Increased hippocampal engagement during learning as a marker of sensitivity to psychotomimetic effects of delta-9-THC

Sagnik Bhattacharyva; Thomas Sainsbury; Chiara Nosarti; Paul Allen; Z. Atakan; Vincent Giampietro; Michael J. Brammer; Philip McGuire

doi:10.1017/S0033291718000387

Increased hippocampal engagement during learning as a marker of sensitivity to psychotomimetic effects of delta-9-THC

Sagnik Bhattacharyva, Thomas Sainsbury, Chiara Nosarti, Paul Allen, Z. Atakan, Vincent Giampietro, Michael J. Brammer, Philip McGuire

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Abstract

Background: Cannabis and its main psychoactive ingredient delta-9- tetrahydrocannibidiol (THC), can induce transient psychotic symptoms in healthy individuals and exacerbate them in those with established psychosis. However, not everyone experiences these effects, suggesting that certain individuals are particularly susceptible. The neural basis of this sensitivity to the psychotomimetic effects of THC is unclear.Methods: We investigated whether individuals who are sensitive to the psychotomimetic effects of THC (TP) under experimental conditions would show differential hippocampal activation compared to those who are not (NP). We studied 36 healthy males under identical conditions under the influence of placebo or THC (10 mg) given orally, on two separate occasions, in a pseudo-randomised, double-blind, repeated measures, within-subject, cross-over design, using psychopathological assessments and functional MRI while they performed a verbal learning task. They were classified into those who experienced transient psychotic symptoms (TP; n=14) following THC administration and those who did not (NP; n=22). Results: Under placebo conditions, there was significantly greater engagement of the left hippocampus (p<0.001) in the TP group compared to the NP group during verbal encoding, which survived leave-one-out analysis. The level of hippocampal activation was directly correlated (spearman's rho= 0.44, p=0.008) with the severity of transient psychotic symptoms induced by THC. This difference was not present when we compared two subgroups from the same sample that were defined by sensitivity to anxiogenic effects of THC. Conclusions: These results suggest that altered hippocampal activation during verbalencoding may serve as a marker of sensitivity to the acute psychotomimetic effects ofTHC. © 2018, Cambridge University Press. This is an author produced version of a paper published in PSYCHOLOGICAL MEDICINE uploaded in accordance with the publisher’s self- archiving policy. The final published version (version of record) is available online at the link. Some minor differences between this version and the final published version may remain. We suggest you refer to the final published version should you wish to cite from it.

Original language	English
Pages (from-to)	2748-2756
Journal	Psychological Medicine
DOIs	https://doi.org/10.1017/S0033291718000387
Publication status	Published - 5 Mar 2018

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Cite this

@article{e2e05d3e86834748bd2b5c6659ff5fa2,

title = "Increased hippocampal engagement during learning as a marker of sensitivity to psychotomimetic effects of delta-9-THC",

abstract = "Background: Cannabis and its main psychoactive ingredient delta-9- tetrahydrocannibidiol (THC), can induce transient psychotic symptoms in healthy individuals and exacerbate them in those with established psychosis. However, not everyone experiences these effects, suggesting that certain individuals are particularly susceptible. The neural basis of this sensitivity to the psychotomimetic effects of THC is unclear.Methods: We investigated whether individuals who are sensitive to the psychotomimetic effects of THC (TP) under experimental conditions would show differential hippocampal activation compared to those who are not (NP). We studied 36 healthy males under identical conditions under the influence of placebo or THC (10 mg) given orally, on two separate occasions, in a pseudo-randomised, double-blind, repeated measures, within-subject, cross-over design, using psychopathological assessments and functional MRI while they performed a verbal learning task. They were classified into those who experienced transient psychotic symptoms (TP; n=14) following THC administration and those who did not (NP; n=22). Results: Under placebo conditions, there was significantly greater engagement of the left hippocampus (p<0.001) in the TP group compared to the NP group during verbal encoding, which survived leave-one-out analysis. The level of hippocampal activation was directly correlated (spearman's rho= 0.44, p=0.008) with the severity of transient psychotic symptoms induced by THC. This difference was not present when we compared two subgroups from the same sample that were defined by sensitivity to anxiogenic effects of THC. Conclusions: These results suggest that altered hippocampal activation during verbalencoding may serve as a marker of sensitivity to the acute psychotomimetic effects ofTHC. {\textcopyright} 2018, Cambridge University Press. This is an author produced version of a paper published in PSYCHOLOGICAL MEDICINE uploaded in accordance with the publisher{\textquoteright}s self- archiving policy. The final published version (version of record) is available online at the link. Some minor differences between this version and the final published version may remain. We suggest you refer to the final published version should you wish to cite from it.",

author = "Sagnik Bhattacharyva and Thomas Sainsbury and Chiara Nosarti and Paul Allen and Z. Atakan and Vincent Giampietro and Brammer, {Michael J.} and Philip McGuire",

year = "2018",

month = mar,

day = "5",

doi = "10.1017/S0033291718000387",

language = "English",

pages = "2748--2756",

journal = "Psychological Medicine",

issn = "0033-2917",

publisher = "Cambridge University Press",

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TY - JOUR

T1 - Increased hippocampal engagement during learning as a marker of sensitivity to psychotomimetic effects of delta-9-THC

