generation run 2026-05-07
87 min completedmodel pipeline-v5plan not recordedrun/647f0c99…Selection
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The model's own caveats
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Reproduce
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18 searches — query, source, results, what was kept and why
| # | source | query | seen | kept | rationale |
|---|---|---|---|---|---|
| 1 | ClinicalTrials.gov | harmaline | 3 | 1 | No harmaline-specific trials; ayahuasca trial most relevant |
| 2 | PubChem | harmaline | 1 | 1 | Primary chemical identity data for the substance |
| 3 | PubMed | harmaline pharmacokinetics human bioavailability metabolism | 5 | 3 | Pharmacokinetic and metabolic data for harmaline |
| 4 | PubMed | harmaline MAO-A inhibition IC50 Ki reversible selective | 1 | 1 | Direct IC50 data for MAO-A inhibition by harmaline |
| 5 | PubMed | harmaline essential tremor model cerebellar olivary | 10 | 3 | Tremor model papers clarify harmaline's neurological mechanisms |
| 6 | OpenAlex | harmaline monoamine oxidase inhibitor pharmacology | 10 | 4 | High citation count = landmark papers on harmaline/ayahuasca pharmacology |
| 7 | PubMed | harmaline pharmacology mechanism of action MAO inhibitor | 15 | 6 | Selected articles with direct pharmacological data for harmaline |
| 8 | ClinicalTrials.gov | harmaline | 3 | 1 | No direct harmaline trials found; ayahuasca trials most relevant |
| 9 | PubMed | harmaline beta-carboline 5-HT2A serotonin receptor hallucinogenic binding | 3 | 2 | Receptor binding data and hallucinogenic mechanism evidence |
| 10 | Web | harmaline discovery isolation history Goebel Fischer | 5 | 1 | Historical context for discovery narrative |
| 11 | Erowid / SyrianRue.org | harmaline legal status scheduling | 2 | 2 | Best available sources for multi-jurisdiction legal status of harmaline |
| 12 | PubMed | get_pubmed_article 20036304 | 1 | 1 | Quantitative alkaloid content data and MAO-A inhibition confirmation |
| 13 | PubMed | Peganum harmala beta-carboline alkaloids harmaline harmine pharmacology review | 2 | 2 | Comprehensive reviews covering multiple harmaline pharmacological activities |
| 14 | PubMed | harmaline CYP1A2 CYP2D6 metabolism cytochrome inhibition | 1 | 1 | Critical metabolic pathway data for harmaline |
| 15 | PubChem REST API | CID 3564 SMILES and synonyms | 1 | 3 | Complete chemical identity verification |
| 16 | Multiple sources · absence | harmaline dose duration data compilation | 0 | 0 | Gap documentation - no pure human dose data available in published literature |
| 17 | PubMed | harmaline Banisteriopsis neural neurogenesis | 1 | 1 | Critical neuroplasticity/neurogenesis data for harmaline |
| 18 | Web / Erowid / SyrianRue.org | harmaline legal status Australia Canada France UK | 2 | 2 | Definitive legal status by jurisdiction |
81 claims by section — every cited sentence, checked against its source
safety20 · 11 ok
At pharmacological doses used for the tremor model (20 mg/kg i.p. in rats), harmaline produces significant cerebellar neurotoxicity at 24 hours: granule cell loss, Purkinje cell apoptosis (caspase-3-mediated), and inferior olivary neuron damagesupported
Harmaline 20 mg/kg i.p. in rats causes tremor plus cerebellar granule/Purkinje cell loss and inferior olivary neuron apoptosis via caspase-3. j.neuropharm.2011.05.015
Claim in safety — inconclusiveinconclusiveworking →
Harmaline possesses vasorelaxant properties that may moderate the pressor response.supported
Review of harmaline pharmacological effects: antileishmanial, antimicrobial, antiplatelet, antiplasmodial, antitumoral, hypothermic, vasorelaxant. j.ejphar.2013.05.003
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
