2026 ECNP Congress

PS03-3007

Thinking about stopping: the effects of atomoxetine on cognitive impulsivity in human cocaine addiction

Tsen Vei Lim — B.J. Sahakian, T.W. Robbins, K.D. Ersche · University of Cambridge, Department of Psychiatry, Cambridge, United Kingdom

2026 ECNP Congress

Introduction

Poor impulse control is a hallmark of cocaine use disorder (CUD), as patients often show elevated impulsive tendencies that impair their ability to regulate cocaine use or maintain abstinence [1]. However, there remains no approved pharmacotherapy to target impulsivity in CUD. Atomoxetine – a selective noradrenaline reuptake inhibitor licensed for Attention-Deficit-Hyperactivity Disorder – has emerged as a potential candidate to improve impulse control [2]. Our prior work has shown that atomoxetine can selectively reduce decisional impulsivity in patients with CUD in a neutral decision-making paradigm [3], but it remains unclear whether these effects translate to better impulse control in drug-related contexts. Using an established response inhibition paradigm, the drug Go/No-go task [4], and multiple analytical approaches, this study investigated the effects of atomoxetine on behavioral inhibition, attentional control, and cognitive impulsivity in a cocaine-related context. Based on our prior work [3], we hypothesized that atomoxetine improves cognitive impulsivity in patients with CUD, but not inhibitory or attentional control.

Methods

In a randomized, double-blind, placebo-controlled, crossover study, 28 patients who met the Diagnostic and Statistical Manual (DSM-5) criteria for moderate-to-severe CUD and 28 healthy volunteers without a history of substance use disorder received either a dose of 40 mg atomoxetine or placebo on two separate sessions. All participants then completed a Cocaine Go/No-go task [4], where they were instructed to quickly respond to target words (cocaine- or food-related) whilst inhibiting prepotent responses to non-targets. The task was completed approximately 2.5 hours post dosing to coincide with peak plasma concentrations. Key outcome measures span across three cognitive domains: behavioral inhibition was reflected by the rate of commission errors; attentional control was measured using a discrimination sensitivity variable (d’) calculated based on signal detection theory; and cognitive impulsivity was indexed by two computational parameters estimated from a validated drift diffusion model [5] – boundary separation (degree of cautiousness) and drift rate (rate of evidence accumulation).

Results

Regardless of whether the target was cocaine- or food-related words, patients with CUD showed markedly reduced behavioral inhibition (F1,54 = 22.3, p < 0.001), impaired attention control (F1,54 = 21.9, p < 0.001) and increased cognitive impulsivity (lower drift rate: F1,54 = 30.7, p < 0.001) in the Go/No-go task, compared with healthy volunteers. However, a single dose of atomoxetine selectively reduced cognitive impulsivity in patients with CUD by increasing the boundary separation parameter in both cocaine- and food-related conditions (F1,54 = 4.46, p = 0.039), suggesting increased cautiousness prior to responding. By contrast, atomoxetine did not measurably affect task performance in healthy volunteers (F < 1).

Conclusions

Consistent with our prior work [3], atomoxetine reduced cognitive impulsivity by enhancing response caution in patients with CUD. These findings suggest that atomoxetine may serve as a useful adjunctive treatment to facilitate recovery by promoting reflection in patients with CUD. However, given that impulse control problems in CUD exist in both drug- and non-drug-related contexts, there is a clear need for alternative therapeutics to address impulsive actions.

References

  1. Perry, J.L., Carroll, M.E., 2008. The role of impulsive behavior in drug abuse. Psychopharmacology 200, 1–26.
  2. Chamberlain, S.R., Hampshire, A., Müller, U., Rubia, K., del Campo, N., Craig, K., Regenthal, R., Suckling, J., Roiser, J.P., Grant, J.E., Bullmore, E.T., Robbins, T.W., Sahakian, B.J., 2009. Atomoxetine Modulates Right Inferior Frontal Activation During Inhibitory Control: A Pharmacological Functional Magnetic Resonance Imaging Study. Biological Psychiatry 65, 550–555.
  3. Lim, T.V., Cardinal, R.N., Ziauddeen, H., Regenthal, R., Sahakian, B.J., Robbins, T.W., Ersche, K.D., 2025. Atomoxetine Reduces Decisional Impulsivity in Human Cocaine Addiction. Biological Psychiatry 97, 627–636.
  4. Passamonti, L., Luijten, M., Ziauddeen, H., Coyle-Gilchrist, I.T.S., Rittman, T., Brain, S.A.E., Regenthal, R., Franken, I.H.A., Sahakian, B.J., Bullmore, E.T., Robbins, T.W., Ersche, K.D., 2017. Atomoxetine effects on attentional bias to drug-related cues in cocaine dependent individuals. Psychopharmacology 234, 2289–2297.
  5. Ratcliff, R., Huang-Pollock, C., McKoon, G., 2018. Modeling individual differences in the go/no-go task with a diffusion model. Decision 5, 42–62.