Psychopharmacological drug manipulation creates causal mechanisms for selectively stimulating or blocking target neurotransmitter receptors known to modulate brain regions engaged in trust behavior. In this chapter, we review studies that used pharmacological agents to act as neuromodulators in the neural signaling pathway mechanisms underlying trust behavior. First, we describe the laboratory measurements of trust behavior, the underlying domain-general large-scale brain networks, and its related target neurotransmitter systems that probe trust behavior. Second, we review the psychopharmacological studies focusing first on studies that implemented the trust game and second on studies that applied trust ratings after cooperative exchange games. Overall, some preliminary evidence exists that neuromodulators such as opiates, monoamine neurotransmitters (e.g., serotonin, dopamine), and pharmacologic agents such as 3,4-Methyl-enedioxy-methamphetamine increase monoamine neurotransmitter activity and impact trust behavior via experimental paradigms that have face validity in laboratory measures of trust. Finally, we indicate shortcomings in the present psychopharmacological research approach and offer guidance for future interdisciplinary research on the neuropsychoeconomic underpinnings of trust –shedding light on trust impairment as a key feature of several neuropsychiatric disorders.

Interpersonal trust is a vital element in the social functioning of our relationships with persons, groups, and organizations. In the past two decades, an increase in task-based and task-free (resting-state) functional magnetic resonance imaging (fMRI) studies have been observed that explored the neuropsychological signatures of trust. In this book chapter, we compared the commonalities and differences between task-based fMRI (tb-fMRI) and task-free fMRI (tf-fMRI) approaches for studying trust and explored how these two approaches can make unique contributions to our understanding of the psychoneurobiological underpinnings of trust. Overlapping brain regions for both approaches have been identified in large-scale domain-general networks – reward (e.g., ventral striatum), salience (e.g., anterior insula), executive-control (i.e., lateral prefrontal cortex), and default-mode (i.e., temporoparietal junction) networks – supporting the underlying motivational, affective, and cognitive aspects of trust. While task-based research investigates dominantly those brain networks in building trust over time at the group level, task-free trust research has identified those networks in predicting trust preferences at the individual level. Future research would benefit from a combination of these two approaches for a broader understanding of the driving psychoneurobiological mechanisms of trust.

Since the early days of humankind, trust has been an essential factor for establishing and maintaining cooperative and mutually beneficial interpersonal relationships with strangers, friends, family members, etc., impacting our social interactions across all aspects of our private and public lives in a wide range of social, economic, and political contexts. Portraying a social dilemma, trust can be conceptualized as a trustor’s investment of resources (e.g., money, time, energy) into another party (i.e., a trustee) that encompasses uncertainty regarding the benefits of reciprocation in the future, thus opening up the possibilities for deceiving and cheating in human society. These interpersonal trust decisions – ranging from small (e.g., trusting that a stranger provides you with a correct route description) to large (e.g., trusting your spouse to be faithful) transactions – are imperative for shaping our social lives and have cascading positive and negative consequences. When people trust each other, society is more inclusive and accessible, economic transactions are facilitated, and feelings of well-being prosper (Rothstein & Uslaner, 2005; Simpson, 2007; Zak & Knack, 2001). For example, the current unprecedented pandemic of COVID-19 has highlighted the significance of trust in regulating our social lives. We not only trust our political leaders to tell the truth about the impact of this virus but also that others take the necessary precautions (e.g., social distancing, wearing face coverings, limiting unnecessary contact, self-isolation and quarantining in the case of an infection) to slow the spread of the virus.