Data analysis
All data were entered and stored in a MACRO database, then exported to and analyzed in IBM SPSS 25 for Windows. The validated database system MACRO was set up in compliance with GCP and the requirements of privacy, the role/rights principle and includes an audit trail. The database was programmed, validated and administered by the Coordinating Centre for Clinical Trials and was hosted on the servers of the Technische Universität Dresden. Missing, questionable, or additional information was requested on a regular basis by the risk-based central and onsite monitoring. The primary endpoint was the difference in cWFA in the CAT (in the naltrexone and placebo group) between session 1 and session 2. Secondary outcome variables were the cumulative work for saline (cWFS), peak and mean BrAC at sessions 1 and 2. The normal distribution of the data was verified by Shapiro–Wilk test. For normally distributed data, the evaluation was performed using two-sided t-tests or Pearson correlation coefficients. For non-normally distributed data, two-sided Mann-Whitney tests or Spearman correlation coefficients were used. One subject in the naltrexone group withdrew consent before the second session. For analyses of the primary outcome in the ITT population, we imputed the missing data by taking his baseline cWFA and subtracting the mean change in cWFA of the other Additional information on methods according to the Consolidated Standards of Reporting Trials is provided in the supplement.