Behavioral and Physiological Effects of Cocaine in Cocaine-dependent Participants Treated With Levodopa in Combination With Carbidopa and Entacapone (LCE)
Condition: Cocaine Abuse
MeSH terms: Cocaine-Related Disorders
Study type: Interventional
Phase: Phase 1

Summary: 
      An inpatient safety study to characterize the cardiovascular and behavioral effects of
      cocaine administration in the presence of LCE. The proposed study involves an inpatient stay
      of 12 days during which participants will have two cocaine-administration sessions, each
      including five doses of smoked cocaine with ascending doses.
    

Detailed description: 
      Cocaine dependence remains a serious public health problem; however no clearly effective
      pharmacological treatments have been identified to date. We hypothesize that identification
      of subgroups of cocaine-dependent patients will help to develop targeted and more effective
      treatments. We hypothesize that individuals who have difficulties in achieving abstinence
      have a deficit in dopaminergic functioning and correcting this deficit using dopaminergic
      medication levodopa in combination with carbidopa and entacapone (LCE) to increase
      availability and uptake of levodopa to synthesize dopamine in the brain will result in
      clinical improvement. We were unable to locate any clinical reports that might provide data
      on the interaction between cocaine and LCE. Therefore, we would like to conduct an inpatient
      safety study to characterize the cardiovascular and behavioral effects of cocaine
      administration in the presence of LCE. The proposed study involves an inpatient stay of 12
      days during which participants will have two cocaine-administration sessions, each including
      five doses of smoked cocaine with ascending doses. Participants will be maintained on placebo
      capsules prior to the first study session and on the LCE prior to the second session.
      Physiological (HR, BP, ECG) as well as behavioral (subjective effects) effects of cocaine
      will be monitored during cocaine-administration sessions. Serial blood samples will also
      follow cocaine administration to assess whether the pharmacokinetics of cocaine is altered
      during treatment with LCE. All participants will also undergo two cognitive testing sessions,
      one on placebo and one on LCE, employing a computerized battery (Quarters, Gambling task,
      Drug Stroop, Threat Responsivity task). There will be an optional functional MRI (fMRI)
      component that will investigate behavioral and neural indicators of reward responsivity,
      thought to reflect dopaminergic transmission. Participants choosing to undergo fMRI testing
      will complete two sessions, on the same days as the cognitive task sessions. Data obtained in
      the present study will be used to inform the large, controlled trial of LCE in treatment
      seeking cocaine-dependent individuals.
    

Intervention name(s): L-dopa / carbidopa / entacapone (LCE)
Intervention type(s): Drug
Intervention description(s): For this trial we propose a target dosage of L-dopa / carbidopa / entacapone of 400 mg L-dopa / 100mg carbidopa / 200 mg entacapone, twice daily.
Other intervention name(s): L/C/E
Intervention MeSH terms: Carbidopa; Entacapone
Intervention model: Single Group Assignment
Masking: Single (Participant)
Primary purpose: Basic Science
Keywords: cocaine