MDMA compared with MDA and two lysine prodrugs in 23 healthy volunteers

The question

How do the acute effects of MDMA compare with those of MDA, a related compound that is also a breakdown product of MDMA, and can attaching the amino acid lysine to either drug create a slow-release version?

What they did

Twenty-three healthy adults (12 women, 11 men) each received five treatments on separate occasions in random order: MDMA (100 mg), MDA (92 mg), lysine-MDMA (172 mg), lysine-MDA (164 mg) and a placebo. Doses were matched so that each contained the same number of drug molecules. Neither participants nor researchers knew which treatment was given on a given day. The team tracked self-reported subjective effects, heart and blood pressure responses, hormone levels, and drug levels in the blood.

What they found

MDMA and MDA both produced clear subjective and bodily effects compared with placebo. MDA’s overall drug effect was stronger and lasted longer than MDMA’s (6.1 ± 0.5 hours versus 4.1 ± 0.4 hours), and MDA also produced more stimulant effects, more “bad drug effects”, more fear and more visual alterations. Lysine-MDA acted like a slow-release form of MDA: it took longer to start working and to peak (1.1 ± 0.2 hours to onset and 3.0 ± 0.4 hours to peak, versus 0.7 ± 0.1 and 2.0 ± 0.1 hours for MDA), but effects were otherwise similar. Lysine-MDMA released no detectable MDMA into the blood and produced no subjective or bodily effects. Blood elimination half-lives were 7.3 hours for MDMA and 8.4 hours for MDA.

The fine print

Only 23 healthy volunteers took part, and each received a single dose of each drug in a laboratory, so the findings say nothing about treatment of any condition. Strong drug effects can make blinding imperfect, since participants may guess what they received. Follow-up covered only the hours after dosing, and this summary is based on the abstract alone.

What it means

In healthy volunteers, MDA produced longer and stronger effects than MDMA but also more unpleasant ones, suggesting a less favourable profile for therapeutic research; attaching lysine slowed the onset of MDA but did not work at all for MDMA.

Evidence grade: Moderate. A randomized, double-blind, placebo-controlled crossover trial, which is a strong design, but it involved only 23 healthy volunteers and measured short-term drug effects rather than treatment outcomes.

This summary is based on the study’s published abstract.