ACS Chemical Neuroscience
December 15, 2022
Michael J. Cunningham, Hailey A. Bock, Inis C. Serrano et al.
65 citations
Ariadne, a non-hallucinogenic analog of the hallucinogen DOM, demonstrates significant therapeutic potential in treating various conditions. In clinical trials, Ariadne led to rapid remission of psychotic symptoms in schizophrenia and improved cognition in elderly patients. It acts as a 5-HT<sub>2A</sub> receptor agonist with modest selectivity for 5-HT<sub>1</sub>, exhibiting lower signaling potency than DOM. Notably, in a Parkinson’s disease model, Ariadne alleviated severe motor deficits comparable to l-DOPA, positioning it as a promising candidate for future psychiatric and neurological therapies.
bioRxiv (Cold Spring Harbor Laboratory)
July 23, 2021
Václav Havel, Andrew C. Kruegel, Benjamin Bechand et al.
3 citations
preprint
A new class of iboga alkaloids, called oxa-iboga, was created by modifying the iboga skeleton to include a benzofuran group. These compounds act as potent kappa opioid receptor agonists but show atypical behavioral effects compared to standard kappa psychedelics. Oxa-noribogaine, a key oxa-iboga compound, demonstrated greater therapeutic efficacy in rat models of opioid use than noribogaine, with no cardiac pro-arrhythmic potential. A single dose produced long-lasting suppression of morphine and fentanyl intake, and a short treatment regimen persistently reduced morphine intake and reinforcing efficacy. It also suppressed drug seeking in relapse models and elevated neurotrophin proteins in brain regions linked to addiction, suggesting targeted neuroplasticity. Oxa-iboga compounds are candidates for a novel pharmacotherapy for opioid use disorder.
Journal of the American Chemical Society
December 26, 2025
Christopher Hwu, Václav Havel, Xavier Westergaard et al.
2 citations
Ibogaine and its main metabolite noribogaine inhibit the vesicular monoamine transporter 2 (VMAT2) with submicromolar potency, as shown in cell-based assays and two-photon microscopy of mouse brain synaptic vesicle clusters. Noribogaine also induces partial serotonin release from synaptic vesicles and binds VMAT2 at a distinct site from the established inhibitor dihydrotetrabenazine. These compounds additionally inhibit plasma membrane monoamine transporters, prominently the serotonin transporter (SERT), and a novel target, organic cation transporter 2 (OCT2). Several iboga analogs display dual inhibition of VMAT2 and SERT with comparable potencies, termed "Synaptic Reuptake Inhibitors" (SynRIs). This profile explains why ibogaine and noribogaine do not induce catalepsy, unlike other VMAT2 inhibitors, and illustrates the complex "matrix pharmacology" of iboga compounds.
ChemRxiv
March 19, 2020
Paola Rodrı́guez, Jessika Urbanavicius, José Pedro Prieto et al.
1 citation
Ibogaine and its main metabolite noribogaine produce antidepressant-like effects in rats in a dose- and time-dependent manner, without altering locomotor activity. Noribogaine's effect is short-lived (30 minutes) and correlates with high brain concentrations (estimated > 8 µM free drug), while ibogaine's effect is significant at 3 hours. At that time, both compounds are present in the brain at concentrations (ibogaine ~0.5 µM, noribogaine ~2.4 µM) that alone cannot produce the same behavioral outcome, suggesting a polypharmacological mechanism underlies their antidepressant-like effects.
Research Square
March 31, 2026
Marcus W. Meinhardt, Ivan Skorodumov, Florian Walter et al.
A compound derived from ibogaine, oxa-noribogaine, reduces alcohol consumption in rats by strengthening learning from negative drinking outcomes. It produces sustained decreases in alcohol intake and relapse-like drinking, matching or exceeding ibogaine's efficacy without detectable motor or cardiac side effects. These effects involve transient changes in prefrontal brain activity, lasting alterations in glutamatergic signaling after aversion-related learning, and normalization of neurotrophic signaling in cortico-striatal circuits. The results generalize across multiple models, genetically diverse animals, and independent study sites, identifying oxa-noribogaine as a promising treatment candidate for alcohol use disorder.
ChemRxiv
October 29, 2018
Soledad Marton, Bruno González, Sebastián Rodríguez et al.
Ibogaine, a psychedelic alkaloid, alters the expression of three neurotrophic factors—GDNF, BDNF, and NGF—in rat brain regions containing dopamine neurons. A single injection of 20 or 40 mg/kg ibogaine increased expression of these factors after 24 hours in a dose- and region-specific manner. The higher dose selectively raised GDNF in the ventral tegmental area and substantia nigra. Both doses increased BDNF in the nucleus accumbens, substantia nigra, and prefrontal cortex, while the higher dose also raised BDNF in the ventral tegmental area. NGF increased in all regions after the higher dose. Mature GDNF protein rose in the ventral tegmental area, and proBDNF increased in the nucleus accumbens. These changes may contribute to ibogaine's anti-addictive properties.