MDMA induces only minimal and comparatively weak alterations of consciousness compared with LSD, according to the first controlled study to conduct a head-to-head comparison of the drugs. The findings have been published in the journal Neuropsychopharmacology.

“MDMA and LSD are both newly used in psychiatric research to treat PTSD and anxiety disorder respectively. However, differences in the acute effects of these two acutely psychoactive compounds have never been compared directly,” said study author Matthias Liechti, a professor of clinical pharmacology at the University Hospital Basel in Switzerland.

In the double-blind study, 28 healthy participants received a single dose of LSD (0.1 mg), MDMA (125 mg), D-amphetamine (40 mg), and placebo in a randomized order. Each drug session was separated by a period of at least 10 days.

The researchers found that LSD produced significantly higher ratings of “any drug effect,” “good drug effect,” “bad drug effect,” and “ego dissolution” compared with MDMA and D-amphetamine. LSD also resulted in greater ratings of “introversion,” “inactivity,” “emotional excitation,” and “anxiety” compared with MDMA and D-amphetamine.

MDMA and D-amphetamine, on the other hand, increased ratings of “concentration” and “extraversion” compared with LSD.

“LSD has much more pronounced and overwhelming subjective effects than MDMA even when MDMA is used at a relatively high dose and LSD at a moderate dose. There is a significantly greater experience of ‘ego dissolution’ with LSD compared with MDMA. There is also a greater risk of anxiety with LSD. However, there may also be greater positive effects such as feelings of bliss,” Liechti told PsyPost.

Only three participants had previously used LSD and eight participants had previously used MDMA, but 96% of the participants were able to correctly identify that they had taken LSD on the day of administration.

On a physiological level, LSD, MDMA, and D-amphetamine all increased pupil size, blood pressure, heart rate, and body temperature compared with placebo. The researchers also found that MDMA but not LSD or D-amphetamine increased plasma concentrations of oxytocin.

“Only single dose levels were compared. A comprehensive comparison would need more than one dose. Additionally, the study was done in healthy subjects. The relevance for patients needs further study,” Liechti noted.

“A similar comparison between different psychedelics such as LSD, psilocybin and mescaline is warranted. Both LSD and psilocybin have a potential to become medications and it will be of interest what the differences in benefits and risks are.”

The study, “Distinct acute effects of LSD, MDMA, and D-amphetamine in healthy subjects“, was authored by Friederike Holze, Patrick Vizeli, Felix Müller, Laura Ley, Raoul Duerig, Nimmy Varghese, Anne Eckert, Stefan Borgwardt, and Matthias E. Liechti.