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Background: Dissociative phenomena, including flashbacks, are common in patients with borderline personality disorder and posttraumatic stress disorder (PTSD). Although dissociative symptoms can be severe and may interfere with psychotherapy, there is no established pharmacotherapy for these symptoms. Evidence suggests that alterations of the endogenous opiate system contribute to dissociative symptoms in patients with borderline personality disorder and PTSD., Method: We treated 2 groups of female borderline personality disorder patients (N = 13, with an overlap of 5 patients between the 2 groups; all met the diagnostic criteria of DSM-IV and the revised Diagnostic Interview for Borderline Patients) who experienced prominent dissociative phenomena including flashbacks with the nonselective opiate receptor antagonist naltrexone, 25 to 100 mg q.i.d., for at least 2 weeks. A self-rated questionnaire measuring dissociation, analgesia, tonic immobility, and tension (DAISS) was applied to 9 patients, who completed it for 7 consecutive days before and during treatment with naltrexone. In addition, 9 patients (with an overlap of 5 patients from the other group) completed a flashback protocol., Results: DAISS scores reflected a highly significant reduction of the duration and the intensity of dissociative phenomena and tonic immobility as well as a marked reduction in analgesia during treatment with naltrexone. Six of 9 patients reported a decrease in the mean number of flashbacks per day., Conclusion: These observations support the hypothesis that an increased activity of the opioid system contributes to dissociative symptoms, including flashbacks, in borderline personality disorder and suggest that these symptoms may respond to treatment with opiate antagonists. In view of these results, a placebo-controlled, double-blind study to assess the potential benefit of naltrexone in a more rigorous way appears justified.