MDMA vs MDA: Which is Better for Therapy & Why?

A study published in the journal Neuropsychopharmacology has directly compared the physical and psychological effects of MDMA (ecstasy) and its chemical cousin, MDA. The results show that MDA produces a longer-lasting therapeutic experience, but with more visual distortions and adverse reactions. This suggests that MDA might be less suitable than standard MDMA for therapeutic purposes.

MDMA is known for promoting feelings of empathy and interpersonal connection. Because of its ability to induce these emotional states, it is being investigated for use in psychotherapy for patients with post-traumatic stress disorder.

MDA, a metabolite of MDMA, is psychoactive and has a history of limited psychiatric exploration. Both substances fall into a class of drugs known as entactogens. Pharmacologically, both drugs work by releasing signaling chemicals in the brain, including serotonin and dopamine. Laboratory models show that MDA targets dopamine slightly more aggressively than MDMA and exhibits a ten-fold higher activation of a specific serotonin receptor.

Participants reported that MDA caused stronger stimulant effects and provoked more visual distortions than MDMA. They also experienced more fear and bad drug experiences under the influence of MDA.

The study, conducted by Isabelle Straumann and her team, involved 23 healthy adult volunteers. Each participant attended five 13-hour testing sessions, separated by at least two weeks. During the sessions, participants received one of five identical capsules: a placebo, a standard recreational dose of MDMA, a chemically equivalent dose of MDA, the lysine-attached version of MDMA, or the lysine-attached version of MDA.

After taking the pill, each volunteer stayed in a quiet hospital room. The research team repeatedly measured the participants' blood pressure, pupil size, heart rate, and body temperature. Volunteers were also asked to rate their subjective emotional and physical experiences on numbered visual scales.

Both chemicals produced comparable increases in body temperature, heart rate, pupil size, and blood pressure. As expected, MDMA triggered a heavy release of oxytocin. Researchers found that MDA also increased circulating levels of oxytocin and its carrier protein, doing so slightly more intensely than MDMA.

Researchers also tracked oxytocin, a hormone associated with social bonding. MDMA triggers a massive release of oxytocin, which scientists suspect plays a role in its therapeutic benefit.

The slow-release versions of the drugs showed mixed results. The lysine-attached MDA pill functioned as intended, delaying the onset of the drug's effects by about an hour. The lysine-attached MDMA pill produced no physical or psychological effects, creating a second placebo group. Volunteers reported greater subjective experiences on this unexpected second placebo day, highlighting the power of expectation in psychiatric research.

Women reported slightly more extreme visual and time alterations than men. Participant genetics also played a role in drug clearance rates. Individuals with a specific variation of the CYP2D6 liver enzyme cleared the active chemicals more slowly.