In this study, the investigators will examine the effects of blocking the orexin system on human behaviour and brain function using daridorexant, a medication that inhibits orexin activity. Orexin is a brain chemical involved in regulating sleep, emotion, motivation, and stress responses, which are often disrupted in mental health disorders. Healthy volunteers will be randomly assigned to receive a single dose of daridorexant or placebo in a double-blind design. Participants will then complete behavioural and cognitive tasks assessing emotional processing, aversive learning, and executive function. The study aims to clarify the role of orexin in emotional and cognitive processes relevant to conditions such as depression and anxiety.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
OTHER
Masking
TRIPLE
Enrollment
62
Acute (single dose) daridorexant encapsulated in an opaque capsule. Oral administration. Daridorexant (brand name Quviviq) is FDA-approved for the treatment of insomnia in adults.
Lactose film-coated tablet will be encapsulated in an opaque capsule (identical to the experimental arm drug).
Department of Psychiatry, University of Oxford
Oxford, United Kingdom
RECRUITINGPavlovian Aversive Learning Task Computational Parameter Estimates
Change in the participant-specific parameter estimates produced by task model fitting.
Time frame: 1-2 hours after single dose of drug or placebo.
Affective Go/No-Go Task Computational Parameter Estimates
Change in the participant-specific parameter estimates produced by task model fitting.
Time frame: 1-2 hours after single dose of drug or placebo.
Pupilometry during Pavlovian Aversive Learning Task
Changes in pupil size (dilation or constriction) in response to task stimuli
Time frame: 1-2 hours after single dose of drug or placebo.
Pupilometry during Affective Go/No-Go Task
Changes in pupil size (dilation or constriction) in response to task stimuli.
Time frame: 1-2 hours after single dose of drug or placebo.
Salivary Alpha Amylase Levels
Changes in Salivary Alpha Amylase Levels before, during and after Pavlovian Aversive Learning Task
Time frame: 1-2 hours after single dose of drug or placebo.
Optimal choice selection during loss and reward conditions in Probabilistic Instrumental Learning Task (PILT)
Optimal choice selection during loss and reward conditions in Probabilistic Instrumental Learning Task (PILT) in drug group compared with the placebo group
Time frame: 2-3 hours after single dose of drug or placebo.
Accuracy of target selection on the Colour Change Detection Task
Accuracy of target selection on the Colour Change Detection Task in pilosant group compared with the placebo group.
Time frame: 2-3 hours after single dose of drug or placebo.
Accuracy of emotional labeling of facial expressions during the facial emotion recognition task
Accuracy of emotion labels (e.g. disgusted face) assigned by participants to expressive faces during the facial emotion recognition task in drug group compared with the placebo group
Time frame: 2-3 hours after single dose of drug or placebo.
Accuracy during categorisation of emotional words
Accuracy to categorise positive and negative descriptor words
Time frame: 2-3 hours after single dose of drug or placebo.
Accuracy during recall of emotional words
Number of words accurately recalled
Time frame: 2-3 hours after single dose of drug or placebo.
Pavlovian Aversive Learning Task Behavioural Performance
Change in behavioural performance (response time; accuracy)
Time frame: 1-2 hours after single dose of drug or placebo.
Affective Go/No-Go Task Behavioural Performance
Change in behavioural performance (response time; accuracy)
Time frame: 1-2 hours after single dose of drug or placebo.
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