The anxiolytic properties demonstrated at low doses in animal models (2 mg/kg i.p.) suggest a dose-dependent bidirectional effect on anxiety, with anxiolysis at lower doses and potential anxiogenesis at higher doses.partially supported
Harmaline 2 mg/kg shows anxiolytic-like effects in elevated plus maze; synergistic with mGluR group III antagonist CPPG. j.neulet.2025.138157
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
The emetic properties of ayahuasca preparations (serotonergic vagal stimulation producing nausea and vomiting at elevated doses) function as an intrinsic dose-limiting mechanism that reduces compulsive escalation.supported
Ritualistic use minimizes overdose risk via vomiting/diarrhea. 02791072.2015.1013202
Yu reviewed β-carboline drug-drug interactions and concluded that interactions with indolealkylamine agents could occur additively at the pharmacokinetic and dynamic levels, leading to severe or even fatal serotonin toxicitysupported
Beta-carboline MAOIs can cause fatal serotonin toxicity in DDIs. s12248-008-9028-5
Claim in safety — inconclusiveinconclusiveworking →
CYP2D6 pharmacokinetic interaction: Harmaline's high-affinity CYP2D6 metabolism (Km = 1.4 µM) means that CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion, quinidine, haloperidol) would significantly increase harmaline plasma levels and prolong its duration of actionsupported
CYP2D6 (50%) and CYP1A2 (20%) are major isozymes for harmaline O-demethylation. CYP2D6 Km = 1.4 uM. CYP2D6 polymorphism affects harmaline pharmacology and toxicology. pmid:12649384
CYP2D6 pharmacokinetic interaction: Harmaline's high-affinity CYP2D6 metabolism (Km = 1.4 µM) means that CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion, quinidine, haloperidol) would significantly increase harmaline plasma levels and prolong its duration of actionsupported
CYP2D6 important in IAA metabolism. Beta-carboline MAOIs can cause fatal serotonin toxicity in DDIs. s12248-008-9028-5
Tryptamine potentiation: Harmaline potentiates the oral bioavailability and psychoactive intensity of DMT and likely other orally administered tryptamines (5-MeO-DMT, bufotenin, psilocybin/psilocin) by inhibiting first-pass MAO-A degradationsupported
Beta-carbolines are reversible MAO inhibitors enabling oral DMT activity. pmid:6587171
Tryptamine potentiation: Harmaline potentiates the oral bioavailability and psychoactive intensity of DMT and likely other orally administered tryptamines (5-MeO-DMT, bufotenin, psilocybin/psilocin) by inhibiting first-pass MAO-A degradationsupported
Predominantly peripheral MAO inhibition. pmid:12660312
Claim in safety — inconclusiveinconclusiveworking →
CYP2D6 poor metabolizer status — substantially elevated harmaline exposure; effect amplification and prolonged duration expected.supported
CYP2D6 polymorphism affects harmaline pharmacology and toxicology. pmid:12649384
Cardiovascular disease — although harmaline's cardiovascular effects appear modest in healthy volunteers, the absence of safety data in cardiovascular-compromised populations warrants caution.supported
Double-blind placebo-controlled trial. Ayahuasca contains harmaline, harmine, tetrahydroharmine plus DMT. pmid:12660312
Claim in safety — inconclusiveinconclusiveworking →
Claim in safety — inconclusiveinconclusiveworking →
pharmacology17 · 16 ok
Using kynuramine as substrate, Herraiz reported an IC₅₀ of 20 nM for harmaline at MAO-A — placing it among the most potent reversible MAO-A inhibitors characterized, more potent than toloxatone and moclobemide, and approximately comparable to the irreversible inhibitor clorgyline (IC₅₀ ~16 nM under identical conditions)partially supported
Harmaline IC50 for MAO-A = 20 nM under experimental conditions; reversible MAO-A inhibitor. More potent than toloxatone and moclobemide. dta.1530
