Effect of Clonidine on Responses to Imagery Scripts
Condition: Cocaine Abuse; Heroin Abuse
MeSH terms: Cocaine-Related Disorders; Heroin Dependence
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

      - Research has shown that clonidine, a drug originally prescribed to treat high blood
      pressure and some symptoms of opioid withdrawal, can help block stress-induced relapse to
      heroin and cocaine seeking in rats. However, it does not seem to block cue-induced relapse in
      rats. Researchers are interested in studying whether clonidine shows the same pattern of
      effects on stress- and cue-induced cravings for heroin or cocaine in humans.

      Objectives:

      - To compare the ability of clonidine to reduce stress- and cue-induced cocaine and heroin
      craving in drug abusers.

      Eligibility:

      - Individuals between 18 and 55 years of age who are current cocaine or heroin users.

      Design:

        -  This study will consist of two visits: a screening visit to determine eligibility and an
           experimental/script session.

        -  Before the script session, participants will provide urine and breath samples for
           testing. Participants will complete questionnaires to measure their current drug craving
           and days since last use of cocaine or heroin.

        -  At the start of the script session, participants will receive a dose of clonidine or
           placebo as directed by the study researchers. Three hours after dosing, participants
           will be read four scripts (two neutral, one stress-inducing, and one drug-cue-related)
           with breaks in between each script. After each script, participants will respond to
           questions about levels of stress and craving.

        -  Participants will provide saliva samples immediately before and during the script
           readings, and will also be measured for skin response to the scripts.
    

Detailed description: 
      Background. Stress and exposure to drug-related cues (environmental stimuli previously
      associated with drug availability) are considered factors that increase the risk of relapse
      to heroin and/or cocaine use. The two factors may act through different neural mechanisms.
      Alpha-2 adrenergic agonists, such as clonidine, have been shown to block stress-induced
      relapse, but not cue-induced relapse, to heroin and cocaine self-administration in rodents.
      The ability of clonidine to attenuate stress- or cue-induced heroin and cocaine craving in
      drug abusers has not been tested. It is important to determine, in humans, whether clonidine
      blocks the acute effects of only one putative class of relapse precipitants, or whether its
      effects are more general.

      Scientific goal. To compare the ability of clonidine to reduce stress-induced and cue-induced
      cocaine and heroin craving in drug abusers.

      Participant population. A total of up to 160 drug abusers using cocaine, heroin, or both will
      be enrolled. Target enrollment will include 40% women and 60% minorities (mostly
      African-American).

      Experimental design and methods. Participants will be randomized to one of three groups
      receiving clonidine 0.1 mg, clonidine 0.2 mg, or placebo orally under double-blind
      conditions. The study will consist of a single 5-6 hr experimental session in which there
      will be baseline measures, drug administration, and four script-guided imagery sets, each
      followed by a period of data collection. Three hours after dosing (when peak plasma clonidine
      concentrations are reached), participants will be exposed to four scripts: one
      stress-inducing, one describing drug cues, and two with neutral content. The standardized
      script-guided imagery procedure has previously been shown to reliably induce negative
      affective states (stress scripts) and/or craving (stress and drug-cue scripts) compared to
      the neutral scripts and to have internal and external validity (Tiffany and Drobes, 1990;
      Maude-Griffin and Tiffany, 1996; Taylor et al., 2000; Sinha et al., 1999, 2000, 2003;
      Singleton et al., 2003; Tiffany and Haekeneworth, 1991; Elash et al., 1995; Drobes and
      Tiffany, 1997; Taylor et al., 2000; Singleton et al., 2003). Outcome measures will include
      subjective ratings of drug craving and mood, autonomic response (galvanic skin response
      [GSR]), and endocrine responses (salivary cortisol and salivary ?-amylase, a measure of
      endogenous adrenergic activity during stress (Chatterton et al., 1996; Nater et al., 2005;
      van Stegeren et al., 2005)).

      Benefits to participants and/or society. There are no direct benefits to participants.
      However, if clonidine is effective in blocking stress-induced and/or cue-induced craving,
      then the results will be used as a basis for designing a treatment trial, and drug abusers
      and society may benefit from the eventual use of clonidine or other alpha agonists for
      prevention of relapse in cocaine and heroin users. In addition, this research will provide
      information on the clinical relevance of a preclinical model of relapse, possibly
      strengthening arguments for its use in medication development.

      Risks to participants. Participants may experience side effects from clonidine such as
      sedation and are expected to experience brief, mild psychological stress and drug craving
      from the laboratory script procedures. Prior to leaving the session, participants will be
      assessed for the presence of continued drug effects. If participants are experiencing any
      stress or craving at the end of the session, they will undergo a 10-minute guided relaxation
      session, which will be repeated until feelings of stress or craving dissipate, before being
      released from the laboratory. Participants may be kept longer than the planned session
      length, up to and including staying overnight on the inpatient ward, because of continued
      side effects or elevated stress or craving. If the MRP deems it medically necessary,
      participants will be sent to JHBMC emergency department for further evaluation and treatment.
    

Intervention name(s): Clonidine; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 0.1 or 0.2 mg oral, one dose; oral capsule 1 dose
Intervention MeSH terms: Clonidine
Allocation: Randomized
Intervention model: Parallel Assignment
Primary purpose: Treatment
Keywords: Drug Cue; Relapse; Stress; Craving