Lacosamide Effects on Alcohol Self Administration and Craving in Heavy Drinkers
Condition: Alcohol Use Disorder
MeSH terms: Alcoholism; Alcoholic Intoxication; Alcohol Drinking
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a double-blind, randomized, placebo-controlled, crossover design trial tested the
      effect of lacosamide on alcohol self-administration and craving following a priming dose of
      alcohol. The specific objective of this study was to determine whether lacosamide, a novel
      anticonvulsant that is FDA-approved for treating partial seizures, has effects on alcohol
      craving and consumption.
    

Detailed description: 
      The present proposal was intended to answer the call for accelerating drug development by
      exploring the potential of a novel anticonvulsant, lacosamide, as a candidate medication for
      the treatment of alcohol use disorder (AUD). This drug, which is approved for the treatment
      of seizure disorders, has unique pharmacological actions that include enhancement of slow
      sodium channel inactivation and inhibition of collapsin response mediator protein-2 (CRMP-2).
      Alcohol consumption in mice that had knockdown of CRMP-2 within the nucleus accumbens was
      decreased from levels seen in control animals. In rodent studies, lacosamide administration
      has produced reductions in 'excessive' drinking and has experimentally-induced decreased
      expression of the CRMP-2 protein. These findings implicate CRMP-2 as playing a role in the
      regulation of alcohol consumption. None of the FDA-approved AUD medications or medications
      commonly used off-label to treat AUD target this CRMP-2 pathway, making lacosamide a
      promising compound for AUD drug development. The aims of this study were to: 1) test the
      effects of lacosamide on alcohol self-administration and craving, 2) test the effects of 7
      days of lacosamide administration on cognitive function, and 3) test the effects of
      lacosamide on alcohol consumption and craving during a 7-day period of exposure. The effects
      of 7 days of lacosamide (300mg) or placebo were evaluated in a human laboratory using an
      alcohol self-administration methodology. In this within-subjects crossover design, heavy
      drinkers (N=27) were randomized to the order of exposure (lacosamide or placebo) prior to
      completing two alcohol self-administration trials. Subjects received a priming drink of
      alcohol and had access to 8 alcoholic drinks over a 2-hour period. The investigators
      anticipated that subjects would consume less alcohol during an alcohol self-administration
      trial when receiving lacosamide compared to when they are receiving placebo. Significant
      lacosamide-induced reductions in the quantity of alcohol self-administered are considered to
      be an indication that this drug may have value as an AUD medication. This study may provide a
      rationale for phase II clinical studies testing lacosamide with a treatment-seeking AUD
      population. These results should also help to spur further pre-clinical investigation into
      the role play by CRMP-2 in regulating both alcohol consumption and alcohol seeking behaviors.
    

Intervention name(s): Lacosamide; Placebo oral capsule
Intervention type(s): Drug; Drug
Intervention description(s): Lacosamide titration was done to a target dose of 300mg. Participants took 100 mg of lacosamide once on day 1, 100 mg twice per day from day 2 through day 6 (200 mg daily total), on day 7 the lacosamide dose was increased to 150 mg twice daily (300 mg daily total), and on day 8 the participant took one dose of 150 mg.; Participants took a placebo oral capsule once on day 1, twice per day from day 2 to day 7, and once on day 8.
Other intervention name(s): Vimpat
Intervention MeSH terms: Lacosamide
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: This is a double-blind, randomized, placebo-controlled, crossover design trial to test the effect of lacosamide on alcohol self-administration and craving following a priming dose of alcohol.This study is a within subjects design in which each subject receives both study drug (lacosamide) and placebo during participation.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Lacosamide; Alcohol craving; Alcohol Urge Questionnaire; Obsessive-Compulsive Drinking Scale; Visual Analog Scale; Alcohol consumption; Alcohol use disorder