Aversive and Reinforcing Opioid Effects

Aversive and Reinforcing Opioid Effects: A Pharmacogenomic Twin Study | Anesthesiology. 2012 Jul | Free Full-text PMC article

The clinical utility of opioids is limited by adverse drug effects including respiratory depression, sedation, nausea, and pruritus. In addition, abuse of prescription opioids is problematic.

Gaining a better understanding of the genetic and environmental mechanisms contributing to an individual’s susceptibility to adverse opioid effects is essential to identify patients at risk.

While more and more studies are showing how frequently and thoroughly genetic differences affect patients, the CDC is denying all this science to arrive at arbitrary “standard” doses of opioids.


A classical twin study paradigm provided estimates for the genetic and familial (genetic and/or shared environment) contribution to acute adverse and affective opioid responses; all secondary outcomes of a larger data set. One hundred and twenty one twin pairs were recruited in a single occasion, randomized, double-blind and placebo controlled study.


Significant heritability was detected for

  • respiratory depression (30%),
  • nausea (59%) and
  • drug disliking (36%).

Significant familial effects were detected for

  • sedation (29%),
  • pruritus (38%), [itching]
  • dizziness (32%), and
  • drug liking (26%).

Significant covariates included

  • age,
  • gender,
  • race,
  • ethnicity,
  • education,
  • mood and
  • depression.

Covariates affected

  • sedation,
  • pruritus,
  • drug liking and disliking, and
  • dizziness.


This study demonstrates that large scale efforts to collect quantitative and well-defined opioid response data are not only feasible but also produce data that are suitable for genetic analysis.

Genetic, environmental and demographic factors work together to control adverse and reinforcing opioid responses, but contribute differently to specific responses.

Addiction to opioids is heritable, and genetic studies have been designed to address the specific molecular underpinning.

While our study paradigm did not allow directly studying the complex clinical phenotype of opioid addiction, we were able to precisely measure acute reinforcing effects such as the liking and disliking of the drug.

  • Liking in response to acute opioid administration is an established index phenotype to predict abuse potential, whereas
  • Disliking upon first exposure is associated with lack of abuse  

What this article tells us that is new

  • The adverse effects of a steady-state alfentanil infusion were studied in 114 monozygotic and dizygotic twin pairs.
  • Genetic effects were detected for decreased respiratory rate, nausea, and drug disliking.
  • Genetic and/or shared environmental effects were detected for increased transcutaneous CO2, sedation, pruritis, dizziness, and drug liking.

One thought on “Aversive and Reinforcing Opioid Effects

  1. Laura P. Schulman, MD, MA

    Reblogged this on Bipolar For Life and commented:
    I’m glad to see this. There’s more behind “drug liking,” and I hope to see it surface in the literature. In fact, I think the work might have already been done. You might know of it.

    My curiosity was initially piqued by conversations I had with addicts who told me that the first time they took an opioid pill, it was as if they felt like their genuine self for the first time. They had always felt somehow empty, incomplete, uncomfortable in their own skin, and then they broke their toe or something and got some Percodan and, wow! The lights came on in color. And their lives ever since kind of revolved around keeping that going.

    So I made the assumption that this subclass of homo sapiens must have a genetic problem in the endogenous oipiate department, felt sorry for them because they couldn’t for some reason get that amazing rush and long-lasting well-being that I got from running, and forgot about it until the recent out of control lunacy.

    I do believe there are people who really can’t produce their own endogenous opiates. What a misery! I can’t imagine.

    I hope the science will be better understood so that these people can be treated for their medical needs without being stigmatized, abused, marginalized, punished….

    Liked by 1 person


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