Abstract

Patients with cocaine use disorder often make risky decisions, whether they are in an experimental setting or in real life, and this tendency significantly jeopardizes their well-being. Despite the abundance of evidence of decision-making deficits in patients with cocaine use disorder, the precise biological mechanism that underpins this tendency is unclear. A neuroendocrinology account proposes that impaired decision-making could be explained by dysregulation in steroidal hormones, but this account has never been formally tested in cocaine use disorder. There is preliminary evidence suggesting that cocaine use disorder patients have abnormal ranges in cortisol and testosterone, two key hormones in the hypothalamus–pituitary–adrenal and hypothalamus–pituitary–gonadal axes, respectively. Growing evidence in neuroeconomics has identified that in financial decision-making settings, cortisol modulates risk preferences, whereas testosterone affects behavioural responses towards risk. If decision-making deficits observed in patients are in part accounted for by imbalances in these hormones, targeting this pathway with existing treatment (e.g., hormone replacement therapy) could present a potential treatment strategy to ameliorate risky behaviour in cocaine use disorder. Therefore, by adopting a psychoneuroendocrinology approach, we propose a cross-sectional study with the goal to characterise the role of steroidal hormones in risky decision-making in cocaine use disorder within social and non-social settings. We will use sophisticated computational modelling techniques to identify the psychological mechanisms that drive risky decision-making and study their relationships with patients’ endocrinological profile. Outcomes of this proof-of-concept study would provide the much-needed scientific rationale for the dire need of novel therapeutics in cocaine use disorder.

Lay summary

We will investigate endocrine disturbances in patients with cocaine use disorder and their implications on learning and decision-making. Insight gained from this work will provide proof of concept for new targeted therapeutic interventions.