Table 6.
Randomized controlled trial outcomes—MDMA
| Measures (Timing from MDMA Administration) | Outcomes | Citation |
|---|---|---|
| ADRENERGIC AGENTS | ||
| Carvedilol-MDMA vs Placebo-MDMA | Hysek et al. 2012c | |
| PHARMACOKINETIC | ||
| Drug & metabolite levels (Cmax) | MDMA ↑4.7%, MDA ↑1.6% | |
| Drug & metabolite levels (AUC0–6 h) | MDMA ↑6.4%, MDA ↑6.5% | |
| Drug & metabolite levels (tmax) | MDMA ↓3.4%, MDA ↓9.1% | |
| PHYSIOLOGICAL | ||
| Vitals (ΔEmax) | Heart rate ↓79.0%***, SBP ↓76.9%***, DBP ↓39.2%*, Temp ↓42.0%* | |
| Circulating catecholamines (ΔEmax) | Epinephrine (nmol/1) ↑204.3%***, Norepinephrine (nmol/1) ↑789.7%*** | |
| Pupil function (Emax) | Pupil size (mm) ↑0.4%, Pupil size after light (mm) ↑3.2%, Constriction amplitude (mm) ↓27.9%, Latency (seconds) ↓0.3%** | (Hysek and Leichti 2012) |
| SUBJECTIVE | ||
| Visual Analog Scale (ΔEmax) | Any drug effect ↑7.4%, Good drug effect ↑8.0%, Bad drug effect ↑86.0%, Drug liking ↑1.5%, Drug high ↑11.6%, Stimulated ↑6.7% | |
| 5-Dimensions of Altered States of Consciousness Rating Scale (ΔEmax) | Global ↑19.7%, Oceanic boundlessness ↑21.8%, Anxious ego dissolution ↓16.1%, Visionary restructuralization ↑69.7% | |
| List of Complaints (3 h & 24 h) | Acute (3 h) Global ↑17.9%, Subacute (24 h) Global ↓7.5% | |
| Pindolol-MDMA vs Placebo-MDMA | Hasler et al. 2009 | |
| PHYSIOLOGICAL | ||
| Vitals (Emax) | Heart rate ↓ ∼ 17.6%***, MAP ↓ ∼ 0.9%, Temp ↔ | (Hysek et al. 2010) |
| SUBJECTIVE | ||
| 5-Dimensions of Altered States of Consciousness Rating Scale (150 m) | Global ↓ ∼ 26.7%**, Oceanic boundlessness ↓ ∼ 31.9%**,Anxious ego dissolution ↑ ∼ 14.3%, Visionary Restructuralization ↓ ∼ 30.0% | |
| Adjective Mood Rating Scale (75 m & 110 m) | Dreaminess ↓95.4%* (75 min) & ↓97.6%* (110 min), no significant differences in any other domains | |
| State Anxiety (75 m & 110 m, 24 h) | Anxiety ↔ | |
| Cambridge Neuropsychological Test Automated Battery (120 min) | Rapid visual processing – total hits ↑4.8%, Paired Associates Learning – total trials ↔, Dimensional Set Shifting – stages completed ↑2.3% | |
| List of Complaints (75 m) | Global ↔ | (Hysek et al. 2010) |
| Clonidine-MDMA vs Placebo-MDMA | Hysek et al. 2012a | |
| PHARMACOKINETIC | ||
| Drug & metabolite levels (Cmax) | MDMA ↓2.9%, MDA ↑2.8% | |
| Drug & metabolite levels (AUC0–6) | MDMA ↑1.1%, MDA ↑4.7% | |
| Drug & metabolite levels (tmax) | MDMA ↔, MDA ↓1.9% | |
| Drug & metabolite levels (t1/2) | MDMA ↑22.1% | |
| PHYSIOLOGICAL | ||
| Vitals (Emax) | Heart rate ↓3.9%, MAP ↓27.2%, SBP ↓24.9%, DBP ↓26.4%, Temp ↔ | |
| Vitals (AUEC0–6 h) | Heart rate ↓2.6%, MAP ↓4.5%*, SBP ↓3.9%*, DBP ↓5.2%*, Temp ↑0.1% | |
| Pupil function (Emax) | Pupil size (mm) ↓2.5%, Pupil size after light (mm) ↓2.6%, Constriction amplitude (mm) ↓13.8%, Latency (seconds) ↑3.7% | (Hysek and Leichti 2012) |
