Effect of Zonisamide on Cocaine Reinforcement, Craving, and Relapse
Condition: Cocaine Dependence
MeSH terms: Cocaine-Related Disorders
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This is a residential pilot trial to evaluate the pharmacodynamic interaction between
      zonisamide and cocaine, with the goal of evaluating zonisamide's potential for the treatment
      of cocaine dependence.
    

Detailed description: 
      This is a residential pilot trial to evaluate the effect of zonisamide (ZNS) on cocaine
      reinforcement, craving and relapse. Cocaine addiction remains a major social and medical
      problem that imposes a significant burden on our society, as more than a half million cocaine
      dependent individuals are seeking treatment every year. Medications that act to antagonize
      the glutamate system and/or increase the GABA-system are new targets in the search towards
      effective cocaine treatment. ZNS is part of a new line of antiepileptic agents that act both
      as glutamate antagonists and to enhance the Gamma-AminoButyric acid (GABA) system.
      Topiramate, a similar agent, showed a positive signal in a pilot trial for cocaine
      dependence. ZNS has the advantages of a longer half-life requiring only once a day dosing
      and, being better tolerated, it requires a shorter induction phase and can be administered at
      higher doses. We hypothesize that ZNS in moderate to high doses will attenuate the central
      effect of cocaine and improve the neural perturbations resulting from cocaine use, thus
      decreasing cocaine craving. Healthy, adult cocaine dependent volunteers will be enrolled on
      our residential unit for 44 days for this double-blind within subject study. The
      pharmacodynamic interactions between ZNS and cocaine will be measured in cocaine
      self-administration procedure offering alternative reinforcers with monetary values. Cocaine
      reinforcing effect will be evaluated over a range of doses, and subjective and objective
      outcomes on mood and behavior will be collected. In addition, the effect of ZNS on ad-lib
      smoking will be studied on the days when no other procedure interferes with smoking
      behaviors. Neurocognitive and psychomotor effects of ZNS treatment will also be studied with
      an extensive test battery on the day of the week when no cocaine is administered. This study
      will explore the potential therapeutic effect of ZNS for the treatment of cocaine dependence
      while providing necessary safety assessments required for possible future outpatient clinical
      trials.
    

Intervention name(s): Zonisamide; Placebo; Cocaine Hydrochloride; Neurocognitive and Performance Battery; Smoking Assessments
Intervention type(s): Drug; Drug; Drug; Behavioral; Behavioral
Intervention description(s): Eight capsules administered daily in split doses at 22:00 and 09:00.; capsules administered in split doses at 22:00 and 09:00.; Cocaine Challenge Sessions: Human laboratory sessions with administration of moderate doses of cocaine by the intravenous route under controlled conditions and cardiovascular monitoring.; Participants will complete tests to assess their abilities and performances on a number of tasks given by a computer or other type of equipment.; Participants answer questions about smoking and smoking behaviors are monitored.
Other intervention name(s): Zonegran,; CAS 68291-97-4,; CAS 50-36-2; methylbenzoylecgonine; benzoylmethylecgonine; C17H21NO4
Intervention MeSH terms: Zonisamide; Cocaine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Other
Keywords: cocaine; addiction; drug dependence; anticonvulsant; zonisamide; drug self-administration; nicotine withdrawal; neurocognition