Skip to main content

1Provenance card

the boundary, as counts

Sources

3328 with DOI

13 strong · 17 moderate · 3 weak

Compilations

12026-05-12T03:23:34.042Z

pipeline-v5 · prompt hash not recorded — run predates 2026-09

Decisions

29last ruled 2026-06-04

0 awaiting a ruling

Issued documents

42026-10-19T20:34:13.368Z

notice · info card · emergency

Searches

231 with no results

queries and counts on the build

Claims checked

7868 supported

68 supported · 10 not

Correspondence

0received

consent field ships in Phase 4

Edges

254

derivations recorded for this entity

Complete over 33 sources, 1 compilation, and 29 decisions.Not here: the private journal (never).Working material — drafts, discards, unsupported claims — is listed below and readable on the working page.Cite: psychedex.org/substances/theacrine/archive

2Build

one panel per compilation run

generation run 2026-05-12

63 min completedmodel pipeline-v5plan not recordedrun/4ae8e3c3…

Selection

results seen131
selected by the model42
consumed as sources33

Verification

claims checked78
supported65
partially supported3
not supported1
inconclusive9
  • record
  • seen / partial
  • working

The model's own caveats

  • safety_data_unverified
  • safety_data_unverified
  • safety_data_unverified
  • sparse_evidence
  • sparse_evidence
  • sparse_evidence
  • sparse_evidence
  • contradictory_sources
  • contradictory_sources
  • contradictory_sources
  • structural_inference
  • structural_inference
  • structural_inference
  • structural_inference
  • structural_inference
  • structural_inference
  • structural_inference

Reproduce

inputs
33 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
23 searches — query, source, results, what was kept and why
23 searches for this run
#sourcequeryseenkeptrationale
1OpenAlextheacrine purine alkaloid pharmacology154High-citation landmark papers on theacrine health effects and biosynthesis
2WebSearchtheacrine legal status scheduling FDA WADA banned substance 2026100Legal status confirmation - unscheduled in major jurisdictions
3WebSearchtheacrine insufflated snorted intranasal route of administration100Investigating brief's claim of insufflated ROA - not supported by evidence
4PubChemtheacrine11Primary chemical identity verification
5PubMedtheacrine adenosine receptor dopamine caffeine11Foundational pharmacological mechanism study
6PubMedtheacrine energy supplement exercise fatigue30Duplicate results already captured
7WebSearchtheacrine 1,3,7,9-tetramethyluric acid first isolation discovery history101Historical discovery context
8PubMedtheacrine (all results)256Adverse effects data (Vieira-Cavalcante 2025), sleep effects (Gardiner 2024), inflammation (Li 2024), cancer (Ko 2019), egaming (Tartar 2021), ergogenic (Jovanov 2025)
9ClinicalTrials.govtheacrine33All completed trials; relevant to clinical data on theacrine
10PubMedtheacrine Camellia kucha biosynthesis104Biosynthesis history and broader pharmacological studies
11PubMedtheacrine human clinical study cognitive performance77Human RCT data on cognitive performance, safety, energy/mood effects
12PubMedtheacrine pharmacokinetics metabolism half-life12Critical PK data - contradicts 5-day half-life in brief
13WebSearchtheacrine SMILES CAS number100Verified CAS number and SMILES for chemical identity section
14PubMedtheacrine pharmacology mechanism action11Neuroprotective pharmacology
15PubMedPMID 12009315 - Zheng 2002 biosynthesis11Foundational history/biosynthesis paper
16WebSearchtheacrine TeaCrine supplement first market Compound Solutions patent history101Commercial history context for substance entry
17PubMedtheacrine NAD3 stem cell supplement aging22Aging/sirtuin pathway effects of theacrine
18PubMedtheacrine cancer breast tumor metastasis11Relevant to anti-cancer properties section
19multiple · absenceinsufflated ROA claim in brief vs published literature00Critical flag: ROA error in seed data
20PubMedPMID 29727630 - NAFLD acylcarnitine11Hepatoprotective/metabolic effects
21PubMedPMID 41323841 - gastric emptying pharmacokinetics11Critical PK data contradicting 5-day half-life claim
22multiplehalf-life discrepancy: brief says 5 days vs literature 21 hours22Critical discrepancy flag for generation agent
23PubMed cross-referenceadverse effects safety summary across all studies63Safety profile compilation
78 claims by section — every cited sentence, checked against its source
safety22 · 21 ok
  • Ziegenfuss and colleagues confirmed hemodynamic safety at 200 mg in acute dosing, with no changes in resting heart rate, gas exchange, or oxygen consumptionsupported

