Acute and post-acute neurobehavioral responses to lysergic acid diethylamide in healthy subjects: a randomized controlled study
This study involved 43 healthy adults (from 45 enrolled) who completed a randomized, double-blind, placebo-controlled crossover trial.
Participants received 100 µg LSD and placebo on separate occasions, with a washout period of more than 4 weeks.
Researchers assessed effects during dosing, 1 day later, and 1 week later using behavioural tests, EEG, transcranial magnetic stimulation (TMS), blood biomarkers, and questionnaires
The researchers concluded that this is the first human study to show improved motor learning after a full psychedelic dose of LSD.
LSD appears to produce measurable changes in neural function that persist beyond the acute drug experience.
The combination of improved motor learning, lower perceived stress, and increased cognitive flexibility supports further research into LSD's potential therapeutic applications, while emphasising that the findings are preliminary and were observed in healthy volunteers, not patients with neurological or psychiatric disorders.
Safety findings
LSD produced the expected acute psychedelic effects.
Most participants described the experience positively.
Side effects were mild, transient, and largely resolved within 24 hours.
No serious adverse events were reported in this healthy volunteer sample.
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.
Calder, A.E., Diehl, V.J., Lietz, M.P. et al. Acute and post-acute neurobehavioral responses to lysergic acid diethylamide in healthy subjects: a randomized controlled study. Neuropsychopharmacol. (2026). Read Paper
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