generation run 2026-05-14
97 min completedmodel pipeline-v5plan not recordedrun/8da9773d…Selection
Verification
- record
- seen / partial
- working
The model's own caveats
1 further caveat recorded as free text — readable on the working page
Reproduce
- inputs
- 41 source keys (listed under Sources)
- plan
- not recorded — template version, prompt hash and git SHA are written from 2026-09 onward
- model
- pipeline-v5
- streams
- none — agent transcripts are persisted from 2026-09 onward
25 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | PubMed | ibogaine cardiac toxicity QT prolongation fatalities | 5 | 4 | All are highly relevant to safety section on cardiac toxicity. hERG blockade paper provides mechanistic data. NPIS paper provides UK case series. |
| 2 | PubMed | ibogaine pharmacokinetics noribogaine CYP2D6 metabolism | 4 | 3 | All selected for pharmacokinetics section. Glue 2015 is the only controlled human PK study at low dose with paroxetine inhibition paradigm. |
| 3 | PubMed | Tabernanthe iboga alkaloids ibogaine pharmacology | 15 | 10 | Selected papers most directly addressing ibogaine pharmacology, clinical use, safety, and effects. Discarded Tabernaemontana arborea alkaloid papers and unrelated bisindole studies. |
| 4 | PubMed | Tabernanthe iboga ethnobotany traditional use Africa | 4 | 1 | Only PMID 8145572 is relevant as background on African Apocynaceae traditional uses. Main iboga ethnobotany requires targeted searches. |
| 5 | OpenAlex | Tabernanthe iboga ibogaine | 15 | 6 | Selected landmark citation-rich papers on ibogaine GDNF mechanism, neurotoxicity, pharmacokinetics, and foundational alkaloid chemistry. Discarded general psychedelic paradigm papers and unrelated substance P paper. |
| 6 | PubMed | ibogaine neurotoxicity Purkinje cells cerebellar degeneration | 8 | 5 | Core neurotoxicology papers establishing mechanisms and dose thresholds. Important for safety section. |
| 7 | PubChem | ibogaine | 1 | 1 | Primary alkaloid chemical identity confirmed. |
| 8 | PubChem | noribogaine | 1 | 1 | Primary metabolite chemical identity confirmed. |
| 9 | WebSearch | ibogaine legal status Schedule I DEA United States 2025 2026 | 10 | 3 | Legal status data from advocacy tracker and news sources. |
| 10 | PubChem | ibogamine | 1 | 1 | Confirms ibogamine chemical identity. |
| 11 | WebFetch | — | 1 | 1 | Comprehensive US state legal status data. |
| 12 | OpenAlex | Tabernanthe iboga ethnobotany Bwiti Africa traditional use | 10 | 3 | Critical alkaloid quantification data and Bwiti ethnobotany sources. |
| 13 | WebSearch | Tabernanthe iboga IUCN conservation status endangered overcollection Gabon | 10 | 2 | Conservation and legal harvest context. |
| 14 | PubMed | ibogaine (broad search) | 15 | 10 | All highly relevant - neuroscience mechanisms, newer therapeutic applications, safety considerations. |
| 15 | PubMed | ibogaine opioid addiction treatment clinical study | 12 | 4 | Key clinical efficacy and safety studies selected. |
| 16 | PubMed | ibogaine PTSD traumatic brain injury veterans Stanford | 3 | 2 | Both directly relevant to newer TBI/PTSD indications. |
| 17 | PubChem | tabernanthine | 1 | 1 | Confirms tabernanthine chemical identity. |
| 18 | WebFetch | — | 1 | 1 | Primary authoritative taxonomy source. |
| 19 | ClinicalTrials.gov | ibogaine addiction opioid treatment | 2 | 3 | All relevant clinical trials identified. |
| 20 | OpenAlex | ibogaine cardiac toxicity safety death fatalities | 8 | 3 | Added meta-analysis and systematic review of clinical trials. |
| 21 | PubMed | ibogaine detection urine plasma drug screening | 1 | 1 | Only relevant detection paper found. |
| 22 | Multiple | Ibogaine dose ranges from clinical studies | 5 | 4 | Dose data triangulated across multiple clinical sources. |
| 23 | Multiple API sources | Ibogaine alkaloid profile, pharmacokinetics, mechanism synthesis | 20 | 3 | Core pharmacological data for research output. |
| 24 | Multiple API sources | Legal status and conservation synthesis | 10 | 4 | Legal status section data. |
