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Distinct effects of {delta}9-tetrahydrocannabinol and cannabidiol on neural activation during emotional processing.

Abstract

CONTEXT

Cannabis use can both increase and reduce anxiety in humans. The neurophysiological substrates of these effects are unknown.

OBJECTIVE

To investigate the effects of 2 main psychoactive constituents of Cannabis sativa (Delta9-tetrahydrocannabinol [Delta9-THC] and cannabidiol [CBD]) on regional brain function during emotional processing.

DESIGN

Subjects were studied on 3 separate occasions using an event-related functional magnetic resonance imaging paradigm while viewing faces that implicitly elicited different levels of anxiety. Each scanning session was preceded by the ingestion of either 10 mg of Delta9-THC, 600 mg of CBD, or a placebo in a double-blind, randomized, placebo-controlled design.

PARTICIPANTS

Fifteen healthy, English-native, right-handed men who had used cannabis 15 times or less in their life.

MAIN OUTCOME MEASURES

Regional brain activation (blood oxygenation level-dependent response), electrodermal activity (skin conductance response [SCR]), and objective and subjective ratings of anxiety.

RESULTS

Delta9-Tetrahydrocannabinol increased anxiety, as well as levels of intoxication, sedation, and psychotic symptoms, whereas there was a trend for a reduction in anxiety following administration of CBD. The number of SCR fluctuations during the processing of intensely fearful faces increased following administration of Delta9-THC but decreased following administration of CBD. Cannabidiol attenuated the blood oxygenation level-dependent signal in the amygdala and the anterior and posterior cingulate cortex while subjects were processing intensely fearful faces, and its suppression of the amygdalar and anterior cingulate responses was correlated with the concurrent reduction in SCR fluctuations. Delta9-Tetrahydrocannabinol mainly modulated activation in frontal and parietal areas.

CONCLUSIONS

Delta9-Tetrahydrocannabinol and CBD had clearly distinct effects on the neural, electrodermal, and symptomatic response to fearful faces. The effects of CBD on activation in limbic and paralimbic regions may contribute to its ability to reduce autonomic arousal and subjective anxiety, whereas the anxiogenic effects of Delta9-THC may be related to effects in other brain regions.

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  • Authors+Show Affiliations

    ,

    Neuroimaging Section, Division of Psychological Medicine, PO67, Institute of Psychiatry, London SE58AF, England. p.fusar@libero.it

    , , , , , , , , , ,

    Source

    Archives of general psychiatry 66:1 2009 Jan pg 95-105

    MeSH

    Adult
    Amygdala
    Anxiety
    Arousal
    Brain
    Cannabidiol
    Double-Blind Method
    Dronabinol
    Emotions
    Facial Expression
    Fear
    Frontal Lobe
    Galvanic Skin Response
    Gyrus Cinguli
    Humans
    Image Processing, Computer-Assisted
    Magnetic Resonance Imaging
    Male
    Oxygen
    Parahippocampal Gyrus
    Parietal Lobe
    Pattern Recognition, Visual
    Psychiatric Status Rating Scales
    Psychoses, Substance-Induced
    Psychotropic Drugs
    Young Adult

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    19124693

    Citation

    Fusar-Poli, Paolo, et al. "Distinct Effects of {delta}9-tetrahydrocannabinol and Cannabidiol On Neural Activation During Emotional Processing." Archives of General Psychiatry, vol. 66, no. 1, 2009, pp. 95-105.
    Fusar-Poli P, Crippa JA, Bhattacharyya S, et al. Distinct effects of {delta}9-tetrahydrocannabinol and cannabidiol on neural activation during emotional processing. Arch Gen Psychiatry. 2009;66(1):95-105.
    Fusar-Poli, P., Crippa, J. A., Bhattacharyya, S., Borgwardt, S. J., Allen, P., Martin-Santos, R., ... McGuire, P. K. (2009). Distinct effects of {delta}9-tetrahydrocannabinol and cannabidiol on neural activation during emotional processing. Archives of General Psychiatry, 66(1), pp. 95-105. doi:10.1001/archgenpsychiatry.2008.519.
    Fusar-Poli P, et al. Distinct Effects of {delta}9-tetrahydrocannabinol and Cannabidiol On Neural Activation During Emotional Processing. Arch Gen Psychiatry. 2009;66(1):95-105. PubMed PMID: 19124693.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Distinct effects of {delta}9-tetrahydrocannabinol and cannabidiol on neural activation during emotional processing. AU - Fusar-Poli,Paolo, AU - Crippa,José A, AU - Bhattacharyya,Sagnik, AU - Borgwardt,Stefan J, AU - Allen,Paul, AU - Martin-Santos,Rocio, AU - Seal,Marc, AU - Surguladze,Simon A, AU - O'Carrol,Colin, AU - Atakan,Zerrin, AU - Zuardi,Antonio W, AU - McGuire,Philip K, PY - 2009/1/7/entrez PY - 2009/1/7/pubmed PY - 2009/1/17/medline SP - 95 EP - 105 JF - Archives of general psychiatry JO - Arch. Gen. Psychiatry VL - 66 IS - 1 N2 - CONTEXT: Cannabis use can both increase and reduce anxiety in humans. The neurophysiological substrates of these effects are unknown. OBJECTIVE: To investigate the effects of 2 main psychoactive constituents of Cannabis sativa (Delta9-tetrahydrocannabinol [Delta9-THC] and cannabidiol [CBD]) on regional brain function during emotional processing. DESIGN: Subjects were studied on 3 separate occasions using an event-related functional magnetic resonance imaging paradigm while viewing faces that implicitly elicited different levels of anxiety. Each scanning session was preceded by the ingestion of either 10 mg of Delta9-THC, 600 mg of CBD, or a placebo in a double-blind, randomized, placebo-controlled design. PARTICIPANTS: Fifteen healthy, English-native, right-handed men who had used cannabis 15 times or less in their life. MAIN OUTCOME MEASURES: Regional brain activation (blood oxygenation level-dependent response), electrodermal activity (skin conductance response [SCR]), and objective and subjective ratings of anxiety. RESULTS: Delta9-Tetrahydrocannabinol increased anxiety, as well as levels of intoxication, sedation, and psychotic symptoms, whereas there was a trend for a reduction in anxiety following administration of CBD. The number of SCR fluctuations during the processing of intensely fearful faces increased following administration of Delta9-THC but decreased following administration of CBD. Cannabidiol attenuated the blood oxygenation level-dependent signal in the amygdala and the anterior and posterior cingulate cortex while subjects were processing intensely fearful faces, and its suppression of the amygdalar and anterior cingulate responses was correlated with the concurrent reduction in SCR fluctuations. Delta9-Tetrahydrocannabinol mainly modulated activation in frontal and parietal areas. CONCLUSIONS: Delta9-Tetrahydrocannabinol and CBD had clearly distinct effects on the neural, electrodermal, and symptomatic response to fearful faces. The effects of CBD on activation in limbic and paralimbic regions may contribute to its ability to reduce autonomic arousal and subjective anxiety, whereas the anxiogenic effects of Delta9-THC may be related to effects in other brain regions. SN - 1538-3636 UR - https://www.unboundmedicine.com/medline/citation/19124693/Distinct_effects_of_{delta}9_tetrahydrocannabinol_and_cannabidiol_on_neural_activation_during_emotional_processing_ L2 - http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=linkout&SEARCH=19124693.ui DB - PRIME DP - Unbound Medicine ER -