Harmaline exhibits negligible MAO-B inhibitory activity at pharmacologically relevant concentrations.supported
MAO-B poorly inhibited. j.fct.2009.12.019
McKenna et al. established this mechanism as the canonical explanation for ayahuasca's oral psychoactivity: harmaline and harmine inhibit peripheral MAO-A, enabling orally inactive DMT to reach systemic circulation intact.supported
Beta-carbolines are reversible MAO inhibitors enabling oral DMT activity. pmid:6587171
CaV3.1 T-type calcium channel potentiation in inferior olivary neurons produces synchronous 4–10 Hz neuronal oscillations propagating through olivocerebellar circuitry — the established mechanism for harmaline-induced tremorsupported
Harmaline potentiates CaV3.1 T-type Ca2+ channels in inferior olive, causing synchronous 4-10 Hz oscillations that underlie harmaline-induced tremor. pnas.1002995107
Voltage-gated sodium channel Nav1.7 blockade occurs at higher concentrations (IC₅₀ = 35.5 µM for peak current)supported
Harmaline inhibits Nav1.7 channel; IC50 35.5 uM. ijms26104636
Weak 5-HT₂A receptor binding (Ki ≈ 42.5 µM) is orders of magnitude less potent than classical psychedelics but shows functional engagement in in vivo alkylation protection assayssupported
Harmaline 5-HT2A affinity = 42.5 uM (micromolar range - weak). Despite low affinity, harmaline provided significant protection from receptor alkylation. pmid:9476990
Harmaline also attenuates dopamine transporter (DAT) activity and promotes dopamine release in striatal synaptosomes, and fully substitutes for the imidazoline I₂-site ligand 2-BFI in drug discrimination — an activity linked to its MAO-A inhibition rather than direct receptor binding.partially supported
Harmaline inhibits MAO-A and significantly attenuates DAT activity and dopamine uptake; also promotes dopamine release in synaptosomes. acschemneuro.4c00789
Harmaline also attenuates dopamine transporter (DAT) activity and promotes dopamine release in striatal synaptosomes, and fully substitutes for the imidazoline I₂-site ligand 2-BFI in drug discrimination — an activity linked to its MAO-A inhibition rather than direct receptor binding.partially supported
Harmaline substitutes for imidazoline I2 site ligand 2-BFI in drug discrimination studies; associated with reversible MAO-A inhibition rather than MAO-B. pmid:11877331
At low doses (2 mg/kg i.p. in mice), harmaline produces anxiolytic-like effects synergistic with group III metabotropic glutamate receptor (mGluR) antagonismsupported
Harmaline 2 mg/kg shows anxiolytic-like effects in elevated plus maze; synergistic with mGluR group III antagonist CPPG. j.neulet.2025.138157
At 5 mg/kg in mice, it attenuates inflammatory pain and paw edema via COX inhibition, nitric oxide pathway modulation, and Nrf-2 antioxidant signaling, with reductions in IL-1β levels and oxidative stress markers.supported
Harmaline 5 mg/kg reduces pain and inflammation in mice via COX and nitric oxide pathways, antioxidant Nrf-2 activation, IL-1beta reduction. s00210-025-04220-w
Harmaline is absorbed across intestinal epithelium by transcellular passive diffusion, with additional contribution from pH- and Na⁺-dependent OATP and OCT/OCTN-mediated transportsupported
Harmaline absorbed by transcellular passive diffusion and pH/Na+-dependent mechanism via OATPs/OCTs. fphar.2017.00541
Unlike harmine, harmaline is not a substrate for the efflux transporter MRP2, contributing to its higher oral bioavailability and greater metabolic stability (CLint approximately 1.49-fold lower than harmine)partially supported
More metabolically stable than harmine. Not an MRP2 substrate. fphar.2017.00541
Bioaccessibility after simulated gastrointestinal digestion has been confirmed without cytotoxicity at tested concentrations.supported
