Clinical utility of fMRI in evaluating of LSD effect on pain-related brain networks in healthy subjects.
A Faramarzi, M Fooladi, M Yousef Pour, E Khodamoradi, A Chehreh, S Amiri, M Shavandi, H Sharini
Heliyon August 15, 2024 DOI: 10.1016/j.heliyon.2024.e34401 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Crossover study Peer reviewed |
|---|---|
| Sample size | 20 |
| Population | Healthy volunteers |
| Intervention | Lysergic acid diethylamide (LSD) |
| Topics | LSD |
| Keywords | Hallucinogens Neuroimaging FMRI Brain scanning Brain imaging Pain perception Pain processing Brain connectivity Alff Dcm Functional connectivity Ica Psychedelics LSD Acid |
| Citations | 4 |
| Key points | LSD modulates the pain neural network by altering brain activity and connectivity in pain-processing regions, indicating a neural basis for its pain-relieving effect. |
Abstract
We aimed to evaluate the effect of Lysergic acid diethylamide (LSD) on the pain neural network (PNN) in healthy subjects using functional magnetic resonance imaging (fMRI). Twenty healthy volunteers participated in a balanced-order crossover study, receiving intravenous administration of LSD and placebo in two fMRI scanning sessions. Brain regions associated with pain processing were analyzed by amplitude of low-frequency fluctuation (ALFF), independent component analysis (ICA), functional connectivity and dynamic casual modeling (DCM). ALFF analysis demonstrated that LSD effectively relieves pain due to modulation in the neural network associated with pain processing. ICA analysis showed more active voxels in anterior cingulate cortex (ACC), thalamus (THL)-left, THL-right, insula cortex (IC)-right, parietal operculum (PO)-left, PO-right and frontal pole (FP)-right in the placebo session than the LSD session. There were more active voxels in FP-left and IC-left in the LSD session compared to the placebo session. Functional brain connectivity was observed between THL-left and PO-right and between PO-left with FP-left, FP-right and IC-left in the placebo session. In the LSD session, functional connectivity of PO-left with FP-left and FP-right was observed. The effective connectivity between left anterior insula cortex (lAIC)-lAIC, lAIC-dorsolateral prefrontal cortex (dlPFC) and secondary somatosensory cortex (SII)-dlPFC were significantly different. Finally, the correlation between fMRI biomarkers and clinical pain criteria was calculated. This study enhances our understanding of the LSD effect on the architecture and neural behavior of pain in healthy subjects and provides great promise for future research in the field of cognitive science and pharmacology.
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 4
- Clinical Research on Lysergic Acid Diethylamide (LSD) in Psychiatry and Neuroscience. Pharmaceuticals March 29, 2025
- Psychedelics and the thalamocortical system: A scoping review Pharmacology, Biochemistry, and Behavior July 9, 2026
- Psilocybin acutely reduces low-frequency BOLD power and frequency-specific connectivity bioRxiv April 13, 2026
- Correlation of Ketamine and Classic Psychedelics with Pain-Related Neural Connectivity: A Scoping Review of Clinical Experiments on a Potential Therapeutic Target Concerning Ketamine and Classical Psychedelics Administration for Pain Relief Psychedelic Medicine September 14, 2026
Cites 10
- Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences April 11, 2016
- Hallucinogens in Mental Health: Preclinical and Clinical Studies on LSD, Psilocybin, MDMA, and Ketamine Journal of Neuroscience November 30, 2020
- Distinct acute effects of LSD, MDMA, and d-amphetamine in healthy subjects Neuropsychopharmacology November 16, 2019
- Receptor-informed network control theory links LSD and psilocybin to a flattening of the brain's control energy landscape. Nature Communications October 3, 2022
- d-Lysergic Acid Diethylamide (LSD) as a Model of Psychosis: Mechanism of Action and Pharmacology International Journal of Molecular Sciences November 23, 2016
and 5 more in the library