Frontiers in pharmacology
January 1, 2018
Joaquín González, José P Prieto, Paola Rodríguez et al.
31 citations
Ibogaine, a psychedelic alkaloid with anti-addictive properties, acutely increases wakefulness and suppresses REM sleep in rats. In a study with polysomnographic recordings over six hours, rats given ibogaine (20 or 40 mg/kg) spent more time awake and less time in slow wave sleep and REM sleep compared to controls. REM sleep latency increased with the higher dose. The wake-promoting and slow wave sleep effects occurred in the first two hours, while REM suppression lasted throughout the recording. Lower doses increased locomotion; higher doses caused tremor and flat body posture. Head shake response, linked to 5HT2A receptor activation, was unchanged. The findings suggest ibogaine produces a waking state with prolonged REM suppression and a dose-dependent motor profile.
ACS pharmacology & translational science
April 9, 2021
Joaquín González, Matías Cavelli, Santiago Castro-Zaballa et al.
26 citations
Ibogaine, a psychedelic alkaloid with anti-addictive potential, produces vivid, dream-like experiences while awake. Analyzing intracranial electroencephalograms in rats, ibogaine-induced wakefulness showed gamma oscillations with greater power than control levels but reduced coherence and complexity. This gamma activity profile resembled that of natural REM sleep, providing biological evidence linking the psychedelic state to REM sleep and advancing understanding of ibogaine's oneirogenic effects.
The European journal of neuroscience
March 1, 2022
Claudia Pascovich, Santiago Castro-Zaballa, Pedro A M Mediano et al.
16 citations
Neural complexity, measured by the Lempel-Ziv (LZ) compression algorithm, is lowest during NREM sleep and similar during REM sleep and wakefulness in cats with intracranial electrodes. Under subanaesthetic doses of ketamine (5, 10, and 15 mg/kg), complexity follows an inverted U-shaped curve in some electrodes, primarily in prefrontal cortex, rising at low doses and falling as doses approach anaesthetic levels. The variability in the ketamine dose-response curve across cats and cortices was larger than across sleep stages, highlighting differential local dynamics. These results replicate findings in humans and other species, showing neural complexity is sensitive to changes in conscious state.
International journal of molecular sciences
January 5, 2024
Sofía Villalba, Bruno González, Stephanie Junge et al.
9 citations
Noribogaine, the primary metabolite of ibogaine, produces sexually dimorphic effects in mice, with some responses depending on the 5-HT2A receptor. A single 40 mg/kg dose reduced locomotion in male but not female wild-type mice. Gene expression of immediate early genes and glutamate receptors differed by sex and genotype. 5-HT2A receptor mRNA increased in the medial prefrontal cortex after noribogaine at 10 mg/kg in males and 40 mg/kg in females. Electrophysiology showed that 40 mg/kg reduced NMDA-mediated postsynaptic current density in layer V pyramidal neurons of the medial prefrontal cortex only in male wild-type mice, an effect absent in 5-HT2A receptor knockout males and all females. The genetic removal of the 5-HT2A receptor blunted noribogaine's effects on NMDA synaptic transmission.
bioRxiv Preprint Server
June 25, 2021
Claudia Pascovich, Santiago Castro-Zaballa, Pedro A.M. Mediano et al.
7 citations
preprint
Neural complexity, measured by the Lempel-Ziv compression algorithm, is lowest during NREM sleep and similar during REM sleep and wakefulness in cats with intracranial electrodes. Under subanesthetic doses of ketamine (5, 10, and 15 mg/kg), complexity follows an inverted U-shaped curve in some electrodes, especially in prefrontal cortex, rising at low doses and falling as doses approach anesthetic levels. Variability in the ketamine dose-response across cats and cortices is larger than sleep-stage differences, revealing distinct local dynamics. These results replicate findings in humans and other species, showing neural complexity is sensitive to conscious state changes and dose-dependent ketamine effects.
bioRxiv (Cold Spring Harbor Laboratory)
June 29, 2020
Joaquín González, Matías Cavelli, Santiago Castro‐zaballa et al.
5 citations
preprint
Ibogaine, a psychedelic alkaloid with anti-addictive properties, produces a waking state that shares brain-wave traits with REM sleep. In rats, ibogaine increased gamma oscillation power in the brain but made those oscillations less coherent and less complex than normal waking levels. This pattern mirrors REM sleep features within the gamma frequency band, providing biological evidence for the long-standing hypothesis that ibogaine induces a dream-like state while awake—a phenomenon called oneirogenesis. The findings offer an empirical basis for understanding how ibogaine's unique subjective effects may contribute to its anti-addictive potential.
Sleep
May 26, 2025
Alejandra Mondino, Amir Jadidian, Brandon A Toth et al.
