MindMed’s MNMD recurring employee, Teacher. Dr. Matthias Liechti of the Basel University Hospital (UHB), will direct a novel Phase 1 clinical trial to compare acute responses to R-MDMA, S-MDMA and MDMA in healthy subjects, which should begin on Tuesday.
The study will compare the acute subjective, physiological and endocrine effects of R-MDMA, S-MDMA and racemic – that is, a mixture with equal amounts of its enantiomeric components S and R – MDMA in 24 healthy volunteers.
Specifically, in this phase 1 randomized, placebo-controlled, double-blind, 5-period crossover trial, patients will receive R-MDMA at doses of 125 and 250 mg, S-MDMA at a dose of 125 mg, MDMA at a dose of 125 mg, and a placebo.
Emphasis is placed on the measurement of acute subjective effects by the Visual Analog Scales (EVA) and the 5 dimensions of altered states of consciousness (5D-ASC)while autonomic effects (blood pressure, heart rate, body temperature), general post-administration mood, endocrine effects, plasma concentration and any other subjective effects will also be assessed.
Dr. Liechti explained that existing preclinical research indicates that S-MDMA primarily releases dopamine, norepinephrine, serotonin, and oxytocin, while R-MDMA may act more directly on 5-HT2A receptors and release prolactin, suggesting therefore the latter enantiomer may have fewer adverse effects and greater prosocial effects than the former.
“But the acute effects of S-MDMA and R-MDMA have never been properly examined in a human study,” and this is what the present study aims to validate at the clinical stage.
Dr. Miri Halperin Wernli, Executive Chair of MindMed added that although animal studies have shown that the two enantiomers act synergistically to produce the subjective effects of MDMA, “this study represents an opportunity to validate the potentially enhanced safety profile and prosocial effects of the R-enantiomer of MDMA”.
He explained further. “Preclinical studies of R-MDMA demonstrate its acute prosocial effectswhile its reduced dopaminergic activity suggests that it will exhibit less stimulatory activity, neurotoxicity, hyperthermia, and abuse potential compared to racemic MDMA or the S-enantiomer.
it is not the first time Dr. Liechti’s lab at UHB and MindMed are working together, as shown in the recently announced Phase 1 trial comparing the effects of MDMA and other related substances.
MindMed’s goal is to develop a pipeline of innovative drugs with and without acute perceptual effects to target the serotonin, dopamine and acetylcholine systems for the treatment of various mental health disorders, including the ongoing development of MM-402 for the treatment of main symptoms of autism spectrum disorder (ASD)a developmental condition “characterized by atypical communication and social interactions, repetitive behaviors and restricted interests” for which there are no approved therapies yet.
“We look forward to exploring the exciting opportunities opened up by Dr. Liechti’s research,” said Dr. Halperin Wernli.
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