Acute effects of intramuscular and sublingual buprenorphine and buprenorphine/naloxone in non-dependent opioid abusers
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Buprenorphine is a partial mu opioid receptor agonist with clinical efficacy as a pharmacotherapy for opioid dependence. A sublingual combination formulation was developed containing buprenorphine and naloxone with the intent of decreasing abuse liability in opioid-dependent individuals. However, the addition of naloxone may not limit abuse potential of this medication when taken by individuals without opioid physical dependence.
The present study investigated the effects of buprenorphine alone and in combination with naloxone administered intramuscularly and sublingually to non-dependent opioid abusers.
In a within-subject crossover design, non-dependent opioid-experienced volunteers (N = 8) were administered acute doses of buprenorphine (4, 8, and 16 mg) and buprenorphine/naloxone (4/1, 8/2, and 16/4 mg) via both intramuscular and sublingual routes, intramuscular hydromorphone (2 and 4 mg as an opioid agonist control), and placebo, for a total of 15 drug conditions. Laboratory sessions were conducted twice per week using a double-blind, double-dummy design.
Buprenorphine and buprenorphine/naloxone engendered effects similar to hydromorphone. Intramuscular administration produced a greater magnitude of effects compared to the sublingual route at the intermediate dose of buprenorphine and at both the low and high doses of the buprenorphine/naloxone combination. The addition of naloxone did not significantly alter the effects of buprenorphine.
These results suggest that buprenorphine and buprenorphine/naloxone have similar abuse potential in non-dependent opioid abusers, and that the addition of naloxone at these doses and in this dose ratio confers no evident advantage for decreasing the abuse potential of intramuscular or sublingual buprenorphine in this population.
KeywordsBuprenorphine Buprenorphine/naloxone Non-dependent Opioid Human
This study is supported by R01 DA08045, K24 DA023186 and T32 DA07209. The authors thank the medical, nursing, and pharmacy staff for work on the protocol, as well as the research assistants for the aid in preparation of this manuscript.
Drugs used in the study described in this article are manufactured by Reckitt Benckiser Pharmaceuticals, Inc. Dr. Strain is a consultant to and a paid member of the Scientific Advisory Board of Reckitt Benckiser Pharmaceuticals. The terms of this arrangement are being managed by Johns Hopkins University in accordance with its conflict of interest policies.
- Jasinski DR (1977) Assessment of the abuse potentiality of morphinelike drugs (methods used in man). In: Martin WR (ed) Drug addiction I. Springer, Berlin, pp 197–258Google Scholar
- Johnson RE, Jaffe JH, Fudala PJ (1992) A controlled trial of buprenorphine treatment for opioid dependence. Arch Gen Psychiatry 35:501–516Google Scholar
- Ling W, Charuvastra C, Collins JF, Batki S, Brown LS Jr, Kintaudi P, Wesson DR, McNicholas L, Tusel DJ, Malkerneker U, Renner JA Jr, Santos E, Casandonte P, Fye C, Stine S, Wang RI, Segal D (1998) Buprenorphine maintenance treatment of opiate dependence: a multicenter, randomized clinical trial. Addiction 93:475–486CrossRefPubMedGoogle Scholar
- Lutfy K, Eitan S, Bryant CD, Yang YC, Saliminejad N, Walwyn W, Kieffer BL, Takeshima H, Carroll FI, Maidment NT, Evans CJ (2003) Buprenorphine-induced antinociception is mediated by mu-opioid receptors and compromised by concomitant activation of opioid receptor-like receptors. J Neurosci 23:10331–10337PubMedGoogle Scholar