Introduction

In recent years, there has been a surge of an increased interest in psychedelic-assisted therapy as a new and potentially more effective way to treat a variety of mental health conditions. One such approach that has gained significant attention is MDMA-assisted therapy. MDMA, commonly known as Molly or ecstasy, is considered an “empathogen” – a class of psychoactive substances known to produce including increased feelings of emotional connection, openness, and empathy towards self and others. When used in safe, therapeutic settings, MDMA has shown promising results in helping individuals overcome trauma, anxiety, and other psychological disorders.

The effects of MDMA on the brain

MDMA, which stands for 3,4-methylenedioxymethamphetamine, works on the brain by acting on various neurotransmitters and regions of the brain.

Brain imaging after administration of MDMA shows there is decreased amygdala activation and reduced fear response. [1][2] For an individual with PTSD, a part of the brain called the amygdala is overactive. The amygdala is highly involved in fear and threat detection, and with trauma the amygdala is highly overactive. It is constantly firing alarm bells, signaling a lack of safety and the need to be in high-alert, protective mode. [8][11] This kind of brain state makes therapy extremely difficult. However, under the influence of MDMA, individuals become less fearful as the amygdala relaxes.

In addition to its effects on the amygdala, MDMA also increases the release of several important neurotransmitters, serotonin, norepinephrine, and dopamine, creating a surge of positive emotions and bringing a sense of calmness, openness, and emotional engagement. While classic psychedelics such as LSD and psilocybin activate serotonin 5-HT2A receptors, MDMA primarily impacts serotonin 5-HT1B receptors, and this seems to be a key component in MDMA’s pro-social, empathogenic effects. [3][4] MDMA also releases a hormone called oxytocin, which may also contribute to MDMA’s emotional effects, however research remains unclear whether there is a causal effect. [5]

So when you give MDMA to a person with PTSD, the fear response is reduced, their fight or flight system relaxes, and they can finally move toward the source of their suffering and emotionally engage in therapy without becoming overwhelmed. MDMA alone is not a cure for PTSD. But because of MDMA’s profound effects on the brain, it makes therapy much more effective and allows patients to address the root cause of the problem—and this is what sets MDMA-assisted therapy apart from other traditional treatments for trauma.

Understanding MDMA-Assisted Therapy

MDMA-assisted therapy involves the administration of a carefully controlled dose of MDMA in conjunction with psychotherapy sessions. Unlike recreational use, which often takes place in a social setting, MDMA-assisted therapy is conducted in a clinical environment, supervised by trained professionals. The therapy typically consists of a few preparatory sessions, the MDMA session itself, and follow-up integration sessions.

During an MDMA-assisted therapy session, the patient ingests a prescribed dose of MDMA, usually in the form of a capsule. As the medicine begins to take effect, a unique therapeutic environment becomes available, allowing individuals to explore traumatic experiences and deeply rooted emotional issues with heightened introspection, self-compassion, and openness.

 

The Potential Benefits of MDMA-Assisted Therapy

• Enhanced therapeutic alliance: MDMA can facilitate a sense of trust, allowing patients to establish a stronger therapeutic alliance with their therapists. This trust can promote a deeper exploration of emotions and experiences that might otherwise be difficult to access.
• Trauma resolution: MDMA-assisted therapy has shown particular promise in treating PTSD, most likely because of the way MDMA can help clients revisit traumatic memories without being overwhelmed by fear or anxiety. By enabling them to confront and process painful experiences from the past, often ones that have been avoided and repressed, individuals can heal deep emotional wounds
• Emotional healing and self-acceptance: MDMA also can help individuals access and release emotions that have been suppressed or repressed, leading to a greater sense of self-acceptance and emotional well-being.
• Reduction in anxiety and depression: Studies have indicated that MDMA-assisted therapy may be effective in reducing symptoms of anxiety and depression. By addressing the root causes of these conditions, the therapy offers the potential for long-lasting relief, rather than just managing symptoms.
• Addiction treatment: MDMA-assisted therapy has also shown promise in the treatment of substance abuse disorders. By providing individuals with a unique perspective and a heightened sense of empathy, it can help them gain insights into the underlying causes of their addictive behaviors and facilitate healing on a deeper level.

 

MDMA Research

Clinical research on MDMA-assisted therapy has gained significant momentum in recent years, with several studies demonstrating promising results. Here are a few examples of notable research and studies conducted in this field:
Phase 3 Trials for PTSD Treatment: The Multidisciplinary Association for Psychedelic Studies (MAPS) has conducted Phase 3 clinical trials investigating the efficacy of MDMA-assisted therapy for treating PTSD. One study published in Nature Medicine in 2021, looked at 90 participants who were dealing with chronic PTSD from a variety of different causes (e.g., abuse, combat, sexual trauma). It’s also important to note that these patients were treatment-resistant, meaning they had suffered from PTSD without relief for an average of 14 years. All participants completed a 12-week treatment program consisting of 3 full-day dosing sessions, during which they received either MDMA or a placebo, plus weekly nondrug psychotherapy sessions. [9]
No serious adverse effects were detected beyond transient, mild symptoms (such as nausea or sweating) during dosing sessions. No increases in suicide risk or potential for abuse were noted in the MDMA group relative to placebo. Most notably, two months after treatment, 67% of the MDMA cohort no longer qualified for PTSD diagnosis, compared with 32% of the placebo group. In addition, 88% of those in the MDMA group experienced a clinically significant reduction in symptoms, and even one year after completing the study, the therapeutic effects continued. These kinds of results are typically unheard of in the world of psychiatry. It means that the majority of these individuals—who had suffered from chronic, severe PTSD for an average of 14 years—can now live a normal life—free from triggers, flashbacks, nightmares, hopelessness or suicidality.

