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Psychopharmacology (Berl). 2016 Oct;233(19-20):3537-52. doi: 10.1007/s00213-016-4383-x. Epub 2016 Sep 2.

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

Author information

1
Clinical Psychopharmacology Unit, University College London, Gower Street, London, WC1E 6BT, UK. will.lawn.12@ucl.ac.uk.
2
Clinical Psychopharmacology Unit, University College London, Gower Street, London, WC1E 6BT, UK.
3
Imanova Ltd, Burlington Danes Building, Imperial College London, Hammersmith Hospital, Du Cane Road, London, UK.
4
Division of Brain Sciences, Imperial College London, London, UK.
5
Psychiatric Imaging Group, Medical Research Council Clinical Sciences Centre, Hammersmith Hospital, London, UK.
6
Division of Psychiatry, University College London, Maple House, London, UK.
7
Psychopharmacology and Addiction Research Centre, University of Exeter, Exeter, UK.
8
Neuropsychopharmacology Unit, Division of Experimental Medicine, Imperial College London, Burlington Danes Building, Du Cane Road, London, UK.

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.

KEYWORDS:

Addiction; Cannabidiol; Cannabinoids; Cannabis; Effort-related decision-making; Motivation; Reinforcement learning; Reward; THC

PMID:
27585792
PMCID:
PMC5021728
DOI:
10.1007/s00213-016-4383-x
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Compliance with ethical standards The study was approved by the UCL ethics committee, all participants provided written informed consent and the study was conducted in accordance with the Declaration of Helsinki. Funding Study 1 was funded by Drug Science. The cannabis used in study 1 was bought from Bedrocan (Veendam, thew Netherlands). Study 2 was funded by WL’s PhD grant from the BBSRC and University College London. Conflicts of interest HVC is a member of the UK MRC boards and Drug Science. DJN is an advisor to the British National Formulary, MRC, GMC, Department of Health; President of European Brain Council; Past President of British Neuroscience Association and European College of Neuropsychopharmacology, Chair of Drug Science (UK); Member of International Centre for Science in Drug Policy; Advisor to Swedish government on drug, alcohol, and tobacco research; editor of the Journal of Psychopharmacology; Member of Advisory Boards of Lundbeck, MSD, Nalpharm, Orexigen, Shire, MSD; has received speaking honoraria (in addition to above) from BMS/Otsuka, GSK, Lilly, Janssen, Servier, AZ, and Pfizer; is a member of the Lundbeck International Neuroscience Foundation; has received grants or clinical trial payments from P1vital, MRC, NHS, Lundbeck, RB; has share options in P1vital; has been an expert witness in a number of legal cases relating to psychotropic drugs; and has edited/written 27 books, some purchased by pharma companies. CJAM has consulted for Janssen and GlaxoSmithKline and received compensation. MBW is employed by Imanova Ltd., a private company that performs contract research work for the pharmaceutical industry. The authors declare that they have no conflict of interest.

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