<p>The endogenous opioid system (EOS) is a neuromodulator of taste, and nicotine can modify both EOS signaling and taste perception. Understanding how nicotine interacts with EOS-driven taste perception is important for dietary guidance and smoking-cessation strategies. In this study, we tested whether opioid blockade with naltrexone vs. placebo differentially affects taste thresholds, intensity, and pleasantness in non-smokers, ad-lib smokers, and smokers in short-term withdrawal. A mixed factorial design was used; with drug (placebo vs. naltrexone) as a within-subject factor and smoking status (non-smoker, ad-lib smoker, withdrawal/abstaining) as a between-subjects factor. Each participant attended two sessions, receiving a placebo in one session and naltrexone in the other (counterbalanced). During each session participants completed (1) a sweet and bitter detection threshold test, and (2) suprathreshold intensity and pleasantness ratings for sweet, salty, sour, umami, and water. Results indicated that neither sweet nor bitter detection thresholds differed by drug or smoking groups. Among ad-lib smokers, however, suprathreshold intensity for sweet, salty, and sour tastes was significantly decreased under naltrexone vs. placebo, whereas pleasantness ratings remained unchanged. No drug effect on either intensity or pleasantness was observed in non-smokers and withdrawal smokers. The study’s results indicate a nicotine-related interaction with the EOS that reduces sensory gain but does not impact hedonic evaluation regarding taste perception</p>