    Part 2 (RCT, 200mg): No resting HR, gas exchange, or hemodynamic changes. 19390211.2016.1178678

  • He and colleagues found no hemodynamic differences between theacrine alone, caffeine alone, and the combination at pharmacokinetic study doses.supported

    No hemodynamic effects. Enhanced oral bioavailability hypothesized mechanism. jcr.2017.0006

  • The most rigorous safety assessment comes from Taylor and colleagues' 8-week RCT (n = 60): oral theacrine at 200 mg/day and 300 mg/day produced no clinically significant changes in heart rate, blood pressure, lipid profiles, complete blood count, or liver, kidney, and immune biomarkerssupported

    8-week RCT (n=60): 200-300 mg/day TeaCrine®. All clinical safety markers within normal limits. s12970-016-0113-3

  • Vieira-Cavalcante and colleagues found that 6 mg/kg theacrine (~420 mg for a 70 kg individual) significantly elevated resting systolic and diastolic blood pressure in trained cyclists (n = 19)supported

    6 mg/kg increased resting systolic and diastolic BP. apnm-2024-0442

  • Stoke and colleagues found no significant heart rate or blood pressure effects at 3, 6, or 9 mg/kg, but observed elevated salivary cortisol at 120–180 minutes post-dose in theacrine conditions.supported

    No significant effects on HR, BP. Increased salivary cortisol at 120-180 min vs placebo. apnm-2025-0380

  • Li and colleagues demonstrated decreased ALT/AST, reduced inflammatory cytokines, and reversed histological liver damage in restraint-stressed micesupported

    Oral theacrine (10-30 mg/kg, 7 days) decreased plasma ALT/AST, reduced hepatic inflammatory cytokines (IL-1β, TNF-α, IL-6, IFN-γ), reversed histological damage. jf400982c

  • Wang and colleagues found protection against non-alcoholic fatty liver disease in an animal modelsupported

    Theacrine protects against NAFLD by targeting acylcarnitine metabolism disorder. j.metabol.2018.04.011

  • Stoke and colleagues documented elevated salivary cortisol at doses of 3–9 mg/kg (approximately 210–630 mg for a 70 kg individual) at 120–180 minutes post-administrationsupported

    RCT (n=19), 3/6/9 mg/kg doses: increased salivary cortisol at 120-180 min vs placebo. apnm-2025-0380

  • Anxiety was not elevated relative to placebo in the 8-week safety trialsupported

    No group × time interactions on energy, focus, anxiety, POMS. s12970-016-0113-3

  • Tartar and colleagues found that a caffeine-theacrine-methylliberine combination increased alertness without increasing anxiety, whereas caffeine alone increased self-reported anxiety.supported

    Caffeine alone increased anxiety but CDT did not. cureus.20534

  • At higher doses (≥6 mg/kg), side-effect reports include subjective distress symptoms — dizziness, head pressure, lack of disposition — that may have a psychological componentsupported

    Reported side effects: GI discomfort, perceived tachycardia, dizziness, headache, head pressure, hand tremor, lack of disposition. apnm-2024-0442

  • Taylor and colleagues' 8-week RCT detected no tachyphylaxis: energy, focus, concentration, and motivation scores remained stable across the full study duration at both 200 mg and 300 mgsupported

    No habituation or tachyphylaxis detected. No group × time interactions on energy, focus, anxiety, POMS. s12970-016-0113-3

  • Feduccia and colleagues independently found no locomotor sensitization or tolerance in chronically dosed ratssupported

    No locomotor sensitization or tolerance after chronic exposure. j.pbb.2012.04.014

  • Caffeine co-administration increases theacrine's plasma exposure (Cmax and AUC) through enhanced presystemic bioavailabilitysupported

    Caffeine co-admin increases theacrine Cmax and AUC without altering half-life. Enhanced oral bioavailability hypothesized mechanism. jcr.2017.0006

  • Cardiovascular parameters are not additively elevated at typical combination doses.supported

    No hemodynamic effects. jcr.2017.0006

  • Cardiovascular parameters are not additively elevated at typical combination doses.supported

