Clinical trials available on ClinicalTrials.gov investigating the use of MDMA as a potential therapeutic approach for PTSD and other psychiatric disorders
For completed trials, the references of published work were added if available either from the ClinicalTrials.gov web site or PubMed upon searching the NCT identifier. If information was available on the main findings of the study, it was added. If the trial was not completed or it was completed but no information was available in the form of a published original manuscript, we reported the main research question(s) the study aims to address.
| Compound | Cohort | Regimen | Research Question/Main Findings | Status | Reference |
|---|---|---|---|---|---|
| MDMA | Post-traumatic stress disorder | 30, 75, or 125 mg, orally, followed by a supplemental half dose 1.5–2 h later, thrice | MDMA-assisted psychotherapy is safe and efficacious for PTSD. MDMA induces large-magnitude effect size decreases in PTSD symptoms. Two-thirds of participants no longer meet PTSD criteria 12 mo after treatment | Completed | ClinicalTrials.gov identifier: NCT03485287, NCT03282123, NCT01211405 (Mithoefer et al., 2018; Gorman et al., 2020) |
| MDMA | Post-traumatic stress disorder | 125 mg, orally, followed by a supplemental half dose 1.5–2 h later, thrice | Decrease in PTSD scores. Rate of clinical response 10 of 12 (83%) in the active treatment group vs. 2 of 8 (25%) in the placebo group. No drug-related serious adverse events or clinically significant blood pressure increases. No relapse 17–74 mo after the original final session | Completed | ClinicalTrials.gov identifier: NCT00090064 (Mithoefer et al., 2011, 2013) |
| MDMA | Post-traumatic stress disorder | 30, 75, or 125 mg, orally, followed by a supplemental half dose 1.5–2 h later, once | Identify psychotherapeutic processes in MDMA-assisted psychotherapy for PTSD | Completed | ClinicalTrials.gov identifier: NCT02102802 |
| MDMA | Post-traumatic stress disorder | 25 or 125 mg, orally, followed by a supplemental half dose 2 h later, thrice | Safety and efficacy of MDMA-assisted psychotherapy for PTSD | Completed | ClinicalTrials.gov identifier: NCT01958593, NCT01689740 |
| MDMA | Post-traumatic stress disorder | 62.5, 125, or 125 + 62.5 mg, orally | Additional MDMA psychotherapy for people who relapsed 1 yr after the first trial | Completed | ClinicalTrials.gov identifier: NCT01458327 |
| MDMA | War- or terrorism-related PTSD | 25 and 125 mg, orally, followed by a supplemental half dose 2–2.5 h later, twice | MDMA-assisted psychotherapy for people with war- or terrorism-related PTSD | Terminated due to staff turnover and its effects on data collection | ClinicalTrials.gov identifier: NCT00402298 |
| MDMA | Post-traumatic stress disorder | 1.5 mg/kg, orally, once | Effects of MDMA on prefrontal and amygdala activation. Relationship between neural changes and acute behavioral effects in patients with PTSD | Recruiting | ClinicalTrials.gov identifier: NCT03752918 |
| MDMA | Post-traumatic stress disorder | 80 and 120 mg, orally, followed by a supplemental half dose 1.5–2 h later, thrice | Multisite phase III study of MDMA-assisted psychotherapy for PTSD | Active, not recruiting | ClinicalTrials.gov identifier: NCT03537014 |
| MDMA | Post-traumatic stress disorder | 80 and 120 mg, orally, followed by a supplemental half dose 1.5–2 h later, twice | First multisite study of MDMA-assisted psychotherapy for PTSD in Europe. Exploration of findings’ reproducibility from FDA-regulated trials in a multisite format to further confirm the phase III study design | Not yet recruiting | ClinicalTrials.gov identifier: NCT04030169 |
| MDMA | Combat-related post-traumatic stress disorder | First session: 80 mg, orally, followed by a supplemental half dose 1.5–2 h later; second and third sessions: 120 mg, orally, followed by a supplemental half dose 1.5–2 h later | Efficacy of MDMA-assisted psychotherapy in veterans with combat-related, refractory PTSD | Not yet recruiting | ClinicalTrials.gov identifier: NCT04264026 |
| MDMA | CBCT in dyads with one member with post-traumatic stress disorder | First session: 75 mg, orally, followed by a supplemental half dose 1.5 h later; second session: 75 or 100 mg, orally, followed by a supplemental half dose 1.5 h later | Safety and effect size of a combination of CBCT and MDMA-assisted psychotherapy in 10 pairs of people, one with and one without PTSD. Changes in PTSD symptoms and relationship issues before and after the course of psychotherapy | Completed | ClinicalTrials.gov identifier: NCT02876172 |
