Acute effects of MDMA and LSD co-administration in a double-blind placebo-controlled study in healthy participants.
Isabelle Straumann, Laura Ley, Friederike Holze, Anna M Becker, Aaron Klaiber, Kathrin Wey, Urs Duthaler, Nimmy Varghese, Anne Eckert, Matthias E. Liechti
Neuropsychopharmacology December 1, 2023 DOI: 10.1038/s41386-023-01609-0 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Double-blind, randomized, placebo-controlled, crossover trial Peer reviewed |
|---|---|
| Sample size | 24 |
| Population | Healthy subjects (12 women, 12 men) |
| Interventions | LSD MDMA LSD + MDMA |
| Dose | 100 mg MDMA, 100 µg LSD |
| Topics | LSD MDMA |
| Keywords | Psychedelics Drug research Clinical trials |
| Citations | 41 |
| Registration | NCT04516902 |
| Key findings | Co-administration of MDMA with LSD did not change the quality of acute subjective effects compared with LSD alone and is unlikely to provide relevant benefits over LSD alone in psychedelic-assisted therapy. |
Abstract
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. Trial registration: ClinicalTrials.gov identifier: NCT04516902.
Comparable studies
Other randomized controlled trials on LSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases Patients with anxiety associated with life-threatening diseases | 2014 | Randomized controlled trial | n = 12 |
| Dose-Response Study of N,N-Dimethyltryptamine in Humans Experienced hallucinogen users | 1994 | Double-blind, saline placebo-controlled, randomized study | n = 12 |
| Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects Healthy subjects (8 women, 8 men) | 2014 | Double-blind, randomized, placebo-controlled, crossover study | n = 16 |
| Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor Healthy human participants | 2018 | Double-blind, randomized, counterbalanced, cross-over study | n = 24 |
| LSD-induced entropic brain activity predicts subsequent personality change. Healthy adults | 2016 | Balanced-order, placebo-controlled study | n = 19 |
Citations in the library
Cited by 40
- Cardiovascular safety of psychedelic medicine: current status and future directions Pharmacological Reports October 24, 2023
- Serotonergic Psychedelics: A Comparative Review of Efficacy, Safety, Pharmacokinetics, and Binding Profile Biological Psychiatry: Cognitive Neuroscience and Neuroimaging February 1, 2024
- Drug–drug interactions involving classic psychedelics: A systematic review Journal of Psychopharmacology November 20, 2023
- Measuring psychotherapeutic processes in the context of psychedelic experiences: Validation of the General Change Mechanisms Questionnaire (GCMQ) Journal of Psychopharmacology May 1, 2024
- Co-use of MDMA with psilocybin/LSD may buffer against challenging experiences and enhance positive experiences Scientific Reports August 22, 2023
and 35 more in the library
Cites 46
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Psilocybin can occasion mystical-type experiences having substantial and sustained personal meaning and spiritual significance Psychopharmacology July 7, 2006
- MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nature Medicine June 1, 2021
- Quality of Acute Psychedelic Experience Predicts Therapeutic Efficacy of Psilocybin for Treatment-Resistant Depression Frontiers in Pharmacology January 17, 2018
and 41 more in the library