Acute and post-acute neurobehavioral responses to lysergic acid diethylamide in healthy subjects: a randomized controlled study
Abigail E. Calder, Vincent J Diehl, Morten P. Lietz, Parsa Yousefi, Nicole Friedli, Fabio Coviello, Antonin Rouaud, Kristian Beichmann, Anne Eckert, Gregor Hasler
Neuropsychopharmacology June 18, 2026 DOI: 10.1038/s41386-026-02454-7 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized crossover trial Peer reviewed |
|---|---|
| Sample size | 45 |
| Population | Healthy subjects (24 women) |
| Intervention | LSD |
| Dose | 100 µg |
| Duration | One week after dosing |
| Topics | LSD |
| Keywords | Transcranial magnetic stimulation Electroencephalography Crossover study Randomized controlled trial Cognition Cognitive flexibility Long-term potentiation Audiology Phosphene Motor cortex Evoked potential Motor learning Placebo Sensory gating |
| Key findings | Offline motor learning significantly improved the day after LSD, and perceived stress was reduced with increased cognitive flexibility one week later. |
Abstract
Preclinical studies suggest that lysergic acid diethylamide (LSD) may induce lasting changes in brain function and learning ability, but evidence in humans is uncertain. Motor learning, in particular, has clinical relevance but has not been investigated in human studies of psychedelics. Forty-five healthy subjects (24 women) participated in this randomized crossover trial comparing 100 µg LSD with a placebo. For up to one week after dosing, we investigated LSD's post-acute neurophysiological effects using auditory tetanization with electroencephalography (EEG), paired associative stimulation (PAS) with transcranial magnetic stimulation (TMS), peripheral levels of brain-derived neurotrophic factor (BDNF). Additionally, online and offline motor learning were assessed one day after dosing with a sequence typing task. Questionnaires assessed perceived stress and cognitive flexibility one week after dosing. We found that offline motor learning significantly improved the day after LSD. One week after LSD, perceived stress was reduced and aspects of cognitive flexibility were increased. EEG data showed that LSD acutely decreased amplitudes of N1 and P2 auditory event-related potentials and still modulated P2 one week later. Motor-evoked potentials measured with TMS showed increased amplitude and faster latency under LSD. LSD did not alter BDNF levels. Our findings encourage future studies on LSD and learning and additionally highlight important challenges in the measurement of long-term potentiation in humans. The observed acute and lasting changes in neural signals provide insight into LSD's effects on the auditory and motor systems.
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
Cites 43
- Psychometric Evaluation of the Altered States of Consciousness Rating Scale (OAV) PLoS One August 31, 2010
- Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin Journal of Psychopharmacology October 6, 2015
- LSD-assisted psychotherapy for anxiety associated with a life-threatening disease: A qualitative study of acute and sustained subjective effects Journal of Psychopharmacology November 11, 2014
- Activation of Serotonin 2A Receptors Underlies the Psilocybin-Induced Effects on Oscillations, N170 Visual-Evoked Potentials, and Visual Hallucinations Journal of Neuroscience June 19, 2013
- Psychedelics reopen the social reward learning critical period Nature June 14, 2023
and 38 more in the library