| Autism Spectrum Disorder | |||||
| MDMA | Autism spectrum disorder | First session: 75 or 100 mg, orally; second session: 100 or 125 mg | MDMA-assisted psychotherapy is safe and elicits rapid and durable therapeutic improvements in social anxiety symptoms in adults with ASD | Completed | ClinicalTrials.gov identifier: NCT02008396 (Danforth et al., 2018) |
| MDMA | Autism spectrum disorder | 1.5 mg/kg, orally | Assess whether MDMA affects the response to affective touch in individuals with a range of autistic traits and healthy volunteers | Recruiting | ClinicalTrials.gov identifier: NCT04053036, NCT03790618 |
| Substance, Alcohol, and Tobacco Abuse | |||||
| MDMA | Alcohol use disorder | 125 mg, orally, followed by a supplemental half dose 2 h later, twice | Feasibility of MDMA-assisted psychotherapy in patients with AUD who have recently undergone detoxification | Active, not recruiting | ClinicalTrials.gov identifier: NCT04158778 |
| MDMA | Substance abuse disorder | 125 mg, orally, once | Oxytocin receptor gene variants may modulate aspects of the prosocial effects of MDMA. MDMA produces significantly greater feelings of trust in rs1042778 TT genotypes compared with G allele carriers. MDMA significantly increases plasma oxytocin. MDMA and oxytocin plasma concentrations do not differ among oxytocin genetic variants | Completed | ClinicalTrials.gov identifier: NCT01270672 (Vizeli and Liechti, 2018) |
| MDMA | Substance abuse disorder | 125 mg, orally, once | Effects of MDMA on social and emotional processing | Completed | ClinicalTrials.gov identifier: NCT01465685 (Hysek et al., 2014; Vizeli and Liechti, 2018) |
| MDMA | Substance abuse disorder | 1.6 mg/kg, orally, once | Evaluate the effects of MDMA on thinking and the relationship between plasma MDMA levels and brain function (fMRI) | Completed | ClinicalTrials.gov identifier: NCT01148342 |
| Others | |||||
| MDMA | Life-threatening illness | 125 mg, orally, followed by a supplemental half dose 1.25–2.5 later, thrice | Safety and efficacy of MDMA-assisted psychotherapy in people with anxiety related to a life-threatening cancer or neurologic illness. Effects of MDMA on neural correlates of emotional processing and anxiety | Completed | ClinicalTrials.gov identifier: NCT02427568, NCT02954562 |
| MDMA | Hepatic impairment | 80 mg, orally, once | Assess the effect of moderate hepatic impairment in the pharmacokinetics of MDMA and its active metabolite MDA to decide whether dosage adjustment is required for moderate hepatic impairment | Recruiting | ClinicalTrials.gov identifier: NCT03606538 |
| MDMA | Recreational users | Depending on self-administration | Ecstasy use is associated with tissue changes in the globus pallidus. Lower cortical postsynaptic 5-HT2A in recent users. Higher 5-HT2A in the occipital cortex of ex-MDMA users. MDMA abuse associated with neuronal damage. Greater MDMA abuse associated with higher depressive scores. No decrease in SERT density in former MDMA abusers | Completed | ClinicalTrials.gov identifier: NCT00235768 (Reneman et al., 2001a,b, 2002b; de Win et al., 2004) |
| MDMA | Recreational users | Depending on self-administration | MDMA users report somatic complaints on day 1, and symptoms of reduced energy, increased fatigue, and weakness persisted up to 4 days post–drug ingestion | Completed | ClinicalTrials.gov identifier: NCT01400204 |
| Healthy Volunteers | |||||
| MDMA | Healthy volunteers | 1.5 mg/kg, orally, once | Female subjects experience more intense physiologic (heart rate and oral temperature) and negative effects (dizziness, sedation, depression, and psychotic symptoms). Genotypes of COMT val158met or 5-HTTLPR with high functionality (val/val or l/*) determine greater cardiovascular effects, and (met/* or s/s) determines negative subjective effects (dizziness, anxiety, sedation). MDMA inhibits CYP2D6 activity. Recovery of CYP2D6 activity half-life 46.6 h. Full recovery after 10 days | Completed | ClinicalTrials.gov identifier: NCT01447472 (O’Mathuna et al., 2008; Yubero-Lahoz et al., 2011; Pardo-Lozano et al., 2012) |
| MDMA | Healthy volunteers | 125 mg, orally, once | Dopamine and norepinephrine transporter-mediated release of norepinephrine is involved in MDMA cardiostimulant effect. No modulatory role of dopamine. MDMA during bupropion therapy may result in higher plasma concentrations and enhanced mood effects but also lower cardiac stimulation. Genetic polymorphisms of the norepinephrine SLC6A2 gene weakly moderates the cardiovascular response to MDMA and may play a minor role in adverse cardiovascular events | Completed | ClinicalTrials.gov identifier: NCT01771874 (Schmid et al., 2015b; Steuer et al., 2015; Vizeli et al., 2018) |
