Methylenedioxymethamphetamine, or MDMA, is an entactogen that increases empathy, distorts one’s perceptions, and can increase a user’s pleasure from sensory experiences (NIH). It is considered a Schedule I drug by the FDA, meaning it has no clinical uses and has a high likelihood to be abused. However, research is being conducted into possible therapeutic uses for treating PTSD (post-traumatic stress disorder). While MDMA is shown to have lots of promise in treating PTSD when paired with psychotherapy, there are also many risks to its use.
The most common treatment for PTSD is psychotherapy. Psychotherapy uses talking and behavioral strategies to improve an individual’s daily functioning and overall quality of life. In the case of a psychological disorder like PTSD, that would entail talking through a traumatic experience and developing coping mechanisms. An example of a type of psychotherapy would be Cognitive Behavioral Therapy (CBT). CBT goes through an individual’s problem thoughts and changes them by encouraging the individual to interpret situations in a different way, and also encourages incremental behavioral changes. One of the symptoms of PTSD is reliving traumatic experiences, and CBT can encourage individuals to think about those experiences differently and to come up with behavioral strategies to reduce fear responses.
MDMA is being investigated as a possible option to boost the effects of psychotherapy on PTSD treatments. Most people would be surprised that currently illegal drugs may have any clinical benefits. However, there is plenty of reason that researchers have to believe that MDMA would be useful. One of the effects described by most MDMA users is a sense of empathy and closeness to those around them. This has to do with the effects MDMA has on the neurotransmitters in the body. It increases the levels of serotonin dramatically, which would put the user in a pleasant mood. It also increases dopamine, which is associated with reward and an increase in pleasure, and norepinephrine, which is associated with the fight or flight response. These neurotransmitters can allow the user to feel safe enough to talk about normally fearful experiences. In addition, an important aspect of MDMA and psychotherapy is fear extinction learning. Brain derived neurotrophic factor regulates memory reconsolidation in the amygdala, and MDMA usage changes the way memories are reconsolidated (NIH). Emotional and traumatic memories are stored differently in the brain after recall with MDMA, meaning that MDMA changes the functioning of the brain. Overall, there is less fear associated with these memories. Fear extinction learning is only one theory as to how MDMA works to reduce trauma from PTSD, but it helps to explain our current understanding of the effects of MDMA on the brain.
Many phase II clinical trials have been conducted on MDMA and psychotherapy in an attempt to prove its effectiveness. In a 2010 study by Mithoefer et al., researchers conducted a randomized controlled trial with 20 participants (Psychiatry Online). The point of the study was to gather data on safety and efficacy with a small number of participants. Each participant had a diagnosis of PTSD according to the Diagnostic and Statistical Manual on Mental Disorders, 4th Ed. Text Revision (DSM-IV-TR). In addition, they had treatment-resistant symptoms, meaning they had attempted psychotherapy and SSRIs as a treatment in the past and had failed to see improvement. These participants had a score greater than or equal to 50 on the Clinician-Administered PTSD Scale (CAPS).
For this experiment, participants were randomly assigned into a placebo (control) group (N=8) or an MDMA (experimental) group (N=12). Both groups would have multiple psychotherapy sessions, and two of the sessions would consist of MDMA for the experimental group or the placebo for the control group. At baseline, there was no difference in the CAPS score for the MDMA group (M = 79.6) and the placebo group (M = 79.2). Only 3-5 days after the first psychotherapy session with MDMA or placebo, there was a significant difference in CAPS (p = .013) between the MDMA group (M = 37.8) and the placebo group (M = 74.1). After the second psychotherapy session with MDMA or placebo, CAPS was measured again, and there was still a significant difference (p = .002) between the MDMA group (M = 29.3) and the placebo group (M = 66.8). 2 months after the second psychotherapy session with MDMA, the difference in CAPS score remained significant (p = .013) between the MDMA group (M = 25.5) and the placebo group (M = 59.1). After the completion of the trial, the average score of the placebo group (M = 59.1) was higher than the minimum criteria required to be considered for the trial, meaning they still had quite a high level of symptoms. More participants in the MDMA group met the criteria for a categorical response (Psychiatry Online), meaning a reduction of at least 30% from baseline CAPS scores.