AU - Bhattacharyva, Sagnik

AU - Sainsbury, Thomas

AU - Nosarti, Chiara

AU - Allen, Paul

AU - Atakan, Z.

AU - Giampietro, Vincent

AU - Brammer, Michael J.

AU - McGuire, Philip

PY - 2018/3/5

Y1 - 2018/3/5

N2 - Background: Cannabis and its main psychoactive ingredient delta-9- tetrahydrocannibidiol (THC), can induce transient psychotic symptoms in healthy individuals and exacerbate them in those with established psychosis. However, not everyone experiences these effects, suggesting that certain individuals are particularly susceptible. The neural basis of this sensitivity to the psychotomimetic effects of THC is unclear.Methods: We investigated whether individuals who are sensitive to the psychotomimetic effects of THC (TP) under experimental conditions would show differential hippocampal activation compared to those who are not (NP). We studied 36 healthy males under identical conditions under the influence of placebo or THC (10 mg) given orally, on two separate occasions, in a pseudo-randomised, double-blind, repeated measures, within-subject, cross-over design, using psychopathological assessments and functional MRI while they performed a verbal learning task. They were classified into those who experienced transient psychotic symptoms (TP; n=14) following THC administration and those who did not (NP; n=22). Results: Under placebo conditions, there was significantly greater engagement of the left hippocampus (p<0.001) in the TP group compared to the NP group during verbal encoding, which survived leave-one-out analysis. The level of hippocampal activation was directly correlated (spearman's rho= 0.44, p=0.008) with the severity of transient psychotic symptoms induced by THC. This difference was not present when we compared two subgroups from the same sample that were defined by sensitivity to anxiogenic effects of THC. Conclusions: These results suggest that altered hippocampal activation during verbalencoding may serve as a marker of sensitivity to the acute psychotomimetic effects ofTHC. © 2018, Cambridge University Press. This is an author produced version of a paper published in PSYCHOLOGICAL MEDICINE uploaded in accordance with the publisher’s self- archiving policy. The final published version (version of record) is available online at the link. Some minor differences between this version and the final published version may remain. We suggest you refer to the final published version should you wish to cite from it.

AB - Background: Cannabis and its main psychoactive ingredient delta-9- tetrahydrocannibidiol (THC), can induce transient psychotic symptoms in healthy individuals and exacerbate them in those with established psychosis. However, not everyone experiences these effects, suggesting that certain individuals are particularly susceptible. The neural basis of this sensitivity to the psychotomimetic effects of THC is unclear.Methods: We investigated whether individuals who are sensitive to the psychotomimetic effects of THC (TP) under experimental conditions would show differential hippocampal activation compared to those who are not (NP). We studied 36 healthy males under identical conditions under the influence of placebo or THC (10 mg) given orally, on two separate occasions, in a pseudo-randomised, double-blind, repeated measures, within-subject, cross-over design, using psychopathological assessments and functional MRI while they performed a verbal learning task. They were classified into those who experienced transient psychotic symptoms (TP; n=14) following THC administration and those who did not (NP; n=22). Results: Under placebo conditions, there was significantly greater engagement of the left hippocampus (p<0.001) in the TP group compared to the NP group during verbal encoding, which survived leave-one-out analysis. The level of hippocampal activation was directly correlated (spearman's rho= 0.44, p=0.008) with the severity of transient psychotic symptoms induced by THC. This difference was not present when we compared two subgroups from the same sample that were defined by sensitivity to anxiogenic effects of THC. Conclusions: These results suggest that altered hippocampal activation during verbalencoding may serve as a marker of sensitivity to the acute psychotomimetic effects ofTHC. © 2018, Cambridge University Press. This is an author produced version of a paper published in PSYCHOLOGICAL MEDICINE uploaded in accordance with the publisher’s self- archiving policy. The final published version (version of record) is available online at the link. Some minor differences between this version and the final published version may remain. We suggest you refer to the final published version should you wish to cite from it.

U2 - 10.1017/S0033291718000387

DO - 10.1017/S0033291718000387

M3 - Article

SN - 0033-2917

SP - 2748

EP - 2756

JO - Psychological Medicine

JF - Psychological Medicine

ER -