Acute and post-acute neurobehavioral responses to lysergic acid diethylamide in healthy subjects: a randomized controlled study

Summary & key facts

Researchers gave 45 healthy people a single moderate dose of LSD (100 micrograms) and compared it with a placebo. They measured brain signals, a blood growth factor, and how people learned a finger-typing sequence one day after the dose and how they felt and thought one week later. The day after LSD, people showed better offline motor learning. One week later they reported lower perceived stress and some improvements in flexible thinking. The study also found immediate changes in auditory and motor brain signals, but no change in the blood growth factor they measured. The authors say these results suggest LSD can change learning and brain activity, but more work is needed to confirm and understand these effects.

Key facts:

• Forty-five healthy people took part in a study where each person received 100 micrograms of LSD on one day and a placebo on another day.
• Researchers used several methods to look for brain and learning changes: electrical brain recordings to measure sound‑related signals, magnetic pulses to test motor responses, a blood test for a brain growth factor, and a finger‑typing task to test motor learning.
• People showed better offline motor learning the day after taking LSD. This means their skill on the typing task improved more between practice sessions than after placebo.
• One week after LSD, participants reported lower perceived stress and showed some gains in tests of cognitive flexibility, which is the ability to switch thinking strategies.
• Electrical brain recordings showed that LSD reduced the size of early sound‑evoked brain signals during the acute effect and still changed one of those signals one week later.
• Magnetic testing of the motor system showed larger and faster motor responses while people were under LSD, suggesting the drug changed motor system excitability.
• LSD did not change levels of the blood marker brain‑derived neurotrophic factor. This means the study did not find evidence for change in that particular growth factor after a single dose.
• The study was done in healthy volunteers and was relatively small. The authors note that measuring long‑lasting changes in human brain plasticity is hard, so more studies are needed before drawing strong conclusions.

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.

Topics

Forensic Toxicology and Drug Analysis Plant and fungal interactions Psychedelics and Drug Studies

Categories

Clinical Psychology Psychology Social Sciences

Tags

Associative learning Audiology Brain-derived neurotrophic factor Cognition Cognitive flexibility Crossover study Electroencephalography Evoked potential Latency (audio) Long-term potentiation Lysergic acid diethylamide Medicine Motor cortex Motor learning Neuromodulation Neurophysiology Neuroscience Phosphene Placebo Primary motor cortex Psychology Randomized controlled trial Sensory gating Stimulation Transcranial direct-current stimulation Transcranial magnetic stimulation

Substances

LSD