TY - JOUR
T1 - Task-independent acute effects of delta-9-tetrahydrocannabinol on human brain function and its relationship with cannabinoid receptor gene expression
T2 - A neuroimaging meta-regression analysis
AU - CBE Consortium
AU - Gunasekera, Brandon
AU - Davies, Cathy
AU - Blest-Hopley, Grace
AU - Veronese, Mattia
AU - Ramsey, Nick F.
AU - Bossong, Matthijs G.
AU - Radua, Joaquim
AU - Bhattacharyya, Sagnik
AU - Pretzsch, Charlotte
AU - McAlonan, Gráinne
AU - Walter, Carmen
AU - Lötsch, Jörn
AU - Freeman, Tom
AU - Curran, Valerie
AU - Battistella, Giovanni
AU - Fornari, Eleonora
AU - Filho, Geraldo Busatto
AU - Crippa, José Alexandre
AU - Duran, Fabio
AU - Zuardi, Antonio Waldo
N1 - Funding Information:
SB is supported by grants from the Medical Research Council, UK; NIHR, UK; Wellcome Trust; European Commission; Dowager Countess Eleanor Peel trust; Psychiatry Research Trust; Parkinson's UK; Rosetrees Trust; Alzheimer's Research UK. SB has participated in advisory boards for or received honoraria as a speaker from Reckitt Benckiser, EmpowerPharm/SanteCannabis and Britannia Pharmaceuticals. All of these honoraria were received as contributions toward research support through King's College London, and not personally. SB also has an ongoing collaboration with Beckley Canopy Therapeutics/ Canopy Growth (investigator initiated research) wherein they are supplying study drug for free for charity (Parkinson's UK) and NIHR (BRC) funded research. MV is funded by the National Institute for Health Research Biomedical Research Centre at South London and Maudsley National Health Service Foundation Trust and King's College London, and by the Wellcome Trust Digital Award 215747/Z/19/Z. MV has received consulting honoraria from GSK. JL was supported by Deutsche Forschungsgemeinschaft, DFG Lo 612/10-1 and European Graduate School GRK757. GM has received previous funding from GW Pharma (now Greenwich Biosciences), and served as an advisor to Greenwich Biosciences. Current funding from Compass Pathways Ltd. AC and AWZ are coinventors of the patent “Cannabinoid-containing oral pharmaceutical composition, method for preparing and using same,” INPI on September 16, 2016 (BR 112018005423–2). FSG, JECH, JAC and AWZ are coinventors of the patent “Fluorinated CBD compounds, compositions and uses thereof. Pub. No.: WO/2014/108899. International Application No.: PCT/IL2014/050023,” Def. US number Reg. 62193296; July 29, 2015; INPI on August 19, 2015 (BR1120150164927; Mechoulam R, Zuardi AW, Kapczinski F, Hallak JEC, Guimarães FS, Crippa JAS, Breuer A). Universidade de São Paulo (USP) has licensed this patent to Phytecs Pharm (USP Resolution No. 15.1.130002.1.1) and has an agreement with Prati-Donaduzzi to “develop a pharmaceutical product containing synthetic CBD and prove its safety and therapeutic efficacy in the treatment of epilepsy, schizophrenia, Parkinson's disease, and anxiety disorders” (outside the submitted work). JAC is a consultant and/or has received speaker fees and/or sits on the advisory board and/or receives research funding from Janssen-Cilag, Torrent Pharm, Prati-Donaduzzi, PurMed Global, BSPG Pharm, and the Australian Centre for Cannabinoid Clinical and Research Excellence (ACRE) – National Health and Medical Research Council (NHMRC) over the past 3 years. AWZ, and JAC reported receiving grants from the São Paulo Research Foundation/FAPESP (2020/12110-9 and 2020/12066-0) and the National Institute of Translational Science and Technology in Medicine (INCT-TM, CNPq, Brasília, Brazil) and CNPq (Produtividade em Pesquisa - 1A). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.
