Abuse Potential with Oral Route of Administration of a Hydrocodone Extended-Release Tablet Formulated with Abuse-Deterrence Technology in Nondependent, Recreational Opioid Users

Pain Med. 2017 Jan 1;18(1):61-77. doi: 10.1093/pm/pnw122.


Objective: To compare the oral abuse potential of hydrocodone extended-release (ER) tablet developed with CIMA ® Abuse-Deterrence Technology with that of hydrocodone immediate release (IR).

Design: Randomized, double-blind, placebo-controlled, crossover study.

Setting and patients: One study site in the United States; adult nondependent, recreational opioid users.

Methods: After confirming their ability to tolerate and discriminate hydrocodone IR 45 mg from placebo, eligible participants were randomized to receive each of the following oral treatments once: finely crushed placebo, hydrocodone IR 45-mg powder, intact hydrocodone ER 45-mg tablet, and finely crushed hydrocodone ER 45-mg tablet. Primary pharmacodynamic measure was "at the moment" drug liking. Secondary measures included overall drug liking, drug effects (e.g., balance, positive, negative, sedative), pupillometry, pharmacokinetics, and safety.

Results: Mean maximum effect (E max ) for "at the moment" drug liking was significantly lower for intact (53.9) and finely crushed hydrocodone ER (66.9) vs. hydrocodone IR (85.2; P < 0.001). Drug liking for intact hydrocodone ER was comparable to placebo (E max : 53.9 vs. 53.2). Secondary measures were consistent with these results, indicating that positive, negative, and sedative drug effects were diminished with intact and crushed hydrocodone ER tablet vs. hydrocodone IR. The 72-hour plasma concentration-time profile for each treatment mimicked its respective "at the moment" drug-liking-over-time profile. Incidence of adverse events was lower with intact hydrocodone ER (53%) vs. hydrocodone IR (79%) and finely crushed hydrocodone ER (73%).

Conclusions: The oral abuse potential of hydrocodone ER (intact and finely crushed) was significantly lower than hydrocodone IR in healthy, nondependent, recreational opioid users. Hydrocodone ER was generally well tolerated.

Keywords: Abuse Potential; Drug Liking; Extended Release; Hydrocodone; Opioid Analgesics; Substance Abuse.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Cross-Over Studies
  • Delayed-Action Preparations / administration & dosage
  • Double-Blind Method
  • Female
  • Humans
  • Hydrocodone / administration & dosage*
  • Hydrocodone / pharmacokinetics*
  • Illicit Drugs / pharmacokinetics
  • Male
  • Opioid-Related Disorders*
  • Powders
  • Tablets
  • Young Adult


  • Delayed-Action Preparations
  • Illicit Drugs
  • Powders
  • Tablets
  • Hydrocodone