Dose-dependent LSD effects on cortical/thalamic and cerebellar activity: brain oxygen level-dependent fMRI study in awake rats.
Ashley Ghaw, Alisha Chunduri, Arnold Chang, Richard J. Ortiz, Milena Kozlowska, Praveen P Kulkarni, Craig F. Ferris
Brain Communications 2024 DOI: 10.1093/braincomms/fcae194 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical experimental study Peer reviewed |
|---|---|
| Population | Female and male rats |
| Intervention | Lysergic acid diethylamide |
| Dose | 10 or 100 µg/kg |
| Duration | 30-min window for BOLD signal recording; resting-state functional connectivity data collected approximately 45-min post-injection |
| Topics | LSD Serotonin |
| Keywords | Cerebellar nuclei Psychedelics LSD Neural pathways |
| Citations | 13 |
| Key findings | LSD produced a dose-dependent increase in negative BOLD signal (decreased brain activity) in the prefrontal cortex, thalamus, and hippocampus, while increasing functional connectivity between the thalamus and somatosensory cortex and between the cerebellar nuclei and brainstem areas. |
Abstract
Lysergic acid diethylamide is a hallucinogen with complex neurobiological and behavioural effects. This is the first study to use MRI to follow functional changes in brain activity in response to different doses of lysergic acid diethylamide in fully awake, drug-naive rats. We hypothesized that lysergic acid diethylamide would show a dose-dependent increase in activity in the prefrontal cortex and thalamus while decreasing hippocampal activity. Female and male rats were given intraperitoneal injections of vehicle or lysergic acid diethylamide in doses of 10 or 100 µg/kg while fully awake during the imaging session. Changes in blood oxygen level-dependent signal were recorded over a 30-min window. Approximately 45-min post-injection data for resting-state functional connectivity were collected. All data were registered to rat 3D MRI atlas with 173 brain regions providing site-specific increases and decreases in global brain activity and changes in functional connectivity. Treatment with lysergic acid diethylamide resulted in a significant dose-dependent increase in negative blood oxygen level-dependent signal. The areas most affected were the primary olfactory system, prefrontal cortex, thalamus and hippocampus. This was observed in both the number of voxels affected in these brains regions and the changes in blood oxygen level-dependent signal over time. However, there was a significant increase in functional connectivity between the thalamus and somatosensory cortex and the cerebellar nuclei and the surrounding brainstem areas. Contrary to our hypothesis, there was an acute dose-dependent increase in negative blood oxygen level-dependent signal that can be interpreted as a decrease in brain activity, a finding that agrees with much of the behavioural data from preclinical studies. The enhanced connectivity between thalamus and sensorimotor cortices is consistent with the human literature looking at lysergic acid diethylamide treatments in healthy human volunteers. The unexpected finding that lysergic acid diethylamide enhances connectivity to the cerebellar nuclei raises an interesting question concerning the role of this brain region in the psychotomimetic effects of hallucinogens.
Comparable studies
Other preclinical and animal studies on LSD, most cited first.
Citations in the library
Cited by 9
- Dose-dependent changes in global brain activity and functional connectivity following exposure to psilocybin: a BOLD MRI study in awake rats Frontiers in Neuroscience May 1, 2025
- Psychedelic experiences elicited by serotonergic psychedelics: Molecular mechanisms and functional connectivity changes in the brain Neuroscience & Biobehavioral Reviews December 16, 2025
- Electrophysiological mechanisms of psychedelic drugs: A systematic review. Neuroscience & Biobehavioral Reviews June 1, 2026
- Beyond the toad's kiss: Mapping acute 5-MeO-DMT effects on brain connectivity across sex and dose using awake rat neuroimaging Neuropharmacology March 6, 2026
- Noribogaine altered intrinsic properties of thalamocortical neurons in a sex-dependent manner Progress in Neuro-Psychopharmacology and Biological Psychiatry August 1, 2025
and 4 more in the library
Cites 28
- Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences April 11, 2016
- The Therapeutic Potential of Psychedelic Drugs: Past, Present, and Future. Neuropsychopharmacology April 26, 2017
- Amphetamine, 3,4-Methylenedioxymethamphetamine, Lysergic Acid Diethylamide, and Metabolites of the Catecholamine Neurotransmitters Are Agonists of a Rat Trace Amine Receptor Molecular Pharmacology December 1, 2001
- Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution. Current Biology April 13, 2016
- The Pharmacology of Lysergic Acid Diethylamide: A Review CNS Neuroscience & Therapeutics November 11, 2008
and 23 more in the library