MDMA-Assisted Therapy

What is MDMA?

The substance 3,4-methylenedioxymethamphetamine, more commonly known as MDMA, is an illicit synthetic drug with stimulant and hallucinogenic properties. It has been used for several decades as a recreational ‘party drug’, due to its effects, which include increased energy, euphoria, sensory and perception changes, and increased social connection and affection.^[1][2]

MDMA is often ingested as a pill or capsule (commonly referred to as Ecstasy or Molly) or inhaled nasally as a crystalline powder. When obtained illicitly, the drug tends to contain very little MDMA and is regularly mixed with other substances, such as amphetamine, cocaine, over-the-counter medicines such as dextromethorphan, or various household substances.^[1]

MDMA can cause dangerous consequences, particularly with heavy or prolonged use, such as severely increased heart rate and blood pressure, seizures, overheating, and dehydration.^[2]

In recent years, MDMA has been studied as a potential medication to treat various mental health conditions.^[3][4]

How does MDMA help with mental health?

Studies have shown that psychedelic drugs, such as MDMA, may be able to increase brain plasticity, meaning that they can help the forming of new connections between neurons. These drugs impact receptors inside cells, which is believed to improve plasticity. In contrast, other medications and compounds, such as antidepressants, only impact receptors on the outside of cells.^[5]

Improved plasticity can improve the brain’s ability to make changes to behavior, thoughts, and personality, thereby having a significant impact on mental health symptoms.^[6]

MDMA is found to greatly increase levels of serotonin and norepinephrine, and slightly increase dopamine. This can have effects on emotion, learning, memory, and fear, all of which can be linked to symptoms of mental health conditions, especially post-traumatic stress disorder (PTSD).^[4]

It is also believed that MDMA impacts the amygdala, influencing fear responses, and increases the release of oxytocin, increasing social connectedness. Similarly, trials have indicated that MDMA can help reduce fear relating to traumatic memories and increase cognitive insight.^[7][8] 

MDMA is not intended to be used as a sole treatment or cure for mental health conditions, but rather as an augmentation of therapeutic interventions. It is believed that by reducing fear and anxiety associated with traumatic memories, trauma-related therapy techniques can be used without causing high levels of emotional distress and therefore can be more effective.^[3][9]

The effects of MDMA suggest that its use alongside psychotherapy can help improve therapeutic relationships and treatment engagement, positively impacting outcomes. This has been demonstrated in several trials, with many individuals experiencing significant improvements in PTSD symptoms following MDMA-assisted therapy.^[7][10]

These trials have involved the use of 2-3 single doses a month apart, with a therapeutic session before and after administration. Therefore, unlike most medicinal mental health treatments, individuals will not require long-term daily dosing.^[9]

The results of these trials show between half and two-thirds of individuals no longer meet PTSD criteria following treatment. Similarly, results indicate improvements in distress tolerance, emotional regulation, cognitive restructuring, sleep quality, empathy, and interpersonal relationships. Results suggest that the treatment can provide long-term positive results within a short timeframe.^[7][10]

As with all medications and substances, the effects are likely to differ depending on the individual, their condition, the severity of their symptoms, and other individual factors.^[8]

What mental health conditions does MDMA help with?

Current research suggests that MDMA can be an effective treatment for PTSD.^[10] 

It is also believed that it can be effective in the treatment of several other conditions, including treatment-resistant depression, obsessive-compulsive disorder (OCD), various anxiety disorders, social anxiety in the context of autism spectrum disorder, eating disorders, and substance use disorders. Further research is required to clarify these uses.^[4]

Is MDMA-assisted therapy legal?

Currently, MDMA-assisted therapy is not approved by the FDA, so it is not a legal treatment in the US.^[3] However, in Australia, this treatment has recently been approved and is currently being used for individuals with PTSD.^[8]

At present, trials in the US are continuing, with various Phase III trials being presented to the FDA to demonstrate the safety and effectiveness of this treatment. It is believed that FDA approval will be granted, thus making MDMA-assisted therapy a legal treatment.^[3][11] 

In the 1970s and early 1980s, MDMA was used as a legal treatment for PTSD. However, due to its abuse, it was made an illegal substance in 1985, with the DEA labeling it a Schedule I controlled substance. Schedule I substances are defined as those with a high abuse potential, unsafe for use, and with no medical purpose.^[2][8]

Because of this classification, research into the therapeutic use of MDMA has required extensive regulation to ensure the meeting of strict criteria and standards.^[4] Recent research has been funded by a nonprofit organization, MAPS, with the intention of developing a safe and effective mental health treatment rather than a commercialized and profitable medication.^[3]

Once the treatment is approved, there will likely be restrictions in place for prescribing and using the medication, due to the potential for abuse and health risks. It is expected that this will require the medication to be used under medical supervision and not within the home.^[4][9]

The current state of MDMA treatment research

After being classified as a Schedule I controlled substance in 1985, MDMA as a mental health treatment was not researched until the 2010s when studies into its potential effects recommenced. Over the previous decade, research into the use of MDMA and other psychedelics (such as LSD, psilocybin, and DMT) in mental health treatment has been prolific.^[8][9]

In recent years, trials have been carried out to test the effectiveness and safety of MDMA-assisted therapy in the treatment of PTSD. During this time, additional research has theorized and investigated its effectiveness in treating other conditions, such as depression and anxiety disorders.^[4]

Medications must go through three trial phases before potentially receiving approval from the FDA. Phase III trials for MDMA-assisted therapy for PTSD have recently been completed with evidence of successful outcomes, therefore indicating a likelihood of FDA approval.^[3][11]

Trials suggest positive results from the use of MDMA-assisted therapy, although side effects have occurred, including restlessness, anxiety, headache, teeth grinding, and nausea. Other potential risks are likely to occur if the drug is used when not prescribed or used in an uncontrolled, unmonitored, or unregulated manner.^[9]

Once MDMA-assisted therapy is approved and begins being used in public populations, it will continue to undergo monitoring by the FDA to ensure its effectiveness and safety. Any detrimental long-term impacts and effects are currently unknown and may become evident during this time.

The American Psychiatric Association has reportedly warned against the public use of MDMA until its effects are clear, as they may differ from results within trials and controlled settings.^[11] Similarly, the long-term outcomes of this treatment are not yet clear, so this will require further investigation and follow-up.^[10]

Research into the use of MDMA as a mental health treatment will likely continue in the upcoming years, such as its use in treatment-resistant depression and substance use disorders. Past and ongoing research, along with the upcoming use of this treatment in public populations, can help develop a better understanding of mental health conditions and appropriate or potential treatments.^[3][4][5]