Comparison of Subjective Responses to Oral and Intravenous Alcohol Administration Under Similar Systemic Exposures

Abstract

Background: Individuals perceive the effects of alcohol differently, and the variation is commonly used in research assessing the risk for developing an alcohol use disorder. Such research is supported by both oral and intravenous (IV) alcohol administration techniques, and any differences attributable to the route employed should be understood. Our objective was to test whether an individual's subjective responses to alcohol are similar when the breath alcohol concentration (BrAC) trajectory resulting from oral administration is matched by IV administration.

Methods: We conducted a 2-session, within-subject study in 44 young adult, healthy, nondependent drinkers (22 females and 22 males). In the first session, subjects ingested a dose of alcohol which was individually calculated, on the basis of total body water, to yield a peak BrAC near 80 mg/dl, and the resulting BrAC trajectory was recorded. A few days later, subjects received an IV alcohol infusion rate profile, precomputed to replicate each individual's oral alcohol BrAC trajectory. In both sessions, we assessed 4 subjective responses to alcohol: SEDATION, SIMULATION, INTOXICATION, and HIGH; at baseline and frequently for 4 hours. We compared the individuals' baseline-corrected responses at peak BrAC and at half-peak BrAC on both the ascending and descending limbs. We also computed and compared Pearson-product moment correlations of responses by route of administration, the Mellanby measure of acute adaptation to alcohol, and the area under the entire response curve for each subjective response.

Results: No significant differences in any measure could be attributed to the route of alcohol administration. Eleven of 12 response comparisons were significantly correlated across the routes of alcohol administration, with 9 surviving correction for multiple measures, as did the Mellanby effect and area under the response curve correlations.

Conclusions: The route of alcohol administration has a minimal effect on subjective responses to alcohol when an individual's BrAC exposure profiles are similar.

Keywords: Mellanby; Route of Administration; Subjective Response; Tolerance.

Figure 1.

Breath Alcohol Concentration (BrAC) Trajectories after Oral (upper) and matched IV (lower) Administration of Alcohol. Substantial experimental variability in BrAC exposure trajectories, resulting from a carefully-controlled, individualized oral dose of alcohol intended to reach a peak BrAC of 80 mg/dl in 44 participants, is apparent (Ramchandani et al., 2009). Each oral dosage was determined for the individual based upon their total body water, and administered under identical experimental conditions. The oral alcohol challenge BrAC response variability was matched during the IV session (lower).

Figure 2.

Subjective Response Trajectories after Oral and matched IV Administration of Alcohol. Substantial between-subject variability is apparent across the Sedation (row 1), Stimulation (row 2), Intoxication (row 3) and High (row 4) Subjective Response Measures in 44 participants to a carefully-controlled, individualized oral dose of alcohol intended to reach a peak BrAC of 80 mg/dl (left column) and subsequent IV session (right column) designed to match each individual’s oral alcohol challenge breath alcohol concentration response curve.

Figure 3:

Subjective Responses to Alcohol by Route of Administration. Responses (N=44 sample mean ± sem) are displayed as baseline-corrected values at times corresponding to individual peak BrAC and half-peak points on the ascending and descending limbs. Sedation and Stimulation values were scaled by a factor of 10 for display purposes.

Figure 4:

Subjective Response to Alcohol Correlations at Peak Breath Alcohol Concentration (BrAC) in Oral vs. IV administered alcohol sessions for 44 subjects. Sedation and Stimulation values were scaled by a factor of 5 for display purposes.