An open-label cocaine-use-disorder pilot showed that participants could reach substantial lisdexamfetamine doses under monitoring, sometimes after dose reductions. It did not provide a placebo-controlled estimate of treatment efficacy.
The study enrolled 17 treatment-seeking adults with cocaine dependence; 16 had post-enrollment data. It tested an eight-week outpatient protocol, including an active medication period and taper, with a target dose up to 140 mg.
The primary outcome was the highest daily dose achieved. Tolerability, cocaine-use reports and retention were secondary outcomes. This distinction matters: a feasibility study can help plan a larger trial without establishing that the intervention reduces drug use better than an alternative.
The mean maximum dose achieved was 118.1 mg. Four of the 16 analyzed participants required reductions because of adverse effects, including combinations of insomnia, anxiety, agitation, appetite loss or cardiovascular findings. No participant discontinued medication because of adverse effects.
Those results do not mean the regimen was free of clinically relevant problems. Retaining someone after lowering a dose is different from demonstrating that the original target was tolerable for everyone. The selected, monitored sample also excluded several important health risks.
Self-reported cocaine spending and use days declined from baseline. However, the study was unblinded and lacked a placebo group. Expectations, clinical contact, other treatment elements and changes associated with seeking care could contribute to those changes.
No serious adverse events occurred in this small study, but uncommon risks cannot be excluded. These were investigational doses under a research protocol, not a dosing recommendation. The report supports feasibility work and controlled testing; it does not establish comparative efficacy, a safe concentration cutoff or individual impairment.
Read our analysis of the separate placebo-controlled lisdexamfetamine cocaine trial.
Open-label pilot study of lisdexamfetamine for cocaine use disorder. doi:10.1080/00952990.2021.1885677.