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Low doses of LSD reduce broadband oscillatory power and modulate event-related potentials in healthy adults

Abstract

Rationale

Classical psychedelics, including psilocybin and lysergic acid diethylamide (LSD), are under investigation as potential therapeutic agents in psychiatry. Whereas most studies utilize relatively high doses, there are also reports of beneficial effects of “microdosing,” or repeated use of very low doses of these drugs. The behavioral and neural effects of these low doses are not fully understood.

Objectives

To examine the effects of LSD (13 μg and 26 μg) versus placebo on resting-state electroencephalography (EEG) and event-related potential (ERP) responses in healthy adults.

Methods

Twenty-two healthy men and women, 18 to 35 years old, participated in 3 EEG sessions in which they received placebo or LSD (13 μg and 26 μg) under double-blind conditions. During each session, participants completed drug effect and mood questionnaires at hourly intervals, and physiological measures were recorded. During expected peak drug effect, EEG recordings were obtained, including resting-state neural oscillations in scalp electrodes over default mode network (DMN) regions and P300, N170, and P100 ERPs evoked during a visual oddball paradigm.

Results

LSD dose-dependently reduced oscillatory power across delta, theta, alpha, beta, and gamma frequency bands during both eyes closed and eyes open resting conditions. During the oddball task, LSD dose-dependently reduced ERP amplitudes for P300 and N170 components and increased P100 latency. LSD also produced dose-related increases in positive mood, elation, energy, and anxiety and increased heart rate and blood pressure. On a measure of altered states of consciousness, LSD dose-dependently increased Blissful State, but not other indices of perceptual or sensory effects typical of psychedelic drugs. The subjective effects of the drug were not correlated with the EEG measures.

Conclusions

Low doses of LSD produced broadband cortical desynchronization over the DMN during resting state and reduced P300 and N170 amplitudes, patterns similar to those reported with higher doses of psychedelics. Notably, these neurophysiological effects raise the possibility that very low doses of LSD may produce subtle behavioral and perhaps therapeutic effects that do not rely on the full psychedelic experience.

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Acknowledgements

We thank Robin Nusslock for the helpful comments on the manuscript.

Funding

This research was supported by the National Institutes of Health [DA02812]. CHM was supported by the National Institutes of Health [T32DA043469]. Additional support was received as a pilot grant from the Department of Psychiatry and Behavioral Neuroscience, University of Chicago.

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Murray, C.H., Tare, I., Perry, C.M. et al. Low doses of LSD reduce broadband oscillatory power and modulate event-related potentials in healthy adults. Psychopharmacology (2021). https://doi.org/10.1007/s00213-021-05991-9

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Keywords

  • LSD
  • EEG
  • ERP
  • Psychedelic
  • Microdose