interpretation of the data; the preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. Michael Bloomfield, Ph.D. was a trial physician. We thank Denisa Clisu, M.Sci. Zarah Rahim Haniff, M.Sc. Elsa Clinton, M.Sc. Tiernan Coughlan M.Sc. and Teodora Perju, M.Sci. for assisting with data collection during their time as undergraduate or graduate students on the study. We are also thankful to the clinical staff at Invicro and to all participants of the CannTeen study. The data from this study are not available. BJS consults for Cambridge Cognition. HVC has consulted for Janssen Research and Development. MBW's primary employer is Invicro LLC, a contract research organization which performs commercial research for the pharmaceutical and biotechnology industries. All other authors report no biomedical financial interests or potential conflicts of interest. ClinicalTrials.gov: Do Adolescents and Adults Differ in Their Acute Subjective, Behavioural and Neural Responses to Cannabis, With and Without Cannabidiol?; https://clinicaltrials.gov/ct2/show/NCT04851392?term=NCT04851392&draw=2&rank=1; NCT04851392. Publisher Copyright: {\textcopyright} 2022 Society of Biological Psychiatry",

year = "2023",

month = feb,

doi = "10.1016/j.bpsc.2022.10.004",

language = "English",

volume = "8",

pages = "219--229",

journal = "Biological Psychiatry: Cognitive Neuroscience and Neuroimaging",

issn = "2451-9022",

publisher = "Elsevier Inc.",

number = "2",

}

TY - JOUR

T1 - The effects of acute cannabis with and without cannabidiol on neural reward anticipation in adults and adolescents

AU - Skumlien, Martine

AU - Curran, H. Valerie

AU - Sahakian, Barbara

AU - Borissova, Anya

AU - Freeman, Tom

AU - Mokrysz, Claire

AU - Lawn, Will

N1 - Funding Information: This study was funded by the Medical Research Council (Grant No. MR/P012728/1 [to HVC and TPF]); an Aker Scholarship from the Aker Foundation (to MS); a fellowship from the National Institute for Health Research (NIHR) UCLH Biomedical Research Centre (to AB) and a NIHR Academic Clinical Fellowship (to AB); the Lundbeck Foundation and the Leverhulme Trust (to BJS); the UK MRC (Grant No. MR/P012728/1), UK Department of Health, and the NIHR UCLH Biomedical Research Centre [to HVC]; and a Wellcome Trust Collaborative Award (Grant No. 200181/Z//15/Z [to CL]). BJS's and CL's research is conducted within the NIHR Cambridge Biomedical Research Centre (Mental-Health Theme and Neurodegeneration Theme) and the NIHR MedTech in vitro diagnostics Co-operative. Funding Information: This study was funded by the Medical Research Council (Grant No. MR/P012728/1 [to HVC and TPF]); an Aker Scholarship from the Aker Foundation (to MS); a fellowship from the National Institute for Health Research (NIHR) UCLH Biomedical Research Centre (to AB) and a NIHR Academic Clinical Fellowship (to AB); the Lundbeck Foundation and the Leverhulme Trust (to BJS); the UK MRC (Grant No. MR/P012728/1), UK Department of Health, and the NIHR UCLH Biomedical Research Centre [to HVC]; and a Wellcome Trust Collaborative Award (Grant No. 200181/Z//15/Z [to CL]). BJS's and CL's research is conducted within the NIHR Cambridge Biomedical Research Centre (Mental-Health Theme and Neurodegeneration Theme) and the NIHR MedTech in vitro diagnostics Co-operative. The funding sources had no role in the design or conduct of the study; the collection, management, analysis, or interpretation of the data; the preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication. Michael Bloomfield, Ph.D. was a trial physician. We thank Denisa Clisu, M.Sci. Zarah Rahim Haniff, M.Sc. Elsa Clinton, M.Sc. Tiernan Coughlan M.Sc. and Teodora Perju, M.Sci. for assisting with data collection during their time as undergraduate or graduate students on the study. We are also thankful to the clinical staff at Invicro and to all participants of the CannTeen study. The data from this study are not available. BJS consults for Cambridge Cognition. HVC has consulted for Janssen Research and Development. MBW's primary employer is Invicro LLC, a contract research organization which performs commercial research for the pharmaceutical and biotechnology industries. All other authors report no biomedical financial interests or potential conflicts of interest. ClinicalTrials.gov: Do Adolescents and Adults Differ in Their Acute Subjective, Behavioural and Neural Responses to Cannabis, With and Without Cannabidiol?; https://clinicaltrials.gov/ct2/show/NCT04851392?term=NCT04851392&draw=2&rank=1; NCT04851392. Publisher Copyright: © 2022 Society of Biological Psychiatry

