• Naltrexone increases prolactin levels and blunts the orgasm-induced prolactin rise.
• Naltrexone reduces sexual arousal along the sexual response cycle.
• The naltrexone-induced prolactin increase may play a role in the treatment of CSBD.
• Disgust sensitivity is not affected by naltrexone treatment.

The use of opioid antagonists is discussed as a feasible and tolerable treatment of Compulsive Sexual Behavior Disorder (CSBD). However, little is known about the influence of opioid blockage on relevant physiological functions such as sexual arousal, pain perception as well as disgust sensitivity during the sexual response cycle (SRC). Healthy participants (N = 64, n = 32 women) were invited to the laboratory twice using a double-blind, randomized cross-over design, with an interval of four weeks between sessions. Participants were randomly subjected to an SRC condition (including an erotic audio play and masturbation to orgasm) and a control condition. Participants received either naltrexone (50 mg, n = 32) or placebo at both sessions. Self-reported sexual arousal and physiological measures of arousal as well as pain perception, odor disgust sensitivity, and prolactin levels were assessed along the SRC. Naltrexone increased prolactin levels and blunted the orgasm-induced prolactin rise. Naltrexone also reduced self-reported sexual arousal throughout the sexual response cycle and blunted respiration rate during masturbation. However, naltrexone did not affect other markers of physiological arousal, pressure pain ratings and odor disgust sensitivity. These findings suggest that naltrexone has an acute negative effect on sexual arousal. Since prolactin levels mediate sexual satiation, we propose that a prolactin-induced increase in sexual satiation could explain the positive effects reported for naltrexone in the treatment of CSBD.