Opposite Effects of Delta-9-Tetrahydrocannabinol and Cannabidiol on Human Brain Function and Psychopathology

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

doi:10.1038/npp.2009.184

Opposite Effects of Delta-9-Tetrahydrocannabinol and Cannabidiol on Human Brain Function and Psychopathology

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

Research output: Contribution to journal › Article

Abstract

Delta-9-tetrahydrocannabinol (Delta-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 Delta-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 Delta-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 Delta-9-THC, CBD, or placebo. BOLD responses were measured using fMRI. In a second experiment, six healthy volunteers were administered Delta-9-THC intravenously on two occasions, after placebo or CBD pretreatment to examine whether CBD could block the psychotic symptoms induced by Delta-9-THC. Delta-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 Delta-9-tetrahydrocannabinol. Delta-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 Delta-9-THC. Neuropsychopharmacology (2010) 35, 764-774; doi:10.1038/npp.2009.184; published online 18 November 2009

Original language	English
Pages (from-to)	764-774
Journal	NEUROPSYCHOPHARMACOLOGY
Volume	35
Issue number	3
DOIs	https://doi.org/10.1038/npp.2009.184
Publication status	Published - 2010

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10.1038/npp.2009.184

http://dx.doi.org/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., Seal, M., Mehta, M. A., Stone, J. M., Tunstall, N., Giampietro, V., Kapur, S., Murray, R. M., Zuardi, A., Crippa, J., Atakan, Z., McGuire, P., & Allen, P. (2010). Opposite Effects of Delta-9-Tetrahydrocannabinol and Cannabidiol on Human Brain Function and Psychopathology. NEUROPSYCHOPHARMACOLOGY, 35(3), 764-774. https://doi.org/10.1038/npp.2009.184

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title = "Opposite Effects of Delta-9-Tetrahydrocannabinol and Cannabidiol on Human Brain Function and Psychopathology",

abstract = "Delta-9-tetrahydrocannabinol (Delta-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 Delta-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 Delta-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 Delta-9-THC, CBD, or placebo. BOLD responses were measured using fMRI. In a second experiment, six healthy volunteers were administered Delta-9-THC intravenously on two occasions, after placebo or CBD pretreatment to examine whether CBD could block the psychotic symptoms induced by Delta-9-THC. Delta-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 Delta-9-tetrahydrocannabinol. Delta-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 Delta-9-THC. Neuropsychopharmacology (2010) 35, 764-774; doi:10.1038/npp.2009.184; published online 18 November 2009",

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

year = "2010",

doi = "10.1038/npp.2009.184",

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Bhattacharyya, S, Morrison, PD, Fusar-Poli, P, Martin-Santos, R, Borgwardt, S, Winton-Brown, T, Nosarti, C, O'Carroll, C, Seal, M, Mehta, MA, Stone, JM, Tunstall, N, Giampietro, V, Kapur, S, Murray, RM, Zuardi, A, Crippa, J, Atakan, Z, McGuire, P & Allen, P 2010, 'Opposite Effects of Delta-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

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T1 - Opposite Effects of Delta-9-Tetrahydrocannabinol and Cannabidiol on Human Brain Function and Psychopathology

AU - Bhattacharyya, S.

AU - Morrison, Paul D.

AU - Fusar-Poli, Paulo

AU - Martin-Santos, Rocio

AU - Borgwardt, Stefan

AU - Winton-Brown, Toby

AU - Nosarti, Chiara

AU - O'Carroll, Colin

AU - Seal, Marc

AU - Mehta, Mitul A.

AU - Stone, James M.

AU - Tunstall, Nigel

AU - Giampietro, Vincent

AU - Kapur, Shitij

AU - Murray, Robin M.

AU - Zuardi, Antonio

AU - Crippa, Jose

AU - Atakan, Zerrin

AU - McGuire, Philip

AU - Allen, Paul

PY - 2010

Y1 - 2010

N2 - Delta-9-tetrahydrocannabinol (Delta-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 Delta-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 Delta-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 Delta-9-THC, CBD, or placebo. BOLD responses were measured using fMRI. In a second experiment, six healthy volunteers were administered Delta-9-THC intravenously on two occasions, after placebo or CBD pretreatment to examine whether CBD could block the psychotic symptoms induced by Delta-9-THC. Delta-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 Delta-9-tetrahydrocannabinol. Delta-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 Delta-9-THC. Neuropsychopharmacology (2010) 35, 764-774; doi:10.1038/npp.2009.184; published online 18 November 2009

AB - Delta-9-tetrahydrocannabinol (Delta-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 Delta-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 Delta-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 Delta-9-THC, CBD, or placebo. BOLD responses were measured using fMRI. In a second experiment, six healthy volunteers were administered Delta-9-THC intravenously on two occasions, after placebo or CBD pretreatment to examine whether CBD could block the psychotic symptoms induced by Delta-9-THC. Delta-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 Delta-9-tetrahydrocannabinol. Delta-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 Delta-9-THC. Neuropsychopharmacology (2010) 35, 764-774; doi:10.1038/npp.2009.184; published online 18 November 2009

U2 - 10.1038/npp.2009.184

DO - 10.1038/npp.2009.184

M3 - Article

SN - 0893-133X

VL - 35

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