What is MDMA?
… and How Is It Transforming Mental Health Treatment?
By Lauren Esmay, MS
It’s been called “The Love Drug” and commonly referred to by names such as Molly, Mandy, and Ecstasy.
More officially, this substance is called MDMA (short for 3,4-Methylenedioxymethamphetamine).
Long associated with dance parties and raves starting in the 1990s, MDMA is also known for an increase in social behaviors such as energy, empathy, and pleasure.
So how exactly did this medicine become key to new research on various mental health concerns, including substance use disorders?
First, let’s take a quick look at MDMA’s history before diving into the current research and how it is revolutionizing treatment options and outcomes.
Early Development of MDMA
Unlike other medicines we’ve discussed in prior blogs, such as psilocybin and peyote, MDMA is not a plant-derived medicine. Instead, MDMA was first developed by Merck —a German pharmaceutical and biotechnology company — in 1912.
MDMA was intended to help synthesize medications that control bleeding. However, researchers found it to be a potent empathogen-enactogen with stimulant and minor psychedelic properties.
Empathogens or entactogens are a class of psychoactive drugs that tend to produce experiences of emotional communion, oneness, relatedness, and emotional openness—ie, empathy or sympathy.
By the 1970’s, psychotherapists and psychiatrists were using MDMA to enhance therapy sessions to achieve greater outcomes for their clients.
However, after MDMA became a popular street drug in the early 1980s, the US Drug Enforcement Agency (DEA) declared an emergency ban on it as part of the Controlled Substances Act of 1986.
The DEA placed MDMA on the list of Schedule I drugs – those with a high potential for abuse and no accepted use for medical treatment in the United States.
The agency justified this decision based upon data showing that frequent high doses of MDA, which is a related compound of MDMA, induced serotonergic nerve terminal degeneration in rat brains.
Despite the DEA’s ban, the FDA approved the first ever human trial of MDMA in 1990 to research pain relief in terminally ill patients, as well as enhancement of psychotherapy outcomes in treatment of mental health issues.
The results from these studies were never published.
However, they did help to establish safety parameters for administering MDMA in controlled clinical settings such as medical research.
MDMA’s Comeback
The mid-2000s were a scientific turning point for MDMA.
In the preceding decades, public agencies had made villainizing, unconfirmed claims about MDMA – specifically, that it caused irreparable brain damage.
Now, researchers began to explore the therapeutic potential of MDMA to heal the brain, especially in conjunction with psychotherapy.
In a step forward, the psychiatrist Michael C. Mithoefer, M.D. was approved by the FDA to conduct the first pilot study of MDMA therapy.
After completing the study in 2009, Mithoefer’s team reported that 10 out of 12 patients with Post-Traumatic Stress Disorder (PTSD) showed significant clinical improvement after only two sessions of MDMA-assisted psychotherapy, versus only 2 out of 8 patients utilizing conventional psychotherapy alone.
Perhaps even more stunning, 83% of the participants no longer qualified for a clinical PTSD diagnosis (as measured by the Clinician-Administered PTSD Scale). A follow-up study with these participants three and half years later showed that about 75% had sustained their reduction of PTSD symptoms.
The study documented no drug-related serious adverse events, adverse neurocognitive effects or clinically significant blood pressure increases.
The researchers concluded that “MDMA-assisted psychotherapy can be administered to posttraumatic stress disorder patients without evidence of harm, and it may be useful in patients refractory to other treatments.”
Mithoefer’s study caught the attention of a group of military veterans, as PTSD is a common concern amongst veterans and is often highly treatment-resistant.
Thus began the comeback of research to examine how MDMA can be helpful for various people undergoing psychotherapy treatment for conditions such as PTSD and substance use disorder.
How MDMA Enhances Treatment for PTSD
According to the National Institute of Mental Health, PTSD is defined as a disorder that develops in some people who have experienced a shocking, scary, or dangerous event and continue to experience the reactions to these traumas over an extended period of time.
“Trauma is not the event that happens to you. Trauma is what happens inside you as a result of what happened to you.” – Gabor Maté, M.D.
While PTSD is often linked to the trauma that Veterans encounter in combat, the largest cause of PTSD is actually non-combat-related trauma – for example, sexual violence, the unexpected death of a loved one, a life-threatening event, or interpersonal violence.
In conjunction with psychotherapy, MDMA can help reduce PTSD symptoms, such as defensiveness and anxiety, while increasing relaxation and improving a person’s mood.
