Effects of buprenorphine sublingual tablet maintenance on opioid drug-seeking behavior by humans

• Published in: Psychopharmacologia 2002-04, Vol.160 (4), p.344-352
• Main Authors: GREENWALD, Mark K, SCHUH, Kory J, HOPPER, John A, SCHUSTER, Charles R, JOHANSON, Chris-Ellyn
• Format: Article
• Language: English
• Subjects: Administration, Sublingual; Adolescent; Adult; Analysis of Variance; Behavior, Addictive - drug therapy; Behavior, Addictive - psychology; Biological and medical sciences; Buprenorphine - administration & dosage; Cross-Over Studies; Drug addictions; Female; Heroin Dependence - drug therapy; Heroin Dependence - psychology; Humans; Male; Medical sciences; Middle Aged; Narcotic Antagonists - administration & dosage; Tablets; Toxicology
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-001-0975-0

Buprenorphine can decrease opioid self-administration by humans and animals, but its ability to decrease drug-seeking behavior and craving (i.e. motivational measures) among outpatient volunteers using clinically relevant dosing schedules has not been extensively studied. We investigated whether daily versus alternating-day administration of high versus low buprenorphine doses influenced choice of, and operant responding for, hydromorphone versus money. Fourteen heroin-dependent outpatients were maintained under four buprenorphine sublingual tablet (double blind) dose conditions using a within-subject, randomized crossover design. All participants received, for 2 weeks each, buprenorphine doses of 2 mg daily, 4 mg/placebo on alternating days, 16 mg daily, and 32 mg/placebo on alternating days. In each laboratory test session, participants chose between money ($2/choice) and drug (1/8 of total hydromorphone, 4 or 24 mg IM in different sessions) alternatives using an eight-trial non-independent progressive ratio schedule (FR 100, 200,.12,800). The drug dose and money amount earned was delivered after the end of the 2.5-h work period. Hydromorphone 24 mg was more reinforcing than 4 mg. Higher versus lower average buprenorphine doses (regardless of daily versus alternate-day schedule) significantly decreased hydromorphone 24 mg choice and increased money choice. Baseline heroin craving questionnaire scores predicted drug choice, and craving scores were significantly decreased by high-dose buprenorphine. High-dose buprenorphine attenuated opioid drug-seeking behavior, heroin craving self-reports and increased sensitivity to alternative reinforcement. These beneficial effects were retained when high-dose buprenorphine was administered on alternate days.