Abuse liability of intravenous buprenorphine/naloxone and buprenorphine alone in buprenorphine-maintained intravenous heroin abusers.
BACKGROUND
Sublingual buprenorphine is an effective maintenance treatment for opioid dependence, yet intravenous buprenorphine misuse occurs. A buprenorphine/naloxone formulation was developed to mitigate this misuse risk. This randomized, double-blind, cross-over study was conducted to assess the intravenous abuse potential of buprenorphine/naloxone compared with buprenorphine in buprenorphine-maintained injection drug users (IDUs).


METHODS
Intravenous heroin users (n = 12) lived in the hospital for 8-9 weeks and were maintained on each of three different sublingual buprenorphine doses (2 mg, 8 mg, 24 mg). Under each maintenance dose, participants completed laboratory sessions during which the reinforcing and subjective effects of intravenous placebo, naloxone, heroin and low and high doses of buprenorphine and buprenorphine/naloxone were examined. Every participant received each test dose under the three buprenorphine maintenance dose conditions.


RESULTS
Intravenous buprenorphine/naloxone was self-administered less frequently than buprenorphine or heroin (P < 0.0005). Participants were most likely to self-administer drug intravenously when maintained on the lowest sublingual buprenorphine dose. Subjective ratings of 'drug liking' and 'desire to take the drug again' were lower for buprenorphine/naloxone than for buprenorphine or heroin (P = 0.0001). Participants reported that they would pay significantly less money for buprenorphine/naloxone than for buprenorphine or heroin (P < 0.05). Seven adverse events were reported; most were mild and transient.


CONCLUSIONS
These data suggest that although the buprenorphine/naloxone combination has intravenous abuse potential, that potential is lower than it is for buprenorphine alone, particularly when participants received higher maintenance doses and lower buprenorphine/naloxone challenge doses. Buprenorphine/naloxone may be a reasonable option for managing the risk for buprenorphine misuse during opioid dependence treatment.
Comer
Sandra D
SD
Department of Psychiatry, Columbia University, New York State Psychiatric Institute, New York, NY 10032, USA. sdc10@columbia.edu
Sullivan
Maria A
MA
Vosburg
Suzanne K
SK
Manubay
Jeanne
J
Amass
Leslie
L
Cooper
Ziva D
ZD
Saccone
Phillip
P
Kleber
Herbert D
HD
D000286:Administration, Sublingual; D000328:Adult; D000704:Analysis of Variance; D016739:Behavior, Addictive; D002047:Buprenorphine / Q000008:administration & dosage* / Q000009:adverse effects; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006556:Heroin Dependence / Q000191:economics / Q000534:rehabilitation*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009270:Naloxone / Q000008:administration & dosage* / Q000009:adverse effects; D009292:Narcotic Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D009294:Narcotics / Q000008:administration & dosage* / Q000009:adverse effects; D057240:Patient Preference; D012646:Self Administration; D015819:Substance Abuse, Intravenous / Q000534:rehabilitation*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy; D055815:Young Adult
D004338:Drug Combinations; D009292:Narcotic Antagonists; D009294:Narcotics; D009270:Naloxone; D002047:Buprenorphine
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