Preliminary Report on the Effects of a Low Dose of LSD on Resting-State Amygdala Functional Connectivity.
Anya K. Bershad, Katrin H. Preller, Royce Lee, Sarah Keedy, Jamie Wren-Jarvis, Michael P. Bremmer, Harriet de Wit
Biological Psychiatry: Cognitive Neuroscience and Neuroimaging December 20, 2019 DOI: 10.1016/j.bpsc.2019.12.007 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Double-blind Peer reviewed |
|---|---|
| Sample size | 20 |
| Population | Healthy young adults, 18 to 35 years old |
| Intervention | LSD |
| Dose | 13 μg |
| Topics | LSD Microdosing Neuroplasticity |
| Keywords | Psychedelics Psychedelic compounds Psychedelic substances Brain connectivity Functional connectivity Brain networks Neural networks Brain connections Brain modulation Emotional processing Emotions Emotional regulation Amygdala Emotional response Low dose Small amount Sub-perceptual dose |
| Citations | 95 |
| Key findings | A single 13 μg dose of LSD altered amygdala functional connectivity with several brain regions, and changes in amygdala–middle frontal gyrus connectivity were positively correlated with positive mood. |
Abstract
BackgroundThe practice of "microdosing," or the use of repeated, very low doses of lysergic acid diethylamide (LSD) to improve mood or cognition, has received considerable public attention, but empirical studies are lacking. Controlled studies are needed to investigate both the therapeutic potential and the neurobiological underpinnings of this pharmacologic treatment.MethodsThe present study was designed to examine the effects of a single low dose of LSD (13 μg) versus placebo on resting-state functional connectivity and cerebral blood flow in healthy young adults. Twenty men and women, 18 to 35 years old, participated in 2 functional magnetic resonance imaging scanning sessions in which they received placebo or LSD under double-blind conditions. During each session, the participants completed drug effect and mood questionnaires, and physiological measures were recorded. During expected peak drug effect, they underwent resting-state blood oxygen level-dependent and arterial spin labeling scans. Cerebral blood flow as well as amygdala and thalamic connectivity were analyzed.ResultsLSD increased amygdala seed-based connectivity with the right angular gyrus, right middle frontal gyrus, and the cerebellum, and decreased amygdala connectivity with the left and right postcentral gyrus and the superior temporal gyrus. This low dose of LSD had weak and variable effects on mood, but its effects on positive mood were positively correlated with the increase in amygdala-middle frontal gyrus connectivity strength.ConclusionsThese preliminary findings show that a very low dose of LSD, which produces negligible subjective changes, alters brain connectivity in limbic circuits. Additional studies, especially with repeated dosing, will reveal whether these neural changes are related to the drug's purported antidepressant effect.
In the evidence
This study is part of the evidence base for a synthesis in the library. Here is how each one recorded it.
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A single 13 μg dose of LSD altered amygdala functional connectivity with several brain regions, and changes in amygdala–middle frontal gyrus connectivity were positively correlated with positive mood, though effects on mood itself were weak and variable.
Synthesized
Comparable studies
Other randomized controlled trials on LSD and microdosing, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Acute Mood-Elevating Properties of Microdosed Lysergic Acid Diethylamide in Healthy Volunteers: A Home-Administered Randomized Controlled Trial. Healthy male volunteers | 2023 | Randomized controlled trial | n = 80 |
| Low doses of lysergic acid diethylamide (LSD) increase reward-related brain activity. Healthy adults | 2023 | Within-subject, double-blind, placebo-controlled experiment | n = 18 |
| Greater subjective effects of a low dose of LSD in participants with depressed mood. Adults with mild depressed mood (scoring high or low on the Beck Depression-II inventory) | 2024 | Randomized controlled trial | n = 39 |
| Inter-individual variability in neural response to low doses of LSD. Healthy participants | 2024 | Randomized controlled trial | n = 53 |
| LSD increases sleep duration the night after microdosing. Healthy adult male volunteers | 2024 | Randomized controlled trial | n = 80 |
Citations in the library
Cited by 84
- Hallucinogens in Mental Health: Preclinical and Clinical Studies on LSD, Psilocybin, MDMA, and Ketamine Journal of Neuroscience November 30, 2020
- Acute dose-dependent effects of lysergic acid diethylamide in a double-blind placebo-controlled study in healthy subjects Neuropsychopharmacology October 15, 2020
- Psychedelics in Psychiatry: Neuroplastic, Immunomodulatory, and Neurotransmitter Mechanisms Pharmacological Reviews December 16, 2020
- Self-blinding citizen science to explore psychedelic microdosing. Elife March 2, 2021
- Low Doses of LSD Acutely Increase BDNF Blood Plasma Levels in Healthy Volunteers ACS Pharmacology & Translational Science August 31, 2020
and 79 more in the library
Cites 17
- The Standardized Psychometric Assessment of Altered States of Consciousness (ASCs) in Humans Pharmacopsychiatry July 1, 1998
- Psilocybin for treatment-resistant depression: fMRI-measured brain mechanisms. Scientific Reports October 13, 2017
- Serotonin research: contributions to understanding psychoses TIPS - Trends in Pharmacological Sciences August 1, 2008
- Changes in global and thalamic brain connectivity in LSD-induced altered states of consciousness are attributable to the 5-HT2A receptor Elife October 25, 2018
- Psilocybin-Induced Decrease in Amygdala Reactivity Correlates with Enhanced Positive Mood in Healthy Volunteers Biological Psychiatry April 26, 2014
and 12 more in the library