Reduced Cognitive and Psychomotor Impairment
with Extended-Release Oxymorphone Versus
Controlled-Release Oxycodone
Authors: Schoedel Kerri A. 
Published: March 2021

Background: Opioids provide effective pain control, yet have risks including adverse events (AEs)
(e.g., constipation, nausea/vomiting, sedation) and cognitive/psychomotor effects.
Objective: To compare cognitive and psychomotor effects of oxymorphone extended release
(OM-ER) versus oxycodone controlled release (OC-CR).
Study design: Randomized, double-blind, 5-way crossover
Setting: Single inpatient research unit
Methods: Nondependent recreational opioid users were administered single intact oral tablets of
placebo, OM-ER (15 and 30 mg), and OC-CR (30 and 60 mg), separated by a 7- to 21-day washout.
The divided attention (DA) test measured psychomotor impairment (e.g., manual tracking [e.g.,
percentage over road], target accuracy [e.g., target hits], reaction time [hit latency]). Visual analog
scales measured alertness/drowsiness, agitation/relaxation, and dizziness. Sedative, stimulant, and
dysphoric effects were measured using the Addiction Research Center Inventory PentobarbitalChlorpromazine-Alcohol (PCAG), Benzedrine Group (BG), and Lysergic Acid Diethylamide (LSD)
scales, respectively. Comparisons were made between equianalgesic doses (OM-ER 15 mg vs OCCR 30 mg; OM-ER 30 mg vs OC-CR 60 mg), within active drug doses, and between active drugs and
placebo using least squares (LS) mean difference of the peak maximum (Emax) or minimum (Emin)
effect using linear mixed model analysis of covariance.
Results: Thirty-five participants received all 5 treatments. Peak cognitive and psychomotor impairment
(LS mean [SE]) was less with OM-ER than equianalgesic doses of OC-CR for reaction time (Emax hit
latency, longer if impaired; 571.2 [13.4] vs 588.1 ms [13.4], P=0.03 for OM-ER 15 mg vs OC-CR 30 mg,
respectively; 572.4 [13.4] vs 604.3 ms [13.4], P<0.001 for OM-ER 30 mg vs OC-CR 60 mg, respectively);
tracking accuracy (Emin percentage over road, lower if impaired; 71.4 [2.4] vs 65.3 [2.4], P=0.007;
69.9 [2.4] vs 59.4 [2.4], P<0.001), and target accuracy (Emin target hits percentage, lower if impaired;
81.0 [3.1] vs 74.5 [3.1], P=0.02; 79.4 [3.1] vs 66.1 [3.1], P<0.001). Several other DA measures showed
that OC-CR, especially 60 mg, produced more psychomotor impairment than equianalgesic OM-ER.
Compared to OM-ER, OC-CR produced more dizziness (Emax, P<0.001 for OM-ER 15 mg vs OC-CR 30
mg and for OM-ER 30 mg vs OC-CR 60 mg), drowsiness (Emax, P<0.001 for both equianalgesic dose
groups), relaxation (Emin, P=0.003 for OM-ER 15 mg vs OC-CR 30 mg; P=0.001 for OM-ER 30 mg
vs OC-CR 60 mg), dysphoria (Emax LSD, P<0.001 for both equianalgesic dose groups), and sedation
(Emax, PCAG; P<0.001 for both equianalgesic dose groups) and less stimulation (BG, Emin; P=0.01 for
OM-ER 15 mg vs OC-CR mg; P<0.001 for OM-ER 30 mg vs OC-CR 60 mg). Several AEs occurred more
commonly with OC-CR than OM-ER (e.g., euphoria, nausea, somnolence, vomiting, dizziness).
Limitations: Participants were young, healthy volunteer nondependent recreational drug users, and
only single doses were evaluated. The effects of tampering or higher doses were not assessed.
Conclusions: Single oral intact low and high doses of OM-ER produced less cognitive and
psychomotor impairment plus less sedation than equianalgesic OC-CR in this exploratory study.
ClinicalTrials.gov registration NCT00955110
Key words: opioid, cognitive effects, psychomotor effects, sedation, dysphoria, oxymorphone,
oxycodone, long-acting opioids