MDMA (3,4-Methylenedioxymethamphetamine) is not a classic psychedelic, like psilocybin or LSD. Rather, it is considered an entactogen or empathogen, a class of substances that increase a person’s feeling of empathy and benevolence towards others, as well as feelings of being socially accepted and connected1 . Ongoing research has examined the way MDMA works in the brain, and how it impacts certain indications. Chemically, MDMA is categorized as a phenethylamine, which is a class of substances with documented psychoactive and stimulant effects that includes amphetamine and methamphetamine. As a result, its mechanism of action is better understood by scientists than the classical psychedelics.
MDMA Science and Research
Things to Know
- MDMA increases the levels of serotonin, dopamine, norepinephrine, and oxytocin, contributing to feelings of connectedness and openness
- MAPS has completed clinical trials in the third and final phase of research required for FDA approval, investigating MDMA-assisted therapy to treat PTSD
- Extensive MDMA research is happening across North America, Europe, and Israel
MDMA Effects on the Brain
MDMA differs from the classic psychedelics like psilocybin and LSD given its different mechanism of action and the resulting experience. MDMA is known as an empathogen: a psychoactive drug that produces experiences of emotional connection and openness2. When using MDMA, people feel more empathetic and sympathetic, and experience an increased sense of closeness to others and self. Furthermore, research shows that MDMA can lead to prosocial behaviors and greater tolerance of one’s own feelings3.
MDMA Mechanism of Action
MDMA is believed to exert its effects by affecting the levels of a number of different neurotransmitters in the brain, namely serotonin, dopamine, and norepinephrine4. The compound increases the levels of these neurotransmitters by interacting with their respective transporter proteins and receptors. Once released, MDMA also inhibits the reuptake of serotonin, further increasing the levels present at the synapse.
Serotonin and dopamine are critical neurotransmitters that are associated with effective mood regulation and positive emotions. Serotonin plays a part in regulating mood and stimulating the production of dopamine, which, in turn, is associated with happiness, positive anticipation, satisfaction, and other positive emotions.
The inability of serotonin to stimulate dopamine, whether due to lack of serotonin or another neurobiological deficit, has been found to play a key role in the onset of depression5. Conversely, researchers believe that people sometimes engage in recreational drug use to increase levels of serotonin and dopamine for the pleasurable effects. As a result, some patterns of personal use can lead to excessive usage.
MDMA increases the levels of serotonin and dopamine in the brain by stimulating increases in serotonin production and reducing uptake. This results in increases in dopamine, as well as hormones that are responsible for the increased feelings of connectedness and openness, like oxytocin.
The increase in levels of these neurotransmitters allows a person undergoing MDMA-assisted therapy for a disorder like PTSD to more deeply and sincerely emotionally engage with the therapeutic process, often at levels of personal and emotional awareness beyond what would typically be accessible in a sober state. This contributes to the positive therapeutic outcomes seen in the research to date.
MDMA Clinical Trials
The Multidisciplinary Association for Psychedelic Studies (MAPS) is currently finishing a full report of clinical trials with MDMA-assisted therapy for the treatment of PTSD6 . The multi-site, double-blind, placebo-controlled randomized study is the third and final phase before FDA approval. MDMA has been placed on the FDA fast track7 to approval.
MDMA Research
MAPS has led the effort towards making MDMA a medicine, when used in conjunction with psychotherapy. This has culminated in the publication of the findings of the successful Phase 3 trial8 and the pending final report of the study. The 90 participants in the trial received 12 therapy sessions of which three were with either placebo or MDMA. Of those who received MDMA, 67% no longer had PTSD, compared to 32% in the placebo group. An additional 21% of those who received MDMA had a clinically meaningful response.
In August 2017, the FDA granted Breakthrough Therapy designation to MDMA-assisted psychotherapy for PTSD. The second half of the phase III trial was completed in 2022. Full approval from the FDA is expected in 2024.Depending on the point in the year when this takes place, patients with PTSD may, during that same year, get access to treatment with MDMA. If this therapy is approved, it will only be available following a referral from a doctor and only in supervised therapeutic settings from certified clinicians.
The clinical trials for MDMA-assisted therapy have been conducted at more than 15 sites in the US9 , Canada10 and Israel11 .
MAPS Europe also is pursuing phase III trials, which will allow MDMA-assisted therapy to be approved by the European Medicines Agency (EMA). Funds are currently being raised, to conduct the Phase III trial in an effort to get EMA approval as quickly as possible after FDA approval.
In 2018, the University of California, Los Angeles (UCLA) conducted a small feasibility study (12 participants) on the impact of MDMA on social anxiety of adults with autism. All of the participants in the study, even those who took a placebo, displayed some improvement. Patients who took the MDMA experienced a significant drop in their anxiety after the first session and another reduction after the second dose. They continued to feel considerably less anxious about social encounters six months after the treatment ended.
At the Ryerson University in Toronto, researchers have conducted the first modern-day studies on MDMA and couples therapy. Of the six couples in the study, one of the partners was suffering from PTSD, but both partners underwent cognitive behavioral conjoint therapy (CBCT). The study found that after the therapy, both partners indicated that they were happier and in a better relationship with each other. The partner suffering from PTSD also felt relief from their symptoms.
MDMA has also been investigated as a treatment for anxiety and other psychological distress related to life-threatening illnesses. A small 2018 study at the Harbor-UCLA Medical Centre found improvements in scores of anxiety, but these results didn’t reach significance. A larger trial, with more participants, may find that MDMA can be beneficial for this patient population.
An ongoing study which is still recruiting patients as of summer 2023, will investigate the safety and feasibility of treating eating disorders with MDMA-assisted therapy. The study will investigate the impact of MDMA-assisted therapy on people with anorexia nervosa restricting subtype (AN-R) and binge-eating disorder (BED). This study is supported by MAPS and is a phase II study that will take place in the coming year in the U.S. and Canada.
Researchers from Imperial College London have published the first results of MDMA-assisted therapy for those with alcohol use disorder (AUD). The study was an open-label trial, meaning all patients knew they were getting MDMA. It involved two sessions with MDMA and then eight further therapy sessions. Patients went from drinking an average of 131 to 19 units of alcohol per week from before the study to one year after completion. Although there was no head-on comparison, other treatments for AUD rarely, if ever, find results of this magnitude.