| MDMA | Healthy volunteers | 125 mg, orally, once | MDMA increases oxytocin but not BDNF plasma levels. No association between interindividual variations in the acute effects of MDMA in humans and DA system gene variants | Completed | ClinicalTrials.gov identifier: NCT03019822 (Vizeli and Liechti, 2019; Holze et al., 2020) |
| MDMA | Healthy volunteers | 125 mg, orally, once | MDMA-induced prolongation of the latency to and reduction of light-induced miosis indicate indirect central parasympathetic inhibition, and the faster recovery time reflects an increased sympathomimetic action | Completed | ClinicalTrials.gov identifier: NCT00886886 (Hysek and Liechti, 2012) |
| MDMA | Healthy volunteers | 125 mg, orally, once | α1-Adrenergic receptor contributes to the acute cardiostimulant effects of MDMA | Completed | ClinicalTrials.gov identifier: NCT01386177 (Hysek et al., 2013) |
| MDMA | Healthy volunteers | 125 mg, orally, once | The combined use of methylphenidate and MDMA enhances cardiovascular and adverse effects | Completed | ClinicalTrials.gov identifier: NCT01465685 (Hysek et al., 2014) |
| MDMA | Healthy volunteers | 125 mg, orally, once | The 5-HT and NE transporter inhibitor duloxetine inhibits MDMA effects (may be useful in the treatment of psychostimulant dependence). MDMA increases copeptin, a marker for arginine vasopressin hormone secretion, in women but not in men. This may explain higher hyponatremia frequency in females | Completed | ClinicalTrials.gov identifier: NCT00990067 (Simmler et al., 2011; Hysek et al., 2012b) |
| MDMA | Healthy volunteers | 125 mg, orally, once | MDMA produces pupil dilation, subjective good drug effects, drug liking, happiness, and trust. MDMA reduces subjective anxiety and fear. MDMA produces sexual arousal-like effects. MDMA increases cortisol, prolactin, and oxytocin | Completed | ClinicalTrials.gov identifier: NCT01951508 (Dolder et al., 2018) |
| MDMA | Healthy volunteers | 1.5 mg/kg, orally, once | Investigate the effects of serotonin release in the subjective effects of MDMA | Completed | ClinicalTrials.gov identifier: NCT00838305 |
| MDMA | Healthy volunteers | 1.6 mg/kg, orally, once | Investigated the interactive effects of the β-blocker pindolol with MDMA on heart rate, blood pressure, body temperature, and adverse effects | Completed | ClinicalTrials.gov identifier: NCT00895804 |
| MDMA | Healthy volunteers | 1 mg/kg, orally, once | Assess the effects of MDMA on encoding and retrieval of emotional and social memories when the drug is administered before encoding and before retrieval | Completed | ClinicalTrials.gov identifier: NCT03050541 |
| MDMA | Healthy volunteers | 100 mg, orally, once | Assess the effects of MDMA on startle response and fear conditioning. Measurement of blood BDNF, oxytocin, and cortisol. Assess the effects of MDMA on sleep | Recruiting | ClinicalTrials.gov identifier: NCT03181763 |
| MDMA | Healthy volunteers | 125 mg, orally, once | Assess the role of MDMA-induced acute serotonin release in the effects of fear extinction | Recruiting | ClinicalTrials.gov identifier: NCT03527316 |
| MDMA | Healthy volunteers | 125 mg, orally, followed by a supplemental half dose 1.25–2.5 h later, once | Assess the effects of MDMA on therapists trained to perform MDMA-assisted psychotherapy research | Enrolling by invitation | ClinicalTrials.gov identifier: NCT01404754 |
| MDMA | Healthy volunteers | 0.75–1.5 mg/kg, orally, once | Assess the effects of MDMA on the functioning of reward-related brain circuits (fMRI) | Not yet recruiting | ClinicalTrials.gov identifier: NCT04060108 |
| MDMA | Healthy volunteers | N/A | Effects of MDMA on mood and cognitive performance | Completed | ClinicalTrials.gov identifier: NCT02033707 |
| MDMA | Healthy volunteers | 120 mg, orally, followed by a supplemental half dose 1.5–2 h later, once | Collect information to support the safety profile of MDMA-assisted psychotherapy. Understand acute effects for use in therapy | Not yet recruiting | ClinicalTrials.gov identifier: NCT04073433 |
AUD, alcohol use disorder; CBCT, cognitive behavioral conjoint therapy; COMT, catechol O-methyltransferase; fMRI, functional magnetic resonance imaging; N/A, not available; NCT, ClinicalTrials.gov identifier; SLC6A2, sodium-dependent noradrenaline transporter; 5-HTTLPR, serotonin transporter-linked polymorphic region.