S D Comer1, E D Collins, M W Fischman. 1. New York State Psychiatric Institute and Department of Psychiatry, College of Physicians and Surgeons of Columbia University, NY 10032, USA. sdc10@columbia.edu
Abstract
RATIONALE: Studies have shown that buprenorphine, a partial mu opioid agonist, effectively reduces heroin taking. While previous research with buprenorphine utilized a liquid formulation, a tablet formulation is proposed for clinical use. However, because recent research suggests that the liquid and tablet differ in bio-availability, it is unclear what dose of the buprenorphine tablet effectively antagonizes the reinforcing effects of heroin. OBJECTIVE: The present study was designed to compare the effects of two sublingual doses of buprenorphine maintenance on heroin self-administration. METHODS:Eight heroin-dependent men participated in a 6-week, double-blind, placebo-controlled inpatient study to evaluate the reinforcing effects of intravenous heroin (0, 6.25, 12.5, 25 mg) during maintenance on 8 or 16 mg sublingual buprenorphine. Participants first sampled the available dose of heroin, and then were allowed to respond under a progressive ratio schedule for either heroin or $20. For each heroin dose, one sample session and three choice sessions occurred. Two sessions per day were conducted. A sample session was followed by the first choice session on one day, and the second and third choice sessions occurred on the following day. These sessions were conducted while participants were maintained on daily doses of 8 or 16 mg buprenorphine (3 weeks each). RESULTS: Relative to placebo, 12.5 and 25 mg heroin produced significant increases in break point values under both maintenance dose conditions. The mean break point value for 12.5 mg heroin was significantly lower under 16 mg buprenorphine, compared to 8 mg. CONCLUSIONS: These results demonstrate that the reinforcing effects of heroin were not fully antagonized by these doses of the tablet formulation of buprenorphine, and that 16 mg buprenorphine reduced heroin self-administration relative to 8 mg.
RCT Entities:
RATIONALE: Studies have shown that buprenorphine, a partial mu opioid agonist, effectively reduces heroin taking. While previous research with buprenorphine utilized a liquid formulation, a tablet formulation is proposed for clinical use. However, because recent research suggests that the liquid and tablet differ in bio-availability, it is unclear what dose of the buprenorphine tablet effectively antagonizes the reinforcing effects of heroin. OBJECTIVE: The present study was designed to compare the effects of two sublingual doses of buprenorphine maintenance on heroin self-administration. METHODS: Eight heroin-dependent men participated in a 6-week, double-blind, placebo-controlled inpatient study to evaluate the reinforcing effects of intravenous heroin (0, 6.25, 12.5, 25 mg) during maintenance on 8 or 16 mg sublingual buprenorphine. Participants first sampled the available dose of heroin, and then were allowed to respond under a progressive ratio schedule for either heroin or $20. For each heroin dose, one sample session and three choice sessions occurred. Two sessions per day were conducted. A sample session was followed by the first choice session on one day, and the second and third choice sessions occurred on the following day. These sessions were conducted while participants were maintained on daily doses of 8 or 16 mg buprenorphine (3 weeks each). RESULTS: Relative to placebo, 12.5 and 25 mg heroin produced significant increases in break point values under both maintenance dose conditions. The mean break point value for 12.5 mg heroin was significantly lower under 16 mg buprenorphine, compared to 8 mg. CONCLUSIONS: These results demonstrate that the reinforcing effects of heroin were not fully antagonized by these doses of the tablet formulation of buprenorphine, and that 16 mg buprenorphine reduced heroin self-administration relative to 8 mg.
Authors: Sandra D Comer; Warren K Bickel; Richard Yi; Harriet de Wit; Stephen T Higgins; Galen R Wenger; Chris-Ellyn Johanson; Mary Jeanne Kreek Journal: Behav Pharmacol Date: 2010-07 Impact factor: 2.293
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