Harmaline bioaccessible after in vitro digestion and bioavailable in Caco-2 model. No cytotoxicity at tested concentrations. molecules26185555
The principal metabolic pathway is O-demethylation to harmalol, mediated by CYP2D6 (~50% contribution; Km = 1.4 µM, Kcat = 39.9 min⁻¹) and CYP1A2 (~20% contribution; Km = 13.3 µM), with minor contributions from CYP1A1, CYP2C9, and CYP2C19partially supported
CYP2D6 (50%) and CYP1A2 (20%) are major isozymes for harmaline O-demethylation to harmalol in human liver microsomes. CYP2D6 Km = 1.4 uM for harmaline (among highest turnover ever reported). pmid:12649384
Claim in pharmacology — inconclusiveinconclusiveworking →
In the ayahuasca context, Riba et al. reported DMT Tmax at approximately 1.5 hours with subjective effects peaking at 1.5–2 hours and lasting 4–5 hours total, though these parameters reflect the combined brew pharmacology rather than isolated harmaline.partially supported
Subjective effects peaked 1.5-2h. pmid:12660312
In the ayahuasca context, Riba et al. reported DMT Tmax at approximately 1.5 hours with subjective effects peaking at 1.5–2 hours and lasting 4–5 hours total, though these parameters reflect the combined brew pharmacology rather than isolated harmaline.partially supported
DMT+harmine combinations induced dose-dependent effects lasting 4-5h in 16 healthy volunteers. j.biopha.2025.117908
summary10 · 7 ok
Harmaline (7-methoxy-1-methyl-4,9-dihydro-3H-pyrido[3,4-b]indole) is a naturally occurring β-carboline alkaloid and potent reversible inhibitor of monoamine oxidase A (RIMA), with an in vitro IC₅₀ of 20 nM at MAO-A — comparable to clorgyline and substantially more potent than clinical RIMAs such as moclobemidepartially supported
Harmaline IC50 for MAO-A = 20 nM under experimental conditions; reversible MAO-A inhibitor. More potent than toloxatone and moclobemide. dta.1530
Claim in summary — inconclusiveinconclusiveworking →
Claim in summary — inconclusiveinconclusiveworking →
Harmaline's primary action is reversible competitive inhibition of MAO-A (IC₅₀ = 20 nM), with negligible MAO-B activitypartially supported
Seed extracts potently inhibit MAO-A (IC50 27 ug/L), predominantly attributed to harmaline and harmine. Competitive/reversible MAO-A inhibition. MAO-B poorly inhibited. j.fct.2009.12.019
Secondary mechanisms include potentiation of CaV3.1 T-type calcium channels in inferior olivary neurons — the established substrate for harmaline-induced tremor — and weak binding at 5-HT₂A receptors (Ki ≈ 42.5 µM)partially supported
Harmaline potentiates CaV3.1 T-type Ca2+ channels in inferior olive, causing synchronous 4-10 Hz oscillations that underlie harmaline-induced tremor. pnas.1002995107
Secondary mechanisms include potentiation of CaV3.1 T-type calcium channels in inferior olivary neurons — the established substrate for harmaline-induced tremor — and weak binding at 5-HT₂A receptors (Ki ≈ 42.5 µM)supported
Harmaline 5-HT2A affinity = 42.5 uM (micromolar range - weak). Despite low affinity, harmaline provided significant protection from receptor alkylation. pmid:9476990
Metabolism proceeds primarily via CYP2D6-mediated O-demethylation to harmalol (Km = 1.4 µM), with CYP1A2 contributing approximately 20% of clearance.supported
CYP2D6 (50%) and CYP1A2 (20%) are major isozymes for harmaline O-demethylation to harmalol in human liver microsomes. CYP2D6 Km = 1.4 uM for harmaline. pmid:12649384
Claim in summary — inconclusiveinconclusiveworking →
High-dose rodent studies (20 mg/kg i.p.) demonstrate cerebellar neurotoxicity including Purkinje cell apoptosis, though relevance to human doses is unestablishedsupported
Harmaline 20 mg/kg i.p. in rats causes tremor plus cerebellar granule/Purkinje cell loss and inferior olivary neuron apoptosis via caspase-3. j.neuropharm.2011.05.015
