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By Sarah Abedi, MD

Post-traumatic stress disorder (PTSD) develops in an individual who has difficulty recovering from experiencing or witnessing a traumatic event. PTSD can be associated with a variety of symptoms including anxiety, disordered sleep, irritable behavior and angry outbursts and irritable bowel syndrome. Patients with PTSD often avoid people, places and activities that remind them of the original traumatic event. This behavior is associated with avoidance of the memory of the traumatic event and with internal numbing. Chronic feelings of anger, guilt, shame, horror or fear are common, and most patients experiencing flashbacks, intrusive memories and nightmares. PTSD can remain undiagnosed for years and may be misdiagnosed as chronic stress, depression, insomnia and anxiety. Current conventional treatments of PTSD offer some relief, but many patients still suffer from its debilitating symptoms. Surprisingly, 3,4-methylenedioxymethamphetamine, known by its scientific acronym MDMA or its non-scientific names “ecstasy” or “molly”, has made a reemergence into the psychiatric world for its groundbreaking therapeutic effects involving PTSD treatment.

Former firefighter Ed Thompson recounts his experience with MDMA-assisted therapy- “I truly couldn’t be happier… and I have no doubt that it saved my life…I was desperate, and kind of grasping at straws for something that could possibly help me get my family back and help me get my life back”

According to the US Department on Veteran Affairs, approximately 7-8% of the general population will have PTSD some time in their life, but this figure jumps to 11-20% of veterans with PTSD.¹ Among US soldiers returning from Iraq and Afghanistan, the incidence of PTSD is 18% with 400,000 – 500,000 US Iraq/Afghanistan veterans reportedly having PTSD. In 2004, US Veterans Administration spent $4.3 billion on PTSD disability payments to approximately 215,000 veterans.²

Conventional treatments used in the treatment of PTSD include centrally acting medications, psychotherapy in particular cognitive behavioral therapy (CBT), as well as eye movement desensitization and reprocessing (EMDR). However, despite the widespread use of these therapies, in clinical trials, 25-50% of patients with PTSD, roughly equating to 2-4 million people, do not respond to conventional treatments.

Magnetic resonance imaging (MRI) studies of the brain in PTSD patients have identified abnormalities in the function of several brain regions involved in emotion regulation, including the hippocampus, prefrontal cortex and the amygdala. The amygdala which plays a crucial role in the conditioning of fear showed increased activation in PTSD patients.The prefrontal cortex which plays an important role in the extinction of the fear response has been shown to have decreased activation in PTSD patients, meaning the brain is less able to turn off the fear response even if is triggered by the same stimulus repeatedly. MDMA reverses some of these abnormalities, leading to a reduction in blood flow in the amygdala and an increase in blood flow to the frontal cortex.³ MDMA has also been shown to increase several neurotransmitters in the brain, including serotonin.

In addition to its various brain effects, MDMA also shows improvement of social interactions with reduced social exclusion.⁴ It has been shown to enable patients to increase trust and empathy while decreasing defensiveness and fear. MDMA increases the range of positive emotions towards others as well as oneself without inhibiting access to emotion. This may allow PTSD patients to revisit traumatic experiences without being overwhelmed. Double-blind, placebo-controlled clinical trials (the most rigorous, gold-standard type of trial in scientific research) have shown that MDMA combined with psychotherapy yields promising results in treating PTSD. In a recent study done by Mithoefer et al (2011), 83% of participants who received MDMA-assisted psychotherapy showed a significant reduction in PTSD symptoms with many no longer reaching the criteria for PTSD. Moreover, benefits from MDMA-assisted psychotherapy were maintained by most participants 3.8 years after treatment.⁵

“The first place I saw was this maze. I went in. There was so much trauma. I had never remembered these terrible, terrible things. And before MDMA, I really did think it was my fault. I felt it in my bones that something was so wrong with me, that I deserved those things. Being on MDMA was the first time I ever felt compassion for myself. I realized that I was a child when it happened. I had no choice.”- Participant in MDMA trial reflecting on a MDMA session.

