Adolescent alcohol use is associated with myriad adverse consequences and contributes to the leading causes of mortality among youth. Despite the magnitude of this public health problem, evidenced-based treatment initiatives for alcohol use disorders in youth remain inadequate. Identifying promising pharmacological approaches may improve treatment options. Naltrexone is an opiate receptor antagonist that is efficacious for reducing drinking in adults by attenuating craving and the rewarding effects of alcohol. Implications of these findings for adolescents are unclear, however, given that randomized trials of naltrexone with youth are nonexistent. We conducted a randomized, double-blinded, placebo-controlled crossover study, comparing naltrexone (50 mg/daily) and placebo in 22 adolescent problem drinkers aged 15 – 19 years (M = 18.36, SD = 0.95; 12 females). The primary outcome measures were alcohol use, subjective responses to alcohol consumption, and alcohol-cue-elicited craving assessed in the natural environment using ecological momentary assessment methods, and craving and physiological reactivity assessed using standard alcohol cue reactivity procedures. Results showed that naltrexone reduced the likelihood of drinking and heavy drinking (p’s ≤ .03), blunted craving in the laboratory and in the natural environment (p’s ≤ .04), and altered subjective responses to alcohol consumption (p’s ≤ .01). Naltrexone was generally well tolerated by participants. This study provides the first experimentally controlled evidence that naltrexone reduces drinking and craving, and alters subjective responses to alcohol in a sample of adolescent problem drinkers, and suggests larger clinical trials with long-term follow ups are warranted.

Theoretical models of alcoholism emphasize the acute reinforcing properties of alcohol as chief determinants of drinking, and animal research suggests adolescents are uniquely sensitive to these effects. Human studies of these phenomena, however, are virtually nonexistent. We used ecological momentary assessment methods to capture adolescents' subjective responses to alcohol in real time in their natural environments. Adolescent participants were 22 problem drinkers, ages 15 to 19 years (M = 18.3, SD = 0.09; 55% female; 55% alcohol dependent). Participants consumed alcohol on 38% of days during a one-week monitoring period, with an average of 5 drinks per occasion. Momentary data revealed that adolescents experience decreased stimulation and increased sedation and ‘high’ across the ascending limb of the blood alcohol curve. Notably, greater craving predicted higher volumes of subsequent alcohol consumption during the episode, whereas greater ‘high’ attenuated use. To test for developmental differences in these effects, we pooled these data with data from a similarly ascertained sample of 36 adult heavy drinkers, ages 24 to 64 years (M = 38.1, SD = 11.8; 50% female; 61% alcohol dependent). Adolescents were more sensitive to the stimulant effects of alcohol than adults. This study provides novel data on how adolescent problem drinkers experience alcohol in their natural contexts and illustrates how these effects, which appear to differ from adult problem drinkers, confer liability for future drinking.

Topiramate reduces drinking, but little is known about the mechanisms that precipitate this effect. This double-blind randomized placebo-controlled study assessed the putative mechanisms by which topiramate reduces alcohol use among 96 adult nontreatment-seeking heavy drinkers in a laboratory-based alcohol cue reactivity assessment and in the natural environment using ecological momentary assessment methods. Topiramate reduced the quantity of alcohol heavy drinkers consumed on drinking days and reduced craving while participants were drinking but did not affect craving outside of drinking episodes in either the laboratory or in the natural environment. Topiramate did not alter the stimulant or sedative effects of alcohol ingestion during the ascending limb of the blood alcohol curve. A direct test of putative mechanisms of action using multilevel structural equation mediation models showed that topiramate reduced drinking indirectly by blunting alcohol-induced craving. These findings provide the first real-time prospective evidence that topiramate reduces drinking by reducing alcohol’s priming effects on craving and highlight the importance of craving as an important treatment target of pharmacotherapy for alcoholism.