Opposite effects of δ-9-tetrahydrocannabinol and cannabidiol on human brain function and psychopathology

Sagnik Bhattacharyya; Paul D. Morrison; Paolo Fusar-Poli; Rocio Martin-Santos; Stefan Borgwardt; Toby Winton-Brown; Chiara Nosarti; Colin M. O'Carroll; Marc Seal; Paul Allen; Mitul A. Mehta; James M. Stone; Nigel Tunstall; Vincent Giampietro; Shitij Kapur; Robin M. Murray; Antonio W. Zuardi; José A. Crippa; Zerrin Atakan; Philip K. McGuire

doi:10.1038/npp.2009.184

Opposite effects of δ-9-tetrahydrocannabinol and cannabidiol on human brain function and psychopathology

Sagnik Bhattacharyya^*, Paul D. Morrison, Paolo Fusar-Poli, Rocio Martin-Santos, Stefan Borgwardt, Toby Winton-Brown, Chiara Nosarti, Colin M. O'Carroll, Marc Seal, Paul Allen, Mitul A. Mehta, James M. Stone, Nigel Tunstall, Vincent Giampietro, Shitij Kapur, Robin M. Murray, Antonio W. Zuardi, José A. Crippa, Zerrin Atakan, Philip K. McGuire

^*Corresponding author for this work

Department of Psychiatry, Psychosomatics and Psychotherapie

627 Citations (Scopus)

Abstract

Δ-9-tetrahydrocannabinol (Δ-9-THC) and Cannabidiol (CBD), the two main ingredients of the Cannabis sativa plant have distinct symptomatic and behavioral effects. We used functional magnetic resonance imaging (fMRI) in healthy volunteers to examine whether Δ-9-THC and CBD had opposite effects on regional brain function. We then assessed whether pretreatment with CBD can prevent the acute psychotic symptoms induced by Δ-9-THC. Fifteen healthy men with minimal earlier exposure to cannabis were scanned while performing a verbal memory task, a response inhibition task, a sensory processing task, and when viewing fearful faces. Subjects were scanned on three occasions, each preceded by oral administration of Δ-9-THC, CBD, or placebo. BOLD responses were measured using fMRI. In a second experiment, six healthy volunteers were administered Δ-9-THC intravenously on two occasions, after placebo or CBD pretreatment to examine whether CBD could block the psychotic symptoms induced by Δ-9-THC. Δ-9-THC and CBD had opposite effects on activation relative to placebo in the striatum during verbal recall, in the hippocampus during the response inhibition task, in the amygdala when subjects viewed fearful faces, in the superior temporal cortex when subjects listened to speech, and in the occipital cortex during visual processing. In the second experiment, pretreatment with CBD prevented the acute induction of psychotic symptoms by Δ-9-tetrahydrocannabinol. Δ-9-THC and CBD can have opposite effects on regional brain function, which may underlie their different symptomatic and behavioral effects, and CBD's ability to block the psychotogenic effects of Δ-9-THC.

Original language	English
Journal	Neuropsychopharmacology
Volume	35
Issue number	3
Pages (from-to)	764-774
Number of pages	11
ISSN	0893-133X
DOIs	https://doi.org/10.1038/npp.2009.184
Publication status	Published - 02.2010

Funding

This work was supported by a grant from the Psychiatry Research Trust, UK. Sagnik Bhattacharyya is supported by a Joint MRC/Priory Clinical research training fellowship from the Medical Research Council, UK. Paul Morrison is supported by the Medical Research Council, UK, the Biomedial Research Centre and the Beckley Foundation. Jose A Crippa is the recipient of a Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil) Productivity fellowship. We thank Glynis Ivin for help with the blinding procedure, storage and dispensing of the drugs. We thank Dr Katya Rubia and Dr Simon Surguladze for allowing us to use the fearful faces and the response inhibition paradigms, respectively.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being
SDG 10 Reduced Inequalities

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10.1038/npp.2009.184

Cite this

Bhattacharyya, S., Morrison, P. D., Fusar-Poli, P., Martin-Santos, R., Borgwardt, S., Winton-Brown, T., Nosarti, C., O'Carroll, C. M., Seal, M., Allen, P., Mehta, M. A., Stone, J. M., Tunstall, N., Giampietro, V., Kapur, S., Murray, R. M., Zuardi, A. W., Crippa, J. A., Atakan, Z., & McGuire, P. K. (2010). Opposite effects of δ-9-tetrahydrocannabinol and cannabidiol on human brain function and psychopathology. Neuropsychopharmacology, 35(3), 764-774. https://doi.org/10.1038/npp.2009.184