Funding Information:
AC and AWZ are coinventors of the patent “Cannabinoid-containing oral pharmaceutical composition, method for preparing and using same,” INPI on September 16, 2016 (BR 112018005423–2 ). FSG, JECH, JAC and AWZ are coinventors of the patent “Fluorinated CBD compounds, compositions and uses thereof. Pub. No.: WO/2014/108899. International Application No.: PCT/IL2014/050023,” Def. US number Reg. 62193296; July 29, 2015; INPI on August 19, 2015 (BR1120150164927; Mechoulam R, Zuardi AW, Kapczinski F, Hallak JEC, Guimarães FS, Crippa JAS, Breuer A). Universidade de São Paulo (USP) has licensed this patent to Phytecs Pharm (USP Resolution No. 15.1.130002.1.1) and has an agreement with Prati-Donaduzzi to “develop a pharmaceutical product containing synthetic CBD and prove its safety and therapeutic efficacy in the treatment of epilepsy, schizophrenia, Parkinson’s disease, and anxiety disorders” (outside the submitted work). JAC is a consultant and/or has received speaker fees and/or sits on the advisory board and/or receives research funding from Janssen-Cilag, Torrent Pharm, Prati-Donaduzzi, PurMed Global, BSPG Pharm , and the Australian Centre for Cannabinoid Clinical and Research Excellence (ACRE) – National Health and Medical Research Council ( NHMRC ) over the past 3 years. AWZ, and JAC reported receiving grants from the São Paulo Research Foundation/FAPESP ( 2020/12110-9 and 2020/12066-0 ) and the National Institute of Translational Science and Technology in Medicine (INCT-TM, CNPq , Brasília, Brazil) and CNPq (Produtividade em Pesquisa - 1A).
Funding Information:
SB is supported by grants from the Medical Research Council , UK; NIHR , UK; Wellcome Trust ; European Commission ; Dowager Countess Eleanor Peel trust ; Psychiatry Research Trust; Parkinson's UK; Rosetrees Trust; Alzheimer's Research UK. SB has participated in advisory boards for or received honoraria as a speaker from Reckitt Benckiser, EmpowerPharm/SanteCannabis and Britannia Pharmaceuticals. All of these honoraria were received as contributions toward research support through King's College London , and not personally. SB also has an ongoing collaboration with Beckley Canopy Therapeutics/ Canopy Growth (investigator initiated research) wherein they are supplying study drug for free for charity (Parkinson's UK) and NIHR (BRC) funded research. MV is funded by the National Institute for Health Research Biomedical Research Centre at South London and Maudsley National Health Service Foundation Trust and King’s College London, and by the Wellcome Trust Digital Award 215747/Z/19/Z . MV has received consulting honoraria from GSK. JL was supported by Deutsche Forschungsgemeinschaft , DFG Lo 612/10-1 and European Graduate School GRK757 . GM has received previous funding from GW Pharma (now Greenwich Biosciences), and served as an advisor to Greenwich Biosciences. Current funding from Compass Pathways Ltd .
PY - 2022/9/30
Y1 - 2022/9/30
N2 - The neurobiological mechanisms underlying the effects of delta-9-tetrahydrocannabinol (THC) remain unclear. Here, we examined the spatial acute effect of THC on human regional brain activation or blood flow (hereafter called ‘activation signal’) in a ‘core’ network of brain regions from 372 participants, tested using a within-subject repeated measures design under experimental conditions. We also investigated whether the neuromodulatory effects of THC are related to the local expression of the cannabinoid-type-1 (CB1R) and type-2 (CB2R) receptors. Finally, we investigated the dose-response relationship between THC and key brain substrates. These meta-analytic findings shed new light on the localisation of the effects of THC in the human brain, suggesting that THC has neuromodulatory effects in regions central to many cognitive tasks and processes, related to dose, with greater effects in regions with higher levels of CB1R expression.
AB - The neurobiological mechanisms underlying the effects of delta-9-tetrahydrocannabinol (THC) remain unclear. Here, we examined the spatial acute effect of THC on human regional brain activation or blood flow (hereafter called ‘activation signal’) in a ‘core’ network of brain regions from 372 participants, tested using a within-subject repeated measures design under experimental conditions. We also investigated whether the neuromodulatory effects of THC are related to the local expression of the cannabinoid-type-1 (CB1R) and type-2 (CB2R) receptors. Finally, we investigated the dose-response relationship between THC and key brain substrates. These meta-analytic findings shed new light on the localisation of the effects of THC in the human brain, suggesting that THC has neuromodulatory effects in regions central to many cognitive tasks and processes, related to dose, with greater effects in regions with higher levels of CB1R expression.
KW - Attention
KW - Cannabis
KW - FMRI
KW - Memory
KW - Meta-analysis
KW - Neuroimaging
KW - PET
KW - Reward
KW - Systematic
KW - Tetrahydrocannabinol
KW - THC
UR - http://www.scopus.com/inward/record.url?scp=85135325782&partnerID=8YFLogxK
U2 - 10.1016/j.neubiorev.2022.104801
DO - 10.1016/j.neubiorev.2022.104801
M3 - Review article
C2 - 35914625
AN - SCOPUS:85135325782
VL - 140
JO - Neuroscience and Biobehavioral Reviews
JF - Neuroscience and Biobehavioral Reviews
SN - 0149-7634
M1 - 104801
ER -