Low doses of LSD reduce broadband oscillatory power and modulate event-related potentials in healthy adults
Conor H. Murray, Ilaria Tare, Claire Perry, Michael Malina, Royce Lee, Harriet de Wit
Psychopharmacology October 6, 2021 DOI: 10.1007/s00213-021-05991-9 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Double-blind Peer reviewed |
|---|---|
| Sample size | 22 |
| Population | Healthy adults aged 18 to 35 years |
| Intervention | LSD |
| Dose | 13 μg and 26 μg |
| Topics | LSD |
| Citations | 75 |
| Key findings | Low doses of LSD produced broadband cortical desynchronization over the default mode network during rest and reduced P300 and N170 amplitudes, patterns similar to those reported with higher doses of psychedelics. |
Abstract
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. 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. 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. 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. 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.
Comparable studies
Other randomized controlled trials on LSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Safety and Efficacy of Lysergic Acid Diethylamide-Assisted Psychotherapy for Anxiety Associated With Life-threatening Diseases Patients with anxiety associated with life-threatening diseases | 2014 | Randomized controlled trial | n = 12 |
| Dose-Response Study of N,N-Dimethyltryptamine in Humans Experienced hallucinogen users | 1994 | Double-blind, saline placebo-controlled, randomized study | n = 12 |
| Acute Effects of Lysergic Acid Diethylamide in Healthy Subjects Healthy subjects (8 women, 8 men) | 2014 | Double-blind, randomized, placebo-controlled, crossover study | n = 16 |
| Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor Healthy human participants | 2018 | Double-blind, randomized, counterbalanced, cross-over study | n = 24 |
| LSD-induced entropic brain activity predicts subsequent personality change. Healthy adults | 2016 | Balanced-order, placebo-controlled study | n = 19 |
Citations in the library
Cited by 59
- Default Mode Network Modulation by Psychedelics: A Systematic Review The International Journal of Neuropsychopharmacology October 21, 2022
- Microdosing with psilocybin mushrooms: a double-blind placebo-controlled study Translational Psychiatry August 2, 2022
- Acute Mood-Elevating Properties of Microdosed Lysergic Acid Diethylamide in Healthy Volunteers: A Home-Administered Randomized Controlled Trial. Biological Psychiatry September 15, 2023
- Ketamine and serotonergic psychedelics: An update on the mechanisms and biosignatures underlying rapid-acting antidepressant treatment Neuropharmacology January 13, 2023
- Cardiovascular safety of psychedelic medicine: current status and future directions Pharmacological Reports October 24, 2023
and 54 more in the library
Cites 41
- The Brain's Default Mode Network Annual Review of Neuroscience May 4, 2015
- Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial Journal of Psychopharmacology November 30, 2016
- Rapid and sustained symptom reduction following psilocybin treatment for anxiety and depression in patients with life-threatening cancer: a randomized controlled trial Journal of Psychopharmacology November 30, 2016
- Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin Proceedings of the National Academy of Sciences January 23, 2012
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics Pharmacological Reviews June 20, 2019
and 36 more in the library