Table 2.

Summary of mean maximum and minimum values following drug challenge

Measure	Drug condition (mg)
	Morphine		Tramadol 200							Tramadol 800
	Placebo	Naloxone	Placebo	Naloxone			Hydromorphone			Placebo	Naloxone			Hydromorphone
	0	0.5	0	0.25	0.5	1.0	1.5	3.0	6.0	0	0.25	0.5	1.0	1.5	3.0	6.0
Maximum values
Antagonist adjective scale
Observer rated	2.1	19.7a	1.8	7.8	10.0	14.3d,e	1.8	2.6	2.9	2.0	10.1	19.0d	26.1d,e	1.6	2.2	1.8
Participant rated	2.2	26.3a	2.0	9.8	11.3	17.7d	1.7	4.2	3.8	1.2	10.6	18.3d	24.8d	1.8	2.3	1.7
Agonist adjective scale
Observer rated	12.7	12.4	12.6	13.0	13.4	12.3	16.0	17.1	22.6d	12.7	12.8	13.7	10.8	14.4	15.6	22.7d
Participant rated	15.8	16.0	13.4	13.9	12.8	14.2	18.6	18.1	24.3d	11.8	13.0	13.3	13.0	15.3	17.0	20.9d
Observer-rated BOWS
Lacrimation	0.2	1.4a	0.1	1.6d	1.2d	1.6d	0	0.2	0.4	0	1.2d	1.9d	2.0d	0	0.2	0
Rhinorrhea	0.1	1.6a	0	0.9d	0.8d,e	1.7d	0	0	0.2	0	0.9d	1.8d,e	2.0d	0.2	0	0
Perspiration	0.1	1.2a	0.2	0.4	0.7	0.8	0.2	1.1	0.2	0.2	0.6	1.4	1.4	0.2	0.6	0.7
Gooseflesh	0	0.8a	0	0.3	0.6	1.1d	0	0	0.2	0	0.1	0.9d	2.0d	0	0.2	0
Bowel sounds	1.7	1.7	1.2	1.6	1.4	1.6	1.2	1.6	1.3	1.4	1.6	1.8	1.4	1.4	1.4	1.5
Yawning	0.8	1.9a	0.9	1.4	1.8d	1.9d	0.1	0.0d	0.4	0.7	1.4	2.0d	2.0d	0.2	0.1	0
Restlessness	0.7	1	0.2	1.0	1.1d	0.9	0.1	0.3	0.7	0.4	0.6	1.3d	1.7d	0.4	0.3	0.3
Total BOWS	2.4	8.6a	2.2	5.7d	6.6d,e	7.8d,e	1.6	3.1	2.6	2.4	5.9d	10.1d,e	11.9d,e	2.0	2.4	2.2
Visual analog scale
High	6.1	2.2	0.8	0	0	1.0	29.8	33.0d	60.8d	0	−1.1	0	−2.3	17.7	38.3d	62.2d
Drug Effect	10.3	68.6a	1.2	25.3	30.2e	53.1d	31.0	38.6	66.3d	1.6	20.0	70.7d,e	72.6d	20.6	40.2d	62.4d
Good Effects	5.4	4.3	1.1	0.1	0.3	0.9	38.7d	38.4d	70.1d	1.6	−1.3	0	−2.6	21.8	40.0d	64.1d
Bad Effects	4.8	75.2a	0	28.1d	30.2d,e	55.2d	2.6	8.6	1.4	0.0	22.6	72.6d,e	80.3d	0.4	0.9	−0.6
Liking	7.4	5.11	0.8	0.2	0	1.3	41.3d	45.6d	73.6d	5.3	−1.2	0	−3.0	23.3	40.3d	65.9d
Feel sick	0.4	46.0a	0	23.2	13.8	31.8d	1.9	8.2	0.0	0	14.2	43.2d	48.6d	0	0	−0.9
Physiological measures
Pupil diameterb (mm)	1.0	1.3	0.2	0.7	0.8	0.6	0	−0.6	−1.6d	0.7	0.7	1.2	0.9	−0.2d	−0.3d	−1.2d
Pulse (bpm)	77.8	85.1a	85.2	86.8	84.5e	88.1	98.3	98.4	98.0	87.5	86.3	92.5e	95.2	84.7	89.4	94.8
Skin temperature (°F)	86.9	86.5	87.3	86.0	87.8	84.9	84.2	85.0	87.4	88.3	85.9	85.8	87.0	89.6	90.1	90.3
Systolic BP (mmHg)	111.4	120.1a	115.2	118.6	118.6e	122.0e	89.1	90.6	92.0d	121.7	123.4	129.1e	138.3d,e	120.3	125.3	129.4
Diastolic BP (mmHg)	61.2	67.3a	66.9	65.9e	70.0e	71.4e	117.6	118.5	125.2	72.2	73.5e	79.5d,e	85.0d,e	72.0	75.5	76.5
Minimum values
Physiological measures
Pupil diameterc (mm)	−0.2	0	−0.7	−0.5	−0.5	−0.6	−1.3	−1.9d	−2.5d	−0.6	−0.4	−0.3	−0.7	−1.4	−2.0d	−2.2d
Oxygen saturation (%)	97.3	97.4	97.4	97.3	97.2	97.5	96.9	96.8	95.8d	97.2	97.5	96.9	96.9	96.9	96.6	96.0
Respiratory rate (bpm)	13.6	14.4	13.6	14.2	13.6	13.6	12.2	11.6	11.6	12.7	13.0	12.7	12.6	12.4	12.0	9.9

Routes of drug administration for daily maintenance and challenge sessions were as follows: morphine 60 mg/day (15 mg QID)—subcutaneous injection; tramadol 200 mg/day (50 mg QID) and 800 mg/day (200 mg QID)—oral; placebo, naloxone, and hydromorphone challenges—intramuscular injection. Variance results were not included due to space limitations but are available upon request

^aSignificant difference (p<0.05) from placebo challenge during morphine maintenance

^bThe mean maximum increase in pupil diameter from baseline

^cThe mean maximum decrease in pupil diameter from baseline

^dSignificant difference (p<0.05) from placebo challenge during tramadol maintenance

^eSignificant difference (p<0.05) between tramadol dose conditions