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Modulation of mediotemporal and ventrostriatal function in humans by Delta9-tetrahydrocannabinol: a neural basis for the effects of Cannabis sativa on learning and psychosis.

Abstract

CONTEXT

Cannabis sativa use can impair verbal learning, provoke acute psychosis, and increase the risk of schizophrenia. It is unclear where C. sativa acts in the human brain to modulate verbal learning and to induce psychotic symptoms.

OBJECTIVES

To investigate the effects of 2 main psychoactive constituents of C. sativa, Delta9-tetrahydrocannabinol (Delta9-THC) and cannabidiol, on regional brain function during verbal paired associate learning.

DESIGN

Subjects were studied on 3 separate occasions using a block design functional magnetic resonance imaging paradigm while performing a verbal paired associate learning task. Each imaging session was preceded by the ingestion of Delta9-THC (10 mg), cannabidiol (600 mg), or placebo in a double-blind, randomized, placebo-controlled, repeated-measures, within-subject design.

SETTING

University research center.

PARTICIPANTS

Fifteen healthy, native English-speaking, right-handed men of white race/ethnicity who had used C. sativa 15 times or less and had minimal exposure to other illicit drugs in their lifetime.

MAIN OUTCOME MEASURES

Regional brain activation (blood oxygen level-dependent response), performance in a verbal learning task, and objective and subjective ratings of psychotic symptoms, anxiety, intoxication, and sedation.

RESULTS

Delta9-Tetrahydrocannabinol increased psychotic symptoms and levels of anxiety, intoxication, and sedation, whereas no significant effect was noted on these parameters following administration of cannabidiol. Performance in the verbal learning task was not significantly modulated by either drug. Administration of Delta9-THC augmented activation in the parahippocampal gyrus during blocks 2 and 3 such that the normal linear decrement in activation across repeated encoding blocks was no longer evident. Delta9-Tetrahydrocannabinol also attenuated the normal time-dependent change in ventrostriatal activation during retrieval of word pairs, which was directly correlated with concurrently induced psychotic symptoms. In contrast, administration of cannabidiol had no such effect.

CONCLUSION

The modulation of mediotemporal and ventrostriatal function by Delta9-THC may underlie the effects of C. sativa on verbal learning and psychotic symptoms, respectively.

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  • Authors+Show Affiliations

    ,

    Section of Neuroimaging, Division of Psychological Medicine and Psychiatry, Institute of Psychiatry, King's College London, Box P067, De Crespigny Park, London SE5 8AF, England. s.bhattacharyya@iop.kcl.ac.uk

    , , , , , , , , , , , ,

    Source

    Archives of general psychiatry 66:4 2009 Apr pg 442-51

    MeSH

    Administration, Oral
    Adult
    Arousal
    Attention
    Cannabidiol
    Cannabis
    Corpus Striatum
    Double-Blind Method
    Dronabinol
    Humans
    Image Processing, Computer-Assisted
    Magnetic Resonance Imaging
    Male
    Mental Recall
    Oxygen
    Paired-Associate Learning
    Parahippocampal Gyrus
    Psychoses, Substance-Induced
    Temporal Lobe

