This study explored the acute and long-term consequences of ultrarapid opioid detoxification (URD) in individuals with opioid dependence. In an open case series, seven patients underwent URD and subsequent treatment with daily naltrexone. Structured interviews, integrated rehabilitation and hair sampling were employed in the 12-week course of longitudinal follow-up. Cardiac and pulmonary physiology did not change significantly during the anesthesia phase of URD, but plasma ACTH and cortisol levels increased 15- and 13-fold, respectively. Marked withdrawal and tachypnea in all patients and respiratory distress in one patient occurred during the acute post-anesthesia phase. Withdrawal scores were significantly elevated for 3 weeks compared with baseline in the face of minimal self-reported craving for opioids. Anxiety, depression and vegetative symptoms improved gradually. Four patients remained abstinent of opioid use, two reported a brief period of opioid intake and one relapsed into daily opioid consumption. Given its effect on breathing and stress hormones, this procedure should be conducted by experienced anesthesiologists. The fact that URD and subsequent naltrexone treatment appears to cause a dissociation effect in the usual relationship between withdrawal and craving has implications for behavioral pharmacology. Further research is needed on the efficacy, safety, mechanisms and neurobiological sequelae of the procedure.