TABLE 2

Pharmacodynamic effects

Values are mean ± S.E.M. of peak changes from baseline (ΔE_max) or peak effects (E_max) in 16 subjects.

		Placebo–Placebo	Bupropion–Placebo	Placebo–MDMA	Bupropion–MDMA	Main Effect of MDMA		Main Effect of Bupropion		Bupropion × MDMA Interaction
						F_1,15	P value	F_1,15	P value	F_1,15	P value
Vital signs
SBP (mm Hg)	∆E_max	9.3 ± 1.5	9.4 ± 1.5	33.1 ± 2.5***	27.7 ± 1.5***	91.22	<0.001	2.76	NS	2.62	NS
DBP (mm Hg)	∆E_max	5.3 ± 0.9	6.1 ± 1.3	17.7 ± 1.3***	16.9 ± 1.4***	72.17	<0.001	0.00	NS	0.50	NS
Heart rate (beats/min)	∆E_max	5.6 ± 1.1	6.6 ± 1.5	30.2 ± 3.1***	18.5 ± 2.2***^,^###	57.97	<0.001	12.38	0.003	13.97	0.002
Body temperature (°C)	∆E_max	0.39 ± 0.07	0.31 ± 0.05	0.63 ± 0.09	0.66 ± 0.07^*	18.26	<0.001	0.19	NS	0.71	NS
Pupillometry
Pupil size (mm)	E_max	6.90 ± 0.14	6.90 ± 0.17	7.74 ± 0.13***	7.76 ± 0.14***	103.06	<0.001	0.04	NS	0.06	NS

Hormones
Prolactin (mU/l)	ΔE_max	−219 ± 34	−211 ± 50	441 ± 191**	388 ± 196**	16.45	0.001	0.11	NS	0.09	NS
Cortisol (nmol/l)	ΔE_max	−414 ± 37	−425 ± 81	150 ± 51***	106 ± 48***	63.08	<0.001	0.20	NS	0.26	NS
Oxytocin (pg/ml)	ΔE_max	−0.9 ± 0.6	−1.0 ± 0.4	86 ± 15***	79 ± 17***	44.56	<0.001	0.11	NS	0.10	NS
Epinephrine (nmol/l)	ΔE_max	0.04 ± 0.02	0.03 ± 0.03	0.5 ± 0.1***	0.4 ± 0.07***	48.68	<0.001	0.72	NS	0.20	NS
Norepinephrine (nmol/l)	ΔE_max	−0.32 ± 0.13	0.10 ± 0.12	0.96 ± 0.19***	0.33 ± 0.12^*^,^#	20.94	<0.001	1.89	NS	9.57	0.007
Dopamine (nmol/l)	ΔE_max	0.03 ± 0.02	−0.01 ± 0.02	0.08 ± 0.03	0.06 ± 0.03	2.61	NS	1.60	NS	0.84	NS

List of complaints (total score)
Acute adverse effects	≤5 h	2.2 ± 0.7	2.6 ± 1.0	15.9 ± 1.8***	15.1 ± 1.0***	97.57	<0.001	0.07	NS	0.50	NS
Subacute adverse effects	≤24 h	1.3 ± 0.6	2.4 ± 0.8	8.4 ± 1.5***	7.9 ± 1.2***	33.38	<0.001	0.14	NS	1.12	NS

Subjective effects
Visual Analog Scale (%max)
Any drug effect	ΔE_max	0.3 ± 0.3	1.4 ± 1.0	75 ± 5***	84 ± 3***	508.82	<0.001	2.81	NS	2.35	NS
	ΔAUEC_0–8h	0.2 ± 0.2	3.6 ± 3.3	191 ± 22***	261 ± 26***^,^#	118.97	<0.001	7.34	0.02	6.56	0.02
Good drug effect	ΔE_max	3.1 ± 3.1	0.9 ± 0.9	69 ± 5***	77 ± 5***	236.03	<0.001	0.93	NS	2.62	NS
	ΔAUEC_0–8h	1.6 ± 1.6	0.5 ± 0.5	167 ± 23***	244 ± 35***^,^#	62.26	<0.001	6.71	0.02	6.69	0.02
Drug high	ΔE_max	0.0 ± 0.0	0.2 ± 0.2	63 ± 7***	76 ± 5***	167.20	<0.001	3.67	NS	3.66	NS
	ΔAUEC_0–8h	0.0 ± 0.0	0.1 ± 0.1	131 ± 26***	188 ± 37***^,^#	29.43	<0.001	5.22	0.04	5.22	0.04
Drug liking	ΔE_max	2.4 ± 2.4	3.3 ± 3.3	72 ± 6***	76 ± 6***	242.54	<0.001	0.85	NS	0.38	NS
	ΔAUEC_0–8h	1.2 ± 1.2	2.5 ± 2.5	173 ± 22***	245 ± 39***^,^#	61.50	<0.001	4.57	0.049	4.61	0.049
Stimulated	ΔE_max	0.0 ± 0.0	0.4 ± 0.4	61 ± 8***	68 ± 7***	102.27	<0.001	0.64	NS	0.56	NS
	ΔAUEC_0–8h	0.0 ± 0.0	0.4 ± 0.4	144 ± 27***	193 ± 40***	28.69	<0.001	3.74	NS	3.69	NS

AUE, area under the effect-time curve; DBP, diastolic blood pressure; NS, not significant; SBP, systolic blood pressure.
↵* P < 0.05, **P < 0.01, ***P < 0.001 compared with placebo-placebo; ^#P < 0.05; ^###P < 0.001 compared with placebo-MDMA.