4 citations
The preoptic area of the hypothalamus, long thought to only promote sleep, contains glutamatergic neurons (MLPO_VGLUT2) that actually drive wakefulness and suppress REM sleep. Using fiber photometry in mice, these neurons were highly active during REM sleep, wakefulness, and brief arousals, but minimally active during non-REM sleep. Chemogenetic stimulation of MLPO_VGLUT2 inhibited REM sleep onset, independent of non-REM fragmentation caused by hypothermia, and blocked the REM sleep rebound normally seen after total sleep deprivation. Chemogenetic inhibition increased REM sleep time only during the light phase. Mapping showed these neurons project to brain regions that promote wakefulness and inhibit REM sleep. The authors conclude that MLPO_VGLUT2 powerfully suppress REM sleep, and their overactivation disrupts REM recovery.
Behavioural brain research
January 5, 2025
Santiago Castro-Zaballa, Joaquín González, Matías Cavelli et al.
4 citations
In cats, high-frequency oscillations (HFO, >100 Hz) in the brain's electrical activity are linked to breathing during wakefulness but not during sleep. A sub-anesthetic dose of ketamine increases the power of these HFO, and they remain tied to the inhalation phase of respiration. The enhanced HFO appear to originate in the olfactory bulb and travel to the prefrontal cortex. Blocking the nostrils reduces the ketamine-enhanced HFO in both regions. Auditory stimulation does not affect these oscillations. The findings suggest that ketamine's enhancement of respiration-coupled HFO may disrupt cortical information processing, potentially contributing to its neuropsychiatric effects.
Psychopharmacology
July 1, 2024
Juan Pedro Castro-Nin, Diego Serantes, Paola Rodríguez et al.
4 citations
Noribogaine, the main metabolite of the psychedelic ibogaine, promotes wakefulness while reducing slow-wave sleep and blocking REM sleep in rats, according to polysomnographic recordings. This pattern of sleep/wake alterations is similar to that previously reported for ibogaine itself. The findings provide new evidence on how iboga alkaloids act in the brain, suggesting that noribogaine contributes to the sleep-suppressing effects observed after ibogaine administration.
Progress in Neuro-Psychopharmacology and Biological Psychiatry
August 1, 2025
Sofía Villalba, Sofia Bosch, Lucia di Constanzo et al.
1 citation
Noribogaine, the primary metabolite of the atypical psychedelic ibogaine, alters thalamic calcium channel gene expression and current density in mice in a sex- and 5-HT2A receptor-dependent manner. A single injection of 10 mg/kg noribogaine increased CACNA1g (T-type) mRNA expression only in wild-type males and knockout females, indicating receptor- and sex-specific effects. The same dose increased CACNA1a (P/Q-type) expression in both sexes and decreased HCN2 expression in females of both genotypes but only in knockout males. Bath-applied noribogaine (50 μM) blocked T-type calcium current density only in knockout females, not in wild-type females or males. Baseline calcium current density was also higher in female ventrobasal neurons, further suggesting sex-dependent differences.
bioRxiv (Cold Spring Harbor Laboratory)
July 28, 2023
Juan Pedro Castro‐nin, Diego Serantes, Paola Rodrı́guez et al.
1 citation
preprint
Noribogaine, the main metabolite of the psychedelic ibogaine, promotes wakefulness and reduces slow-wave sleep while completely blocking REM sleep in rats. These sleep-wake alterations mirror those caused by ibogaine itself, suggesting that noribogaine is responsible for the sleep-suppressing effects previously attributed to ibogaine. The findings point to serotonin reuptake inhibition as a likely mechanism underlying the wake-promoting and REM sleep-suppressing actions of both compounds.
Pharmacology Biochemistry and Behavior
July 9, 2026
Sofía Villalba, Agustín Martínez Christensen, Lucia di Costanzo et al.
Psychedelics show promise as therapeutic interventions for depression, terminal illnesses, substance use disorder, neurodegenerative diseases, trauma, and obsessive-compulsive disorder. Research on psychedelics has advanced understanding of the neurobiological mechanisms behind the 'psychedelic state of consciousness' and both physiological and pathological thalamocortical functioning. Several psychiatric conditions—such as depression, schizophrenia, bipolar disorder, and autism—involve alterations in the thalamocortical system, so deeper understanding of thalamic function could significantly impact psychedelic research and biological psychiatry. This scoping review (using the PRISMA method) synthesizes preclinical and clinical evidence on effects of psychedelics (NMDA receptor antagonists, serotonin 2A receptor agonists, and mixed-pharmacology compounds like iboga alkaloids) on the thalamocortical system, suggesting its importance for clinical practice and understanding psychedelic neurobiology.