Reward drinking and naltrexone treatment response among young adult heavy drinkers

Addiction. 2021 Sep;116(9):2360-2371. doi: 10.1111/add.15453. Epub 2021 Mar 18.


Aims: Theory-driven, exploratory study to: (i) identify a reward drinking phenotype in young adults; (ii) evaluate this phenotype as a predictor of naltrexone response; and (iii) examine mechanisms of naltrexone in reward drinkers.

Design: Secondary analysis of a randomized controlled trial.

Setting: USA.

Participants: A total of 128 young adult (ages 18-25) heavy drinkers.

Interventions: Naltrexone versus placebo.

Measurements: Daily surveys assessed affect, urge, drinking, and context. The Drinking Motives Questionnaire was used to identify phenotypes based on reward (enhancement motives) and relief (coping motives) drinking.

Findings: We identified three profiles: "Low reward/Low relief" (14.1%; low enhancement/low coping motives); "Reward drinkers" (62.2%; high enhancement/low coping motives); and "High reward/High relief" (22.7%; high enhancement/high coping motives). Among reward drinkers (versus low profile), naltrexone significantly reduced percent days drinking to intoxication (blood alcohol concentration [BAC] ≥0.08) (PDI) (d = 0.56; 95% CI [0.17, 0.96]) and percent high intensity drinking days (PHID) (8/10 drinks for women/men) (d = 0.32; 95% CI [0.01, 0.68]). Among the high reward/high relief profile drinkers (versus low profile), naltrexone reduced PHID (d = 0.69; 95% CI [0.02, 1.50]). Using profile-informed cutoffs and observed scores (for clinical applicability): (i) among cutoff-derived reward drinkers, we found a medium-to-large (d = 0.66; 95% CI [0.24, 1.16]) and small effect (d = 0.28; 95% CI [0.04, 0.72]) of naltrexone in reducing PDI and PHID, respectively; and (ii) among the cutoff-derived high reward/high relief subgroup, we found a medium-to-large effect (d = 0.63; 95% CI [0.05, 1.1]) of naltrexone in reducing PHID. Among reward drinkers (not other profiles), naltrexone reduced drinking on days a drinking event occurred by weakening the within-day association between positive affect and urges (P < 0.05).

Conclusions: Naltrexone has pronounced effects in reducing risky drinking among young adult reward drinkers (high reward/low relief) by reducing urges on days when individuals have higher positive affect and are exposed to a drinking event. Naltrexone also appears to reduce risky drinking among young adult high reward/high relief drinkers, but not via the same mechanism.

Keywords: Heavy drinking; mechanisms; naltrexone; precision medicine; reward drinker; young adults.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alcohol Drinking
  • Alcoholism* / drug therapy
  • Blood Alcohol Content
  • Female
  • Humans
  • Male
  • Naltrexone* / therapeutic use
  • Reward
  • Young Adult


  • Blood Alcohol Content
  • Naltrexone