This study explores the effects of single-dose losartan (50mg) versus placebo on emotional processing in healthy volunteers.

The renin-angiotensin system is a major hormone system involved in blood pressure regulation. However, its major receptors are also found in the brain, particularly in areas implicated in anxiety and depression. In line with this topography, drugs blocking angiotensin-II receptors have been shown to have effects on cognition that are opposite to those seen in emotional disorders. For instance, angiotensin receptor blockade improves fear extinction, and it dampens stress responsivity to highly aversive images. In line with such cognitive effects, population-based studies suggest that angiotensin receptor blockers - compared to other antihypertensive drugs - prevent the development of post-traumatic stress disorder following trauma exposition and improve outcomes in patients taking SSRI.

This study aims to shed further light on how the renin-angiotensin system affects different aspects of cognitive processing in humans relevant to emotional disorders. In a double-blind, randomized between-group design, we will investigate the effects of a single dose of losartan (50mg) versus placebo on emotional processing in N=60 healthy volunteers aged 18-50 years. Results from this study will help us understand how the renin-angiotensin system affects emotional processing in humans, and they will help us identify potential synergistic overlaps with the cognitive mechanisms of action of effective treatment of emotional disorders.

Inclusion Criteria:

• Willing and able to provide informed consent
• Aged 18-50 years
• Score of or below 45 on the Dimensional Anhedonia Rating Scale (DARS; Rizvi et al., 2015)
• Sufficient written and spoken English skills to understand what the study involves, and to complete the questionnaires
• Non- or light-smoker (5 cigarettes a day)

Exclusion Criteria:

• Past or present DSM-5 axis-I diagnosis (based on SCID results at screening) other than anxiety disorder, dysthymia or unipolar depression
• First-degree family member with severe psychiatric illness
• CNS-medication last 6 weeks (including as part of another study)
• Current blood pressure or other heart medication (especially aliskiren or beta blockers)
• Diagnosis of intravascular fluid depletion or dehydration
• History of angioedema
• Impaired kidney function (based on self-report)
• Very low blood pressure (defined as repeated (at least three consecutive measurements) measures of blood pressure under standardised conditions where either the systolic or the diastolic blood pressure or both are below 90/50 mmHg (in accordance with established standard definitions: DOI 10.1186/s12887-016-0633-7))
• Lifetime history of epilepsy or other neurological disease (e.g. autism, ADHD)
• Lifetime history of 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
• Significant loss of hearing that is not corrected with a hearing device
• Women: pregnancy, breast-feeding

double-blind