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 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.

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.”

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

Notes

Despite a large body of research indicating the positive outcomes of microdosing, many of the studies use self-reported measures such as surveys and questionnaires and 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 in order to determine the safety and efficacy of microdosing and to avoid any potential harms.

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.

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