PY - 2023/2

Y1 - 2023/2

N2 - Background: Adolescents may respond differently to cannabis than adults, yet no previous functional magnetic resonance imaging study has examined acute cannabis effects in this age group. In this study, we investigated the neural correlates of reward anticipation after acute exposure to cannabis in adolescents and adults. Methods: This was a double-blind, placebo-controlled, randomized, crossover experiment. Forty-seven adolescents (n = 24, 12 females, ages 16–17 years) and adults (n = 23, 11 females, ages 26–29 years) matched on cannabis use frequency (0.5–3 days/week) completed the Monetary Incentive Delay task during functional magnetic resonance imaging after inhaling cannabis with 0.107 mg/kg Δ⁹-tetrahydrocannabinol (“THC”) (8 mg THC for a 75-kg person) or with THC plus 0.320 mg/kg cannabidiol (“THC+CBD”) (24 mg CBD for a 75-kg person), or placebo cannabis. We investigated reward anticipation activity with whole-brain analyses and region of interest analyses in the right and left ventral striatum, right and left anterior cingulate cortex, and right insula. Results: THC reduced anticipation activity compared with placebo in the right (p = .005, d = 0.49) and left (p = .003, d = 0.50) ventral striatum and the right insula (p = .01, d = 0.42). THC+CBD reduced activity compared with placebo in the right ventral striatum (p = .01, d = 0.41) and right insula (p = .002, d = 0.49). There were no differences between “THC” and “THC+CBD” conditions and no significant drug by age group interaction effect, supported by Bayesian analyses. There were no significant effects in the whole-brain analyses. Conclusions: In weekly cannabis users, cannabis suppresses the brain's anticipatory reward response to money, and CBD does not modulate this effect. Furthermore, the adolescent reward circuitry is not differentially sensitive to acute effects of cannabis on reward anticipation.

AB - Background: Adolescents may respond differently to cannabis than adults, yet no previous functional magnetic resonance imaging study has examined acute cannabis effects in this age group. In this study, we investigated the neural correlates of reward anticipation after acute exposure to cannabis in adolescents and adults. Methods: This was a double-blind, placebo-controlled, randomized, crossover experiment. Forty-seven adolescents (n = 24, 12 females, ages 16–17 years) and adults (n = 23, 11 females, ages 26–29 years) matched on cannabis use frequency (0.5–3 days/week) completed the Monetary Incentive Delay task during functional magnetic resonance imaging after inhaling cannabis with 0.107 mg/kg Δ⁹-tetrahydrocannabinol (“THC”) (8 mg THC for a 75-kg person) or with THC plus 0.320 mg/kg cannabidiol (“THC+CBD”) (24 mg CBD for a 75-kg person), or placebo cannabis. We investigated reward anticipation activity with whole-brain analyses and region of interest analyses in the right and left ventral striatum, right and left anterior cingulate cortex, and right insula. Results: THC reduced anticipation activity compared with placebo in the right (p = .005, d = 0.49) and left (p = .003, d = 0.50) ventral striatum and the right insula (p = .01, d = 0.42). THC+CBD reduced activity compared with placebo in the right ventral striatum (p = .01, d = 0.41) and right insula (p = .002, d = 0.49). There were no differences between “THC” and “THC+CBD” conditions and no significant drug by age group interaction effect, supported by Bayesian analyses. There were no significant effects in the whole-brain analyses. Conclusions: In weekly cannabis users, cannabis suppresses the brain's anticipatory reward response to money, and CBD does not modulate this effect. Furthermore, the adolescent reward circuitry is not differentially sensitive to acute effects of cannabis on reward anticipation.

UR - http://www.scopus.com/inward/record.url?scp=85146453151&partnerID=8YFLogxK

U2 - 10.1016/j.bpsc.2022.10.004

DO - 10.1016/j.bpsc.2022.10.004

M3 - Article

SN - 2451-9022

VL - 8

SP - 219

EP - 229

JO - Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

JF - Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

IS - 2

ER -

The effects of acute cannabis with and without cannabidiol on neural reward anticipation in adults and adolescents

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