| 25 | Knuijver et al. 2022 | QTc clinical data ibogaine safety | 1 | 3 | Most comprehensive clinical safety data point. |
89 claims by section — every cited sentence, checked against its source
safety37 · 12 ok
Ibogaine and noribogaine block the hERG potassium channel (I_Kr), which governs cardiac repolarizationsupported
hERG IC50: ibogaine (semisynthesis) 4.09 µM, ibogaine (extraction) 3.53 µM, noribogaine 2.86 µM. s12012-015-9311-5
Published IC₅₀ values for hERG blockade are: ibogaine 3.53 μM, noribogaine 2.86 μM, and voacangine 2.25 μMsupported
hERG IC50: ibogaine (extraction) 3.53 µM, noribogaine 2.86 µM, voacangine 2.25 µM. s12012-015-9311-5
By comparison, 18-methoxycoronaridine (18-MC), an experimental safer structural-analog, shows IC₅₀ greater than 50 μM.supported
18-MC IC50 >50 µM. s12012-015-9311-5
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Fatal cardiac arrhythmias attributed to ibogaine have been reported, with deaths primarily occurring in unsupervised settings where continuous cardiac monitoring was absentsupported
life-threatening complications and sudden death cases accumulating. Ibogaine propensity to induce cardiac arrhythmias. molecules20022208
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
In rats, ibogaine causes indirect (trans-synaptic) excitotoxic degeneration of Purkinje cells in the cerebellar vermis via activation of the olivocerebellar projectionsupported
Inferior olive ablation prevents ibogaine-induced Purkinje cell degeneration. Ibogaine activates inferior olivary neurons causing glutamate release at climbing fibers — indirect excitotoxic mechanism. pmid:9348351
In rats, ibogaine causes indirect (trans-synaptic) excitotoxic degeneration of Purkinje cells in the cerebellar vermis via activation of the olivocerebellar projectionsupported
Both ibogaine and harmaline caused selective degeneration of Purkinje cells in rat cerebellar vermis. Mechanism: sustained activation of inferior olivary neurons leading to excitotoxic damage via climbing fiber glutamate. pmid:8377927
Dose-response studies established 100 mg/kg (i.p.) as consistently neurotoxic and 25 mg/kg as the no-observed-adverse-effect level (NOAEL)supported
Purkinje cell degeneration at 75-100 mg/kg (rats). NOAEL 25 mg/kg. pmid:10966515
At 40 mg/kg — within the anti-addictive dose range in rodents — ibogaine did not cause Purkinje cell degeneration, suggesting that anti-addictive and neurotoxic properties may be dissociable at the dose level.supported
40 mg/kg ibogaine (anti-addictive dose) produced no Purkinje cell degeneration. High doses (100 mg/kg) caused degeneration in lateral/intermediate cerebellum. pmid:8930373
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
In a controlled human pharmacokinetic study, pretreatment with paroxetine (a potent cyp2d6 inhibitor) substantially elevated ibogaine AUC, with a strong correlation (r = 0.82) between CYP2D6 phenotype and ibogaine exposuresupported
Paroxetine doubles active moiety exposure. CYP2D6 phenotype correlated with ibogaine AUC r=0.82. jcph.471
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Any history of QT prolongation, cardiac arrhythmia, structural heart disease, or heart failure precludes ibogaine administration due to the established hERG blockade mechanism.supported
hERG IC50: ibogaine (extraction) 3.53 µM, noribogaine 2.86 µM. Voltage-dependent low-affinity blockade. s12012-015-9311-5
Any history of QT prolongation, cardiac arrhythmia, structural heart disease, or heart failure precludes ibogaine administration due to the established hERG blockade mechanism.supported
Ibogaine treatment of OUD patients induces clinically relevant but reversible QTc prolongation, bradycardia, and severe ataxia. add.15448
Individuals with reduced CYP2D6 activity experience approximately double the active moiety exposure, substantially increasing cardiac and neurological adverse event risksupported