| Circulating catecholamines (Emax) | Epinephrine ↓29.4%, Norepinephrine ↓109.8%** | |
| SUBJECTIVE | ||
| Visual Analog Scale (Emax) | Any drug effect ↓9.0%, Good ↓12.9%, Bad ↑18.3%, Liking ↓11.2%, Drug high ↓11.9%, Stimulated ↓8.9%, Tiredness ↓2.9%, Closeness to others ↑2.8%, Open ↓0.3% | |
| Adjective Mood Rating Scale (Emax) | Emotional excitation ↑2.2%, Well being ↑1.2%, Extroversion ↑18.2%, Dreaminess ↓24.4%, Activity ↑61.9%, Inactivation ↓10.2%, Anxiety-depression ↑162.5% | |
| State-Trait Anxiety Inventory (Emax) | State-anxiety ↑29.7% | |
| 5-Dimensions of Altered States of Consciousness Rating Scale | Oceanic boundlessness ↓ ∼9%, Anxious ego dissolution ↑ ∼ 26%, Visionary restructuralization ↔, Insightfulness ↓ ∼ 52%*, Global ↔ | |
| List of Complaints (3 h & 24 h) | Acute (3 h) Global ↑23.3%, Subacute (24 h) Global ↑85.7% | |
| Doxazosin-MDMA vs Placebo-MDMA | Hysek et al. 2013 | |
| PHARMACOKINETIC | ||
| Drug & metabolite levels (Cmax) | MDMA ↓1.6%, MDA ↓12.1%*, HMMA inc 0.6% | |
| Drug & metabolite levels (AUC0–6) | MDMA ↓3.6%, MDA ↓14.6%**, HMMA ↑ 1.8% | |
| Drug & metabolite levels (tmax) | MDMA ↑ 16.0%, MDA ↓5.3%, HMMA ↑ 10.5% | |
| PHYSIOLOGICAL | ||
| Vitals (Emax) | Heart rate ↑ 9.6%*, MAP ↓ 6.8%*, Temp ↓ 26.8% | |
| Circulating catecholamines (Emax) | Epinephrine (nmol/l) ↑28.2%, Norepinephrine (nmol/l) ↑102.8%*** | |
| Pupil function (Emax) | Pupil size (mm) ↓3.2%, Pupil size after light (mm) ↓1.0%, Constriction amplitude (mm) ↓3.7%, Latency (seconds) ↓10.5% | (Hysek and Leichti 2012) |
| SUBJECTIVE | ||
| Visual Analog Scale (ΔEmax) | Any drug effect ↓0.1%, Good drug effect ↓1.7%, Bad drug effect ↓9.5%, Drug liking ↓1.2%, Drug high ↓1.6%, Stimulated ↑9.7% | |
| Adjective Mood Rating Scale (Emax) | Emotional excitation ↓1.9%, Self-reported activation ↓38.5%, Heightened mood ↓40%, Extroversion ↓23.3%, Self-confidence ↓14.3%, Dreaminess ↓2.6% | |
| Adjective Mood Rating Scale (AUEC0–6 h) | Self-reported activation ↓84.9%, Heightened mood ↓85.7* | |
| 5-Dimensions of Altered States of Consciousness Rating Scale (Emax) | Global ↓ ∼ 15%, Oceanic boundlessness ↓ ∼ 9%, Anxious ego dissolution ↔, Visionary restructuralization ↓ ∼ 36%, Auditory Alterations ↓ ∼ 20%, Vigilance reduction ↓ ∼ 16% | |
| List of Complaints (3 h & 24 h) | Acute (3 h) Global ↑9.5%; Subacute (24 h) Global ↑1.5% | |
| ANTIPSYCHOTICS | ||
| Haloperidol-MDMA vs Placebo-MDMA | Liechti and Vollenweider 2000b | |
| PHYSIOLOGICAL | ||
| Vitals (120 m) | Heart rate ↑13.7%, SBP ↑5.0%, DBP ↑2.3%, Temp ↑1.4% | |
| Startle Response (90 m) | Mean startle magnitude: First block of startle testing ↔; Last block of startle testing ↑ ∼ 5% Mean percent prepulse inhibition of startle response ↑ ∼ 6% |
