This experimental medicine study explores whether a single dose of losartan (50mg) versus placebo affects the processing of positive and negative stimuli, using fMRI.

Losartan has been shown to accelerate fear extinction in animals and to prevent the development of anxiety disorders in humans, emphasising its potential to possibly enhance exposure therapy in humans. This study explores the basic effects of losartan on emotional processing, to identify neural mechanisms by which the drug might have synergistic effects on psychological treatment in humans.

In a double-blind between-groups design, 30 healthy volunteers will be randomised to a group receiving a single dose of losartan (50mg) versus placebo, and this study will measure the effects of probing renin-angiotensin function on emotional information processing, using functional magnet resonance imaging (fMRI). Such knowledge will ultimately be essential for the development of more effective pharmaco-psychological treatment approaches for anxiety disorders.

Inclusion Criteria:

• willing and able to provide informed consent
• male or Female, aged 18-50
• body mass index (BMI) of 18-30 kg/m2
• fluent English skills
• non- or light-smoker (< 5 cigarettes a day)

Exclusion Criteria:

• Female participant who is pregnant or breast-feeding
• central nervous system (CNS) active medication during the last 6 weeks
• Current blood pressure/other heart medication (esp. aliskiren or beta blockers)
• Intravascular fluid depletion
• Past or present DSM-IV (Diagnostic and Statistical Manual of Mental Disorders) axis-I diagnosis
• Alcohol or substance abuse
• First-degree family member with a history of a severe psychiatric disease
• Impaired liver or kidney function
• Lifetime history of epilepsy or other neurological disease, systemic infection, or clinically significant hepatic, cardiac, obstructive respiratory, renal, cerebrovascular, metabolic, endocrine or pulmonary disease or disorder which, in the opinion of the investigator, may either put the participants at risk because of participation in the study, or may influence the result of the study, or the participant's ability to participate in the study.
• Insufficient English skills
• participated in another study involving certain medication during last 6 weeks
• Contraindication to magnet resonance imaging (MRI) scanning (e.g. pacemaker)

Study medication and placebo are over-encapsulated to look identical, and both the participants and investigators in direct contact with partiicpants are blind to group allocation.