PMID- 37258715 OWN - NLM STAT- MEDLINE DCOM- 20231023 LR - 20231116 IS - 1740-634X (Electronic) IS - 0893-133X (Print) IS - 0893-133X (Linking) VI - 48 IP - 13 DP - 2023 Dec TI - Acute effects of MDMA and LSD co-administration in a double-blind placebo-controlled study in healthy participants. PG - 1840-1848 LID - 10.1038/s41386-023-01609-0 [doi] AB - 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 microg) 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 (C(max) 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 microg). The combined use of MDMA and LSD is unlikely to provide relevant benefits over LSD alone in psychedelic-assisted therapy. Trial registration: ClinicalTrials.gov identifier: NCT04516902. CI - (c) 2023. American College of Neuropsychopharmacology. FAU - Straumann, Isabelle AU - Straumann I AD - Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research, University Hospital Basel, Basel, Switzerland. AD - Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland. FAU - Ley, Laura AU - Ley L AD - Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research, University Hospital Basel, Basel, Switzerland. AD - Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland. FAU - Holze, Friederike AU - Holze F AUID- ORCID: 0000-0003-3143-1519 AD - Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research, University Hospital Basel, Basel, Switzerland. AD - Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland. FAU - Becker, Anna M AU - Becker AM AD - Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research, University Hospital Basel, Basel, Switzerland. AD - Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland. FAU - Klaiber, Aaron AU - Klaiber A AD - Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research, University Hospital Basel, Basel, Switzerland. AD - Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland. FAU - Wey, Kathrin AU - Wey K AD - Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research, University Hospital Basel, Basel, Switzerland. AD - Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland. FAU - Duthaler, Urs AU - Duthaler U AUID- ORCID: 0000-0002-7811-3932 AD - Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research, University Hospital Basel, Basel, Switzerland. AD - Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland. FAU - Varghese, Nimmy AU - Varghese N AUID- ORCID: 0000-0001-8598-0535 AD - Psychiatric University Hospital, University of Basel, Basel, Switzerland. AD - Transfaculty Research Platform Molecular and Cognitive Neuroscience, University of Basel, Basel, Switzerland. FAU - Eckert, Anne AU - Eckert A AUID- ORCID: 0000-0002-9341-3669 AD - Psychiatric University Hospital, University of Basel, Basel, Switzerland. AD - Transfaculty Research Platform Molecular and Cognitive Neuroscience, University of Basel, Basel, Switzerland. FAU - Liechti, Matthias E AU - Liechti ME AUID- ORCID: 0000-0002-1765-9659 AD - Clinical Pharmacology and Toxicology, Department of Biomedicine and Department of Clinical Research, University Hospital Basel, Basel, Switzerland. matthias.liechti@usb.ch. AD - Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland. matthias.liechti@usb.ch. LA - eng SI - ClinicalTrials.gov/NCT04516902 PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20230531 PL - England TA - Neuropsychopharmacology JT - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JID - 8904907 RN - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine) RN - 0 (Hallucinogens) RN - 8NA5SWF92O (Lysergic Acid Diethylamide) SB - IM MH - Male MH - Humans MH - Female MH - *N-Methyl-3,4-methylenedioxyamphetamine/pharmacology MH - *Hallucinogens/pharmacology MH - Healthy Volunteers MH - Lysergic Acid Diethylamide/pharmacology MH - Double-Blind Method MH - Cross-Over Studies PMC - PMC10584820 COIS- MEL is a consultant for Mind Medicine, Inc. The other authors declare no competing interests. Knowhow and data associated with this work and owned by the University Hospital Basel were licensed by Mind Medicine, Inc. Mind Medicine, Inc., had no role in planning or conducting the present study or the present publication. EDAT- 2023/06/01 01:08 MHDA- 2023/10/23 12:45 PMCR- 2023/05/31 CRDT- 2023/05/31 23:27 PHST- 2023/03/07 00:00 [received] PHST- 2023/05/12 00:00 [accepted] PHST- 2023/04/17 00:00 [revised] PHST- 2023/10/23 12:45 [medline] PHST- 2023/06/01 01:08 [pubmed] PHST- 2023/05/31 23:27 [entrez] PHST- 2023/05/31 00:00 [pmc-release] AID - 10.1038/s41386-023-01609-0 [pii] AID - 1609 [pii] AID - 10.1038/s41386-023-01609-0 [doi] PST - ppublish SO - Neuropsychopharmacology. 2023 Dec;48(13):1840-1848. doi: 10.1038/s41386-023-01609-0. Epub 2023 May 31.