Human Abuse Potential of Single Oral Doses of Sunobinop, a Novel, Highly Potent, and Selective Partial Agonist for Nociceptin/Orphanin-FQ Peptide (NOP) Receptors.

BACKGROUND: Sunobinop is a selective, partial agonist of the nociceptin/orphanin FQ peptide receptor and has multiple potential indications, including insomnia, bladder disorders, and alcohol use disorder. The purpose of this study was to examine the abuse potential and pharmacodynamic effects of sunobinop compared with triazolam in healthy adults with a history of nonmedical use of central nervous system drugs with depressant/sedative properties.

METHODS: This was a single-dose, randomized, double-blind, double-dummy, placebo-controlled and positive-controlled crossover study. Each participant received 6 treatments: sunobinop 1 mg, 6 mg, and 10 mg plus triazolam placebo, sunobinop placebo plus triazolam 0.5 mg and 1 mg, and sunobinop placebo plus triazolam placebo. The primary endpoint for the treatment phase was "at this moment" drug-liking visual analog scale (VAS) maximum effect (0 to 100).

RESULTS: Fifty participants completed the study. The mean "at this moment" drug-liking VAS scores for sunobinop 1 mg remained within the neutral range (40 to 60) with a peak score of 54.1 and comparable with placebo at all time points. In contrast, "at this moment" drug-liking VAS scores for triazolam control doses increased over time, peaking ∼2 hours following dosing at a mean score of 65.0 and 63.4 for triazolam 0.5 mg and 1.0 mg, respectively.

CONCLUSIONS: Drug-liking following sunobinop at a potential therapeutic dose was not different from placebo and was significantly lower compared with triazolam at a recommended dose. In addition, its good tolerability profile suggests sunobinop may be a useful new treatment option, particularly in at-risk populations.