Buprenorphine (BUP)-naloxone interactions were examined at peak buprenorphine effects in opioid-dependent outpatients. After being stabilized on a maintenance dose of 8 mg/ 70 kg (n=1) or 16 mg/ 70 kg (n=9) of BUP every other day, subjects participated in challenge sessions every other week. Challenge sessions were conducted at Low (half maintenance), Medium (maintenance), and High (double maintenance) BUP doses, in either an ascending (n= 5) or descending (n=5) sequence. One placebo and one active naloxone challenge session were conducted in random order at each condition. Subjects received each BUP dose for at least 10 days prior to the first challenge session at each condition. Subjects received 3 injections (i.m.) spaced 45 min apart during each challenge session. BUP was administered 150 min before the first injection. During active sessions, a saline placebo injection was followed by 3.0 mg/ 70 kg and 13 mg/ 70 kg doses of naloxone using a cumulative dosing procedure. All injections contained saline during placebo sessions. Dependent measures included an Adjective Withdrawal Scale, Visual Analog Scale, Observer Ratings of opioid withdrawal and agonist effects, Addiction Research Center Inventory, Digit-Symbol Substitution Test, vital signs, and pupil diameter. Measures of precipitated withdrawal were directly related to naloxone dose across all BUP doses. Across measures of withdrawal, significant effects of naloxone dose and significant BUP-naloxone dose interactions were more frequently obtained in subjects experiencing the BUP doses in an ascending sequence. Data from these subjects suggest precipitated withdrawal may be less pronounced at lower BUP doses. Data collection is complete and a manuscript is in preparation.
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