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      Acute and chronic effects of cannabinoids on effort-related decision-making and reward learning: an evaluation of the cannabis ‘amotivational’ hypotheses

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          Abstract

          Rationale

          Anecdotally, both acute and chronic cannabis use have been associated with apathy, amotivation, and other reward processing deficits. To date, empirical support for these effects is limited, and no previous studies have assessed both acute effects of Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), as well as associations with cannabis dependence.

          Objectives

          The objectives of this study were (1) to examine acute effects of cannabis with CBD (Cann + CBD) and without CBD (Cann-CBD) on effort-related decision-making and (2) to examine associations between cannabis dependence, effort-related decision-making and reward learning.

          Methods

          In study 1, 17 participants each received three acute vaporized treatments, namely Cann-CBD (8 mg THC), Cann + CBD (8 mg THC + 10 mg CBD) and matched placebo, followed by a 50 % dose top-up 1.5 h later, and completed the Effort Expenditure for Rewards Task (EEfRT). In study 2, 20 cannabis-dependent participants were compared with 20 non-dependent, drug-using control participants on the EEfRT and the Probabilistic Reward Task (PRT) in a non-intoxicated state.

          Results

          Cann-CBD reduced the likelihood of high-effort choices relative to placebo ( p = 0.042) and increased sensitivity to expected value compared to both placebo ( p = 0.014) and Cann + CBD ( p = 0.006). The cannabis-dependent and control groups did not differ on the EEfRT. However, the cannabis-dependent group exhibited a weaker response bias than the control group on the PRT ( p = 0.007).

          Conclusions

          Cannabis acutely induced a transient amotivational state and CBD influenced the effects of THC on expected value. In contrast, cannabis dependence was associated with preserved motivation alongside impaired reward learning, although confounding factors, including depression, cannot be disregarded. This is the first well powered, fully controlled study to objectively demonstrate the acute amotivational effects of THC.

          Electronic supplementary material

          The online version of this article (doi:10.1007/s00213-016-4383-x) contains supplementary material, which is available to authorized users.

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          Most cited references82

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          Dysfunction of the prefrontal cortex in addiction: neuroimaging findings and clinical implications.

          The loss of control over drug intake that occurs in addiction was initially believed to result from disruption of subcortical reward circuits. However, imaging studies in addictive behaviours have identified a key involvement of the prefrontal cortex (PFC) both through its regulation of limbic reward regions and its involvement in higher-order executive function (for example, self-control, salience attribution and awareness). This Review focuses on functional neuroimaging studies conducted in the past decade that have expanded our understanding of the involvement of the PFC in drug addiction. Disruption of the PFC in addiction underlies not only compulsive drug taking but also accounts for the disadvantageous behaviours that are associated with addiction and the erosion of free will.
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            Comparison of Beck Depression Inventories -IA and -II in psychiatric outpatients.

            The amended (revised) Beck Depression Inventory (BDI-IA; Beck & Steer, 1993b) and the Beck Depression Inventory-II (BDI-II; Beck, Steer, & Brown, 1996) were self-administered to 140 psychiatric outpatients with various psychiatric disorders. The coefficient alphas of the BDI-IA and the BDI-II were, respectively, .89 and .91. The mean rating for Sadness on the BDI-IA was higher than it was on the BDI-II, but the mean ratings for Past Failure, Self-Dislike, Change in Sleeping Pattern, and Change in Appetite were higher on the BDI-II than they were on the BDI-IA. The mean BDI-II total score was approximately 2 points higher than it was for the BDI-IA, and the outpatients also endorsed approximately one more symptom on the BDI-II than they did on the BDI-IA. The correlations of BDI-IA and BDI-II total scores with sex, ethnicity, age, the diagnosis of a mood disorder, and the Beck Anxiety Inventory (Beck & Steer, 1993a) were within 1 point of each other for the same variables.
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              A Neural Substrate of Prediction and Reward

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                Author and article information

                Contributors
                will.lawn.12@ucl.ac.uk
                Journal
                Psychopharmacology (Berl)
                Psychopharmacology (Berl.)
                Psychopharmacology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0033-3158
                1432-2072
                2 September 2016
                2 September 2016
                2016
                : 233
                : 19
                : 3537-3552
                Affiliations
                [1 ]Clinical Psychopharmacology Unit, University College London, Gower Street, London, WC1E 6BT UK
                [2 ]Imanova Ltd, Burlington Danes Building, Imperial College London, Hammersmith Hospital, Du Cane Road, London, UK
                [3 ]Division of Brain Sciences, Imperial College London, London, UK
                [4 ]Psychiatric Imaging Group, Medical Research Council Clinical Sciences Centre, Hammersmith Hospital, London, UK
                [5 ]Division of Psychiatry, University College London, Maple House, London, UK
                [6 ]Psychopharmacology and Addiction Research Centre, University of Exeter, Exeter, UK
                [7 ]Neuropsychopharmacology Unit, Division of Experimental Medicine, Imperial College London, Burlington Danes Building, Du Cane Road, London, UK
                Article
                4383
                10.1007/s00213-016-4383-x
                5021728
                27585792
                30a1748f-801f-4a79-989a-0fe1f8367435
                © The Author(s) 2016

                Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 28 January 2016
                : 16 July 2016
                Funding
                Funded by: University College London (UCL)
                Categories
                Original Investigation
                Custom metadata
                © Springer-Verlag Berlin Heidelberg 2016

                Pharmacology & Pharmaceutical medicine
                cannabis,cannabinoids,thc,cannabidiol,motivation,reward,effort-related decision-making,reinforcement learning,addiction

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