(Liechti et al 2001) |
| SUBJECTIVE | ||
| Adjective Mood Scale (EWL) (2 h) | Well-being ↓ ∼ 31%*, Efficiency-activation ↓ ∼ 25%, Inactivation ↑ ∼ 100%, Extro-/Introversion ↓ ∼ 20%, Emotional excitability ↑ ∼ 20% | |
| State-Trait Anxiety Inventory (75 & 120 m) | 75 min: ↑ ∼ 47%**, 120 min: ↑ ∼ 29% | |
| Altered State of Consciousness Scale Rating (2 h) | Oceanic boundlessness ↓ ∼ 59%*, Anxious ego-dissolution ↑ ∼ 100%, Visionary restructuralization ↔ | |
| List of Complaints (on drug, 1 day, 3 days) | Global: on drug ↑ ∼ 14%, 1 day ↓ ∼ 14%, 3 days ↓ ∼ 33% | |
| NOREPINEPHRINE-DOPAMINE REUPTAKE INHIBITORS | ||
| Bupropion-MDMA vs Placebo-MDMA | Schmid et al 2015 | |
| PHARMACOKINETIC | ||
| Drug & metabolite levels (Cmax) | MDMA ↑14.3%**, MDA ↓14.6%**, HMMA ↓75.9%***, bupropion ↑18.0%# | |
| Enantiomer Drug & metabolite levels (Cmax) | R-MDMA ↑9%*, S-MDMA ↑16%*; R-MDA ↓27%*, S-MDA ↓24%* | (Steuer et al 2016) |
| Drug & metabolite levels (AUC0–24 h) | MDMA ↑ 33.1%***, MDA ↓12.4%, HMMA ↓66.8%***, bupropion ↑27.5%## | |
| Enantiomer levels (AUC0–24 h) | R-MDMA ↑25%*, S-MDMA ↑38%*; R-MDA ↓26%*, S-MDA ↓20%* | (Steuer et al 2016) |
| PHYSIOLOGICAL | ||
| Vitals (ΔEmax) | Heart rate ↓38.7%***, SBP ↓16.3%, DBP ↓4.5%, Temp ↑4.76% | |
| Pupillometry (Emax) | Pupil size (mm) ↑0.3% | |
| Circulating Catecholamines/Hormones (Emax) | Norepinephrine (nmol/l) ↓65.6%*, Prolactin (mU/l) ↓12.0%, Cortisol (nmol/l) ↓29.3%, Oxytocin (pg/ml) ↓8.1%, Epinephrine (nmol/l) ↓20.0%, Dopamine (nmol/l) ↓25.0% | |
| SUBJECTIVE | ||
| Visual Analog Scale (ΔEmax) | Any drug effect ↑12.0%, Good drug effect ↑11.6%, Drug high ↑17.1%, Drug liking ↑5.6%, Stimulated ↑11.5% | |
| Visual Analog Scale (ΔAUEC0–8 h) | Any drug effect ↑36.7%*, Good drug effect ↑46.1%*, Drug high ↑43.5%*, Drug liking ↑41.6%*, Stimulated ↑34.0% | |
| List of Complaints (5 h & 24 h) | Acute (5 h) ↓5.0%, Subacute (24 h) ↓6.0% | |
| NMDA ANTAGONISTS | ||
| Memantine-MDMA vs Placebo-MDMA | de Sousa Fernandes Perna et al. 2014 | |
| PHARMACOKINETIC | ||
| Drug levels (1 h) | MDMA ↓1.0% | |
| SUBJECTIVE | ||
| Memory (95–165 m) | Visual Verbal Learning Task – total immediate recall ↓6.0% and delayed recall ↓0.8%, Prospective Memory Task – reaction time ↓3.5% and accuracy no-go ↑1.3%, Sternberg Memory Test – reaction time ↑0.4% and correct ↓1.4%, Abstract Visual Pattern Learning Task – reaction time ↑13.6% and correct ↓1.8% | |
| Profile of Mood States (90 m) | Arousal ↑0.7%, Elation ↓13.1%, Positive Mood ↓41.1%, Vigor ↓16.0, Anxiety ↑7.1% | |
| Visual Analog Scale (90 m and 120 m) | Subjective high ↑20.9% (90 min) and ↑70.3% (120 min) | |
| Psychomotor Performance (95–165 m) | Critical Tracking Task ↓1.4%, Divided Attention Task – tracking error ↓2.8% and reaction time ↑0.1% | |