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    19349314

    Citation

    Bhattacharyya, Sagnik, et al. "Modulation of Mediotemporal and Ventrostriatal Function in Humans By Delta9-tetrahydrocannabinol: a Neural Basis for the Effects of Cannabis Sativa On Learning and Psychosis." Archives of General Psychiatry, vol. 66, no. 4, 2009, pp. 442-51.
    Bhattacharyya S, Fusar-Poli P, Borgwardt S, et al. Modulation of mediotemporal and ventrostriatal function in humans by Delta9-tetrahydrocannabinol: a neural basis for the effects of Cannabis sativa on learning and psychosis. Arch Gen Psychiatry. 2009;66(4):442-51.
    Bhattacharyya, S., Fusar-Poli, P., Borgwardt, S., Martin-Santos, R., Nosarti, C., O'Carroll, C., ... McGuire, P. (2009). Modulation of mediotemporal and ventrostriatal function in humans by Delta9-tetrahydrocannabinol: a neural basis for the effects of Cannabis sativa on learning and psychosis. Archives of General Psychiatry, 66(4), pp. 442-51. doi:10.1001/archgenpsychiatry.2009.17.
    Bhattacharyya S, et al. Modulation of Mediotemporal and Ventrostriatal Function in Humans By Delta9-tetrahydrocannabinol: a Neural Basis for the Effects of Cannabis Sativa On Learning and Psychosis. Arch Gen Psychiatry. 2009;66(4):442-51. PubMed PMID: 19349314.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Modulation of mediotemporal and ventrostriatal function in humans by Delta9-tetrahydrocannabinol: a neural basis for the effects of Cannabis sativa on learning and psychosis. AU - Bhattacharyya,Sagnik, AU - Fusar-Poli,Paolo, AU - Borgwardt,Stefan, AU - Martin-Santos,Rocio, AU - Nosarti,Chiara, AU - O'Carroll,Colin, AU - Allen,Paul, AU - Seal,Marc L, AU - Fletcher,Paul C, AU - Crippa,José A, AU - Giampietro,Vincent, AU - Mechelli,Andrea, AU - Atakan,Zerrin, AU - McGuire,Philip, PY - 2009/4/8/entrez PY - 2009/4/8/pubmed PY - 2009/4/23/medline SP - 442 EP - 51 JF - Archives of general psychiatry JO - Arch. Gen. Psychiatry VL - 66 IS - 4 N2 - CONTEXT: Cannabis sativa use can impair verbal learning, provoke acute psychosis, and increase the risk of schizophrenia. It is unclear where C. sativa acts in the human brain to modulate verbal learning and to induce psychotic symptoms. OBJECTIVES: To investigate the effects of 2 main psychoactive constituents of C. sativa, Delta9-tetrahydrocannabinol (Delta9-THC) and cannabidiol, on regional brain function during verbal paired associate learning. DESIGN: Subjects were studied on 3 separate occasions using a block design functional magnetic resonance imaging paradigm while performing a verbal paired associate learning task. Each imaging session was preceded by the ingestion of Delta9-THC (10 mg), cannabidiol (600 mg), or placebo in a double-blind, randomized, placebo-controlled, repeated-measures, within-subject design. SETTING: University research center. PARTICIPANTS: Fifteen healthy, native English-speaking, right-handed men of white race/ethnicity who had used C. sativa 15 times or less and had minimal exposure to other illicit drugs in their lifetime. MAIN OUTCOME MEASURES: Regional brain activation (blood oxygen level-dependent response), performance in a verbal learning task, and objective and subjective ratings of psychotic symptoms, anxiety, intoxication, and sedation. RESULTS: Delta9-Tetrahydrocannabinol increased psychotic symptoms and levels of anxiety, intoxication, and sedation, whereas no significant effect was noted on these parameters following administration of cannabidiol. Performance in the verbal learning task was not significantly modulated by either drug. Administration of Delta9-THC augmented activation in the parahippocampal gyrus during blocks 2 and 3 such that the normal linear decrement in activation across repeated encoding blocks was no longer evident. Delta9-Tetrahydrocannabinol also attenuated the normal time-dependent change in ventrostriatal activation during retrieval of word pairs, which was directly correlated with concurrently induced psychotic symptoms. In contrast, administration of cannabidiol had no such effect. CONCLUSION: The modulation of mediotemporal and ventrostriatal function by Delta9-THC may underlie the effects of C. sativa on verbal learning and psychotic symptoms, respectively. SN - 1538-3636 UR - https://www.unboundmedicine.com/medline/citation/19349314/Modulation_of_mediotemporal_and_ventrostriatal_function_in_humans_by_Delta9_tetrahydrocannabinol:_a_neural_basis_for_the_effects_of_Cannabis_sativa_on_learning_and_psychosis_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=19349314.ui DB - PRIME DP - Unbound Medicine ER -