Clinical TrialNeuroimaging & Brain MeasuresMDMAMDMAPlaceboCompleted

Neurobiology and Pharmacokinets of Acute MDMA Administration

Randomised, double-blind, within-subject crossover study (n=187) examining acute MDMA effects and pharmacokinetics at placebo, 1.0 mg/kg and 1.6 mg/kg with concurrent fMRI and biological sampling.

Target Enrollment
187 participants
Study Type
Phase I interventional
Design
Randomized, double Blind

Detailed Description

This study evaluates MDMA effects on brain function using fMRI alongside detailed pharmacokinetic sampling in blood, urine, oral fluid, sweat, breath and hair to relate plasma concentrations to cognitive and neural changes.

A randomized, balanced, double-blind within-subject design compares placebo, low (1.0 mg/kg) and high (1.6 mg/kg) MDMA across three scanning sessions; participants perform memory, attention and decision-making tasks during scanning.

Pharmacokinetic goals include characterising MDMA and metabolite disposition across matrices to improve interpretation of drug tests and inform safety and forensic applications.

Study Protocol

Preparation

sessions

Dosing

3 sessions

Integration

sessions

Study Arms & Interventions

MDMA crossover

experimental

Within-subject, balanced crossover comparing placebo, low (1.0 mg/kg) and high (1.6 mg/kg) MDMA with fMRI and pharmacokinetic sampling.

Interventions

  • MDMA1 mg/kg
    via Oral• single dose

    Low dose (~70 mg/70 kg)

  • MDMA1.6 mg/kg
    via Oral• single dose

    High dose (~112 mg/70 kg)

  • Placebo
    via Oral• single dose

    Placebo condition

Participants

Ages
18 – 40
Sexes
Male & Female

Inclusion Criteria

  • Participants must:
  • 1. Be between the ages of 18 and 40.
  • 2. If MDMA group, have consumed at least five tablets of ecstasy in their lifetime with no clinically significant adverse medical or psychiatric reactions and have used at least once within the past 30 days; history supported by ≥1 positive urine amphetamines or hair MDMA test within past 90 days. Urine tests at scanning visits must not be positive for drugs other than amphetamines and cannabis; scanning visits may be rescheduled once for a positive urine test for other drugs.
  • 3. If control group, have no history of MDMA use and negative urine test for amphetamines; non-drug-using controls must have negative urine for non-therapeutic psychoactive drugs at screening and scanning visits; lifetime cannabis use ≤10 times and no use in past 2 years for non-drug-using controls.
  • 4. Be without current clinically significant medical problems that would preclude safe participation.
  • 5. If female, use reliable birth control or abstain from sexual intercourse; counselled on pregnancy detection limits.
  • 6. Have an eighth-grade reading/comprehension level.
  • Additional for neurocognitive testing:
  • 7. IQ ≥85 (WASI).
  • 8. Right-handed.
  • 9. Speak English as first language.

Exclusion Criteria

  • Participants must NOT:
  • 1. Have a known major medical or Axis I psychiatric diagnosis other than substance abuse; individuals with substance dependence other than nicotine or cannabis excluded; those who smoke >2 packs/day excluded.
  • 2. If MDMA user, be currently using (within 30 days) strong inhibitors/inducers of CYP2D6 or CYP3A4 (extensive list provided in protocol); advised to limit grapefruit juice; minimum 30-day abstention from listed compounds prior to MDMA administration.
  • 3. If MDMA user, SBP >135 or DBP >85 after 5 minutes rest, resting HR >100 bpm, or total cholesterol >250 mg/dL if >30 years.
  • 4. If MDMA user, hemoglobin <12.5 g/dL (male) or <12 g/dL (female).
  • 5. If MDMA user, clinically significant abnormal resting 12-lead ECG.
  • 6. If female, pregnancy or nursing.
  • 7. Liver function tests >3× upper limit of normal.
  • 8. Unable to comply with task demands.
  • 9. History of neurological illnesses (stroke, CNS tumour, encephalitis, MS, epilepsy, movement disorders, severe migraine requiring treatment).
  • 10. If non-drug-using control, hair test positive for non-therapeutic psychoactive drugs.
  • 11. If drug-using control, hair results inconsistent with self-report.
  • Additional for neurocognitive testing:
  • 12. Head trauma with loss of consciousness >3 minutes.
  • 13. Positive HIV serology (retested after six months).
  • 14. ADHD Screening score ≥24 on A or B subscale.
  • 15. Positive FTA-ABS confirmatory test for syphilis.

Study Details

Locations

National Institute on Drug Abuse, Biomedical Research Center (BRC) — Baltimore, Maryland, United States

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