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MDMA-Assisted Therapy protocol

Compound: MDMA

Status: research

Entactogen for PTSD treatment, nearing FDA approval

Dosing

Dose: 80 to 120 mg initial, with an optional supplemental half dose 1.5 to 2 hours later

Route: Oral, in trials

Duration: 6 to 8 hour session

Sessions: Three dosing sessions spaced about a month apart, embedded in roughly 12 preparation and integration sessions

Safety

Monitoring: Blood pressure and temperature monitoring during sessions, two clinicians present in trial protocols, structured suicidal ideation tracking across the course of treatment.

Side effects

  • Jaw clenching
  • Reduced appetite
  • Transient anxiety
  • Elevated heart rate and blood pressure
  • Post-session fatigue and low mood in the following days

Contraindications

  • Significant cardiovascular disease
  • History of psychosis or mania
  • Uncontrolled hypertension
  • Serotonergic drug interactions
  • Pregnancy
  • Hyperthermia risk factors

Overview

Mechanism: MDMA promotes release of serotonin, norepinephrine, dopamine, and oxytocin, reducing fear response while preserving emotional engagement. In therapy it is used to widen the window in which traumatic material can be processed without overwhelm.

Indications

  • Post-traumatic stress disorder (investigational)
  • Studied adjunct to trauma-focused psychotherapy

Evidence level: Two positive Phase 3 trials (MAPP1 2021, MAPP2 2023). In 2024 the US FDA declined approval and requested an additional Phase 3 trial, so MDMA-assisted therapy remains investigational in the US. Australia moved to allow authorized prescribing for PTSD in 2023.

Citations

Doi: 10.1038/s41591-021-01336-3

Year: 2021

Title: MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study (MAPP1)

Doi: 10.1038/s41591-023-02565-4

Year: 2023

Title: MDMA-assisted therapy for moderate to severe PTSD: a randomized, placebo-controlled phase 3 trial (MAPP2)

Integration

Prompts

  • What became approachable that was not before?
  • What did your body hold onto and what did it release?
  • What support do you need in the week after a session?

Framework: Trial protocols pair each dosing session with three integration sessions focused on consolidating trauma processing, tracking symptoms with standard scales, and translating session material into daily life.

Preparation

Screening

  • Full psychiatric evaluation including trauma history and dissociation
  • Cardiovascular screening: MDMA raises heart rate and blood pressure
  • Medication washout planning, particularly SSRIs and MAOIs
  • Hyperthermia and hyponatremia risk counseling
  • Informed consent covering investigational status

Set setting: In trials: a comfortable clinical room, two-therapist team, eyeshades and curated music available, sessions lasting a full day with overnight contact available.

Legal status: MDMA is a Schedule I controlled substance in the United States. Clinical use is limited to authorized research settings. Australia permits authorized psychiatrist prescribing for PTSD under strict conditions. This page is reference material, not medical advice.

Reference material only. Nothing on this page is medical advice or a personal recommendation.

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