Acute effects of MDMA and LSD co-administration in a double-blind placebo-controlled study in healthy participants

This double-blind, randomized, placebo-controlled, crossover study (n=24) investigates the co-administration of MDMA (100mg) and LSD (100µg) compared to their individual use and placebo. Findings reveal that while the combination doesn’t enhance the quality of subjective effects compared to LSD alone, it prolongs these effects, elevates plasma concentrations of LSD, and extends LSD’s plasma elimination half-life. However, the combination also increases blood pressure, heart rate, and pupil size more than LSD alone. It does not improve the safety profile of LSD, indicating that combining MDMA and LSD may not offer substantial benefits over LSD alone in psychedelic-assisted therapy.

Abstract of Acute effects of MDMA and LSD co-administration in a double-blind placebo-controlled study in healthy participants

“There is renewed interest in the use of lysergic acid diethylamide (LSD) in psychiatric research and practice. Although acute subjective effects of LSD are mostly positive, negative subjective effects, including anxiety, may occur. The induction of overall positive acute subjective effects is desired in psychedelic-assisted therapy because positive acute experiences are associated with greater therapeutic long-term benefits. 3,4-Methylenedioxymethamphetamine (MDMA) produces marked positive subjective effects and is used recreationally with LSD, known as “candyflipping.” The present study investigated whether the co-administration of MDMA can be used to augment acute subjective effects of LSD. We used a double-blind, randomized, placebo-controlled, crossover design with 24 healthy subjects (12 women, 12 men) to compare the co-administration of MDMA (100 mg) and LSD (100 µg) with MDMA and LSD administration alone and placebo. Outcome measures included subjective, autonomic, and endocrine effects and pharmacokinetics. MDMA co-administration with LSD did not change the quality of acute subjective effects compared with LSD alone. However, acute subjective effects lasted longer after LSD + MDMA co-administration compared with LSD and MDMA alone, consistent with higher plasma concentrations of LSD (Cmax and area under the curve) and a longer plasma elimination half-life of LSD when MDMA was co-administered. The LSD + MDMA combination increased blood pressure, heart rate, and pupil size more than LSD alone. Both MDMA alone and the LSD + MDMA combination increased oxytocin levels more than LSD alone. Overall, the co-administration of MDMA (100 mg) did not improve acute effects or the safety profile of LSD (100 µg). The combined use of MDMA and LSD is unlikely to provide relevant benefits over LSD alone in psychedelic-assisted therapy.”

Authors: Isabelle Straumann, Laura Ley, Friederike Holze, Anna M. Becker, Aaron Klaiber, Kathrin Wey, Urs Duthaler, Nimmy Varghese, Anne Eckert & Matthias E. Liechti

Summary of Acute effects of MDMA and LSD co-administration in a double-blind placebo-controlled study in healthy participants

LSD is a classic serotonergic psychedelic that produces mostly positive experiences of alterations of consciousness, but may also produce negative subjective effects, including acute anxiety. Positive experiences are associated with more favourable long-term therapeutic improvements in patients in psychedelic-assisted therapy.

MDMA induces positive subjective effects, including well-being, empathy, trust, and closeness to others. The combined administration of MDMA and LSD induces synergistic acute positive mood effects, including more positive mood and less anxiety than LSD administration alone.

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Find this paper

Acute effects of MDMA and LSD co-administration in a double-blind placebo-controlled study in healthy participants

https://doi.org/10.1038/s41386-023-01609-0

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Cite this paper (APA)

Straumann, I., Ley, L., Holze, F., Becker, A. M., Klaiber, A., Wey, K., ... & Liechti, M. E. (2023). Acute effects of MDMA and LSD co-administration in a double-blind placebo-controlled study in healthy participants. Neuropsychopharmacology, 1-9.

Study details

Compounds studied
MDMA LSD Placebo

Topics studied
Healthy Subjects

Study characteristics
Original Placebo-Controlled Double-Blind Within-Subject Randomized

Participants
24 Humans

Authors

Authors associated with this publication with profiles on Blossom

Matthias Liechti
Matthias Emanuel Liechti is the research group leader at the Liechti Lab at the University of Basel.

Institutes

Institutes associated with this publication

University of Basel
The University of Basel Department of Biomedicine hosts the Liechti Lab research group, headed by Matthias Liechti.

Compound Details

The psychedelics given at which dose and how many times

LSD 100 μg | 2x MDMA 100 mg | 2x

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Linked Clinical Trial

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This completed double-blind, placebo-controlled trial (n=24) aimed to investigate the effects of co-administering MDMA with LSD in healthy subjects. The study, conducted by the University Hospital in Basel, Switzerland, assessed the acute subjective and autonomic effects of LSD alone and in combination with MDMA.

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