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Δ9-Tetrahydrocannabinol decreases willingness to exert cognitive effort in male rats.

Abstract

BACKGROUND

Acceptance of cannabis use is growing. However, prolonged use is associated with diminished psychosocial outcomes, potentially mediated by drug-induced cognitive impairments. Δ9-Tetrahydrocannabinol (THC) is the main psychoactive ingredient in cannabis, yet other phytocannabinoids in the plant, such as cannabidiol (CBD), have unique properties. Given that CBD can modulate the undesirable effects of THC, therapeutic agents, such as nabiximols, contain higher CBD:THC ratios than illicit marijuana. We tested the hypothesis that THC impairs a relevant cognitive function for long-term success, namely willingness to exert cognitive effort for greater rewards, and that CBD could attenuate such decision-making impairments.

METHODS

Male Long-Evans rats (n = 29) performing the rat cognitive effort task (rCET) received acute THC and CBD, independently and concurrently, in addition to other cannabinoids. Rats chose between 2 options differing in reward magnitude, but also in the cognitive effort (attentional load) required to obtain them.

RESULTS

We found that THC decreased choice of hard trials without impairing the animals' ability to accurately complete them. Strikingly, this impairment was correlated with CB1 receptor density in the medial prefrontal cortex - an area previously implicated in effortful decision-making. In contrast, CBD did not affect choice. Coadministration of 1:1 CBD:THC matching that in nabiximols modestly attenuated the deleterious effects of THC in "slacker" rats.

LIMITATIONS

Only male rats were investigated, and the THC/CBD coadministration experiment was carried out in a subset of individuals.

CONCLUSION

These findings confirm that THC, but not CBD, selectively impairs decision-making involving cognitive effort costs. However, coadministration of CBD only partially ameliorates such THC-induced dysfunction.

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  • Authors+Show Affiliations

    ,

    From the Department of Psychology, University of British Columbia, Vancouver, B.C. (Silveira, Adams, Winstanley); the Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, B.C. (Silveira, Adams, Winstanley); and the Hotchkiss Brain Institute, Departments of Cell Biology and Anatomy & Psychiatry, University of Calgary, Calgary, Alta. (Hill).

    ,

    From the Department of Psychology, University of British Columbia, Vancouver, B.C. (Silveira, Adams, Winstanley); the Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, B.C. (Silveira, Adams, Winstanley); and the Hotchkiss Brain Institute, Departments of Cell Biology and Anatomy & Psychiatry, University of Calgary, Calgary, Alta. (Hill).

    ,

    From the Department of Psychology, University of British Columbia, Vancouver, B.C. (Silveira, Adams, Winstanley); the Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, B.C. (Silveira, Adams, Winstanley); and the Hotchkiss Brain Institute, Departments of Cell Biology and Anatomy & Psychiatry, University of Calgary, Calgary, Alta. (Hill).

    ,

    From the Department of Psychology, University of British Columbia, Vancouver, B.C. (Silveira, Adams, Winstanley); the Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, B.C. (Silveira, Adams, Winstanley); and the Hotchkiss Brain Institute, Departments of Cell Biology and Anatomy & Psychiatry, University of Calgary, Calgary, Alta. (Hill).

    From the Department of Psychology, University of British Columbia, Vancouver, B.C. (Silveira, Adams, Winstanley); the Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, B.C. (Silveira, Adams, Winstanley); and the Hotchkiss Brain Institute, Departments of Cell Biology and Anatomy & Psychiatry, University of Calgary, Calgary, Alta. (Hill).

    Source

    MeSH

    Animals
    Attention
    Cannabidiol
    Cannabinoid Receptor Modulators
    Cognition
    Decision Making
    Dose-Response Relationship, Drug
    Dronabinol
    Male
    Motivation
    Neuropsychological Tests
    Prefrontal Cortex
    Psychotropic Drugs
    Rats, Long-Evans
    Receptor, Cannabinoid, CB1
    Receptor, Cannabinoid, CB2
    Reward

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    28245177

    Citation

    Silveira, Mason M., et al. "Δ9-Tetrahydrocannabinol Decreases Willingness to Exert Cognitive Effort in Male Rats." Journal of Psychiatry & Neuroscience : JPN, vol. 42, no. 2, 2017, pp. 131-138.
    Silveira MM, Adams WK, Morena M, et al. Δ9-Tetrahydrocannabinol decreases willingness to exert cognitive effort in male rats. J Psychiatry Neurosci. 2017;42(2):131-138.
    Silveira, M. M., Adams, W. K., Morena, M., Hill, M. N., & Winstanley, C. A. (2017). Δ9-Tetrahydrocannabinol decreases willingness to exert cognitive effort in male rats. Journal of Psychiatry & Neuroscience : JPN, 42(2), pp. 131-138.
    Silveira MM, et al. Δ9-Tetrahydrocannabinol Decreases Willingness to Exert Cognitive Effort in Male Rats. J Psychiatry Neurosci. 2017;42(2):131-138. PubMed PMID: 28245177.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Δ9-Tetrahydrocannabinol decreases willingness to exert cognitive effort in male rats. AU - Silveira,Mason M, AU - Adams,Wendy K, AU - Morena,Maria, AU - Hill,Matthew N, AU - Winstanley,Catharine A, PY - 2017/3/1/entrez PY - 2017/3/1/pubmed PY - 2018/1/9/medline SP - 131 EP - 138 JF - Journal of psychiatry & neuroscience : JPN JO - J Psychiatry Neurosci VL - 42 IS - 2 N2 - BACKGROUND: Acceptance of cannabis use is growing. However, prolonged use is associated with diminished psychosocial outcomes, potentially mediated by drug-induced cognitive impairments. Δ9-Tetrahydrocannabinol (THC) is the main psychoactive ingredient in cannabis, yet other phytocannabinoids in the plant, such as cannabidiol (CBD), have unique properties. Given that CBD can modulate the undesirable effects of THC, therapeutic agents, such as nabiximols, contain higher CBD:THC ratios than illicit marijuana. We tested the hypothesis that THC impairs a relevant cognitive function for long-term success, namely willingness to exert cognitive effort for greater rewards, and that CBD could attenuate such decision-making impairments. METHODS: Male Long-Evans rats (n = 29) performing the rat cognitive effort task (rCET) received acute THC and CBD, independently and concurrently, in addition to other cannabinoids. Rats chose between 2 options differing in reward magnitude, but also in the cognitive effort (attentional load) required to obtain them. RESULTS: We found that THC decreased choice of hard trials without impairing the animals' ability to accurately complete them. Strikingly, this impairment was correlated with CB1 receptor density in the medial prefrontal cortex - an area previously implicated in effortful decision-making. In contrast, CBD did not affect choice. Coadministration of 1:1 CBD:THC matching that in nabiximols modestly attenuated the deleterious effects of THC in "slacker" rats. LIMITATIONS: Only male rats were investigated, and the THC/CBD coadministration experiment was carried out in a subset of individuals. CONCLUSION: These findings confirm that THC, but not CBD, selectively impairs decision-making involving cognitive effort costs. However, coadministration of CBD only partially ameliorates such THC-induced dysfunction. SN - 1488-2434 UR - https://www.unboundmedicine.com/medline/citation/28245177/Δ9_Tetrahydrocannabinol_decreases_willingness_to_exert_cognitive_effort_in_male_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/10.1503/jpn.150363 DB - PRIME DP - Unbound Medicine ER -