Abuse liability of intravenous buprenorphine/naloxone and buprenorphine alone in buprenorphine-maintained intravenous heroin abusers

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00710385.

Figure 1

(A) Mean drug progressive ratio breakpoints for intravenous test doses across all buprenorphine maintenance doses. (B) Mean progressive ratio breakpoints for test drug stratified by buprenorphine maintenance dose. BupNx, buprenorphine/naloxone; Bup, buprenorphine. * P < 0.01 compared with placebo. ^†P < 0.01 compared with heroin. ^‡P ≤ 0.055 compared with heroin. ^§P < 0.03 compared with 8 mg buprenorphine maintenance dose. ^‖P < 0.05 compared with 2 mg buprenorphine maintenance dose.

Figure 1

(A) Mean drug progressive ratio breakpoints for intravenous test doses across all buprenorphine maintenance doses. (B) Mean progressive ratio breakpoints for test drug stratified by buprenorphine maintenance dose. BupNx, buprenorphine/naloxone; Bup, buprenorphine. * P < 0.01 compared with placebo. ^†P < 0.01 compared with heroin. ^‡P ≤ 0.055 compared with heroin. ^§P < 0.03 compared with 8 mg buprenorphine maintenance dose. ^‖P < 0.05 compared with 2 mg buprenorphine maintenance dose.

Figure 2

(A) Mean “drug liking” responses from the Drug Effects Questionnaire across all buprenorphine maintenance doses. (B) Mean “drug liking” responses from the Drug Effects Questionnaire stratified by buprenorphine maintenance dose. BupNx, buprenorphine/naloxone; Bup, buprenorphine. * P < 0.001 compared with placebo. ^†P < 0.005 compared with heroin. ^§P < 0.03 compared with 8 mg buprenorphine maintenance dose. ^‖P < 0.05 compared with 2 mg buprenorphine maintenance dose.

Figure 2

(A) Mean “drug liking” responses from the Drug Effects Questionnaire across all buprenorphine maintenance doses. (B) Mean “drug liking” responses from the Drug Effects Questionnaire stratified by buprenorphine maintenance dose. BupNx, buprenorphine/naloxone; Bup, buprenorphine. * P < 0.001 compared with placebo. ^†P < 0.005 compared with heroin. ^§P < 0.03 compared with 8 mg buprenorphine maintenance dose. ^‖P < 0.05 compared with 2 mg buprenorphine maintenance dose.

Figure 3

(A) Mean “willing to take the drug again” responses from the Drug Effects Questionnaire across all buprenorphine maintenance doses. (B) Mean “willing to take the drug again” responses from the Drug Effects Questionnaire stratified by buprenorphine maintenance dose. BupNx, buprenorphine/naloxone; Bup, buprenorphine. * P < 0.001 compared with placebo. ^†P < 0.005 compared with heroin. ^‖P < 0.05 compared with 2 mg buprenorphine maintenance dose.

Figure 3

(A) Mean “willing to take the drug again” responses from the Drug Effects Questionnaire across all buprenorphine maintenance doses. (B) Mean “willing to take the drug again” responses from the Drug Effects Questionnaire stratified by buprenorphine maintenance dose. BupNx, buprenorphine/naloxone; Bup, buprenorphine. * P < 0.001 compared with placebo. ^†P < 0.005 compared with heroin. ^‖P < 0.05 compared with 2 mg buprenorphine maintenance dose.