| PSYCHOSTIMULANTS | ||
| Methylphenidate-MDMA vs Placebo-MDMA | Hysek, et al. 2014b | |
| PHARMACOKINETIC | ||
| Drug & metabolite levels (Cmax) | MDMA ↓3.5%, MDA ↓3.6%, HMMA ↓12.1%, Methylphenidate# ↑0.7% | |
| Drug & metabolite levels (AUC0–24) | MDMA ↑3.2%, MDA ↓3.4%, HMMA ↓4.2%, Methylphenidate# ↓0.1% | |
| Drug & metabolite levels (tmax) | MDMA ↑45.8%*, MDA ↑13.8%*, HMMA ↑16.7%, Methylphenidate# ↑4.3% | |
| Drug & metabolite levels (t1/2) | MDMA ↔, MDA ↑2.5%, HMMA ↑5.2%, Methylphenidate# ↔ | |
| PHYSIOLOGICAL | ||
| Vitals (Emax) | SBP ↑2.6%, DBP ↔, Heart Rate ↑15.1%***, Rate Pressure Product ↑16.8%***, Temp change ↑6.0% | |
| Pupillometry (Emax) | Pupil size (mm) ↑1.8% & after light reflex ↓2.2% | |
| Hormones (ΔEmax) | Cortisol (nmol/l) ↑26.8%, Prolactin(mU/l) ↓29.5% | |
| Circulating catecholamines; (ΔEmax) | Epinephrine (nmol/l) ↑54.6%**, Norepinephrine (nmol/l) ↓41.1%, Dopamine (nmol/l) ↓52.9% | |
| SUBJECTIVE | ||
| Visual Analog Scale (ΔEmax) | Any drug effect ↓1.4%, Drug liking ↓8.4%, Drug high ↓13.7%, Stimulated ↑2.1%, Happy ↓29.8%, Close to others ↓20.4% | |
| Adjective Mood Rating Scale (ΔEmax) | Emotional excitation ↑59.5%, Well-being ↓12.5%, Extroversion ↔, Activity ↑16.7%, Concentration ↑500.0%*, Anger ↑166.7% | |
| Addictions Research Center Inventory (ΔEmax) | Amphetamine ↑6.4%, Benzedrine ↑7.4%, Morphine-benzedrine ↓10.2%, Phenobarbital-alcohol ↑8.7%, LSD ↑15.5% | |
| Altered State of Consciousness Rating Scale | Global ↓10.0%, Oceanic boundlessness ↓22.2%, Anxious ego dissolution ↑23.3%, Visionary restructuralization ↓3.5% | |
| Facial emotion recognition task (1.5 h) | Global ↓1.8%, Neutral ↑0.9%, Happy ↓11.4%*, Sad ↑11.4%, Anger ↓5.3%, Fear ↔ | |
| List of Complaints (5 h & 24 h) | Acute (5 h) Global ↑86.5%**, Dry mouth (n = 15v13), Lack of appetite (n = 16v8), Palpitations (n = 9v4), Headache (n = 7v4), Nausea (n = 5v1); Subacute (24 h) Global ↑191.9%*** | |
| SELECTIVE SEROTONIN REUPTAKE INHIBITORS | ||
| Citalopram-MDMA vs Placebo-MDMA | Liechti and Vollenweider 2000a | |
| PHYSIOLOGICAL | ||
| Vitals (60 m) | Heart rate ↓12.3%*, SBP ↓4.2%**, DBP ↓1.2%, Temp ↓0.3% | |
| Vitals (120 m) | Heart rate ↓9.6%, SBP↓6.5%**, DBP↓5.8%*, Temp ↓0.3% | |
| Startle response (90 m) | Mean startle magnitude: First block of startle testing ↑ ∼ 3%, Last block of startle testing ↔ Mean percent prepulse inhibition of startle response ↓ ∼ 10%* |
(Liechti et al 2001) |
| SUBJECTIVE | ||
| Altered State of Consciousness Rating Scale (Emax) | Oceanic boundlessness ↓ ∼ 60%*, Anxious ego dissolution ↓ ∼ 63%*, Visionary restructuralization ↓ ∼ 70%* | (Liechti 2000) |
