Across the spectrum: Acute alcohol responses in young adults with mild, moderate, and severe alcohol use disorder.

Background: Little is known about acute subjective and physiological responses to alcohol in individuals with alcohol use disorder (AUD), particularly as it pertains to the spectrum of AUD severity. This study examined acute biphasic alcohol response phenotypes in participants with mild, moderate, and severe AUD.

Methods: Study data was from the third cohort of the Chicago Social Drinking Project (N = 101, 50 % male; M age=27.1 years). AUD severity was determined based on the DSM-5; 20 % of participants had mild, 20 % had moderate, and 60 % had severe AUD. In a random-order, within-subject, oral alcohol administration paradigm, participants received a high alcohol dose (0.8g/kg), a very high alcohol dose (1.2g/kg), and placebo in separate sessions. Breath alcohol concentration (BrAC), subjective responses (liking, wanting, stimulation, and sedation), and cortisol levels were measured.

Results: Analyses revealed that, relative to those with mild AUD, both very high and high alcohol doses (vs. placebo) significantly increased liking, wanting, and stimulation in the severe AUD subgroup, with a dose-response relationship (very high dose > high dose > placebo) in the moderate AUD subgroup. Alcohol produced lower sedation in participants with moderate and severe AUD relative to mild AUD, suggestive of tolerance to alcohol's sedating and fatiguing effects. Cortisol response to alcohol did not differ across groups, except for higher baseline levels in the severe AUD subgroup, which carried forward.

Conclusions: Taken together, these findings indicate that higher AUD severity is associated with enhanced sensitivity to alcohol's positive effects, challenging traditional notions of global alcohol tolerance and reward deficit in people who drink excessively.