When practiced with intention and in the correct and safe setting, MDMA can also increase the bond between the therapist and patient, allowing the patient to safely explore the traumatic events without being retraumatized.
“As a molecule, MDMA allows us to access trauma without being overwhelmed by fear and to access the compassion, the self-acceptance, the sense of safety and trust, and the ability to feel the love that’s necessary for healing.” – Rick Doblin, Ph.D.
The therapeutic use of MDMA helps reduce the anxiety associated with the trauma and of recalling the traumatic experience, while also allowing the person to experience an increase in insight and memory.
This can facilitate therapeutic sessions where the person can engage more substantively with the feelings associated with the trauma.
MDMA’s Role in Treatment of Substance Use Disorder
As many entheogenic compounds are being pursued as potential treatments for substance use disorder, recent studies have shown that MDMA may also have a similar therapeutic mechanism.
MDMA has some shared features and chemical structures with psychedelic compounds.
And since both types of medicines are used in treatment for PTSD, it is believed that MDMA – based on these shared features – may also be promising in the treatment for substance use disorder.
A study by the Multidisciplinary Association for Psychedelic Studies (MAPS) concluded that MDMA may show promising results in future substance use disorder treatment by:
directly treating biochemical imbalances associated with addiction;
indirectly assisting with the therapeutic process;
and/or reducing symptoms of co-occurring psychiatric conditions which would allow for a more effective opportunity to address problematic substance use.
It’s also important to point out that MDMA-Assisted Therapy has not been found to increase the risk of substance use.
PTSD, Opioid Use Disorder, and MDMA
So, what’s the link between using MDMA to help treat PTSD and using MDMA as a treatment option for opioid use disorder?
Data shows that individuals who use opioids suffer from high rates of PTSD, and that such “Comorbid PTSD-OUD” is often complex and intertwined.
Researchers theorize that “a common neurobiologic circuit is suggested for the mechanism of this comorbidity.”
In addition, clinicians who work with patients observe that “Best outcomes occur when treatment addresses both comorbidities simultaneously, known as parallel or integrative approaches.”
So with all of the information we have currently, treating both PTSD and OUD at the same time is the most effective and logical approach.
However, options and access to such parallel treatments are sorely lacking.
Because of MDMA’s documented efficacy in treating PTSD and additional potential to treat OUD, it could be an important new integrative approach to simultaneous healing of the two disorders.
PTSD in Veterans and Women
PTSD is slightly more common among Veterans than civilians, affecting 7% of Veterans versus 6% of all adults sometime in their lifetime.
Veterans may find difficulties in readjusting to civilian life after military service, and with the additional component of PTSD, may develop substance use disorder through trying to cope.
More than 20% of Veterans with PTSD also have substance use disorder, and about a third of veterans seeking treatment for substance use disorder also have PTSD.
Military demographics skew heavily male, with women currently making up only about 10% of the overall Veteran population in America.
However, overall in the U.S., women are far more likely to have PTSD than men are.
Women are almost three times more likely to have PTSD than men (5.2% versus 1.8%) among U.S. adults aged 18 or older, according to the National Institute of Mental Health (NIMH). The disparity is even greater among U.S. adolescents aged 13-18 (8% versus 2.3%).
According to the VA’s National Center for PTSD, “This is in part due to the types of traumatic events that women are more likely to experience—such as sexual assault—compared to men.
PTSD is also more common among female Veterans versus male Veterans, with 13% versus 6% rates, respectively.
MDMA’s Path Forward
In December 2023, Lykos Therapeutics (formely MAPS PBC) submitted a New Drug Application (NDA) to the FDA for MDMA-assisted therapy for PTSD treatment.
The FDA has granted the application priority review and has assigned a target action (decision) date of August 11, 2024.
Priority review is a status assigned to drugs that, if approved, would represent significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications.
If approved, this would be the first federally legal MDMA-assisted therapy and psychedelic-assisted therapy.
It would allow further research into the specific effects of MDMA for PTSD, which would facilitate a better understanding of how MDMA can be useful in other conditions such as substance use disorders.
Lykos Therapeutics is also partnering with the University of New Mexico (UNM) to supply the MDMA for its groundbreaking clinical trial starting in early 2024, treating new mothers who have both PTSD and OUD.
This post is for informational purposes only and does not constitute medical or legal advice. It is best to consult a licensed health practitioner about any symptoms or conditions you have and to discuss the use of herbal supplements.
