Open-label, single-group study in 20 adults with fibromyalgia evaluating two MDMA-assisted therapy sessions paired with EEG/fMRI and integrative therapy.
Participants complete baseline EEG/fMRI, three 90-minute preparatory sessions, two 8-hour experimental MDMA sessions (100 mg initial, optional 50 mg supplemental at 1.5–2 h), four 90-minute integrative sessions, and a 3‑month follow-up.
Primary outcomes include clinical pain and function; secondary objectives examine patient–clinician neural concordance and therapeutic alliance using neuroimaging and behavioural measures.
Study Protocol
Preparation
3 sessions
90 min each
Dosing
Locations
Massachusetts General Hospital — Charlestown, Massachusetts, United States
2 sessions
480 min each
Integration
4 sessions
90 min each
Therapeutic Protocol
support
Study Arms & Interventions
MDMA-assisted therapy
experimental
Two-session MDMA-assisted psychotherapy with neuroimaging and integrative therapy.
Interventions
MDMA100 - 150 mg
via Oral• single dose• 2 doses total
Initial 100 mg oral dose with optional 50 mg supplemental dose 1.5–2 h later.
Participants
Ages
21 – 65
Sexes
Male & Female
BMI
-
Psychosis History
-
Inclusion Criteria
Inclusion Criteria:
Are at least 21 years to 65 years of age inclusive, at the time of signing the informed consent.
Have a clinical diagnosis of fibromyalgia and meet the Wolfe et al 2011 research criteria for fibromyalgia for at least one year.
Typical fibromyalgia pain intensity of 4/10 or greater.
Fluent in speaking and reading English.
Able to swallow pills.
Agree to have some study visits audiovisually recorded, including Experimental Sessions/ neuroimaging sessions.
Able to provide a contact (relative, spouse, close friend, or other support person) who is willing and able to be reached by the investigators in the event of the participant becoming unwell or unreachable.
Able to identify appropriate support person(s) to stay with the participant on the evenings of the Experimental Sessions
Have a body weight of at least 45 kilograms (kg). Participants with a body weight of 45 to 48 kg must also have a body mass index (BMI) within the range of 18 to 30 kg/m2
Participants assigned female sex at birth must not be pregnant or become pregnant throughout participation in the study
Capable of giving signed informed consent
Are on stable doses of allowable medication for 30 days prior to entering the study and agree not to change medications or dosages during the trial, except for medications falling under the tapering scheduling
Exclusion Criteria
Exclusion Criteria:
Presence of any medical or psychiatric illness that is judged to interfere with the study (ex. Fibromyalgia, PTSD, bipolar, schizophrenia) determined by a self-report measure.
Presence of any contraindications to fMRI scanning or EEG scanning. (ex. Cardiac pacemaker, metal implants, fear of enclosed spaces, pregnancy).
Unwillingness to receive brief experimental pain
Lower extremity pain or vascular issues that may interfere with the study procedures
Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.
Have a history of any medical condition that could make receiving a sympathomimetic drug harmful because of increases in blood pressure and heart rate. This includes, but is not limited to, a history of myocardial infarction, cerebrovascular accident, heart failure, severe coronary artery disease, or aneurysm.
Have a diagnosis of uncontrolled hypertension, defined as repeated blood pressure readings of ≥140 mmHg systolic or ≥90 mmHg diastolic.
Have a history of ventricular arrhythmia at any time, other than occasional premature ventricular contractions (PVCs) in the absence of ischemic heart disease.
Have Wolff-Parkinson-White syndrome or any other accessory pathway that has not been successfully eliminated by ablation.
Have a history of arrhythmia, other than premature atrial contractions (PACs) or occasional PVCs in the absence of ischemic heart disease, within 12 months of screening.
Have a history of additional risk factors for Torsade de pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome).
Have engaged in a new form of psychiatric or mental health care within 12 weeks of enrollment, including Electroconvulsive Therapy (ECT), and ketamine-assisted therapy.
Have a current moderate or severe alcohol or cannabis use disorder within the 12 months prior to enrollment.
Have an active illicit drug (other than cannabis) or prescription drug substance use disorder at any severity within 12 months prior to enrollment.
Any participant presenting current serious suicide risk, as determined through psychiatric interview, responses to C-SSRS, and clinical judgment of the investigator will be excluded; however, history of suicide attempts is not an exclusion.
Unable or unwilling to safely taper-off prohibited psychiatric and non-psychiatric medication with exceptions determined by study staff or require use of prohibited medications during experimental sessions.
Require use of concomitant medications that could prolong the QT interval during Experimental Sessions.
Have used Ecstasy (unregulated material represented as containing MDMA) more than 10 times within the last 10 years, or at least once within 6 months of the first Experimental Session.
Current enrollment in any other clinical study involving an investigational study treatment or any other type of medical research, unless approved by the study clinician.
Have current Personality and/or Psychotic Disorders.
Have a current eating disorder with compensatory behaviors.
Have current major depressive disorder with psychotic features.
Have a history of, or a current primary psychotic disorder, bipolar affective disorder type 1.
Sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the sponsor-investigator or study clinician, contraindicates participation in the study.
Are currently engaged in compensation litigation whereby financial gain would be achieved from prolonged symptoms of fibromyalgia or any psychiatric disorders.
Lack social support or lack a stable living situation.
Previous participation in a MAPS-sponsored MDMA clinical trial.
Employees (and their immediate family members) of MAPS, MAPS Public Benefit Corporation, or MAPS Europe B.V; or individuals in a personal relationship with the site investigator.
Presence of any medical or psychiatric illness that is judged to interfere with trial
Presence of any contraindications to fMRI scanning or EEG scanning (ex. Cardiac pacemaker, metal implants, fear of closed spaces)
Lower extremity pain or vascular issues that may interfere with study procedures
Comorbid chronic pain condition that is rated by the subject as more painful than fibromyalgia
Have any severe anxiety disorders or significant anxiety symptoms interfering with fMRI scanning (e.g. panic)
Is a current patient of the matched dyad clinician enrolled in the study
Would present a serious risk to others as established through clinical interview and contact with treating psychiatrist.
Have any current problem which, in the opinion of the sponsor-investigator or study clinician, might interfere with study participation or prevent satisfactory completion of study protocol.