Reinforcing Effects of Intranasal (IN) Buprenorphine Versus Buprenorphine/Naloxone
Condition: Heroin Dependence
MeSH terms: Heroin Dependence
Study type: Interventional
Phase: Phase 3

Summary: 
      The study is designed to compare the abuse liabilities of intranasal buprenorphine and
      buprenorphine/naloxone in individuals who are physically dependent on sublingual
      buprenorphine. The investigators hypothesize that the abuse liability of
      buprenorphine/naloxone is lower than that of buprenorphine alone.
    

Detailed description: 
      Although sublingual buprenorphine is an effective treatment for opioid addiction, the
      medication itself has abuse liability and, in some countries, has largely replaced heroin as
      the opioid drug of choice. In response to the reports of diversion and abuse of sublingual
      (SL) buprenorphine, a potentially less abusable formulation of buprenorphine that contains
      naloxone is being marketed in several countries. However, the relative abuse liability of
      buprenorphine alone and the buprenorphine/naloxone combination in buprenorphine-dependent
      individuals is unclear. Preliminary data from a study funded by Schering-Plough Corporation
      suggest that the buprenorphine/naloxone combination, when given intravenously (IV), does
      indeed have less abuse liability than IV buprenorphine in buprenorphine-dependent
      individuals. In addition to IV abuse of buprenorphine, epidemiological data suggest that
      buprenorphine is widely abused by the intranasal (IN) route. However, no data exist on the
      abuse liability of either IN buprenorphine alone or the buprenorphine/naloxone combination.
      Several studies have shown that naloxone is an effective antagonist of opioid agonist effects
      when given intravenously, but it is not clear whether naloxone given intranasally is as
      effective as when it is given by other routes of administration. Some studies have suggested
      that they are equally effective (Loimer et al., 1994), but others have shown that naloxone
      given intranasally is less effective (i.e., has a slower onset of effects) than when given by
      other routes of administration (Kelly et al., 2005). How this may impact on the ability of
      naloxone to reduce the reinforcing effects of IN buprenorphine is unclear. The primary aim of
      the current study proposal is to compare the reinforcing effects of IN buprenorphine and
      buprenorphine/naloxone in IN opioid abusers who are maintained on SL buprenorphine using a
      study design parallel to that used in our recent studies of the abuse liability of IV
      buprenorphine and buprenorphine/naloxone. Placebo, heroin, and naloxone will be used as
      neutral, positive, and negative controls, respectively. Secondary aims are to compare the
      subjective, performance, and physiological effects of IN buprenorphine and
      buprenorphine/naloxone. Overall, this study will complement our investigations of IV
      buprenorphine products by allowing for a complete overview within the same laboratory
      self-administration model of both the intravenous and intranasal abuse liability of
      buprenorphine versus buprenorphine/naloxone in individuals maintained on buprenorphine. The
      primary aim of the study is to compare the reinforcing effects of IN buprenorphine and IN
      buprenorphine/naloxone in opioid abusers maintained on different doses of sublingual
      buprenorphine. Secondary aims of the study are to compare the subjective, performance and
      physiological effects of IN buprenorphine and IN buprenorphine/naloxone. IN-administered
      placebo (lactose powder), naloxone alone, and heroin alone will be tested as neutral,
      negative, and positive control conditions, respectively. Participants (N=12 completers) will
      reside on an inpatient unit (5-South) during a 7 to 8-week study. This research will provide
      useful information to clinicians treating opioid dependent individuals with buprenorphine,
      and importantly, will provide information about the abuse potential and effects of
      buprenorphine on multiple measures of human functioning.
    

Intervention name(s): Intranasal challenge drug
Intervention type(s): Drug
Intervention description(s): Each of the experimental challenge drugs were administered intranasally to all participants in random order.
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: In this study's design, all participants received each of the 9 intranasal test drugs under investigation. This study employed a Latin-square randomization procedure, therefore, the sequence of testing for the 9 intranasal drugs was unique for each participant.
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: opioid dependence