Study on Social Anxiety in Autistic Adults: Another study examined the effects of MDMA-assisted therapy on social anxiety in autistic adults. Currently, there are no FDA-approved drug treatments for autistic adults with social anxiety, and conventional anti-anxiety medications lack clinical effectiveness in this population. [6]
MAPS sponsored a randomized, double-blind, placebo-controlled exploratory pilot study that aimed to assess MDMA-assisted therapy for treating social anxiety in 12 adults on the autism spectrum. Participants were randomized to receive either MDMA (75, 100, and 125 mg) or inactive placebo during two 8-hour dosing sessions. The primary outcome was change in Leibowitz Social Anxiety Scale (LSAS) scores from baseline to one month after the second experimental session. Outcomes were measured again five months later. [6]

Results showed an improvement in LSAS scores, meaning reduced symptoms of social anxiety, that was significantly greater for the MDMA group than the placebo group. Six month follow-up scores continued to show similar results, with a reduction in LSAS scores that remained statistically significant. The findings suggest that MDMA-assisted therapy may be a promising approach for addressing social anxiety and improving social functioning in this unique patient population.
Pilot Study for Anxiety Associated with Life-Threatening Illness: A pilot study published in 2019 explored the use of MDMA-assisted therapy in alleviating anxiety and existential distress in individuals with life-threatening illnesses. The 18 participants received either a 125 mg dose of MDMA or placebo during two day-long experimental sessions. These were also paired with two 8-hour psychotherapy sessions. [10]
The study found that those in the MDMA group had greater improvements in anxiety, depression, and quality of life measures compared to those who received placebo. suggesting that MDMA-assisted therapy may be a valuable adjunctive treatment for addressing psychological distress in this specific population. [10] Participants’ attitudes towards death shifted after MDMA, as well as their daily coping mechanisms, as demonstrated by greater emotional and functional quality of life at the study endpoint. These preliminary findings suggest that MDMA-assisted psychotherapy might have the potential to provide long-term benefits for people who have or are overcoming a serious illness.
These studies, among others, demonstrate the growing body of evidence supporting the potential efficacy of MDMA-assisted therapy in various mental health conditions. Continued research and clinical trials are underway to further elucidate the therapeutic benefits, optimize treatment protocols, and ensure the safety and efficacy of this innovative approach to psychotherapy.

Challenges and Considerations

While the results of MDMA-assisted therapy are promising, it is essential to acknowledge the challenges and considerations associated with its use. These include:

• Safety and regulation: MDMA is a controlled substance, and its therapeutic use must be conducted in a strictly regulated environment. Ensuring the safety of patients and preventing misuse or recreational use of MDMA is of utmost importance.
• Potential risks: While adverse effects of MDMA in a therapeutic setting are generally minimal, there are potential risks, such as increased heart rate and blood pressure. These risks must be carefully managed and monitored by trained professionals.
• Long-term effects: The long-term effects of MDMA-assisted therapy are still being studied. Continued research is necessary to understand its potential benefits and any potential long-term consequences fully.

Conclusion

MDMA is now on track to be the first psychedelic medicine likely to win FDA approval, perhaps as early as next year. It’s an exciting milestone in psychiatry. Assuming this gets approved, it will be the first medicine approved that’s a curative approach to trauma, instead of just treating the symptoms. It would also be the first FDA-approved medicine requiring concurring therapy. Meaning, you cannot get a prescription for this medicine if you’re not committed to the therapy.

MDMA-assisted therapy represents a promising approach to mental health treatment, offering a unique and transformative experience for individuals struggling with trauma, anxiety, and other psychological disorders. While it is not a standalone

References:

1. Mitchell JM, Bogenschutz M, Lilienstein A, et al. MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nat Med. 2021;27(6):1025-1033.
2. Bedi G, Phan KL, Angstadt M, de Wit H. Effects of MDMA on sociability and neural response to social threat and social reward. Psychopharmacology (Berl). 2009;207(1):73-83.
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123941/
4. https://www.sciencedirect.com/science/article/abs/pii/S0149763411002168
5. https://www.sciencedirect.com/science/article/abs/pii/S0306453014001255?via%3Dihub
6. Wolfson PE, Andries J, Feduccia AA, et al. MDMA-assisted psychotherapy for treatment of anxiety and other psychological distress related to life-threatening illnesses: a randomized pilot study. Sci Rep. 2020;10(1):20442. Published 2020 Nov 24. doi:10.1038/s41598-020-75706-1
7. https://link.springer.com/article/10.1007/s00213-018-5010-9
8. Morey RA, Gold AL, LaBar KS, et al. Amygdala volume changes in posttraumatic stress disorder in a large case-controlled veterans group. Arch Gen Psychiatry. 2012;69(11):1169–1178. doi:10.1001/archgenpsychiatry.2012.50
9. Hysek CM, Schmid Y, Simmler LD, et al. MDMA enhances emotional empathy and prosocial behavior. Soc Cogn Affect Neurosci. 2014;9(11):1645-1652.
10. https://www.nature.com/articles/s41598-020-75706-1
11. Mitchell JM, Bogenschutz M, Lilienstein A, et al. MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nat Med. 2021;27(6):1025-1033.