As a RIMA, harmaline poses serotonin syndrome risk when combined with serotonergic medications — a class-level inference not confirmed by harmaline-specific case reportssupported
Beta-carboline MAOIs can cause fatal serotonin toxicity in DDIs. s12248-008-9028-5
receptor-pharmacology7 · 7 ok
Harmaline's discriminative stimulus (3.0 mg/kg i.p.) showed partial substitution with the 5-HT₂A agonist DOM (76% harmaline-appropriate responding at 1.25 mg/kg DOM), suggesting a 5-HT₂A component to its pharmacological profile at higher doses.partially supported
Harmaline used as training drug in drug discrimination at 3.0 mg/kg i.p. in rats. Stimulus similarity to DOM (hallucinogen) demonstrated. pmid:9649961
Harmaline potentiates CaV3.1 T-type calcium channels in inferior olivary neurons, shifting the voltage dependence of activation in a hyperpolarizing direction and amplifying subthreshold oscillations to produce synchronous 4–10 Hz tremorsupported
Harmaline potentiates CaV3.1 T-type Ca2+ channels in inferior olive, causing synchronous 4-10 Hz oscillations that underlie harmaline-induced tremor. pnas.1002995107
Harmaline inhibits MAO-A with an IC₅₀ of 20 nM under in vitro conditions using kynuramine as substratesupported
Harmaline IC50 for MAO-A = 20 nM under experimental conditions; reversible MAO-A inhibitor. dta.1530
Harmaline displays weak affinity at 5-HT₂A receptors: Helsley et al. measured Ki ≈ 42.5 µM in rat brain tissue — orders of magnitude less potent than classical psychedelics such as LSD (Ki ~1–3 nM) or psilocin (Ki ~100–300 nM)supported
Harmaline 5-HT2A affinity = 42.5 uM (micromolar range - weak). pmid:9476990
CaV3.1 knockout mice lack harmaline-induced tremor entirely, and selective CaV3.1 knockdown via shRNA in the inferior olive suppresses the tremor phenotype.partially supported
CaV3.1 knockout mice lack harmaline tremor. pnas.1002995107
This activity provides a mechanistic rationale for harmaline's traditional use in pain medicine.supported
Potential anti-nociceptive implications. ijms26104636
Harmaline fully substitutes for the selective imidazoline I₂-site ligand 2-BFI in drug discrimination studies in rats, while irreversible MAO inhibitors do not consistently substitutesupported
Harmaline substitutes for imidazoline I2 site ligand 2-BFI in drug discrimination studies; associated with reversible MAO-A inhibition rather than MAO-B. pmid:11877331
neuroscience5 · 5 ok
Harmaline potentiates CaV3.1 T-type calcium channels in neurons of the inferior olive, generating synchronous 4–10 Hz oscillations that propagate via climbing fibers to cerebellar Purkinje cells, producing the characteristic harmaline tremorsupported
Harmaline potentiates CaV3.1 T-type Ca2+ channels in inferior olive, causing synchronous 4-10 Hz oscillations that underlie harmaline-induced tremor. CaV3.1 knockout mice lack harmaline tremor. pnas.1002995107
This mechanism has made harmaline the standard pharmacological model for essential tremor research for over five decades.supported
Comprehensive review of harmaline-induced tremor model. Harmaline and harmine are tremorigenic beta-carbolines inducing acute postural/kinetic tremor in animals. d8td9w2p
SPECT neuroimaging following ayahuasca administration (which contains harmaline) revealed increased cerebral blood flow in frontal and paralimbic regions — including anterior cingulate cortex, insular cortex, and frontal polesupported
Ayahuasca (containing harmaline) produces increased frontal and paralimbic brain activation as measured by neuroimaging. s00213-006-0358-7
Harmaline also demonstrates neuroprotective antioxidant activity, protecting brain mitochondria and synaptosomes against dopamine- and 6-hydroxydopamine (6-OHDA)-induced oxidative damage via reactive oxygen species scavenging and inhibition of thiol oxidationsupported