After the completion of the clinical trial, those who were in the placebo group had the option to have psychotherapy sessions with MDMA (basically, to switch to active treatment). 7 of the 8 participants did so. In 4-6 weeks, or after the second experimental session with MDMA, every participant exhibited a clinical response. Simply stated, the effects of the experiment that were shown in the participants in the experimental group during the study were repeated with the placebo group after the completion of the trial when they switched to the MDMA treatment. After the completion of this trial, the researchers measured the CAPS score (M = 24.6) and attempted to do follow-ups across 17-74 months. The CAPS scores after 74 months showed no significant difference (M = 23.7) (Psychiatry Online). The effects of the MDMA and psychotherapy on PTSD symptoms are durable for at least 74 months. This may be due to continued use of psychotherapy after the completion of the trial. However, this is promising for PTSD patients since many experience a recurrence of symptoms, and few treatments have been proven to have such durable effects on symptom reduction.
While the study from Mithoefer et al. found many benefits to MDMA and psychotherapy on PTSD, MDMA therapy also comes with many risks. Clinicians should be aware of all the potential risks and make an evaluative decision for each patient. While MDMA is often associated with positive emotions, like empathy, negative emotions can be boosted while on the drug as well. In addition, the effects of coming off the drug can cause intense levels of depression. MDMA causes a dramatic increase in serotonin, and therefore a burst of positive mood. When coming off the drug, the brain attempts to stabilize itself by dramatically reducing the amount of serotonin produced. This process leads to neurochemical depletion in the brain. Moving from very high to very low levels of neurotransmitters such as serotonin, dopamine, and norepinephrine can cause users to feel depressed, with some even having clinical levels of depression (Taylor and Francis Online). The term “Midweek Blues” came from the depressed feeling users experienced after coming off the drug. Recreational users would take the drug at club scenes over the weekend, and the brain would stabilize neurotransmitter levels throughout the week, leading to depression by mid-week and “Suicide Tuesday”. The higher levels of depression experienced by MDMA users are a problem for people who are already vulnerable, like PTSD patients who may be extremely depressed.
MDMA also should be limited in the patients it is given to. It is being tested for PTSD treatment and for those facing terminal illness and has shown some success in those areas. However, individuals who experience psychosis should not take MDMA (Taylor and Francis Online). These biological vulnerabilities are exacerbated by MDMA use and can lead to greater symptom presentation. For those who self-medicate with MDMA, this can lead to greater stress due to addiction and tolerance to MDMA levels. Overall, MDMA is most effective when paired with psychotherapy rather than as an individual treatment.
One of the known effects of MDMA is damage to the serotonin system (Taylor and Francis Online). After repeated usage, serotonin levels in the brain decrease, serotonin metabolites decrease, serotonin transporters decrease, and the serotonin terminals degenerate. It was already established that serotonin is responsible for mood. With naturally lower levels of serotonin in the brain, an individual may be in a constant state of depression. This effect on the serotonin system may exacerbate any psychological problems a person previously had.
While MDMA does have many risk factors associated with it, the positive effects of MDMA when paired with psychotherapy are undeniable. Due to the serious symptoms of PTSD, the use of MDMA may be looked to as a breakthrough when it comes to treatment options. While clinicians should be careful and evaluate each individual case, the benefits of MDMA and psychotherapy, under monitored conditions, far outweigh the risks for those who are suffering from severe symptoms of PTSD and need to improve their quality of life in order to live a normal, functional reality. Patients should consider the risks and benefits and make informed decisions about whether MDMA and psychotherapy would be beneficial for treating their PTSD.