    No HR or BP changes. nu7115484

  • Claim in safety — inconclusiveinconclusiveworking →

  • The 21-hour half-life necessitates a minimum washout period of approximately 4 days before adenosine-dependent procedures.supported

    Theacrine elimination t1/2 = 21.00 ± 7.55 hours. j.ijpx.2025.100442

  • Cardiovascular conditions (relative). Blood pressure elevation at doses ≥6 mg/kg and perception of tachycardia at supplementation doses suggest caution in individuals with uncontrolled hypertension, cardiac arrhythmias, or other cardiovascular diseasesupported

    6 mg/kg increased resting systolic and diastolic BP. Reported side effects: perceived tachycardia. apnm-2024-0442

  • Anxiety disorders (relative). Although theacrine appears less anxiogenic than caffeine at typical doses, its stimulant mechanism (adenosine antagonism, dopaminergic facilitation) warrants caution in individuals with panic disorder or generalized anxiety disorder, particularly at higher doses.supported

    Caffeine alone increased anxiety but CDT did not. cureus.20534

  • HPA axis disorders (relative). The cortisol-elevating effect at doses ≥3 mg/kg suggests caution in individuals with Cushing's syndrome, adrenal insufficiency under glucocorticoid replacement, or other HPA axis pathology.supported

    Increased salivary cortisol at 120-180 min vs placebo. apnm-2025-0380

  • Discontinuation before such procedures is required, with the 21-hour half-life dictating a minimum washout period of approximately 4 days (4–5 half-lives).supported

    Theacrine elimination t1/2 = 21.00 ± 7.55 hours. j.ijpx.2025.100442

clinical-evidence9 · 9 ok
  • The foundational safety study is Taylor and colleagues' 8-week, double-blind, randomized controlled trial (n = 60) evaluating TeaCrine® at 200 mg/day and 300 mg/day against placebosupported

    8-week RCT (n=60): 200-300 mg/day TeaCrine®. All clinical safety markers within normal limits. No habituation or tachyphylaxis detected. s12970-016-0113-3

  • Ziegenfuss and colleagues confirmed hemodynamic safety at 200 mg in a two-part acute study, finding no changes in resting heart rate, gas exchange, or hemodynamic parameters.supported

    Part 2 (RCT, 200mg): No resting HR, gas exchange, or hemodynamic changes. 19390211.2016.1178678

  • Gardiner and colleagues examined dose-response (100 mg and 400 mg) and consumption timing effects on cognitive performance and sleep in a within-subjects designsupported

    100mg and 400mg theacrine: no significant sleep disruption. Within 8h of bedtime improved next-morning PVT lapses (400mg). s41598-024-79046-2

  • Stoke and colleagues administered higher doses (3, 6, and 9 mg/kg) and found no significant cognitive performance improvements at any dose, but observed elevated salivary cortisol at 120–180 minutes post-dose.supported

    RCT (n=19), 3/6/9 mg/kg doses: increased salivary cortisol at 120-180 min vs placebo. No significant effects on cognitive performance. apnm-2025-0380

  • Vieira-Cavalcante and colleagues administered 3 and 6 mg/kg theacrine to trained cyclists (n = 19) and found no improvement in 4 km time trial performancesupported

    RCT (n=19): 3 and 6 mg/kg theacrine did not improve cycling TT. apnm-2024-0442

  • Kuhman and colleagues (n = 20) evaluated theacrine combined with caffeine against placebo and caffeine alone, finding higher subjective attentiveness, alertness, focus, and energy with the combination, alongside reduced lethargy and grogginesssupported

    RCT (n=20): TheaTrim (theacrine+caffeine) vs caffeine 150mg vs placebo. Subjective improvements in attentiveness, alertness, focus, and energy. nu7115484

  • Lints and colleagues demonstrated that a caffeine-theacrine combination improved cognitive performance in military personnel under physically fatiguing conditions, suggesting synergistic cognitive effects under stress.supported

    Military tactical personnel: caffeine+theacrine combination improved cognitive performance under physical fatigue. 15502783.2025.2536146

  • Bello and colleagues studied TeaCrine® combined with caffeine in high-level soccer players, reporting endurance and cognitive benefits during simulated match conditions.supported

    High-level athletes: TeaCrine® alone improved time-to-exhaustion 27-38%; combination with caffeine provided greater cognitive benefits than either independently. s12970-019-0287-6

  • Cesareo and colleagues found no ergogenic effect of TeaCrine® on muscular strength, endurance, or power in resistance-trained men.supported