Harmaline protects brain mitochondria and synaptosomes against dopamine/6-OHDA oxidative damage via ROS scavenging and thiol oxidation inhibition. pmid:11403679
Ayahuasca administration modulates REM and slow-wave sleep architecture in healthy volunteers — consistent with serotonergic modulation of brainstem sleep-wake circuitrysupported
Ayahuasca (containing harmaline) modulates REM and slow-wave sleep in healthy volunteers; serotonergic mechanism via 5-HT1A and 5-HT2A activity. pmid:18030450
alkaloid-profile4 · 3 ok
Quantitative analysis of ayahuasca beverages reported harmaline concentrations ranging from 27.5 to 181.3 µg/mL, with substantial batch-to-batch variability.supported
Harmaline concentrations in ayahuasca: 27.5-181.3 ug/mL. 02791072.2015.1013202
Harmine — the fully aromatic β-carboline (1-methyl-7-methoxy-β-carboline). A comparably potent MAO-A inhibitor in vitro but with lower oral bioavailability than harmaline due to MRP2 efflux and faster hepatic clearance.supported
More metabolically stable than harmine. Not an MRP2 substrate. fphar.2017.00541
In P. harmala seeds, harmaline and harmine together account for virtually all MAO-A inhibitory activity, with negligible MAO-B inhibition from any alkaloid fractionsupported
Seed extracts potently inhibit MAO-A (IC50 27 ug/L), predominantly attributed to harmaline and harmine. MAO-B poorly inhibited. j.fct.2009.12.019
Claim in alkaloid-profile — inconclusiveinconclusiveworking →
botanical-overview4 · 4 ok
The seeds are the richest natural source: harmaline and harmine together account for virtually all MAO-A inhibitory activity in P. harmala seed extracts (combined IC₅₀ ~27 µg/L)supported
Seed extracts potently inhibit MAO-A (IC50 27 ug/L), predominantly attributed to harmaline and harmine. Competitive/reversible MAO-A inhibition. j.fct.2009.12.019
McKenna et al. identified harmaline alongside harmine and tetrahydroharmine as the principal β-carboline alkaloids in B. caapi bark preparationssupported
B. caapi contains harmine, harmaline, and tetrahydroharmine. pmid:6587171
Harmaline has also been identified at trace levels in tobacco (Nicotiana tabacum), where it functions as an endogenous MAO-A inhibitor contributing to the dopaminergic effects of tobacco smokesupported
Harmaline inhibits MAO-A and significantly attenuates DAT activity and dopamine uptake; also promotes dopamine release in synaptosomes. acschemneuro.4c00789
Multianalytical investigation of a Ptolemaic Egyptian ritual Bes-vase dated to the 2nd century BCE identified P. harmala residues alongside Nymphaea nouchali var. caerulea, indicating deliberate psychoactive use of harmaline-containing plant material in ritual contexts predating Islamic traditional medicine by over a millennium.supported
Peganum harmala identified in 2nd century BCE Egyptian ritual vase alongside Nymphaea and Cleome. Suggests ancient psychotropic ritual use of P. harmala. s41598-024-78721-8
history4 · 4 ok
Tanasi et al. identified P. harmala residues in a Ptolemaic Egyptian ritual vessel dated to the 2nd century BCE, representing the earliest confirmed archaeological evidence of deliberate usesupported
Peganum harmala identified in 2nd century BCE Egyptian ritual vase alongside Nymphaea and Cleome. s41598-024-78721-8
McKenna et al. published the landmark phytochemical and pharmacological characterization of β-carboline alkaloids in South American ayahuasca preparations in 1984, identifying harmaline in B. caapi and establishing the MAOI mechanism by which these alkaloids enable oral activity of DMTpartially supported
