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

This double-blind study (n=22) investigated the effects of microdosing LSD (13μg and 26μg) on resting-state electroencephalography (EEG) and event-related potential (ERP) in healthy adults. The study found that microdoses of LSD produced desynchronization patterns similar to those reported with higher doses of psychedelics, leading the authors to believe that microdoses of LSD may produce therapeutic effects in the absence of a full psychedelic experience.


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 behavioural 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 a 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 the 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 the 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 a 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 behavioural and perhaps therapeutic effects that do not rely on the full psychedelic experience.”

Authors: Conor H. Murray, Ilaria Tare, Claire M. Perry, Michael Malina, Royce Lee & Harriet de Wit


Despite a large body of research indicating the positive outcomes of microdosing, many studies use self-reported measures such as surveys and questionnaires. As a result, cannot be used as reliable clinical evidence. Furthermore, although a significant number of positive anecdotal reports from people who microdose exist, barely any scientific studies have taken place exploring both the physiological and pharmacological effects of microdosing. Such studies are needed to determine the safety and efficacy of microdosing and to avoid any potential harm.

The present study is one of the first studies to examine the effects microdosing LSD has on cognitive processes in healthy adults. This double-blinded placebo-controlled study assessed electroencephalography (EEG) and event-related potential (ERP) responses, techniques commonly used in psychedelic studies involving larger doses, to determine the effect 13ug or 26ug of LSD has on human brain function. In comparison to fMRI, EEG is much better at capturing events over time, but at lower ‘resolution’.

The study found that:

  • Low doses of LSD reduced oscillatory power across frequency bands indicative of cortical desynchronization during rest, both with eyes closed and eyes open. Effects were dose dependent i.e the higher dose of LSD (26μg) produced greater effects.
  • The observed cortical desynchronization was similar to that found in studies using higher doses of psychedelics.
  • Participants in the study also reported increases in positive mood, energy, elation, anxiety and intellectual efficiency.

This study provides hope that low doses of LSD may produce behavioural and even therapeutics effects in the absence of a full psychedelic experience. Such findings may indicate that repeated low doses of psychedelics, in combination with sufficient support and preparation, may provide an alternative treatment model to the current high dosing procedures.

This way, similar outcomes could be reached without the costs associated with having one or two trained therapists sitting a full psychedelic experience. Using a microdose could also open up these forms of treatment to those not wanting to have a full psychedelic experience or not being able to for health (or again costs) reasons.


Classical psychedelics are under investigation as potential therapeutic agents in psychiatry. However, the effects of very low doses are not fully understood.


Low doses of LSD have been shown to improve ratings of vigor, decrease attentional lapses, and affect time perception, but have few other effects on mood or cognition. However, it is possible that low doses of LSD subtly change neural function, which ultimately affects behavior.

LSD and psilocybin are partial agonists of serotonin receptors, with some affinity to dopamine receptors. They stimulate the release of glutamate, which increases the excitability of cortical networks.

Several studies have investigated the effects of psychedelic drugs on functional connectivity in the brain using functional magnetic resonance imaging (fMRI), most at relatively high doses. These studies indicate that psychedelic drugs increase functional connectivity across networks while decreasing connectivity within networks.

Several studies have examined the effects of psychedelic drugs on EEG, particularly the effects of LSD and psilocybin on the posterior cingulate cortex (PCC), which is a major hub of the default mode network (DMN), a major resting-state network implicated in self-referential processing. Psilocybin reduced ERPs in one study, and N170 responses to fearful faces in another study. These findings are consistent with fMRI findings that psychedelic drugs increase neural complexity while reducing event-related neural responses.

The present study examined the effects of low doses of LSD on neural function in healthy adults and examined the relationship between these neural effects and the drug’s subjective effects.

Study design

This study used a within-subject, double-blind design to assess the effects of low doses of LSD on mood and EEG in healthy young adults.


Healthy subjects were screened for physical and psychiatric health with a physical examination, electrocardiogram, modified Structural Clinical Interview for DSM-5, and self-reported health and drug-use history. They provided written, informed consent prior to beginning the study.

Orientation session

Subjects attended an orientation session, provided informed consent, received presession instructions, practice study tasks and questionnaires, and were instructed to abstain from drugs and medications for 48 h before and 24 h after each session.

Experimental sessions

Subjects attended three 5-h sessions from 8 am to 1 pm, separated by at least 7 days, and provided urine samples for pregnancy tests. LSD was administered sublingually under double-blind conditions, and subjects completed end-of-session questionnaires and were discharged.


The drug was manufactured by Organix and prepared by the University of Chicago Investigational Pharmacy. It was administered in a volume of 0.5 mL.

Drug effect measures

Subjective drug effects were assessed before and at regular intervals after drug administration using the Drug Effects Questionnaire, the Addiction Research Center Inventory, and the Profile of Mood States during each session. Blood pressure and heart rate were monitored every 60 min.

