The Effects of MDMA on Prefrontal and Amygdala Activation in PTSD
Double-blind, placebo-controlled, randomised crossover neuroimaging study (n=20) testing single oral MDMA 1.5 mg/kg versus niacin 250 mg in adults with PTSD to assess mPFC and amygdala activation.
Detailed Description
This double-blind, randomised, within-subject crossover study uses HCP-style task and resting-state fMRI to determine the effects of MDMA on medial prefrontal cortex and amygdala activation in adults with PTSD.
Investigators hypothesise MDMA will increase mPFC and decrease amygdala responses to negative stimuli, and will relate these neural changes to performance on Ekman’s Emotional Facial Expression task and trauma severity.
Resting-state effects will be explored with Coupled Intrinsic Connectivity Distribution (Coupled-ICD) analyses. Participants receive single oral MDMA 1.5 mg/kg or niacin 250 mg with a 2-week washout before crossover; acute neural and behavioural responses plus preliminary connectivity data are collected.
Study Protocol
Preparation
Dosing
Integration
Study Arms & Interventions
MDMA
experimentalSingle oral MDMA 1.5 mg/kg in a within-subject crossover neuroimaging session.
Interventions
- MDMA1.5 mg/kgvia Oral• single dose• 1 doses total
Single dose administered once per session.
Niacin
placeboSingle oral niacin 250 mg as active placebo comparator in crossover.
Interventions
- Placebo250 mgvia Oral• single dose• 1 doses total
Niacin 250 mg (active placebo).
Participants
Inclusion Criteria
- Inclusion Criteria:
- Males or females between the ages of 21-55 years. Females included if not pregnant and agree to utilize a medically (non-hormonal) accepted birth control method (implant, condom, diaphragm with spermicide, IUD, tubal ligation, abstinence, or partner vasectomy) or if post-menopausal for ≥1 year, or surgically sterile.
- Able to provide written informed consent according to Yale HIC guidelines.
- Able to read and write English as a primary language.
- Diagnosis of PTSD as determined by CAPS-5.
- Score ≥23 on CAPS-5 at screening.
- No more than mild TBI per modified Brief TBI Screen.
- No medical/neurological problem or medication that would render MDMA unsafe by history or evaluation.
- No prior exposure to MDMA.
- Willing to remain overnight at study site after each experimental session and be driven home the day after sessions.
- Not currently taking any listed excluded medications.
- Willing to sign medical release for investigators to communicate with therapist/doctors.
- Willing to abstain from alcohol, street drugs, and tobacco while in the study.
Exclusion Criteria
- Exclusion Criteria:
- Diagnostic history of bipolar disorder, schizophrenia or schizoaffective disorder or current psychotic features per MINI 7.0.
- Serious suicide or homicide risk as assessed by evaluating clinician.
- Substance abuse or dependence in the 6 months prior to screening or positive pre-study urine drug screen.
- Any significant history of serious medical or neurological illness.
- Signs of major medical or neurological illness on exam or ECG/lab screening (e.g., positive urine tox, positive HIV tests).
- Abnormality on physical exam unless study physician deems it safe to include.
- Pregnant or lactating women or positive urine pregnancy test for women of child-bearing potential at screening or prior to imaging day.
- Any history indicating learning disability, intellectual disability, or ADHD.
- Family history of cardiovascular diseases; history of hypertension with baseline BP >140/90 mmHg; any history of syncope or baseline BP <100 mmHg systolic.
- History of claustrophobia.
- BMI > 30 kg/m2 or >250 pounds.
- Use of anxiolytic, neuroleptic and SRI medications (off SRIs for 4 weeks, fluoxetine 5 weeks).
- Females taking hormonal contraceptives are excluded.
- Any metal or electromagnetic implants (pacemaker, artificial heart valve, defibrillator, aneurysm clip, cochlear implants, shrapnel, neurostimulators), significant sensory impairment, history of seizures or current anticonvulsant use.