The Nonclassic Psychedelic Ibogaine Disrupts Cognitive Maps.
Victorita E. Ivan, David P Tomàs-Cuesta, Ingrid M. Esteves, Davor Curic, Majid Mohajerani, Bruce L McNaughton, Joern Davidsen, Aaron J. Gruber
Biological Psychiatry Global Open Science 2024 DOI: 10.1016/j.bpsgos.2023.07.008 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Head-fixed mice running on a treadmill |
| Intervention | Ibogaine |
| Dose | 40 mg/kg intraperitoneally |
| Topics | Ibogaine |
| Keywords | Neuronal avalanches Path integration Psychedelics Retrosplenial cortex Compounds Substances Neurocognition Cognitive map Brain representations Neural activity patterns Brain function Spatial navigation Internal navigation Infer position Spatial awareness Neural networks Network dynamics |
| Citations | 7 |
| Key findings | Ibogaine destabilized the cognitive map in the retrosplenial cortex when mice had to infer position between tactile landmarks, increasing neural activity rates and disrupting correlation structure. |
Abstract
The ability of psychedelic compounds to profoundly alter mental function has been long known, but the underlying changes in cellular-level information encoding remain poorly understood. We used two-photon microscopy to record from the retrosplenial cortex in head-fixed mice running on a treadmill before and after injection of the nonclassic psychedelic ibogaine (40 mg/kg intraperitoneally). We found that the cognitive map, formed by the representation of position encoded by ensembles of individual neurons in the retrosplenial cortex, was destabilized by ibogaine when mice had to infer position between tactile landmarks. This corresponded with increased neural activity rates, loss of correlation structure, and increased responses to cues. Ibogaine had surprisingly little effect on the size-frequency distribution of network activity events, suggesting that signal propagation within the retrosplenial cortex was largely unaffected. Taken together, these data support proposals that compounds with psychedelic properties disrupt representations that are important for constraining neocortical activity, thereby increasing the entropy of neural signaling. Furthermore, the loss of expected position encoding between landmarks recapitulated effects of hippocampal impairment, suggesting that disruption of cognitive maps or other hippocampal processing may be a contributing mechanism of discoordinated neocortical activity in psychedelic states.
Comparable studies
Other preclinical and animal studies on ibogaine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Noncompetitive Functional Inhibition at Diverse, Human Nicotinic Acetylcholine Receptor Subtypes by Bupropion, Phencyclidine, and Ibogaine TE671/RD cells (human muscle-type nAChR) and SH-SY5Y neuroblastoma cells (human... | 1999 | In vitro study | |
| Degeneration of Purkinje cells in parasagittal zones of the cerebellar vermis after treatment with ibogaine or harmaline. Ibogaine- or harmaline-treated rats | 1993 | Experimental animal study | |
| Effects and aftereffects of ibogaine on morphine self-administration in rats. Rats | 1991 | Preclinical experimental study | |
| Effects of iboga alkaloids on morphine and cocaine self-administration in rats: relationship to tremorigenic effects and to effects on dopamine release in nucleus accumbens and striatum. Rats | 1994 | Experimental study | |
| Glial Cell Line-Derived Neurotrophic Factor Mediates the Desirable Actions of the Anti-Addiction Drug Ibogaine against Alcohol Consumption Rats | 2005 | Experimental study |
Citations in the library
Cited by 7
- Changes in functional connectivity preserve scale-free neuronal and behavioral dynamics Physical review. E November 2, 2023
- Psilocybin reduces functional correlation and the encoding of spatial information by neurons in mouse retrosplenial cortex European Journal of Neuroscience October 4, 2024
- Not Losing Momentum: Cross-Sectional Insights into Ibogaine Clinical Trials. Journal of Psychoactive Drugs April 18, 2025
- Psilocybin reduces functional connectivity and the encoding of spatial information by neurons in mouse retrosplenial cortex April 22, 2024
- Psychedelics and Autism Therapy: A Review of Current Research and Future Directions Current Issues in Molecular Biology April 18, 2026
and 2 more in the library
Cites 31
- 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
- Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences April 11, 2016
- Classic psychedelics: An integrative review of epidemiology, therapeutics, mystical experience, and brain network function. Pharmacology & Therapeutics May 1, 2019
- Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels Neuropsychopharmacology January 26, 2019
and 26 more in the library