| Adjective Mood Rating Scale (Emax) | Efficiency-activation ↓ ∼ 52%*, Self-confidence ↓ ∼ 30%*, Heightened mood ↓ ∼ 21%, Apprehension-anxiety ↓ ∼ 25%, Depressiveness ↓ ∼ 6%, Thoughtfulness-contemplativeness ↓ ∼ 23%, Extroversion ↓ ∼ 32%**, Introversion ↓ ∼ 3%, Inactivation ↑ ∼ 20%, Dazed state ↑ ∼ 15%, Tiredness ↑ ∼ 25%, Sensitivity ↓ ∼ 5%, Aggression-anger ↑ ∼ 23%, Emotional excitability ↔ | |
| List of Complaints, acute (during session, n drug combo versus n MDMA alone) | Global ↓ ∼ 46%**, Difficulty concentrating (7v10), Impaired balance (5v8), Lack of appetite (6v8), Dizziness (4v8), Palpitations (4v7), Restlessness (5v7), Bruxism (3v7), Being cold (1v6), Thirst (3v6), Hot flashes (1v5), Paresthesias (1v5), Fatigue (0v3), Nausea (3v3), Tremor (0v3), Inner tension (8v3), Fear (0v2), Headache (3v1) | |
| List of Complaints, sub-acute (24 h; n drug combo versus n MDMA alone) | Global ↑ ∼ 14%, Headache (6v7), Fatigue (6v6), Lack of appetite (8v6), Difficulty concentrating (4v4), Brooding (4v3), Decreased libido (0v3), Bad dreams (2v3), Thirst (4v3), Forgetfulness (1v3), Inner tension (5v2), Gloomy thoughts (0v2), Insomnia (6v2), Increased need to sleep (4v2), Dizziness (4v2), Bruxism (0v2), Palpitations (3v1), Private/job related worries (1v1), Tremor (3v1), Irritability (2v1), Nausea (3v0) | |
| Fluoxetine-MDMA vs Placebo-MDMA | Tancer and Johanson 2006 | |
| PHYSIOLOGICAL | ||
| Vitals (Emax) | Heart rate ↓14.6%*, SBP ↓4.2%, DBP ↓2.1% | |
| SUBJECTIVE | ||
| Visual Analog Scale (Emax) | Drug Liking ↓31.2%*, High ↓47.6%*, Stimulated ↓40.1%*, Anxious ↓51.9%, Friendly ↓19.2%, Good Drug Effect ↓28.1%, Talkative ↓30% | |
| Addictions Research Center Inventory (Emax) | Morphine-benzedrine ↓33.7%*, Amphetamine ↓14.3%, LSD ↓9.2%, Benzedrine ↓7.9%, Pentobarbital-Chlorpromazine-Alcohol ↑53.3% | |
| Profile of Mood States (Emax) | Arousal ↓41.7%*, Elation ↓29.2%*, Positive Mood ↓33.3%*, Vigor ↓40.9%*, Anxiety ↓30% | |
| Hallucinogen Rating Scale (Emax) | Affect ↓33.3%*, Soma ↓41.7%*, Intensity ↓38.1%, Cognition ↓14.3%, Perception ↓50% | |
| Multiple-Choice Procedure (8 h) | ↓63.9% | |
| End-of-Session Liking Questionnaire (8 h) | ↓29.3% * | |
| Paroxetine-MDMA vs Placebo-MDMA | Farré et al 2007 | |
| PHARMACOKINETIC | ||
| Drug & metabolite plasma levels (Cmax) | MDMA ↑16.0%**, HMMA ↓49.3%** | |
| Drug & metabolite plasma levels (AUC0–21 h) | MDMA ↑21.6%**, HMMA ↓38.2%** | |
| Drug & metabolite plasma levels (tmax) | MDMA ↑16.7%, HMMA ↑33.3% | |
| Drug & metabolite plasma levels (t1/2) | MDMA ↓5.8%, HMMA ↑37.3%** | |
| PHYSIOLOGICAL | ||
| Vitals (Emax) | Heart rate ↓ ∼ 42%*, SBP ↓ ∼ 41%***, Temp ↓ ∼ 40%*, Pupillary diameter (mm) ↓63.1%*** | |
| Psychomotor Performance (Emax) | Simple reaction time errors ↓88.9%*, Esophoria (Maddox-wing, diopters) ↑54.9%* | |
