Could High Habitual Alcohol Consumption Attenuate the Effects of Opioids?

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During the study, participants received 10 mg intravenous oxycodone and were assessed for opioid responses at 11 time points until 480 minutes.

Alcohol consumption appears to affect opioid central effects according to a study published in Pharmacology, Biochemistry and Behavior.

Researchers from the University of Washington recruited community dwelling adults (N=128) aged 35 to 95 years who had up to moderate chronic pain and were free from physical limitations. Participants were asked to refrain from alcohol consumption for 24 hours; herbal medications, sedatives, antihistamines, and antifungals for 48 hours; and nonsteroidal anti-inflammatory drugs, benzodiazepines, acetaminophen, and opioids for 1 week.

During the study visit, participants received 10 mg intravenous oxycodone and were assessed for opioid responses at 11 time points until 480 minutes. In addition, the participants were evaluated for balance, cognitive performance, and responded to questionnaires at 90 minutes and 5 and 8 hours.

The study population was aged mean 59 (standard deviation [SD], 13) years, 40% were women, 90% were White, and they consumed 1.9 (SD, 1.7) average drinks per day.

There was a significant miotic pupil effect in response to oxycodone (P <.01). Stratified by low (<0.3 μM total blood phosphatidylethanol) and high (≥0.3 μM total blood phosphatidylethanol) customary alcohol consumption, those who consumed more alcohol regularly had a reduced miotic effect (P <.023). Further stratifying participants by middle (35 to 59 years) and older (≥60 years) ages indicated that middle aged participants who consumed more alcohol had the lowest miotic effect compared with other groups at all time points (P <.001).

In general, cognitive measures declined from baseline after oxycodone administration. The opioid effect on cognition was attenuated among high alcohol consumers for verbal memory (P <.001), working memory (P <.001), and Phased Go, no Go sustained attention (P <.05) and the high alcohol consumers improved their performance in the Digit Symbol Substitution Test sustained attention (P <.001), a simulated driving task (P <.01), and selective attention task (P <.01).

The effect of oxycodone on cold pressor test tolerance was slightly attenuated among the high alcohol consumers, although this difference did not reach statistical significance. The investigators did observe a significant gender effect (P <.05).

On the day after oxycodone use, high consumers of alcohol more strongly endorsed oxycodone’s “good” effects (P <.05), and more women rated oxycodone as having “strong” (P <.05) and “bad” (P <.05) effects than men. Individuals with previous drug experience were more willing to take the drug again (P <.05).

This study may not be generalizable to individuals with even higher customary alcohol consumption as participants with alcohol withdrawal symptoms were excluded as well as individuals who were unwilling to abstain from alcohol use for 24 hours.

This study found that customary alcohol consumption attenuated some of the effects of oxycodone. These findings could indicate that individuals who consume high levels of alcohol may be at increased risk for continued use or abuse. These effects appeared to be exacerbated among men as they were more likely to positively endorse the drug’s effects.


Cherrier MM, Shen DD, Shireman L, et al. Elevated customary alcohol consumption attenuates opioid effects. Pharmacol Biochem Behav. 2021;211:173295. doi:10.1016/j.pbb.2021.173295