Efficacy and safety of an alpha 7-nicotinic acetylcholine receptor agonist, VQW-765, in subjects with performance anxiety: randomised, double-blind, placebo-controlled trial

• Published in: British journal of psychiatry Vol. 227; no. 1; pp. 473 - 480
• Main Authors: He, Yunsheng, Polymeropoulos, Christos M., Mohrman, Michael A., Truslow, Sunny O., Xiao, Changfu, Wu, Yukun, Birznieks, Gunther, Polymeropoulos, Mihael H.
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 01.07.2025
• Subjects: Acetylcholine receptors (nicotinic); Adult; Agonists; alpha7 Nicotinic Acetylcholine Receptor - agonists; Anti-Anxiety Agents - administration & dosage; Anti-Anxiety Agents - adverse effects; Anti-Anxiety Agents - pharmacokinetics; Anxiety - drug therapy; Anxiety disorders; Anxiety Disorders - drug therapy; Anxiolytics; Candidates; Clinical research; Clinical trials; Double-Blind Method; Efficacy; Female; Females; Heart rate; Humans; Male; Mental disorders; Middle Aged; Neuropsychiatry; Nicotinic Agonists - administration & dosage; Nicotinic Agonists - adverse effects; Nicotinic Agonists - pharmacokinetics; Original; Original Article; Performance anxiety; Pharmacodynamics; Pharmacokinetics; Placebos; Psychological distress; Psychotherapy; Public speaking; Social anxiety; Social interactions; Social stress; Speaking; Stress; Test anxiety; Treatment Outcome; Variance analysis; Young Adult; United States > US; Trier Social Stress Test; Performance anxiety; alpha-7 nicotinic acetylcholine receptor; social anxiety disorder
• ISSN: 0007-1250; 1472-1465; 1472-1465
• DOI: 10.1192/bjp.2025.84

Despite the high prevalence of social and performance anxiety, current treatments do not meet the full needs of patients. Development of novel anxiolytics with rapid onset of action for on-demand treatment of social and performance anxiety is an active area of clinical research. To examine the anxiolytic effect of VQW-765, an α7-nAChR agonist, in subjects with performance anxiety. We conducted a randomised, double-blind, placebo-controlled trial of 230 adults with a history of public speaking anxiety. Participants were randomly assigned to receive a single oral dose of 10 mg VQW-765 ( = 116) or placebo ( = 114), followed by a Trier Social Stress Test (TSST). Anxiety levels were assessed by the Subjective Units of Distress Scale (SUDS). Heart rate was monitored during the TSST. Plasma concentration of VQW-765 was measured after the TSST. Subjects receiving VQW-765 showed a trend of improvement in intensity of anxiety, as measured by the SUDS, during the performance phase of a TSST compared with placebo ( = 0.1443). Females showed a larger magnitude and significant response to VQW-765 ( = 0.034). The pharmacokinetic/pharmacodynamic analysis observed an inverted U-shaped exposure-response relationship. Subjects in the middle 50% quantiles of VQW-765 plasma concentration showed significant improvement in the SUDS rating compared with placebo ( = 0.033); however, subgroup analysis revealed this was true only for females ( = 0.005). VQW-765 was safe and well tolerated. This is the first study showing anxiolytic effect of an α7-nAChR agonist in humans. VQW-765 is a promising candidate to be developed for on-demand treatment of social anxiety disorder.