The studies of MDMA-assisted psychotherapy have also revealed that patients start to understand that suppressing their emotions may not benefit their wellbeing, and their mental health continues to improve as they learn how to process emotions and bring them to the surface. Of the participants that received MDMA-assisted psychotherapy that no longer had PTSD at their two-month follow-up, nearly two-thirds of them continued to be symptom free at the one-year follow-up mark. The one-third of patients still exhibiting PTSD symptoms reported marked reductions in their PTSD symptoms. On May 3, 2021 the first phase three trial of any psychedelic-assisted therapy studying MDMA-assisted therapy for PTSD showed 67% of the group who received MDMA no longer qualified for a PTSD diagnosis after three treatment sessions.⁶

“I literally went from being in a VA mental health inpatient ward to working on a presidential campaign on a national level in two years…this isn’t just veterans…this is domestic violence, this is law enforcement, firefighters- everybody that can suffer from PTSD… do you know how a big a difference it is when you go (from) living every minute of your life thinking tomorrow you’re going to kill yourself to believing you’re going to be alive next week?” – Jonathan Lubecky, former Marine in Iraq war recounting his experience with MDMA-assisted psychotherapy.

It is believed that the core principle associated with MDMA-assisted therapy includes the inner healing intelligence. This intelligence refers to the person’s intrinsic ability and wisdom to heal- in other words, the participant is creating their own healing. Set and setting play a crucial role in fostering a healing environment. Set refers to the mindset of the person taking the substance. Participants are encouraged to reflect on an intention for the session while remaining curious and surrendering to the experience. They are encouraged to remain open to whatever emerges and develop trust in their own inner healing intelligence. Setting refers to the physical environment including the safety, comfort, aesthetics of the room, as well as trained practitioner. The practitioner that administers the MDMA focuses on facilitating curiosity and openness for the participant while creating a non-judgmental space. The presence of the practitioner should create a space of safety and security that can allow patients to access difficult memories and emotions with greater purpose, compassion and clarity.

“You understand why it’s ok to experience unconditional love for yourself.” – Scott Ostrom, Iraq war veteran who participated in a study of MDMA.

It is not uncommon for participants to experience non-ordinary states of consciousness. These perceptions may lead one to a place of complete openness with a profound connection to one’s own humanity and the interconnectedness of the world. A typical MDMA-assisted therapy experience includes a screening, three 90-minute preparatory sessions followed by three 8-hour MDMA-assisted sessions. After each MDMA session, the patient goes through a 90-minute integration sessions. These integration sessions are critical to allow for processing from the MDMA experience.

The groundbreaking effects of MDMA on PTSD has made scientists and clinicians question if this drug really should remain a Schedule I drug which per the Food and Drug Administration (FDA) has a high potential for abuse with no currently accepted medical use and the potential to create severe psychological and/or physical dependence. In the right clinical setting under proper guidance this drug may in fact liberate patients from the detrimental psychological post traumatic distress they have been holding on to and allow for an experience of peace and healing not otherwise attained from other therapeutic modalities.

References

1. Hoge, C.W., et al. (2004). Combat duty in Iraq and Afghanistan, mental health problems, and barriers to care. N Engl J Med, 351: 13-22.
2. Wooditch, J.A. (2005). Acting Inspector General Department Of Veterans Affairs, in Committee On Veterans’ Affairs Subcommittee On Disability Assistance And Memorial Affairs: Washington, DC. Public Statement
3. Hughes, S., Shin, L. M. (2011). Functional neuroimaging studies of post-traumatic stress disorder. Expert Review of Neurotherapeutics, 11, 2, 275-285.
4. Frye, C. G., Wardle, M. C., Norman, G. J., and de Wit, H. (2014). MDMA decreases the effects of simulated social rejection. Pharmacology Biochemistry and Behavior, 117, 1-6.
5. Mithoefer, M. C., Wagner, M. T., Mithoefer, A. T., Jerome, L., & Doblin, R. (2011). The safety and efficacy of±3, 4-methylenedioxymethamphetamine-assisted psychotherapy in subjects with chronic, treatment-resistant posttraumatic stress. J Psychopharmacol 25(4): 439-452.
6. Mitchell, J.M., Bogenschutz M…Doblin, R. (2021) MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nature 27, 1025-1033.

Sarah Abedi, MD is an emergency medicine doctor practicing in Southern California. She completed her medical school at UC Irvine and finished her emergency medicine residency at Harbor UCLA. Her medical interests lie in the science of disease prevention which motivated her to create The Hidden Body Podcast.