EEG acquisition

EEG recordings were collected using 128 sintered Ag/ AgCl active electrodes placed according to equiradial layout on the head cap. Data was acquired continuously, amplified, and digitized using Biosemi ActiveView software, and processed offline based on data stored on computer workstation hard drives.

Resting state

EEG data were continuously recorded while subjects rested comfortably with eyes closed for 5 min, followed by eyes open for 5 min with eyes rested on a fixation cross.

Emotional faces oddball task

Event-related potentials were assessed when subjects viewed frequent happy faces and infrequent neutral and angry faces in a 3:1 ratio. The main analysis was the response to infrequent facial expressions, and in secondary analyses, we compared the rare neutral to rare angry faces.

Subjective and cardiovascular effects

LSD had similar effects on all measures, and a one-way repeated measures analysis of variance was used to compare each dose with placebo.

EEG preprocessing

Data were preprocessed using the EEGLAB extension v2021.0 for MATLAB, and gross movement artifacts were removed after manual inspection. Peripheral electrodes were removed from analysis after independent component analysis.

Resting‑state analyses

After ICA and removal of artifactual noise, oscillatory power was calculated in five frequency bands using fast Fourier transform on scalp electrodes during eyes closed or eyes open resting state.

ERP analyses

Data were collected using ICA and analyzed using EEGLAB Study function with multiple designs. ERP analyses were performed on Pz and PO 10 electrodes and statistical analysis was performed using SPSS software.

Drug response measures

LSD significantly increased subjective and cardiovascular measures over the course of the 5-h session, including ratings on the DEQ Feel Drug, Feel High, Like Drug, and Want More. It also significantly increased measures of elation, anxiety, positive mood, and energy and intellectual efficiency.

EEG recordings

LSD reduced oscillatory power in the posterior cingulate cortex, the medial prefrontal cortex, and the left and right temporoparietal cortices during eyes closed resting state, and also reduced oscillatory power in the left temporoparietal cortices during eyes open resting state.

LSD dose-dependently reduced error rates, decreased amplitudes for the P300 and N170, but not the P100 ERP, and increased the latency of the P100 component without affecting the latency of the later N170 or P300 components.

End of session questionnaires

Participants correctly guessed “placebo” on placebo sessions and “hallucinogen” on 26 g LSD sessions, but LSD (26 g only) significantly increased scores on Blissful State on the 5D-ASC.


This study examined the effects of low doses of LSD on resting-state EEG, visual oddball paradigm, and subjective measures of energy, positive mood, elation, anxiety, and intellectual efficiency.

Low doses of LSD reduced broadband oscillatory power, and moderate intravenous doses of psilocybin increased oscillatory power in the posterior cingulate cortex, anterior cingulate cortex, and retrosplenial cortex. This shift in oscillatory power toward excitation was attributed to increased excitability of deep-layer pyramidal neurons. LSD (75 g) decreased oscillatory power across delta, alpha, theta, and beta bands and increased “diversity” in neural signals, which have been used to index levels of sedation and sleep. We did not include dipole or distributed source detection of intracranial spectral density, so our interpretation is limited until further confirmation using intracranial EEG or source estimations. LSD reduced neural responses to unexpected stimuli in the visual oddball paradigm, and may affect cognitive and perceptual processing associated with facial recognition.

Low doses of LSD did not impair behavioral responses to facial stimuli, but instead improved responses by reducing error rates. The findings suggest that even microdoses of LSD have effects on brain processing of visual stimuli that parallel that seen with higher doses of LSD and other psychedelic drugs.

Low doses of LSD increased positive mood and produced some stimulant-like effects. However, the subjective effects of low doses of LSD are completely blocked by a 5-HT2a antagonist, raising the possibility that some of these effects are mediated by dopamine rather than serotonin.

The present findings can be related to studies with other drugs, such as D-amphetamine, which reduces resting-state neuronal oscillations in delta, theta, and alpha bands. Low doses of LSD facilitate cortical neuronal activity, which may explain the positive mood response.


These data suggest that low doses of LSD may have therapeutic effects without producing psychedelic states, and that repeated low doses may provide an alternative model alongside high dosing procedures that have shown therapeutic benefits.

Study details

Compounds studied

Topics studied
Neuroscience Microdosing

Study characteristics
Original Double-Blind Within-Subject

22 Humans


Authors associated with this publication with profiles on Blossom

Harriet de Wit
Harriet de Wit is a Professor of Psychiatry and Behavioral Neuroscience at the University of Chicago. Her research focuses on the physiological, subjective (i.e., mood-altering), and behavioral effects of drugs in healthy human volunteers.


Institutes associated with this publication

University of Chicago
Research with psychedelics is taking place at the Human Behavioral Pharmacology Lab at the University of Chicago.

Compound Details

The psychedelics given at which dose and how many times

Placebo 13 - 26
μg | 2x