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


OBJECTIVE
We investigated whether daily versus alternating-day administration of high versus low buprenorphine doses influenced choice of, and operant responding for, hydromorphone versus money.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Greenwald
Mark K
MK
Addiction Research Institute, Wayne State University School of Medicine, 2761 E. Jefferson, Detroit, MI 48207, USA. mgreen@med.wayne.edu
Schuh
Kory J
KJ
Hopper
John A
JA
Schuster
Charles R
CR
Johanson
Chris-Ellyn
CE
D000286:Administration, Sublingual; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D016739:Behavior, Addictive / Q000188:drug therapy* / Q000523:psychology; D002047:Buprenorphine / Q000008:administration & dosage*; D018592:Cross-Over Studies; D005260:Female; D006556:Heroin Dependence / Q000188:drug therapy* / Q000523:psychology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009292:Narcotic Antagonists / Q000008:administration & dosage*; D013607:Tablets
D009292:Narcotic Antagonists; D013607:Tablets; D002047:Buprenorphine