Evaluation of the abuse potential of difelikefalin, a selective kappa-opioid receptor agonist, in recreational polydrug users.
Difelikefalin, a selective kappa-opioid receptor agonist with limited central nervous system penetration, is being developed for the treatment of chronic pruritic conditions. This randomized, double-blind, active- and placebo-controlled, four-way crossover study was designed to evaluate the abuse potential of difelikefalin in healthy recreational polydrug users. Using a 4 × 4 Williams design, nondependent adult users of opioids and hallucinogens (N 44) were randomized to receive single intravenous (i.v.) injections of difelikefalin at supratherapeutic doses (5 and 15 mcgkg) pentazocine (0.5 mgkg), a schedule IV mu-opioid partial agonist and kappa-opioid receptor agonist and placebo. The abuse potential of difelikefalin was compared with pentazocine and placebo using the maximal score (maximum effect E