| MDMA-induced immune response (Emax) | CD4/CD3 suppression ↓ ∼ 33%**, CD8 ↔, Natural killer cell increase ↓ ∼ 55%**, IL-2 reduction ↓67%**, IL-10 & TGFβ1 increase ↓ > 90%**, phytohemagglutinin suppression ↓3.9%**, Concanavalin A suppression ↓2.0%** | (Pacifici et al 2004) |
| Hormones (AUC0–9 h) | Cortisol stimulation ↓21.5%**, Prolactin stimulation ↓24.1%** | |
| SUBJECTIVE | ||
| Visual Analog Scale (Emax) | Stimulated ↓ ∼ 65%**, High ↓ ∼ 68%***, Good effects ↓ ∼ 62%***, Liking ↓ ∼ 62%***, Different body sensation ↓ ∼ 53%** | |
| Addictions Research Center Inventory (Emax) | Morphine-benzedrine ↓45.0%**, Amphetamine ↓30.4%**, LSD ↓21.1% | |
| Evaluation of the Subjective Effects of Substances with Abuse Potential | Pleasure and sociability ↓80.7%*, Psychosomatic anxiety ↓51.4%**, Activity and energy ↓79.5%** | |
| SEROTONIN-NOREPINEPHRINE REUPTAKE INHIBITORS | ||
| Duloxetine-MDMA vs Placebo-MDMA | Hysek et al. 2012d | |
| PHARMACOKINETIC | ||
| Drug & metabolite plasma levels (Cmax) | MDMA ↑14.6%**, MDA ↓9.2%, HMMA ↓40.5%***, duloxetine# ↑4.6% | |
| Drug & metabolite plasma levels (AUC0–6 h) | MDMA ↑16.2%**, MDA ↓10.0%, HMMA ↓40.0%***, duloxetine# ↑1.8% | |
| Drug & metabolite plasma levels (tmax) | MDMA ↑13.7%, MDA ↓4.5%, HMMA ↑2.7%, duloxetine# ↑15.8% | |
| Drug & metabolite plasma levels (t1/2) | MDMA ↓12.6%, duloxetine# ↑3.6% | |
| Ex vivo: monoamine transporter binding | NET ↓41.5%***, SERT ↓ > 94.4%***, DAT ↔ | |
| Osmolality (120 m) | Women: Copeptin (pmol/l, 60 min) ↓ ∼ 96%***, arginine vasopressin (pmol/l) ↓ ∼ 60%, Urinary osmolality (mmol/kg) ↓ ∼ 22%, Urinary sodium (mmol/l) ↓ ∼ 12%, Plasma osmolality (mmol/kg) ↓ ∼ 2%, plasma sodium (mmol/l) ↓ ∼ 1% Men: Copeptin (60 min) ↔, arginine vasopressin ↑ ∼ 18%, Urinary osmolality ↑ ∼7%, Urinary sodium ↓ ∼ 27%, Plasma osmolality ↓ ∼ 1%, plasma sodium ↓ ∼ 1% |
(Simmler et al 2011) |
| PHYSIOLOGICAL | ||
| Vitals (Emax) | Heart rate ↓57.4%***, MAP ↓60.8%***, SBP ↓63.5%***, DBP ↓58.3%***, Temp ↓27.8% | |
| Pupil function (Emax) | Pupil size (mm) ↑1.7%, Pupil size after light (mm) ↓8.1%**, Constriction amplitude (mm) ↑126.9***, Latency (seconds) ↓35.0% | (Hysek and Leichti 2012) |
| Circulating catecholamines (Emax) | Epinephrine (nmol/l) ↓48.0%, Norepinephrine (nmol/l) ↓143.2%*** | |
| SUBJECTIVE | ||
| Visual Analog Scale (Emax) | Any drug effect ↓61.7%***, Good drug effect ↓54.6%***, Drug liking ↓57.7%***, Drug high ↓67.0%***, Stimulated ↓70.8%***, Closeness to others ↓83.1%***, Talkative ↓63.0%***, Open ↓81.3%*** | |
| Adjective Mood Rating Scale (Emax) | Well-being ↓49.6%**, Emotional excitation ↓73.5%***, Extroversion ↓58.9%***, Introversion ↓35.5%, Dreaminess ↓38.4%, Activity ↑40.1% | |
| 5-Dimensions of Altered States of Consciousness Rating Scale (4 h) | Global ↓ ∼ 84%***, Oceanic Boundlessness ↓ ∼ 87%***, Anxious Ego Dissolution ↓ ∼ 71%*, Visionary Restructuralization ↓ ∼ 92%*** | |
