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Int J Neuropsychopharmacol. 2014 Dec 25;18(6). pii: pyu094. doi: 10.1093/ijnp/pyu094.

Neural effects of cannabinoid CB1 neutral antagonist tetrahydrocannabivarin on food reward and aversion in healthy volunteers.

Author information

1
School of Psychology and Clinical Language Sciences, University of Reading, Reading, United Kingdom (Mr Tudge and Dr McCabe); Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, United Kingdom (Ms Williams and Prof Cowen).
2
School of Psychology and Clinical Language Sciences, University of Reading, Reading, United Kingdom (Mr Tudge and Dr McCabe); Department of Psychiatry, Warneford Hospital, University of Oxford, Oxford, United Kingdom (Ms Williams and Prof Cowen). c.mccabe@reading.ac.uk.

Abstract

BACKGROUND:

Disturbances in the regulation of reward and aversion in the brain may underlie disorders such as obesity and eating disorders. We previously showed that the cannabis receptor subtype (CB1) inverse agonist rimonabant, an antiobesity drug withdrawn due to depressogenic side effects, diminished neural reward responses yet increased aversive responses (Horder et al., 2010). Unlike rimonabant, tetrahydrocannabivarin is a neutral CB1 receptor antagonist (Pertwee, 2005) and may therefore produce different modulations of the neural reward system. We hypothesized that tetrahydrocannabivarin would, unlike rimonabant, leave intact neural reward responses but augment aversive responses.

METHODS:

We used a within-subject, double-blind design. Twenty healthy volunteers received a single dose of tetrahydrocannabivarin (10mg) and placebo in randomized order on 2 separate occasions. We measured the neural response to rewarding (sight and/or flavor of chocolate) and aversive stimuli (picture of moldy strawberries and/or a less pleasant strawberry taste) using functional magnetic resonance imaging. Volunteers rated pleasantness, intensity, and wanting for each stimulus.

RESULTS:

There were no significant differences between groups in subjective ratings. However, tetrahydrocannabivarin increased responses to chocolate stimuli in the midbrain, anterior cingulate cortex, caudate, and putamen. Tetrahydrocannabivarin also increased responses to aversive stimuli in the amygdala, insula, mid orbitofrontal cortex, caudate, and putamen.

CONCLUSIONS:

Our findings are the first to show that treatment with the CB1 neutral antagonist tetrahydrocannabivarin increases neural responding to rewarding and aversive stimuli. This effect profile suggests therapeutic activity in obesity, perhaps with a lowered risk of depressive side effects.

KEYWORDS:

THCv; cannabinoid; fMRI; obesity; reward

PMID:
25542687
PMCID:
PMC4438540
DOI:
10.1093/ijnp/pyu094
[Indexed for MEDLINE]
Free PMC Article

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