Tabernaemontana arborea and ibogaine induce paroxysmal EEG activity in freely moving mice: Involvement of serotonin 5-HT1A receptors.
María Eva González-Trujano, Felix Krengel, Ricardo Reyes-Chilpa, Benjamín Villasana-Salazar, José David González-gómez, Fernando Santos-Valencia, Edgar Urbina-Trejo, Adrián Martínez, David Martínez-Vargas
Neurotoxicology March 1, 2022 DOI: 10.1016/j.neuro.2022.01.002 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Interventions | ibogaine voacangine |
| Dose | 30, 56.2, and 100 mg/kg for extract; 30 mg/kg for ibogaine and voacangine |
| Topics | Ibogaine Serotonin |
| Keywords | 5-ht1a EEG Seizures Voacangine Brain electrical activity Brain activity Tabernaemontana arborea Compounds Plant substances Unusual Receptors |
| Citations | 14 |
| Key findings | Tabernaemontana arborea extract at high doses induces abnormal EEG activity partly through ibogaine and serotonin 5-HT1A receptor involvement, but does not modify PTZ-induced seizures. |
Abstract
Several Apocynaceae species, most notably Tabernanthe iboga, Voacanga africana and many Tabernaemontana species, produce ibogan-type alkaloids. Although a large amount of information exists about the Tabernaemontana genus, knowledge concerning chemistry and biological activity remains lacking for several species, especially related to their effects on the central nervous system (CNS). The aim of this study was to evaluate the effect of Tabernaemontana arborea Rose ex J.D.Sm. (T. arborea) hydroalcoholic extract (30, 56.2 and 100 mg/kg, i.p.) and two of its main alkaloids (ibogaine and voacangine, 30 mg/kg, i.p.) on electroencephalographic (EEG) activity alone and in the presence of the chemical convulsant agent pentylenetetrazole (PTZ, 85 mg/kg, i.p.) in mice. EEG spectral power analysis showed that T. arborea extract (56.2 and 100 mg/kg) and ibogaine (30 mg/kg, i.p.) promoted a significant increase in the relative power of the delta band and a significant reduction in alpha band values, denoting a CNS depressant effect. Voacangine (30 mg/kg, i.p.) provoked an EEG flattening pattern. The PTZ-induced seizures were not modified in the presence of T. arborea, ibogaine, or voacangine. However, sudden death was observed in mice treated with T. arborea extract at 100 mg/kg, i.p., combined with PTZ. Because T. arborea extract (100 mg/kg, i.p.) and ibogaine (30 mg/kg, i.p.), but not voacangine (30 mg/kg, i.p.), induced paroxysmal activity in the EEG, both were explored in the presence of a serotonin 5-HT1A receptor antagonist (WAY100635, 1 mg/kg, i.p.). The antagonist abolished the paroxysmal activity provoked by T. arborea (100 mg/kg, i.p.) but not that observed with ibogaine, corroborating the participation of serotonin neurotransmission in the T. arborea effects. In conclusion, high doses of the T. arborea extract induced abnormal EEG activity due in part to the presence of ibogaine and involving serotonin 5-HT1A receptor participation. Nevertheless, other possible constituents and mechanisms might participate in this complex excitatory activity that would be interesting to explore in future studies.
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 4
- Antidepressant- and anxiolytic-like activities and acute toxicity evaluation of the Psilocybe cubensis mushroom in experimental models in mice. Journal of Ethnopharmacology February 10, 2024
- 5-MeO-DMT: An atypical psychedelic with unique pharmacology, phenomenology & risk? Psychopharmacology December 11, 2023
- Main targets of ibogaine and noribogaine associated with its putative anti-addictive effects: A mechanistic overview. Journal of Psychopharmacology December 1, 2023
- Central nervous system activity of a Tabernaemontana arborea alkaloid extract involves serotonergic and opioidergic neurotransmission in murine models. Fitoterapia September 1, 2023
Cites 18
- 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. Brain Research September 19, 1994
- The ibogaine medical subculture. Journal of Ethnopharmacology January 4, 2008
- The Anti-Addiction Drug Ibogaine and the Heart: A Delicate Relation Molecules January 29, 2015
- Ibogaine Detoxification Transitions Opioid and Cocaine Abusers Between Dependence and Abstinence: Clinical Observations and Treatment Outcomes. Frontiers in Pharmacology 2018
- Ibogaine in the treatment of substance dependence. Current Drug Abuse Reviews March 1, 2013
and 13 more in the library