Drug and Alcohol Dependence 64 (2001) 111–116 Short communication Limits to buprenorphine dosing: a comparison between quintuple and sextuple the maintenance dose every 5 days Anke Gross a, *, Eric A. Jacobs a,1 , Nancy M. Petry a,2 , Gary J. Badger b , Warren K. Bickel a a Substance Abuse Treatment Center, Uniersity of Vermont, 1 South Prospect Street, Burlington, VT 05401, USA b Department of Psychiatry and Department of Psychology, Medical Statistics, Uniersity of Vermont, Burlington, VT 05401, USA Received 2 May 2000; received in revised form 15 November 2000; accepted 15 November 2000 Abstract The relative efficacy of quintuple and sextuple buprenorphine dosing in abating withdrawal symptoms for 120 h was compared in opioid-dependent outpatients. Fourteen subjects received buprenorphine in a double-blind, placebo-controlled, cross-over design. Daily sublingual maintenance doses were 4 mg/70 kg (n =4) and 8 mg/70 kg (n =10). After a stabilization period of daily maintenance administration, subjects received quintuple (5 × daily maintenance dose) and sextuple (6 × daily maintenance dose) doses every 120 h. Measures of opioid agonist and withdrawal effects were assessed daily. Subjective ratings of withdrawal were significantly greater than baseline ratings beyond 96-h post dosing under both regimens. There was no evidence, however, that those subjective ratings of withdrawal differed between the two regimens. Thus, these data suggest that sextuple buprenorphine dosing, administered every 5 days, does not abate opioid-withdrawal beyond 96 hours. © 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Buprenorphine; Heroin dependence; Human; Opioid withdrawal; Treatment www.elsevier.com/locate/drugalcdep 1. Introduction Buprenorphine, a high affinity, partial -opioid ago- nist is a new, promising alternative to methadone and levo-acetyl alpha methadol (LAAM) for opioid agonist maintenance treatment. Numerous clinical trials con- ducted over the past decade confirmed buprenorphine’s utility for opioid dependence treatment. In double- blind, randomized clinical trials the efficacies of various doses of buprenorphine and methadone or LAAM were compared to find the most appropriate dosages of buprenorphine for the treatment of opioid dependence (Bickel et al., 1988; Johnson et al., 1992; Kosten et al., 1993; Strain et al., 1994, 1996; Ling et al., 1996; Schot- tenfeld et al., 1997). Subsequent research demonstrated that buprenorphine is a safe, effective candidate for long-term maintenance (Johnson et al., 1995; Ling et al., 1998; Johnson et al., 2000) and that it produces significant substantial improvements in psychosocial functioning over time (Strain et al., 1996). Buprenorphine dissociates relatively slowly from - opioid receptors (Rance and Dickens, 1978), resulting in a long duration of action (Jasinski et al., 1978). Because of buprenorphine’s long duration of action it can be, unlike methadone and like LAAM, adminis- tered on a less than daily basis (Amass et al., 1994, 1998; Fudala et al., 1990; Johnson et al., 1995). Our laboratory has been engaged in a series of investiga- tions to identify how long the interdosing interval can be extended by increasing the buprenorphine dose. We have shown, for example, that opioid-dependent indi- * Corresponding author. Tel.: +1-802-6568714; fax: +1-802- 6565793. E-mail address: agross@zoo.uvm.edu (A. Gross). 1 Present address: Southern Illinois University, Carbondale, IL 62901-6502, USA. 2 Present address: Department of Psychiatry, University of Con- necticut Health Center, Farmington, CT 06030-1517, USA. 0376-8716/01/$ - see front matter © 2001 Elsevier Science Ireland Ltd. All rights reserved. PII:S0376-8716(00)00227-1