Introduction

You survived the accident and physically recovered. But mentally, you still struggle. Months passed, but every time you close your eyes, you still see your car running uncontrollably off the road. You hear the crash, and then the silence. Flashbacks during the day, nightmares during the night. As days pass, you are getting angrier. You do not want to talk to anyone about what happened, and you start to avoid people. Finally, you seek help, but the treatment does not work as you expected. But maybe a new approach with MDMA can help your post-traumatic stress disorder.

What is post-traumatic stress disorder?

Post-traumatic stress disorder and its symptoms

Post-traumatic stress disorder (PTSD) is a serious mental health condition that is followed by a life-threatening traumatic event. A traumatic event (or trauma) poses a great risk to someone’s physical, emotional and spiritual well-being, endangers their existence and sense of safety. It can be a sudden, one-time event, like a car accident, a severe injury or a natural disaster, but it can also mean frequent negative events, such as surviving a war or frequent childhood abuse. Around 61-80% of people experience a major trauma in their lives, and 5-10% will develop PTSD.¹

Typical symptoms of PTSD are intense, unwanted thoughts and feelings, nightmares, and sudden, vivid flashbacks. Patients often try to avoid reminders of the traumatic event and talking about their painful memories. They can no longer enjoy activities, and negative thoughts often occupy their minds. Other typical signs are anger issues, irritability, and hypervigilance, when someone is constantly alert. These symptoms cause distress in someone’s life and affect their quality of life, preventing them from working, fulfilling daily duties and attending social gatherings.²

Biological mechanism behind PTSD and its current treatment

It is unclear why people react differently to trauma, but it is known that certain hormones and neurotransmitters, the messenger molecules between the nerve cells, play a role in the development of PTSD. Cortisol, often called the “stress hormone, " regulates the bodily response to stressful situations, and PTSD patients have a lower level of it. People affected by this mental disease often have a higher level of norepinephrine (or noradrenaline) in their bodies. This hormone and neurotransmitter is responsible for the fight-or-flight response, which is a natural defence mechanism of the body for a dangerous or life-threatening situation, and is accompanied by increased alertness, attention and elevated blood pressure. The dysregulation of other neurotransmitters is also observed in PTSD, such as gamma-aminobutyric acid, glutamate, and serotonin.³

In the case of PTSD, the patients’ brains show differences from those of healthy people. The size of the hippocampus, which regulates motivation, emotions, memory and learning, decreases. The amygdala, which is responsible for emotions like fear, is constantly active, while the medial prefrontal cortex, which partly controls the emotional response of the amygdala, is smaller and less responsive.⁴

Common treatments for PTSD involve talk therapies and medications. Talk therapies focus on the trauma, provide a method to process the negative event, and try to alter unhelpful beliefs about the trauma. Typical talk therapies are cognitive processing therapy, a type of cognitive behavioural therapy, and prolonged exposure therapy.⁵

Medications often target the regulatory system of serotonin and/or norepinephrine.⁶ Selective serotonin reuptake inhibitors, such as the frequently prescribed paroxetine and sertraline, increase the serotonin level in the brain, leading to better mood, appetite, and sleep. Selective serotonin-norepinephrine reuptake inhibitors, like venlafaxine, affect not only the serotonin but the norepinephrine level, too. Although these drugs can bring positive changes in PTSD patients, they are effective in only 40-60% of the cases.⁷ Other complementary drug therapy can involve second-generation antipsychotics (e.g., quetiapine), but with strong and extensive side effects, and benzodiazepines, which have a questionable effect and can only ease related symptoms such as insomnia.³

A new approach: the MDMA-assisted psychotherapy

What is MDMA?

MDMA, or 3,4-methylenedioxymethamphetamine in its full name, is a lab-made synthetic and popular party drug, which is more commonly called ecstasy or ‘Molly’. It has a stimulant effect, causing euphoria, well-being, warmth, openness towards others and a boost in sexuality. MDMA is also a psychedelic drug, as it can cause changes in visual and time perception, and increase sensitivity to sights, sounds, touch and smells.

