Course of cocaine craving/use in trials of cocaine use disorder is heterogeneous.

Three distinct trajectories of cocaine craving and use were identified.

The decreasing craving and cocaine use trajectory had most improvement on other outcomes.

Modafinil 200 mg daily was significantly associated with decreasing craving and use trajectory.

There is limited research on the course of drug craving in treatment trials of stimulant use disorders. This study examined trajectories of cocaine craving and use and their associations with other outcomes of cocaine use disorder in pharmacotherapy trials of cocaine use disorder.

In 1070 participants from 6 randomized controlled trials testing selegiline, baclofen, cabergoline, modafinil, reserpine, and tiagabine, we used multi-trajectory modeling to identify joint trajectories of weekly-measured cocaine craving and use. Association of these trajectories with Addiction Severity Index (ASI) health and social outcomes was assessed.

A 3-trajectory model with High craving/High use (40.0 %), Decreasing craving/High use (36.8 %), and Decreasing craving/Decreasing use (23.2 %) groups was the most parsimonious. Compared to the High craving/High use group, the Decreasing craving/Decreasing use group experienced significantly greater improvement on ASI domains of drug use (change score = −13.7 vs. −3.3), alcohol use (-7.3 vs. −4.4), psychiatric status (-5.6 vs. 0.7) and relationships status (-7.0 vs. −2.8) (all p < 0.05). Compared to placebo, those on modafinil 200 mg/day were more likely to be in the Decreasing craving/Decreasing use group (Relative Risk Ratio [RRR]=4.84, 95 % CI=1.38–17.00) or Decreasing craving/High use group (RRR=5.55, 2.04–14.08) than in the High craving/High use group.

Trajectories of craving/drug use in clinical trials for cocaine use disorder are heterogeneous. Participants experiencing the greatest reduction in cocaine craving/use experienced the greatest improvement in other measures of drug use and psychosocial functioning, supporting the utility of reduced craving/use as a clinically relevant outcome in pharmacotherapy trials of people with cocaine use disorder.

Cocaine use disorder

Stimulants

Craving

Recovery

Secondary data analysis

Non-abstinence outcomes

Harm reduction

© 2025 The Author(s). Published by Elsevier B.V.