| List of Complaints (3 h & 24 h) | Acute (3 h) Global ↓122.5%**, Sub-acute (24 h) Global ↓109.8%* | |
| Reboxetine-MDMA vs Placebo-MDMA | Hysek et al. 2011 | |
| PHARMACOKINETIC | ||
| Drug & metabolite levels (Cmax) | MDMA ↑17.8%**, MDA ↑21.1%, Reboxetine# ↑12.2%* | |
| Drug & metabolite levels (AUC0–24 h) | MDMA ↑8.1%*, MDA ↑44.1%**, Reboxetine# ↑8.3% | |
| Drug & metabolite levels (tmax) | MDMA ↑7.7%, MDA ↑48.9%, Reboxetine# ↑9.1% | |
| Drug & metabolite levels (t1/2) | MDMA ↓27.1%, MDA ↑7.5%, Reboxetine# ↓3.6% | |
| Ex vivo: monoamine transporter binding (1 h) | NET ↓67.8%***, SERT ↔, DAT ↔ | |
| PHYSIOLOGICAL | ||
| Vitals (Emax) | Heart rate ↓26.2%*, MAP ↓37.2%**, SBP ↓46.5%***, DBP ↓24.0%, Temp ↓31.2% | |
| Circulating catecholamines (1 h) | Epinephrine (nmol/l) ↓40%, Norepinephrine (nmol/1) ↓36.1%** | |
| Pupil function (Emax) | Pupil size (mm) ↑10.4%***, Pupil size after light (mm) ↑10.8%***, Constriction amplitude (mm) ↑11.7%, Latency (seconds) ↑1.0% | (Hysek and Leichti 2012) |
| SUBJECTIVE | ||
| Visual Analog Scale (Emax) | Any drug effect ↓20.7%**, Drug high ↓24.3%*, Stimulated ↓28.9%*, Closeness ↓38.6%*, Good drug effect ↓15.2%, Liking ↓10.0% | |
| Adjective Mood Rating Scale (Emax) | Activity ↑10.0%, Inactivation ↓20.6%, Extroversion 13.3%, Introversion ↑60.3%**, Well-being ↓3.9%, Emotional excitation ↓47.5%*, Anxiety-depression ↓38.7%, Dreaminess ↓20.3% | |
| State-Trait Anxiety Inventory (Emax) | State-anxiety ↓62.6% * | |
| 5-Dimensions of Altered States of Consciousness Rating Scale (4 h) | Global ↓ ∼ 33%**, Oceanic boundlessness ↓ ∼ 42%**, Anxious ego dissolution ↓ ∼ 24%, Visionary restructuralization ↓ ∼ 26%*, | |
| List of Complaints (3 h & 24 h) | Acute (3 h) Global ↓80.8%*; Lack of appetite (n = 8v12), Tremor (n = 3v9), Restlessness (n = 4v8), Dizziness (n = 4v6); Subacute (24 h) Global ↓91.8%* | |
Percent change reported for [psych med] + MDMA vs. placebo + MDMA
#
= [psych med] + MDMA vs [psych med] + placebo
↔ no change in response, ∼ = estimated percentage change approximated from graphical representation of outcome data
*
p < .05
**
p < .01, and
***
p < .001 (in bold)
AUC area under the curve, AUEC area under the effect-time curve, Cmax peak plasma concentration, DAT dopamine transporter, DBP diastolic blood pressure (mmHg), Emax peak effects, HMMA 4-hydroxy-3-methoxymethamphetamine, MAP mean arterial pressure, MDA 3,4-methylenedioxyamphetamine, MDMA 3,4-Methylenedioxymethamphetamine, NET norepinephrine transporter, SBP systolic blood pressure (mmHg), SERT sertraline transporter, Temp temperature (C°), t1/2 half-life, tmax time to maximum plasma concentration, Δ change from baseline