Lacosamide Effects on Alcohol Self Administration and Craving in Heavy Drinkers

The present proposal is 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 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 are to: 1) test the
effects of lacosamide on alcohol self-administration and craving, 2) test the effects of 5
days of lacosamide administration on cognitive function, and 3) test the effects of
lacosamide on alcohol consumption and craving during a 8-day period of exposure. The effects
of 8-days of locasamide (300mg) or placebo will be evaluated in a human laboratory using an
alcohol self-administration methodology. In this within-subjects crossover design, heavy
drinkers (N=28) will be randomized to the order of exposure (lacosamide or placebo) prior to
completing two alcohol self-administration trials. Subjects will receive a priming drink of
alcohol and will have access to 8 alcoholic drinks over a 2-hour period. The investigators
anticipate that subjects will 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 will be 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.

Inclusion criteria

1. 21-35 years of age

2. Can provide proof of age with state-issued or federal picture ID

3. Exceeds safe weekly drinking limits (14 drinks for women or 21 drinks for men per
week)

4. Reports at least one episode of binge drinking (>3 for women, >4 for men) in each of
the four weeks prior to baseline screening

5. Meets DSM-5 criteria for mild alcohol use disorder or greater severity.

6. Have a smartphone to complete some of the study assessments.