Effects of Biperiden (Cholinergic Muscarinic m1/m4 Receptor Antagonist) on Craving Nicotine: A Proof-Of-Concept Clinical Study

The purpose of this study was to evaluate the effect of biperiden on nicotine craving in a proof-of-concept clinical study. The study involved 46 male participants (mean age: 45.3±9.31 years) who smoked an average of 20.8 (10.0) cigarettes per day. Participants were randomly assigned to either a biperiden (4 mg/day) or placebo group, with treatment lasting seven days. The outcomes were assessed at baseline (T0) and after seven days (T1) using self-reported questionnaires, including the Questionnaire of Smoking Urges-Brief, the Fagerström Tolerance Questionnaire, and the Beck Anxiety and Depression Inventories. Results: Repeated measures ANOVA revealed a significant Time×Treatment interaction for cigarette consumption (p < 0.001, η²ₚ = 0.340) and craving (p = 0.002, η²ₚ = 0.203), indicating that participants in the biperiden group showed greater reductions than those receiving placebo. For dependence, anxiety, and depression, only the main effect of time was significant (p < 0.05), suggesting general improvement across both groups. Ethnicity did not significantly influence any outcomes, and no relevant adverse effects were reported. These findings suggest that biperiden may represent a promising pharmacological approach for reducing nicotine craving. Further studies with prolonged administration are warranted to evaluate its therapeutic potential for smoking cessation. Registration Number: ensaiosclinicos.gov.br/ Identifier RBR-7qtvbh3.