MDMA Therapy for PTSD

MDMA therapy for PTSD is an emerging treatment. Post-traumatic stress disorder, better known as PTSD, affects an estimated 13 million Americans. A common cause is witnessing or experiencing a traumatic event. The condition can be debilitating for some individuals.

If PTSD is severe, treatment is usually required. While various approaches have been used in the past, such as cognitive behavior therapies (CBT) [1], new investigations into using psychedelic drugs as a pharmacological adjunct to psychotherapy has produced promising results. 

What is PTSD? 

PTSD used to be called shell shock or combat fatigue, as it frequently appeared in combat veterans. However, today we know that PTSD does not only result from combat scenarios; it can occur after experiencing or witnessing a traumatic occurrence or series of events like abuse, assault, or a serious accident. 

After the event, individuals with PTSD typically experience disturbing and intense thoughts that can sometimes be difficult to distinguish from real life. They may have nightmares or flashbacks triggered by stimuli, such as loud sounds or touch, and detachment, anger, sadness, anxiety, and hostility may also occur. PTSD symptoms persist for more than a month following the event and cause significant disruption to an individual’s daily life. 

The symptoms of PTSD can often interfere with a person’s day-to-day activities and often present with other conditions such as memory problems or substance abuse, making treatment essential. 

How Can We Use Psychedelic Therapy for PTSD? 

The psychedelic substance most associated with PTSD is MDMA. The acronym is the common name for 3,4-methyl​enedioxy​methamphetamine, classified as an entactogen or empathogen due to its heart opening effects. It works on the same receptors as antidepressant serotonin reuptake inhibitors (SSRI). The neurotransmitter serotonin is responsible for mood regulation and regulating sleep, anxiety, appetite, and other bodily functions. MDMA increases the release of serotonin (and to a lesser extent dopamine and norepinephrine) and prevents these neurotransmitters from reabsorbing into the brain’s neurons [2].

Studies have begun focusing on how entactogens, like MDMA, can be used with psychotherapy, such as CBT, to produce immediate relief and lasting changes in those with PTSD. Initial results for MDMA-supported psychotherapy have been promising, leading to the FDA granting a Breakthrough Therapy Designation for MDMA-assisted therapy for PTSD [3]. 

The public benefit corporation MAPS PBC is completing trials that include three administrations of MDMA along with psychotherapy and integration over 12 weeks. The second phase 3 study trial was recently completed but results have not yet been published. 

After the first MDMA phase 3 trial, 68% of the participants who received MDMA-assisted psychotherapy treatment no longer had PTSD [4]. Researchers think that MDMA not only works to increase serotonin levels but also reduces the individual’s fear response to triggers and stimuli that increase anxiety. Additionally, scientists theorize that MDMA helps increase introspection and interpersonal trust, maximizing the effects of psychotherapy [5]. It is important to note that in all the MDMA studies that produced positive results, the PTSD participants underwent three 90-minute non-drug preparatory sessions and nine sessions of integrative psychotherapy following each MDMA-assisted therapy session [6].

Researchers are investigating other psychedelics for their potential benefits to people with PTSD, including ketamine, psilocybin, LSD, dimethyltryptamine (DMT), and Ayahuasca. However, beside ketamine for PTSD [7], there are little to no trials involving these drugs as treatment methods for PTSD are currently underway in the United States. 

How to Administer Psychedelic Therapy for PTSD? 

Individuals should always undergo the use of psychedelics as a treatment for PTSD in a medically controlled setting which is currently only legal in clinical trials (with the exception of ketamine). During the MDMA trials, the drug is used as a pharmacological adjunct to psychotherapy, meaning that the psychotherapy sessions before and after drug administration are imperative to the positive outcomes observed in trials. 

Setting plays an important role. Setting refers to the physical environment around you, including the people, sounds, and tactile elements, like a couch. A therapist will administer a psychedelic (currently only ketamine is legal outside of clinical trials) in an aesthetically pleasing medical setting. It may include neutral tones, comfortable furniture, relaxing art, and a calming music playlist [8]. 