Ecstasy is potentially addictive, and a person needs more of the drug to reach the same effect over time. Although there are documented cases of death due to MDMA use, it is a drug with moderate side effects. It became popular in nightclubs in the 1980s, but the clinical research to use MDMA for PTSD treatment started in the last 20-30 years. 

How can MDMA be used in psychotherapy?

MDMA-assisted psychotherapy is when the drug is used to help the success of psychotherapy. A typical programme is 2-3 months long, but only a few sessions involve MDMA treatment. Non-drug sessions last up to 90 mins, while the MDMA-assisted sessions are up to 8 hours long. During the drug sessions, patients receive a dose of MDMA (typically 125 mg), and then they are asked to relax. They spend the first 90 minutes lying, with their eyes covered, minimal talking, and listening to music to help them acclimate to the environment. Often, two therapists (a male and a female) lead the session, who gently guide the patient through their trauma issues. Patients are encouraged to remain seated or lying down and limit movements. Because of the possible side effects, vital signs, such as heart rate, blood pressure and temperature, are monitored. The effect of MDMA wears off approximately after 5 hours, but it is usually required for safety concerns to stay overnight at the facility.⁸

Over the last few decades, several studies have shown the effectiveness of MDMA in the treatment of PTSD. This result comes from mainly placebo-controlled studies, in which MDMA is compared to an ineffective chemical compound.^3,9,10 A study shows that an increased amount of MDMA during psychotherapy reduced the symptoms in veterans and first responders in chronic cases, and its side effects were well-tolerable.¹¹ Further studies aimed to find out the safety and effectiveness of MDMA in contrast to paroxetine and sertraline. The results show that MDMA is better and has more tolerable side effects than the other commonly used medications.¹² Comprehensive studies also show that MDMA is beneficial in the treatment of PTSD, rarely causes addiction,^8,13 although others warn about the possible side effects and encourage limitations and controls in its use.^7,14

How does MDMA affect PTSD symptoms?

MDMA can reduce the sense of fear that prevents a patient from recalling their traumatic memory, help patients to open up during the sessions and decrease the avoidance behaviour. In the following, there is a summary of the possible positive effects of MDMA on PTSD symptoms:⁸

• Reduces anxiety and hypervigilance
• Increases motivation to engage in therapy
• Allows the patient to recall the traumatic memories without getting overwhelmed by fear
• Improves the relationship between the patient and the therapist
• Opportunity to reflect upon painful memories and see old problems in a new light

What are the possible mechanisms of the effectiveness of MDMA?

A study suggests two key biological mechanisms behind the MDMA effect in PTSD.¹⁵ One possible explanation is memory reconsolidation. It is assumed that during MDMA sessions, the memories enter into a more unstable, malleable state. Neurotransmitters, like dopamine, can enhance this effect and help to reshape the trauma with less fear and greater emotional safety. The other possible explanation is fear extinction. MDMA may create an internal, safe environment that can help to reduce the learnt and conditioned fear response.

Neuroimaging evidence suggests that there is increased activity between the hippocampus and amygdala parts in the brain, which regions play a role in the development of PTSD. MDMA also activates three neurotransmitters: serotonin, norepinephrine and dopamine. It also leads to an increase in certain hormones’ levels, such as dehydroepiandrosterone, vasopressin, prolactin, cortisol and oxytocin.³

Besides the immediate reactions, MDMA can also have a long-term effect on the neurons of the brain. Research on rats found that MDMA damages the nerve cells' connections, particularly in the hippocampus, but it can also induce the redevelopments of new neuronal connections in the frontal cortex. This effect can contribute to the therapeutic use of MDMA treatment for PTSD.¹⁶

Summary

Post-traumatic stress disorder is a mental condition that causes nightmares, flashbacks, anger issues, and avoidance after a trauma. Patients often avoid people and situations to talk about their negative experiences. Usual medications are only effective in 40-60% of the cases, which requires new approaches. MDMA (or ecstasy) is a drug with stimulant effects, causing euphoria, well-being, and openness towards others. These characteristics can be useful in cases such as PTSD, when the patients have problems opening up about their memories. Several studies have proven the usefulness of MDMA-assisted psychotherapy, which can help patients overcome their fear and reshape their traumatic memories.