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Induction of psychosis by Δ9-tetrahydrocannabinol reflects modulation of prefrontal and striatal function during attentional salience processing.
Arch Gen Psychiatry 2012; 69(1):27-36AG

Abstract

CONTEXT

The aberrant processing of salience is thought to be a fundamental factor underlying psychosis. Cannabis can induce acute psychotic symptoms, and its chronic use may increase the risk of schizophrenia. We investigated whether its psychotic effects are mediated through an influence on attentional salience processing.

OBJECTIVE

To examine the effects of Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) on regional brain function during salience processing.

DESIGN

Volunteers were studied using event-related functional magnetic resonance imaging on 3 occasions after administration of Δ9-THC, CBD, or placebo while performing a visual oddball detection paradigm that involved allocation of attention to infrequent (oddball) stimuli within a string of frequent (standard) stimuli.

SETTING

University center.

PARTICIPANTS

Fifteen healthy men with minimal previous cannabis use.

MAIN OUTCOME MEASURES

Symptom ratings, task performance, and regional brain activation.

RESULTS

During the processing of oddball stimuli, relative to placebo, Δ9-THC attenuated activation in the right caudate but augmented it in the right prefrontal cortex. Δ9-Tetrahydrocannabinol also reduced the response latency to standard relative to oddball stimuli. The effect of Δ9-THC in the right caudate was negatively correlated with the severity of the psychotic symptoms it induced and its effect on response latency. The effects of CBD on task-related activation were in the opposite direction of those of Δ9-THC; relative to placebo, CBD augmented left caudate and hippocampal activation but attenuated right prefrontal activation.

CONCLUSIONS

Δ9-Tetrahydrocannabinol and CBD differentially modulate prefrontal, striatal, and hippocampal function during attentional salience processing. These effects may contribute to the effects of cannabis on psychotic symptoms and on the risk of psychotic disorders.

Authors+Show Affiliations

Department of Psychosis Studies, Institute of Psychiatry, King's College London, De Crespigny Park, London, England. sagnik.2.bhattacharyya@kcl.ac.ukNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22213786

Citation

Bhattacharyya, Sagnik, et al. "Induction of Psychosis By Δ9-tetrahydrocannabinol Reflects Modulation of Prefrontal and Striatal Function During Attentional Salience Processing." Archives of General Psychiatry, vol. 69, no. 1, 2012, pp. 27-36.
Bhattacharyya S, Crippa JA, Allen P, et al. Induction of psychosis by Δ9-tetrahydrocannabinol reflects modulation of prefrontal and striatal function during attentional salience processing. Arch Gen Psychiatry. 2012;69(1):27-36.
Bhattacharyya, S., Crippa, J. A., Allen, P., Martin-Santos, R., Borgwardt, S., Fusar-Poli, P., ... McGuire, P. K. (2012). Induction of psychosis by Δ9-tetrahydrocannabinol reflects modulation of prefrontal and striatal function during attentional salience processing. Archives of General Psychiatry, 69(1), pp. 27-36. doi:10.1001/archgenpsychiatry.2011.161.
Bhattacharyya S, et al. Induction of Psychosis By Δ9-tetrahydrocannabinol Reflects Modulation of Prefrontal and Striatal Function During Attentional Salience Processing. Arch Gen Psychiatry. 2012;69(1):27-36. PubMed PMID: 22213786.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Induction of psychosis by Δ9-tetrahydrocannabinol reflects modulation of prefrontal and striatal function during attentional salience processing. AU - Bhattacharyya,Sagnik, AU - Crippa,José Alexandre, AU - Allen,Paul, AU - Martin-Santos,Rocio, AU - Borgwardt,Stefan, AU - Fusar-Poli,Paolo, AU - Rubia,Katya, AU - Kambeitz,Joseph, AU - O'Carroll,Colin, AU - Seal,Marc L, AU - Giampietro,Vincent, AU - Brammer,Michael, AU - Zuardi,Antonio Waldo, AU - Atakan,Zerrin, AU - McGuire,Philip K, PY - 2012/1/4/entrez PY - 2012/1/4/pubmed PY - 2012/2/23/medline SP - 27 EP - 36 JF - Archives of general psychiatry JO - Arch. Gen. Psychiatry VL - 69 IS - 1 N2 - CONTEXT: The aberrant processing of salience is thought to be a fundamental factor underlying psychosis. Cannabis can induce acute psychotic symptoms, and its chronic use may increase the risk of schizophrenia. We investigated whether its psychotic effects are mediated through an influence on attentional salience processing. OBJECTIVE: To examine the effects of Δ9-tetrahydrocannabinol (Δ9-THC) and cannabidiol (CBD) on regional brain function during salience processing. DESIGN: Volunteers were studied using event-related functional magnetic resonance imaging on 3 occasions after administration of Δ9-THC, CBD, or placebo while performing a visual oddball detection paradigm that involved allocation of attention to infrequent (oddball) stimuli within a string of frequent (standard) stimuli. SETTING: University center. PARTICIPANTS: Fifteen healthy men with minimal previous cannabis use. MAIN OUTCOME MEASURES: Symptom ratings, task performance, and regional brain activation. RESULTS: During the processing of oddball stimuli, relative to placebo, Δ9-THC attenuated activation in the right caudate but augmented it in the right prefrontal cortex. Δ9-Tetrahydrocannabinol also reduced the response latency to standard relative to oddball stimuli. The effect of Δ9-THC in the right caudate was negatively correlated with the severity of the psychotic symptoms it induced and its effect on response latency. The effects of CBD on task-related activation were in the opposite direction of those of Δ9-THC; relative to placebo, CBD augmented left caudate and hippocampal activation but attenuated right prefrontal activation. CONCLUSIONS: Δ9-Tetrahydrocannabinol and CBD differentially modulate prefrontal, striatal, and hippocampal function during attentional salience processing. These effects may contribute to the effects of cannabis on psychotic symptoms and on the risk of psychotic disorders. SN - 1538-3636 UR - https://www.unboundmedicine.com/medline/citation/22213786/Induction_of_psychosis_by_Δ9_tetrahydrocannabinol_reflects_modulation_of_prefrontal_and_striatal_function_during_attentional_salience_processing_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=22213786.ui DB - PRIME DP - Unbound Medicine ER -