Lidocaine Infusion as a Treatment for Cocaine Relapse and Craving

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.

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.

Eligibility Criteria:
Inclusion Criteria:

* 25-60 years old
* men or women
* any race or ethnicity
* cocaine addition is primary present and lifetime drug of abuse
* live locally

Exclusion Criteria:

* Patients with active DSM (Diagnostic Statistical Manual)-IV other Substance Dependence (except nicotine) within the previous three months, Affective Disorder, Schizophrenic Disorders.
* significant cognitive impairment (WTAR\<70) (Wechsler Test of Adult Reading \<70)..
* use of tricyclic anti-depressants, benzodiazepines, cimetidine, mood stabilizers, opioids, lithium, sympathomimetics, anticonvulsants, sedative/hypnotics, β-blockers, or dopamine agonists will be excluded from the study.
* Medical conditions that might limit cooperation (e.g. dementia) or put the patient at medical risk (i.e. significant hematologic, hepatic, renal, or cardiovascular pathology - particularly arrhythmias) will be excluded.
* Patients with congenital or idiopathic methemoglobinemia or patients taking medications associated with increased risk of methemoglobinemia (including sulfonamides, acetaminophen, acetanilid, aniline dyes, benzocaine, chloroquine, dapsone, naphthalene, nitrates and nitrites, nitrofurantoin, nitroglycerin, nitroprusside, pamaquine, paraaminosalicylic acid, phenacetin, phenobarbital, phenytoin, primaquine, quinine) will be excluded.
* Patients with past or present neurologic disorders (i.e. severe head trauma, transient ischemic attacks, stroke, tumor, etc.) will be excluded. - Active suicidal ideation, pregnant or nursing women, and prisoners will be excluded from the study.