@article{dd60e380522747b9916eccd338b6b416,

title = "Opposite effects of δ-9-tetrahydrocannabinol and cannabidiol on human brain function and psychopathology",

abstract = "Δ-9-tetrahydrocannabinol (Δ-9-THC) and Cannabidiol (CBD), the two main ingredients of the Cannabis sativa plant have distinct symptomatic and behavioral effects. We used functional magnetic resonance imaging (fMRI) in healthy volunteers to examine whether Δ-9-THC and CBD had opposite effects on regional brain function. We then assessed whether pretreatment with CBD can prevent the acute psychotic symptoms induced by Δ-9-THC. Fifteen healthy men with minimal earlier exposure to cannabis were scanned while performing a verbal memory task, a response inhibition task, a sensory processing task, and when viewing fearful faces. Subjects were scanned on three occasions, each preceded by oral administration of Δ-9-THC, CBD, or placebo. BOLD responses were measured using fMRI. In a second experiment, six healthy volunteers were administered Δ-9-THC intravenously on two occasions, after placebo or CBD pretreatment to examine whether CBD could block the psychotic symptoms induced by Δ-9-THC. Δ-9-THC and CBD had opposite effects on activation relative to placebo in the striatum during verbal recall, in the hippocampus during the response inhibition task, in the amygdala when subjects viewed fearful faces, in the superior temporal cortex when subjects listened to speech, and in the occipital cortex during visual processing. In the second experiment, pretreatment with CBD prevented the acute induction of psychotic symptoms by Δ-9-tetrahydrocannabinol. Δ-9-THC and CBD can have opposite effects on regional brain function, which may underlie their different symptomatic and behavioral effects, and CBD's ability to block the psychotogenic effects of Δ-9-THC.",

author = "Sagnik Bhattacharyya and Morrison, \{Paul D.\} and Paolo Fusar-Poli and Rocio Martin-Santos and Stefan Borgwardt and Toby Winton-Brown and Chiara Nosarti and O'Carroll, \{Colin M.\} and Marc Seal and Paul Allen and Mehta, \{Mitul A.\} and Stone, \{James M.\} and Nigel Tunstall and Vincent Giampietro and Shitij Kapur and Murray, \{Robin M.\} and Zuardi, \{Antonio W.\} and Crippa, \{Jos{\'e} A.\} and Zerrin Atakan and McGuire, \{Philip K.\}",

note = "Funding Information: This work was supported by a grant from the Psychiatry Research Trust, UK. Sagnik Bhattacharyya is supported by a Joint MRC/Priory Clinical research training fellowship from the Medical Research Council, UK. Paul Morrison is supported by the Medical Research Council, UK, the Biomedial Research Centre and the Beckley Foundation. Jose A Crippa is the recipient of a Conselho Nacional de Desenvolvimento Cient{\'i}fico e Tecnol{\'o}gico (CNPq, Brazil) Productivity fellowship. We thank Glynis Ivin for help with the blinding procedure, storage and dispensing of the drugs. We thank Dr Katya Rubia and Dr Simon Surguladze for allowing us to use the fearful faces and the response inhibition paradigms, respectively.",

year = "2010",

month = feb,

doi = "10.1038/npp.2009.184",

language = "English",

volume = "35",

pages = "764--774",

journal = "Neuropsychopharmacology",

issn = "0893-133X",

publisher = "Springer Nature",

number = "3",

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Bhattacharyya, S, Morrison, PD, Fusar-Poli, P, Martin-Santos, R, Borgwardt, S, Winton-Brown, T, Nosarti, C, O'Carroll, CM, Seal, M, Allen, P, Mehta, MA, Stone, JM, Tunstall, N, Giampietro, V, Kapur, S, Murray, RM, Zuardi, AW, Crippa, JA, Atakan, Z & McGuire, PK 2010, 'Opposite effects of δ-9-tetrahydrocannabinol and cannabidiol on human brain function and psychopathology', Neuropsychopharmacology, vol. 35, no. 3, pp. 764-774. https://doi.org/10.1038/npp.2009.184

TY - JOUR

T1 - Opposite effects of δ-9-tetrahydrocannabinol and cannabidiol on human brain function and psychopathology

AU - Bhattacharyya, Sagnik

AU - Morrison, Paul D.

AU - Fusar-Poli, Paolo

AU - Martin-Santos, Rocio

AU - Borgwardt, Stefan

AU - Winton-Brown, Toby

AU - Nosarti, Chiara

AU - O'Carroll, Colin M.

AU - Seal, Marc

AU - Allen, Paul

AU - Mehta, Mitul A.