B. caapi contains harmine, harmaline, and tetrahydroharmine. Beta-carbolines are reversible MAO inhibitors enabling oral DMT activity. pmid:6587171
The identification of CaV3.1 T-type calcium channels as the inferior olivary pacemaker substrate for harmaline tremor by Park et al. in 2010 represented the most mechanistically rigorous advance in understanding the phenomenon.partially supported
Harmaline potentiates CaV3.1 T-type Ca2+ channels in inferior olive, causing synchronous 4-10 Hz oscillations that underlie harmaline-induced tremor. pnas.1002995107
Contemporary harmaline research has expanded beyond the tremor model into several domains: neuroplasticity and adult neurogenesis, neuroprotection against oxidative damage, anti-inflammatory and antinociceptive activity, and novel ion channel pharmacology including Nav1.7 sodium channel blockadesupported
Harmaline protects brain mitochondria and synaptosomes against dopamine/6-OHDA oxidative damage via ROS scavenging and thiol oxidation inhibition. pmid:11403679
pharmacokinetic-detail4 · 4 ok
Harmaline crosses intestinal epithelium via transcellular passive diffusion, supplemented by pH- and Na⁺-dependent uptake through organic anion-transporting polypeptides (OATPs) and organic cation transporters (OCTs/OCTNs)supported
Harmaline absorbed by transcellular passive diffusion and pH/Na+-dependent mechanism via OATPs/OCTs. fphar.2017.00541
Bioaccessibility following simulated gastrointestinal digestion (oral, gastric, and intestinal phases) has been confirmed, with absorption across Caco-2 cell monolayers proceeding without cytotoxicity.supported
Harmaline bioaccessible after in vitro digestion and bioavailable in Caco-2 model. No cytotoxicity at tested concentrations. molecules26185555
All values from Yu et al..supported
CYP2D6 (50%) and CYP1A2 (20%) are major isozymes for harmaline O-demethylation to harmalol in human liver microsomes. CYP2D6 Km = 1.4 uM. pmid:12649384
This has two important consequences: (1) CYP2D6 genetic polymorphism — poor metabolizer status (5–10% of Europeans, ~1% of East Asians) — will produce disproportionately elevated harmaline plasma levels and prolonged duration; and (2) co-administration of CYP2D6 inhibitors (fluoxetine, paroxetine, bupropion, quinidine) would substantially increase harmaline exposure.partially supported
CYP2D6 important in IAA metabolism. Beta-carboline MAOIs can cause fatal serotonin toxicity in DDIs. s12248-008-9028-5
clinical-evidence3 · 3 ok
Egger et al. examined the pharmacokinetic and pharmacodynamic interaction of DMT and harmine (close analog of harmaline) in 16 healthy volunteers in a dose-ranging designsupported
DMT+harmine combinations induced dose-dependent effects lasting 4-5h in 16 healthy volunteers. j.biopha.2025.117908
Palhano-Fontes et al. conducted a randomized, double-blind, placebo-controlled trial (NCT02914769) of ayahuasca in 29 patients with treatment-resistant major depressionsupported
First RCT of ayahuasca (containing harmaline) in treatment-resistant depression (n=29). s0033291718001356
Dos Santos et al. systematically reviewed the evidence for antidepressant and anxiolytic effects of ayahuasca, concluding that the available literature supports therapeutic potential warranting further controlled investigation.supported
Systematic review of ayahuasca (containing harmaline) antidepressant and anxiolytic effects in both animal and human studies. 1516-4446-2015-1701
chemistry2 · 0 ok
comparative-pharmacology1 · 1 ok
Compared to moclobemide — the only RIMA widely available as a pharmaceutical — harmaline is substantially more potent at MAO-A in vitro (IC₅₀ 20 nM vs. moclobemide IC₅₀ typically 6,000–20,000 nM)supported
Harmaline IC50 for MAO-A = 20 nM under experimental conditions; reversible MAO-A inhibitor. More potent than toloxatone and moclobemide. dta.1530