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, crossover 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 3 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 3 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, it is lower than for buprenorphine alone, particularly when participants received higher maintenance dosages and lower buprenorphine/naloxone challenge doses. Buprenorphine/naloxone may be a reasonable option for managing the risk for buprenorphine misuse during opioid dependence treatment.

Diversion of Methadone and Buprenorphine from Opioid Substitution Treatment: A Staff Perspective

“…This confirms previous research, which has shown that buprenorphine-naloxone has lower abuse potential 44 and lower street-value 45 than mono-buprenorphine. Therefore, buprenorphine-naloxone should, as far as it is possible, 46 be given priority over monobuprenorphine.…”

Intravenous Misuse of Methadone, Buprenorphine and Buprenorphine-Naloxone in Patients Under Opioid Maintenance Treatment: A Cross-Sectional Multicentre Study

“…Similarly, the average BUP daily dose was 11 mg and that of BUP-NLX was 8 mg, both of them below the usual maintenance daily dose range of 12-24 mg [42]. The low OMT dosage might be the main reason for intravenous misuse in our patients and a potential bias in the interpretation of the data, since previous studies reported an association between sub-optimal OMT doses and higher misuse to reduce withdrawal symptoms [11,20,31,34]. However, the daily oral morphine milligram equivalent dosage was not significant in any of the 3 multivariate analyses, possibly arguing against the importance of this factor.…”

“…Sublingual combination of BUP and low-dose naloxone (NLX) was marketed, assuming that NLX would antagonize the euphoric properties of BUP, or precipitate withdrawal symptoms in opioid-tolerant people when injected intravenously, thus reducing the risk of diversion and misuse [19,20]. In contrast, when used sublingually, BUP-NLX tablets skip hepatic first pass and offer good plasma levels of BUP, with low NLX bioavailability resulting in low risk of severe and protracted withdrawal symptoms [21].…”

“…According to previous reports, risk factors for OMT misuse include younger age, risky behaviours associated with opioid overdose, needle fixation (i.e., the act of injecting becoming compulsive and rewarding), opioid and benzodiazepine injection, polydrug abuse, self-treatment of withdrawal symptoms, concurrent pain or psychiatric symptoms, desire to obtain rapid onset of drug effect and low OMT dosage [1,7,10,11,14,[18][19][20]23].…”

Designing a tool allowing for a standardized assessment of resistance to drug diversion

“…Some laboratories developed tamper-resistant formulations to try to avoid these problems of drug product diversion, [3,[16][17][18][19][20][21][22][23][24][25][26][27], (offering some type of physical resistance to crushing, chewing, snorting) [28][29][30] or abuse deterrent formulations (formulations that have added excipient to reduce the attractiveness of the product for abusers) [2,[31][32][33]. Nevertheless, tamper-resistant dosage forms do not avoid these problems; and more specifically, they cannot prevent the ingestion of high doses required to obtain some effects.…”