AU - Stone, James M.

AU - Tunstall, Nigel

AU - Giampietro, Vincent

AU - Kapur, Shitij

AU - Murray, Robin M.

AU - Zuardi, Antonio W.

AU - Crippa, José A.

AU - Atakan, Zerrin

AU - McGuire, Philip K.

N1 - Funding Information: This work was supported by a grant from the Psychiatry Research Trust, UK. Sagnik Bhattacharyya is supported by a Joint MRC/Priory Clinical research training fellowship from the Medical Research Council, UK. Paul Morrison is supported by the Medical Research Council, UK, the Biomedial Research Centre and the Beckley Foundation. Jose A Crippa is the recipient of a Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq, Brazil) Productivity fellowship. We thank Glynis Ivin for help with the blinding procedure, storage and dispensing of the drugs. We thank Dr Katya Rubia and Dr Simon Surguladze for allowing us to use the fearful faces and the response inhibition paradigms, respectively.

PY - 2010/2

Y1 - 2010/2

N2 - Δ-9-tetrahydrocannabinol (Δ-9-THC) and Cannabidiol (CBD), the two main ingredients of the Cannabis sativa plant have distinct symptomatic and behavioral effects. We used functional magnetic resonance imaging (fMRI) in healthy volunteers to examine whether Δ-9-THC and CBD had opposite effects on regional brain function. We then assessed whether pretreatment with CBD can prevent the acute psychotic symptoms induced by Δ-9-THC. Fifteen healthy men with minimal earlier exposure to cannabis were scanned while performing a verbal memory task, a response inhibition task, a sensory processing task, and when viewing fearful faces. Subjects were scanned on three occasions, each preceded by oral administration of Δ-9-THC, CBD, or placebo. BOLD responses were measured using fMRI. In a second experiment, six healthy volunteers were administered Δ-9-THC intravenously on two occasions, after placebo or CBD pretreatment to examine whether CBD could block the psychotic symptoms induced by Δ-9-THC. Δ-9-THC and CBD had opposite effects on activation relative to placebo in the striatum during verbal recall, in the hippocampus during the response inhibition task, in the amygdala when subjects viewed fearful faces, in the superior temporal cortex when subjects listened to speech, and in the occipital cortex during visual processing. In the second experiment, pretreatment with CBD prevented the acute induction of psychotic symptoms by Δ-9-tetrahydrocannabinol. Δ-9-THC and CBD can have opposite effects on regional brain function, which may underlie their different symptomatic and behavioral effects, and CBD's ability to block the psychotogenic effects of Δ-9-THC.

AB - Δ-9-tetrahydrocannabinol (Δ-9-THC) and Cannabidiol (CBD), the two main ingredients of the Cannabis sativa plant have distinct symptomatic and behavioral effects. We used functional magnetic resonance imaging (fMRI) in healthy volunteers to examine whether Δ-9-THC and CBD had opposite effects on regional brain function. We then assessed whether pretreatment with CBD can prevent the acute psychotic symptoms induced by Δ-9-THC. Fifteen healthy men with minimal earlier exposure to cannabis were scanned while performing a verbal memory task, a response inhibition task, a sensory processing task, and when viewing fearful faces. Subjects were scanned on three occasions, each preceded by oral administration of Δ-9-THC, CBD, or placebo. BOLD responses were measured using fMRI. In a second experiment, six healthy volunteers were administered Δ-9-THC intravenously on two occasions, after placebo or CBD pretreatment to examine whether CBD could block the psychotic symptoms induced by Δ-9-THC. Δ-9-THC and CBD had opposite effects on activation relative to placebo in the striatum during verbal recall, in the hippocampus during the response inhibition task, in the amygdala when subjects viewed fearful faces, in the superior temporal cortex when subjects listened to speech, and in the occipital cortex during visual processing. In the second experiment, pretreatment with CBD prevented the acute induction of psychotic symptoms by Δ-9-tetrahydrocannabinol. Δ-9-THC and CBD can have opposite effects on regional brain function, which may underlie their different symptomatic and behavioral effects, and CBD's ability to block the psychotogenic effects of Δ-9-THC.

UR - https://www.scopus.com/pages/publications/75749126485

U2 - 10.1038/npp.2009.184

DO - 10.1038/npp.2009.184

M3 - Journal articles

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AN - SCOPUS:75749126485

SN - 0893-133X

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SP - 764

EP - 774

JO - Neuropsychopharmacology

JF - Neuropsychopharmacology

IS - 3

ER -

Opposite effects of δ-9-tetrahydrocannabinol and cannabidiol on human brain function and psychopathology

Abstract

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