We are pleased to announce the publication of our study protocol, “Adjunctive ketamine for affective symptoms, craving, and relapse prevention in opioid use disorder: protocol for a randomised, double-blind, placebo-controlled clinical trial,” in BMC Psychiatry. The article brings together a wide team. From the Department of Psychology and the Center for Applied Neuroscience at the University of Cyprus, the University of Cyprus Medical School, the University of Wisconsin–Milwaukee, the European University Cyprus, the State Health Services Organization of Cyprus and the “GEFYRA” Substitute Substance Unit.
Opioid use disorder is a chronic, relapsing condition with high mortality. Medications for opioid use disorder help many patients, but relapse remains common. Depression and other affective symptoms that emerge during treatment, or when opioid use is reduced, may drive people back to opioid use. Ketamine has shown promise as a rapid-acting treatment for mood disorders, but we still know little about how effective and safe it is in this population, or how it acts biologically. The protocol describes a randomised, double-blind, placebo-controlled phase II trial. Participants receiving standard medication for opioid use disorder are given six intravenous infusions of ketamine (0.5 mg/kg) or placebo over two weeks, and are followed for up to nine months after their final infusion. The primary outcome is the change in depressive symptoms on the Montgomery–Åsberg Depression Rating Scale. Secondary and exploratory outcomes include craving, withdrawal, staying in treatment, lapse and relapse, safety, EEG, heart rate variability and blood-based biomarkers.
The trial has been recruiting in Cyprus since April 2024, with no serious adverse events reported so far. Besides measuring clinical effects and safety, it aims to find biological markers that predict who responds to ketamine. Its findings will help design larger multicentre trials of ketamine for depressive symptoms and relapse risk in opioid use disorder. The study is funded by the Research and Innovation Foundation of Cyprus and registered in the EU Clinical Trials Information System (2025-520843-34-00).
Congratulations to the whole team!
The full article is available at https://doi.org/10.1186/s12888-026-08628-3.