Generally, two professionals, called the co-therapy team, will be present throughout the process. Preceding the session, patients undergo 90-minute preparatory sessions. After the session, therapists lead them through the integrative period that generally consists of the patient revisiting what came up during the MDMA session and further processing the experience. 

In addition, therapists facilitate the unfolding of their emotional and mental processes. The effects of MDMA typically lasts five to eight hours depending on if the person took one or two doses (a second dose equal to half the first dose is offered approximately 2 hours into the session). Following MDMA, the post-psychotherapy sessions take place over some months. 

During the clinical trials, therapists will follow the standardized treatment manual created for MDMA-assisted psychotherapy for PTSD. 

Are There Any Drawbacks? 

MDMA has the potential to produce some adverse side effects, including anxiety, fatigue, headaches, and tight jaw [3]. In most cases, these anxiety symptoms can occur when the drug effects first become noticeable or when the patient is recalling traumatic memories. MDMA may cause low mood and fatigue in the days following a session. 

However, a therapist can help the patient manage these symptoms with supportive psychotherapy and coping techniques. 

Depending on the dose, MDMA can increase body temperature, blood pressure and heart rate. MDMA should not be taken by people with uncontrolled hypertension or specific cardiovascular issues. 

Takeaway 

MDMA-assisted therapy has the most promising results for treating PTSD. Clinical evidence is still limited to a small number of study participants (roughly 300 patients will be treated across MAPS phase 2 and 3 trials), but the Breakthrough Therapy Designation is a strong signal from the FDA that this treatment is novel and potentially advantageous over available options. MAPS anticipates submitting clinical evidence by the end of 2024 to support FDA marketing approval of MDMA-assisted therapy as a treatment for PTSD.

References

1. Mendes, D. D., Mello, M. F., Ventura, P., de Medeiros Passarela, C., & de Jesus Mari, J. (2008). A systematic review on the effectiveness of cognitive behavioral therapy for posttraumatic stress disorder. The International Journal of Psychiatry in Medicine, 38(3), 241-259.
2. De la Torre, R., Farré, M., Roset, P. N., Pizarro, N., Abanades, S., Segura, M., … & Camí, J. (2004). Human pharmacology of MDMA: pharmacokinetics, metabolism, and disposition. Therapeutic drug monitoring, 26(2), 137-144.
3. Feduccia, A. A., Jerome, L., Yazar-Klosinski, B., Emerson, A., Mithoefer, M. C., & Doblin, R. (2019). Breakthrough for trauma treatment: safety and efficacy of MDMA-assisted psychotherapy compared to paroxetine and sertraline. Frontiers in psychiatry, 10, 650.
4. Mitchell, J. M., Bogenschutz, M., Lilienstein, A., Harrison, C., Kleiman, S., Parker-Guilbert, K., … & Doblin, R. (2021). MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nature medicine, 27(6), 1025-1033.
5. Krediet, E., Bostoen, T., Breeksema, J., van Schagen, A., Passie, T., & Vermetten, E. (2020). Reviewing the potential of psychedelics for the treatment of PTSD. International Journal of Neuropsychopharmacology, 23(6), 385-400.
6. Mithoefer, M. C., Feduccia, A. A., Jerome, L., Mithoefer, A., Wagner, M., Walsh, Z., … & Doblin, R. (2019). MDMA-assisted psychotherapy for treatment of PTSD: study design and rationale for phase 3 trials based on pooled analysis of six phase 2 randomized controlled trials. Psychopharmacology, 236, 2735-2745.
7. Du, R., Han, R., Niu, K., Xu, J., Zhao, Z., Lu, G., & Shang, Y. (2022). The Multivariate Effect of Ketamine on PTSD: Systematic Review and Meta-Analysis. Frontiers in psychiatry, 13.
8. Strickland, J. C., Garcia-Romeu, A., & Johnson, M. W. (2020). Set and setting: a randomized study of different musical genres in supporting psychedelic therapy. ACS Pharmacology & Translational Science, 4(2), 472-478.