Task-independent acute effects of delta-9-tetrahydrocannabinol on human brain function and its relationship with cannabinoid receptor gene expression: A neuroimaging meta-regression analysis

CBE Consortium

doi:10.1016/j.neubiorev.2022.104801

Task-independent acute effects of delta-9-tetrahydrocannabinol on human brain function and its relationship with cannabinoid receptor gene expression: A neuroimaging meta-regression analysis

CBE Consortium

King's College London
Università di Padova
Wilhelmina Children's Hospital
University of Barcelona
The Karolinska Institute
Johann Wolfgang Goethe-Universitat Frankfurt am Main
Fraunhofer Institute of Translational Medicine and Pharmacology
University College London
University of California San Francisco
Lausanne University Hospital
Departamento de Psiquiatria da Faculdade de Medicina da USP
University of São Paulo
Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

Research output: Contribution to journal › Review article › peer-review

9 Citations (SciVal)

Abstract

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.

Original language	English
Article number	104801
Journal	Neuroscience and Biobehavioral Reviews
Volume	140
Early online date	30 Jul 2022
DOIs	https://doi.org/10.1016/j.neubiorev.2022.104801
Publication status	Published - 30 Sept 2022

Bibliographical note

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 .

Funding

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. 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). 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 .

Keywords

Attention
Cannabis
FMRI
Memory
Meta-analysis
Neuroimaging
PET
Reward
Systematic
Tetrahydrocannabinol
THC

ASJC Scopus subject areas

Neuropsychology and Physiological Psychology
Cognitive Neuroscience
Behavioral Neuroscience

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10.1016/j.neubiorev.2022.104801Licence: CC BY

Cite this

@article{8c8b5ef0f61344f283415dd95b74127b,

title = "Task-independent acute effects of delta-9-tetrahydrocannabinol on human brain function and its relationship with cannabinoid receptor gene expression: A neuroimaging meta-regression analysis",

abstract = "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 {\textquoteleft}activation signal{\textquoteright}) in a {\textquoteleft}core{\textquoteright} 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.",

keywords = "Attention, Cannabis, FMRI, Memory, Meta-analysis, Neuroimaging, PET, Reward, Systematic, Tetrahydrocannabinol, THC",

author = "\{CBE Consortium\} and Brandon Gunasekera and Cathy Davies and Grace Blest-Hopley and Mattia Veronese and Ramsey, \{Nick F.\} and Bossong, \{Matthijs G.\} and Joaquim Radua and Sagnik Bhattacharyya and Charlotte Pretzsch and Gr{\'a}inne McAlonan and Carmen Walter and J{\"o}rn L{\"o}tsch and Tom Freeman and Valerie Curran and Giovanni Battistella and Eleonora Fornari and Filho, \{Geraldo Busatto\} and Crippa, \{Jos{\'e} Alexandre\} and Fabio Duran and Zuardi, \{Antonio Waldo\}",

note = "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, Guimar{\~a}es FS, Crippa JAS, Breuer A). Universidade de S{\~a}o 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 S{\~a}o 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, Bras{\'i}lia, 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, Guimar{\~a}es FS, Crippa JAS, Breuer A). Universidade de S{\~a}o 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{\textquoteright}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 S{\~a}o 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 , Bras{\'i}lia, 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{\textquoteright}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 . ",

year = "2022",

month = sep,

day = "30",

doi = "10.1016/j.neubiorev.2022.104801",

language = "English",

volume = "140",

journal = "Neuroscience and Biobehavioral Reviews",

issn = "0149-7634",

publisher = "Elsevier",

}

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 - https://www.scopus.com/pages/publications/85135325782

U2 - 10.1016/j.neubiorev.2022.104801

DO - 10.1016/j.neubiorev.2022.104801

M3 - Review article

C2 - 35914625

AN - SCOPUS:85135325782

SN - 0149-7634

VL - 140

JO - Neuroscience and Biobehavioral Reviews

JF - Neuroscience and Biobehavioral Reviews

M1 - 104801

ER -

Task-independent acute effects of delta-9-tetrahydrocannabinol on human brain function and its relationship with cannabinoid receptor gene expression: A neuroimaging meta-regression analysis

Abstract

Bibliographical note

Funding

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