Placebo–Placebo | Bupropion–Placebo | Placebo–MDMA | Bupropion–MDMA | Main Effect of MDMA | Main Effect of Bupropion | Bupropion × MDMA Interaction | |||||
---|---|---|---|---|---|---|---|---|---|---|---|
F1,15 | P value | F1,15 | P value | F1,15 | P value | ||||||
Vital signs | |||||||||||
SBP (mm Hg) | ∆Emax | 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) | ∆Emax | 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) | ∆Emax | 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) | ∆Emax | 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) | Emax | 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) | ΔEmax | −219 ± 34 | −211 ± 50 | 441 ± 191** | 388 ± 196** | 16.45 | 0.001 | 0.11 | NS | 0.09 | NS |
Cortisol (nmol/l) | ΔEmax | −414 ± 37 | −425 ± 81 | 150 ± 51*** | 106 ± 48*** | 63.08 | <0.001 | 0.20 | NS | 0.26 | NS |
Oxytocin (pg/ml) | ΔEmax | −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) | ΔEmax | 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) | ΔEmax | −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) | ΔEmax | 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 | ΔEmax | 0.3 ± 0.3 | 1.4 ± 1.0 | 75 ± 5*** | 84 ± 3*** | 508.82 | <0.001 | 2.81 | NS | 2.35 | NS |
ΔAUEC0–8h | 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 | ΔEmax | 3.1 ± 3.1 | 0.9 ± 0.9 | 69 ± 5*** | 77 ± 5*** | 236.03 | <0.001 | 0.93 | NS | 2.62 | NS |
ΔAUEC0–8h | 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 | ΔEmax | 0.0 ± 0.0 | 0.2 ± 0.2 | 63 ± 7*** | 76 ± 5*** | 167.20 | <0.001 | 3.67 | NS | 3.66 | NS |
ΔAUEC0–8h | 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 | ΔEmax | 2.4 ± 2.4 | 3.3 ± 3.3 | 72 ± 6*** | 76 ± 6*** | 242.54 | <0.001 | 0.85 | NS | 0.38 | NS |
ΔAUEC0–8h | 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 | ΔEmax | 0.0 ± 0.0 | 0.4 ± 0.4 | 61 ± 8*** | 68 ± 7*** | 102.27 | <0.001 | 0.64 | NS | 0.56 | NS |
ΔAUEC0–8h | 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.