As seen in Psychology Today.
There is a groundswell of support for the use of 3,4-methylenedioxymethamphetamine (MDMA) in the treatment of severe post-traumatic stress disorder (PTSD). Though the use of the drug is still controversial, the results of studies involving MDMA in patients with PTSD have been nothing short of remarkable, especially considering the fact that chronic PTSD is one of the more difficult psychiatric conditions to treat. Particularly among veterans, who are especially prone to developing PTSD, even the best treatments tend to merely manage symptoms. For approximately two thirds of veterans, conventional treatment does not lead to remission.
However, a multi-site, randomized, double-blind, confirmatory phase 3 study recently published in Nature Medicine by Mitchell and colleagues on the use of MDMA assisted therapy in treating PTSD found that 86.5% of participants experienced a clinically significant benefit, and that 71.2% of participants no longer met criteria for PTSD once the study was over. For a condition that affects approximately 5% of the U.S. population each year, this could be the closest thing to a cure we have.
To be clear, MDMA is not simply given to patients in the same way as antidepressants or sedatives are. Rather, patients typically undergo two or three 90-minute preparation sessions before the drug is administered, as recommended by the Multidisciplinary Association of Psychedelic Studies (MAPS). These sessions may involve just the therapist or a two-person therapy team. Subsequently, the patient meets with the therapist (or therapy team) and the drug is administered in a split oral dose of between 120-180 mg. The initial dose typically falls within the range of 75-125 mg, while the booster dose administered later is significantly less.
Following the session, the patient typically returns to talk about their experience with their therapist and to incorporate the experience into a larger psychotherapeutic framework. Additional MDMA sessions (usually only two or three) may follow with talk therapy occurring subsequent to each session.
The Mitchell Study
The Mitchell study followed similar parameters. Enrolled participants met with a two-person therapy team for three 90-minute sessions before receiving either placebo with therapy or MDMA assisted therapy. MDMA sessions were spaced approximately one month apart with therapy in between.
There were 104 participants in the randomized study, with 53 assigned to the MDMA group and 51 assigned to the placebo group. The participants were ethno-racially diverse, with 35 of 104 (33.7%) identifying as other than White. Participants assigned female sex at birth were overrepresented (74 or 71.2%) in the study and the placebo group (42/51, 82.4%) when compared to the MDMA group (32/53, 60.4%).
Symptomology was measured over the course of 18 weeks using the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5), which ranges from 0 (no symptoms) to 80 (most severe symptoms possible). At the end of the 18-week study, the mean CAPS-5 score for the placebo group had fallen by 14.8, while the mean score for the MDMA group had fallen by 23.7. Moreover, 45 of 52 (86.5%) within the MDMA group achieved a clinically meaningful benefit, as defined in this study by a 10-point decline in CAPS-5 score. As noted above, 37 (71.2%) participants from the MDMA group no longer met criteria for PTSD. The team also noted that MDMA-assisted therapy reduced functional impairment as measured with the Sheehan Disability Scale (SDS), which ranges from 0 (unimpaired) to 30 (highly impaired). The MDMA group experienced an average decline in score of 3.3 and the placebo group saw an average decline of 2.1.
The vast majority of total participants (102 of 104, 98.1%) experienced at least one treatment-emergent adverse event (TEAE), while a total of 7 experienced a severe TEAE (5 in the MDMA group; 2 in the placebo group). The most common TEAEs included nausea, decreased appetite, muscle tightness, and excessive sweating. Of note, no serious TEAEs were reported.
How Does MDMA Work for Patients with PTSD?
Patients with PTSD do not experience identical clusters of symptoms, but they all have experienced a traumatic event, and their symptoms arise because of their inability to successfully process that trauma. They repetitively recall the traumatic event, and the moment the memory was created which is then experienced as new trauma. Some may experience less impairment except when triggered by reminders of the trauma, while others may feel overwhelmed by intrusive memories. Still others may ruminate about the event endlessly and feel as though they are a prisoner of their past.
MDMA is a psychoactive substance that induces a sense of empathy or connectivity to others, euphoria, and reduced fear responses. Consequently, it is commonly referred to as an empathogen. The effects of MDMA are mediated through the stimulation and release of neurotransmitters like serotonin, norepinephrine, and dopamine. It also causes the release of oxytocin, often referred to as “the love hormone”. While the euphoric effects of MDMA have made it a popular drug of abuse, particularly within clubs (where it is often referred to as ecstasy, XTC, or molly), these same effects can be used in a clinical setting to allow therapists to delve into patients’ traumatic memories without triggering negative emotional symptoms characteristic of PTSD. The therapist and patient then work together to process and integrate the trauma. Successful treatment does not mean eliminating traumatic memories; rather, it means the patient has integrated them into a normalized narrative, and they no longer experience severe emotional responses to the same memories. It allows the emotional wound to close, but it does not eliminate the scar.
To be clear, it is not the drug alone that allows the patient to work through the trauma and enhance their capacity to have crucial insights. Without concomitant guided therapy, it will not produce the same results. Simply put, MDMA puts the patient in the right frame of mind to undergo intensive work with their therapist on an accelerated timeline, and the Mitchell study is one more piece of evidence showing just how much potential this treatment has.
Of note, this article was written entirely by a human with no assistance from generative AI tools.