Effects of repeated tramadol and morphine administration on psychomotor and cognitive performance in opioid-dependent volunteers

Tramadol is an atypical, mixed mechanism analgesic used to treat moderate to severe pain. Based on evidence that tramadol has relatively low abuse potential and can relieve opioid withdrawal, tramadol may be useful for treating opioid dependence. The purpose of this study was to assess the performance side-effect profile of tramadol. Nine opioid-dependent volunteers completed a performance battery following 5-7 days of subcutaneous morphine (15 mg, 4 times/day) and two doses of oral tramadol (50, 200 mg, 4 times/day) in a within subject cross-over design. Morphine was always the first condition, and the order of the two tramadol doses was randomized and double blind. Performance was significantly worse in the morphine condition relative to one or both tramadol doses on measures of psychomotor speed/coordination (circular lights task), psychomotor speed/pattern recognition (DSST speed measure) and psychomotor speed/set shifting (trail-making tasks). There were no significant differences among conditions in DSST accuracy, simple reaction time, divided attention, working memory, episodic memory, metamemory, or time estimation. Neither tramadol dose was associated with worse performance than morphine on any measure. Although practice sessions were conducted prior to the first session to reduce order effects, the possibility that residual practice effects contributed to the differences between tramadol and morphine cannot be ruled out. The high tramadol dose produced worse performance than the low dose only on the balance measure. These findings suggest that tramadol is generally a safe medication with respect to cognitive and psychomotor measures and support tramadol's further evaluation as an opioid-dependence treatment.