Lidocaine Infusion as a Treatment for Cocaine Relapse and Craving
Condition: Cocaine Addiction
MeSH terms: Cocaine-Related Disorders; Behavior, Addictive
Study type: Interventional
Phase: Phase 2

Summary: 
      We propose that the systemic administration of lidocaine following the induction of
      cue-induced craving, relative to saline plus cue-induced craving or lidocaine without
      cue-induced craving, will block the reconsolidation of cue memories. This will lead to a
      reduction in cue-induced craving upon repeated testing as well as subsequent cocaine use and
      basal craving.
    

Detailed description: 
      Cocaine dependence is among the most tenacious of the substance use disorders yet remains one
      of the few lacking an effective pharmacological intervention. As other pharmacologic
      approaches have not been fruitful, new targets are required. A novel treatment approach is to
      disrupt the neural processes involved in cue-related memories (memory links between the
      external stimuli associated with drug use and the subjective drug effect). These engrained
      memories, when reactivated by cues, elicit craving and a return to drug use. Each cue
      re-exposure, however, requires the re-remembering (or reconsolidation) of the drug cue. Key
      molecular processes required for memory reconsolidation are NMDA (N-methyl-D-aspartate)
      receptor activation, the induction of nitric oxide (NO) synthesis and increased extracellular
      signal-regulated kinase (ERK) activity. In rodent models, blocking these processes changes
      the cue-related memory; the cue loses its potency to induce a return to drug
      self-administration. Lidocaine is an FDA (Food and Drug Administration) approved medication
      that inhibits activation of NMDA (N-methyl-D-aspartate) receptors and suppresses production
      of NO (nitric oxide) and ERK (extracellular signal-regulated kinase). Lidocaine, like
      cocaine, is a local anesthetic with potent effects as a sodium-channel blocker. Unlike
      cocaine, lidocaine is essentially devoid of activity at monoamine re-uptake transporters and
      has no rewarding or addictive properties. As lidocaine suppresses the molecular processes
      required for drug cue reconsolidation and has relatively specific effects upon the striatal
      regions necessary for drug cue reconsolidation, lidocaine may offer a novel approach for
      interfering with memory reconsolidation. Two other (Sodium) Na+ channel blockers have also
      decrease craving and/or substance use in substance-dependent subjects. We propose that the
      systemic administration of lidocaine following the induction of cue-induced craving, relative
      to saline plus cue-induced craving or lidocaine without cue-induced craving, will block the
      reconsolidation of cue memories. This will lead to a reduction in cue-induced craving upon
      repeated testing as well as subsequent cocaine use and basal craving. If our hypotheses are
      proven correct, these findings will 1) support a role for lidocaine in cocaine addiction
      treatment, 2) demonstrate the feasibility and efficacy of attenuating cue-induced memories,
      and 3) guide the development of a larger study with lidocaine.
    

Intervention name(s): lidocaine following cue-induced craving; lidocaine following neutral stimulus; saline
Intervention type(s): Drug; Drug; Drug
Intervention description(s): as described in Arm Description; as described in Arm Description; as described in Arm Description
Other intervention name(s): Xylocaine; Xylocaine; 0.9% Sodium chloride
Intervention MeSH terms: Lidocaine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: cocaine; addiction; lidocaine; memory; drug abuse