Paroxetine doubles active moiety exposure. Genotyping recommended before ibogaine treatment. jcph.471
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
neuroscience17 · 4 ok
NMDA antagonism: Attenuates opioid and stimulant withdrawal through glutamatergic normalizationsupported
Ibogaine and noribogaine bind kappa opioid and NMDA receptors and serotonin uptake sites. j.1749-6632.1998.tb08237.x
Claim in neuroscience — inconclusiveinconclusiveworking →
In a controlled study of a single 20 mg dose in 21 healthy volunteers, CYP2D6 activity correlated strongly with ibogaine exposure (r = 0.82)supported
CYP2D6 phenotype correlated with ibogaine AUC r=0.82. jcph.471
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
Multiple converging pathways have been identified:supported
Ibogaine and noribogaine bind kappa opioid and NMDA receptors and serotonin uptake sites; ibogaine also sigma-2 and nicotinic receptors. j.1749-6632.1998.tb08237.x
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
Claim in neuroscience — inconclusiveinconclusiveworking →
Mystical experience intensity during the ibogaine session predicted both PTSD symptom improvement and EEG changes.partially supported
Greater mystical experiences during ibogaine associated with larger PTSD reductions immediately and 1 month post-treatment. MEQ30 by time interaction significant. j.jad.2025.120722
summary13 · 3 ok
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
The 2024 MISTIC trial demonstrated large effect sizes for PTSD and traumatic brain injury in veterans, and a 2026 US executive order directed accelerated regulatory review — though ibogaine remains Schedule I at the US federal level.supported
MISTIC: 30 male SOF veterans with TBI. Significant improvements in functioning, PTSD, depression, anxiety at 1 month. No SAEs. Magnesium co-administration. s41591-023-02705-w
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Fatal arrhythmias have been reported, predominantly in unsupervised settingssupported
life-threatening complications and sudden death cases accumulating. Ibogaine propensity to induce cardiac arrhythmias. molecules20022208
Claim in summary — inconclusiveinconclusiveworking →
CYP2D6 poor metabolizers face approximately double the active moiety exposure, making pharmacogenomic screening a prerequisite for safe administrationsupported
Paroxetine doubles active moiety exposure. Genotyping recommended before ibogaine treatment. jcph.471
Claim in summary — inconclusiveinconclusiveworking →
preparations9 · 1 ok
Claim in preparations — inconclusiveinconclusiveworking →
Claim in preparations — inconclusiveinconclusiveworking →
Claim in preparations — inconclusiveinconclusiveworking →
Claim in preparations — inconclusiveinconclusiveworking →
Claim in preparations — inconclusiveinconclusiveworking →
The MISTIC study (NCT04313712) administered ibogaine with magnesium co-supplementation as a cardiac risk mitigation strategy in 30 male special operations veterans with traumatic brain injurysupported
MISTIC: 30 male SOF veterans with TBI. No SAEs. Magnesium co-administration. NCT04313712. s41591-023-02705-w
Claim in preparations — inconclusiveinconclusiveworking →
Claim in preparations — inconclusiveinconclusiveworking →
Claim in preparations — inconclusiveinconclusiveworking →
alkaloid-profile6 · 1 ok
Noribogaine (12-hydroxyibogamine; C₁₉H₂₄N₂O; MW 296.4 g/mol) is formed in vivo by cyp2d6-mediated O-demethylation of ibogainesupported
CYP2D6 mediates conversion of ibogaine to noribogaine. jcph.471
Claim in alkaloid-profile — inconclusiveinconclusiveworking →
Claim in alkaloid-profile — inconclusiveinconclusiveworking →
Claim in alkaloid-profile — inconclusiveinconclusiveworking →
Claim in alkaloid-profile — inconclusiveinconclusiveworking →
Claim in alkaloid-profile — inconclusiveinconclusiveworking →
history6 · 0 ok
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
Claim in history — inconclusiveinconclusiveworking →
botanical-overview1 · 0 ok
Claim in botanical-overview — inconclusiveinconclusiveworking →