Effects of repeated lysergic acid diethylamide (LSD) on the mouse brain endocannabinoidome and gut microbiome.
Antonio Inserra, Giada Giorgini, Sebastien Lacroix, Antonella Bertazzo, Jocelyn Choo, Athanasios Markopolous, Emily Grant, Armita Abolghasemi, Danilo de Gregorio, Nicolas Flamand, Geraint Rogers, Stefano Comai, Cristoforo Silvestri, Gabriella Gobbi, Vincenzo Di Marzo
British Journal of Pharmacology March 1, 2023 DOI: 10.1111/bph.15977 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Population | Adult C57BL/6N male mice |
| Intervention | lysergic acid diethylamide (LSD) |
| Duration | 7 days |
| Topics | LSD |
| Keywords | 5-hydroxytryptamine system Endocannabinoidome Gut microbiome Kynurenine Repeated Serotonergic system Sociability Psychedelics LSD Hallucinogens Neuroscience brain chemistry |
| Citations | 38 |
| Key findings | Repeated LSD administration increased sociability and altered hippocampal endocannabinoidome mediators and gut microbiota composition in male mice. |
Abstract
Psychedelics elicit prosocial, antidepressant and anxiolytic effects via neuroplasticity, neurotransmission and neuro-immunomodulatory mechanisms. Whether psychedelics affect the brain endocannabinoid system and its extended version, the endocannabinoidome (eCBome) or the gut microbiome, remains unknown. Adult C57BL/6N male mice were administered lysergic acid diethylamide (LSD) or saline for 7 days. Sociability was assessed in the direct social interaction and three chambers tests. Prefrontal cortex and hippocampal endocannabinoids, endocannabinoid-like mediators and metabolites were quantified via high-pressure liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). Neurotransmitter levels were assessed via HPLC-UV/fluorescence. Gut microbiome changes were investigated by 16S ribosomal DNA sequencing. LSD increased social preference and novelty and decreased hippocampal levels of the N-acylethanolamines N-linoleoylethanolamine (LEA), anandamide (N-arachidonoylethanolamine) and N-docosahexaenoylethanolamine (DHEA); the monoacylglycerol 1/2-docosahexaenoylglycerol (1/2-DHG); the prostaglandins D2 (PGD2 ) and F2α (PGF2α ); thromboxane 2 and kynurenine. Prefrontal eCBome mediator and metabolite levels were less affected by the treatment. LSD decreased Shannon alpha diversity of the gut microbiota, prevented the decrease in the Firmicutes:Bacteroidetes ratio observed in saline-treated mice and altered the relative abundance of the bacterial taxa Bifidobacterium, Ileibacterium, Dubosiella and Rikenellaceae RC9. The prosocial effects elicited by repeated LSD administration are accompanied by alterations of hippocampal eCBome and kynurenine levels, and the composition of the gut microbiota. Modulation of the hippocampal eCBome and kynurenine pathway might represent a mechanism by which psychedelic compounds elicit prosocial effects and affect the gut microbiome.
Comparable studies
Other preclinical and animal studies on LSD, most cited first.
Citations in the library
Cited by 29
- The Bright Side of Psychedelics: Latest Advances and Challenges in Neuropharmacology International Journal of Molecular Sciences January 10, 2023
- Seeking the Psilocybiome: Psychedelics meet the microbiota-gut-brain axis. International journal of clinical and health psychology : IJCHP 2023
- Psychedelics in neuroinflammation: Mechanisms and therapeutic potential Progress in Neuro-Psychopharmacology and Biological Psychiatry January 31, 2025
- Epigenetic mechanisms of rapid-acting antidepressants Translational Psychiatry September 4, 2024
- The immunomodulatory effects of classical psychedelics: A systematic review of preclinical studies Progress in Neuro-Psychopharmacology and Biological Psychiatry September 7, 2024
and 24 more in the library
Cites 31
- mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Science August 19, 2010
- Trial of Psilocybin versus Escitalopram for Depression New England Journal of Medicine April 14, 2021
- Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder JAMA Psychiatry November 4, 2020
- Psychedelics Promote Structural and Functional Neural Plasticity Cell Reports June 1, 2018
- MDMA-assisted therapy for severe PTSD: a randomized, double-blind, placebo-controlled phase 3 study. Nature Medicine June 1, 2021
and 26 more in the library