MDMA, MDA, and novel lysine slow-release forms directly compared for acute subjective effects in healthy volunteers

The empathogen 3,4-methylenedioxymethamphetamine (MDMA), a serotonin (5-HT) and oxytocin releaser, is recognized for its positive subjective effects, empathy, and trust induction. It's used recreationally, as a research tool, and is under investigation for MDMA-assisted psychotherapy. MDMA is partially metabolized into 3,4-methylenedioxyamphetamine (MDA), another psychoactive substance. While these substances offer therapeutic potential, acute negative psychological effects like anxiety and rapid onset of euphoria, increasing abuse risk, are concerns. Rapid increases in blood pressure at onset also pose a risk. Slow-release formulations could mitigate these issues by attenuating rapid drug effects.

This Phase 1 study, with an enrollment of 25 healthy volunteers, aims to directly compare the acute effects of MDMA and MDA for the first time in the same subjects. Additionally, the study will characterize and compare the effects of lysine-MDMA and lysine-MDA against their immediate-release counterparts. The primary objective is to test the concept of attenuated effects with slow-release formulations, specifically focusing on mitigating anxiety, rapid euphoria, and rapid blood pressure changes. Modern psychological and psychometric tests will be employed to assess subjective drug effects, alongside physiological measurements.

This study is designed to characterize and directly compare the acute subjective and physiological effects of MDMA and MDA in healthy volunteers. It also aims to evaluate novel lysine-MDMA and lysine-MDA slow-release formulations, hypothesizing that these will attenuate rapid drug onset effects. The primary objective is to determine if slow-release forms can mitigate negative subjective effects like anxiety, reduce the rapid onset of euphoria (linked to abuse potential), and temper rapid increases in blood pressure at drug onset. The study will utilize modern psychological and psychometric tests to quantify these effects and provide a comprehensive comparison across all four compounds. The findings are expected to inform safer therapeutic and recreational use strategies.