Tetrodotoxin (TTX) is a neurotoxin found in puffer fish and other marine animals. New clinical studies suggest that low-dose TTX can safely relieve severe, treatment-resistant cancer pain. The therapeutic potential of TTX in addiction is supported by studies in laboratory animals. The purpose of this double-blind, placebo-controlled study was to assess the effect of a single intramuscular dose of TTX on cue-induced craving and anxiety in abstinent heroin addicts. Forty-five abstinent heroin addicts were randomly assigned to three treatment groups: placebo, 5 µg TTX, or 10 µg TTX. Participants were exposed to a neutral video or a heroin-related video. Craving, anxiety, blood pressure, and heart rate were measured pre- and post-exposure. Heroin-related cues increased both craving and anxiety and had no effect on blood pressure and heart rate. A single dose of TTX dose-dependently attenuated the increases in craving and anxiety while having no effect on blood pressure or heart rate. The results suggest that low-dose TTX is acutely effective in reducing cue-induced increases in heroin craving and associated anxiety.