    RCT (n=12): TeaCrine 300mg did not improve 1RM strength, RTF, or power vs placebo. s12970-019-0316-5

pharmacology9 · 6 ok
  • In Long Evans rats, pre-treatment with theacrine significantly attenuated the motor depression induced by co-administration of the A₁ agonist CPA and the A₂A agonist CGS-21680, establishing functional antagonism at both receptor subtypessupported

    Theacrine significantly enhances locomotor activity via adenosinergic (A1/A2A antagonism) and dopaminergic (D1/D2) mechanisms in rats. j.pbb.2012.04.014

  • Claim in pharmacology — inconclusiveinconclusiveworking →

  • At low doses in rodents (3 mg/kg intragastric), theacrine acts as a sedative/hypnotic agent — increasing NREM sleep duration, shortening wake time, and augmenting pentobarbital-induced sleep through what appears to be adenosine agonism-like activitysupported

    Theacrine 3mg/kg (i.g.) enhanced pentobarbital sleep, increased NREM, no effect on REM. A1 and A2A receptor antagonists reversed sleep effect. Increased adenosine in hippocampus. j.neulet.2017.08.063

  • Claim in pharmacology — inconclusiveinconclusiveworking →

  • Claim in pharmacology — inconclusiveinconclusiveworking →

  • Half-life. The elimination half-life in humans is 21.00 ± 7.55 hours (salivary pharmacokinetics), substantially longer than caffeine's 3–6 hourssupported

    Theacrine elimination t1/2 = 21.00 ± 7.55 hours. j.ijpx.2025.100442

  • He and colleagues conducted a crossover pharmacokinetic study (n = 8) demonstrating that co-administration of caffeine (150 mg) with theacrine (125 mg) significantly increased theacrine's Cmax and AUC without altering its elimination half-lifesupported

    Crossover PK study (n=8): theacrine alone shows consistent PK; caffeine co-admin increases theacrine Cmax and AUC without altering half-life. jcr.2017.0006

  • Tartar and colleagues genotyped participants for the CYP1A2*1F allele in a caffeine-theacrine-methylliberine combination study; allele status did not moderate outcomes, though this single observation does not resolve the metabolic pathway question.supported

    CYP1A2*1F allele status did not moderate effects. cureus.20534

  • The caffeine-mediated enhancement of theacrine exposure suggests presystemic losses are pharmacologically relevant but modifiable.supported

    Caffeine co-admin increases theacrine Cmax and AUC without altering half-life. Enhanced oral bioavailability hypothesized mechanism. jcr.2017.0006

summary8 · 8 ok
  • Individual response varies with caffeine co-consumption, which increases theacrine's systemic exposure through enhanced oral bioavailability.supported

    Caffeine co-admin increases theacrine Cmax and AUC without altering half-life. No hemodynamic effects. Enhanced oral bioavailability hypothesized mechanism. jcr.2017.0006

  • Distinguished from caffeine by C8 oxidation and N9 methylation of the purine scaffold, theacrine produces wakefulness and cognitive stimulation at oral doses of 100–300 mg with a notably prolonged elimination half-life of approximately 21 hours.partially supported

    Identified theacrine synthase CkTcS from Kucha with N9-methyltransferase activity; C8 oxidation precedes N9-methylation. s41467-020-15324-7

  • Distinguished from caffeine by C8 oxidation and N9 methylation of the purine scaffold, theacrine produces wakefulness and cognitive stimulation at oral doses of 100–300 mg with a notably prolonged elimination half-life of approximately 21 hours.partially supported

    Theacrine elimination t1/2 = 21.00 ± 7.55 hours. j.ijpx.2025.100442

  • First reported as a minor tea constituent in 1937, theacrine remained pharmacologically uncharacterized until Feduccia and colleagues established its adenosine and dopamine receptor involvement in 2012supported

    Theacrine significantly enhances locomotor activity via adenosinergic (A1/A2A antagonism) and dopaminergic (D1/D2) mechanisms in rats. j.pbb.2012.04.014

  • The compound's primary research significance lies in its non-habituating profile: an 8-week randomized controlled trial detected no tolerance to subjective energy, focus, or motivation effects at doses up to 300 mg/day — a property that distinguishes it from caffeine and most other adenosine-targeting stimulants.supported

    8-week RCT (n=60): 200-300 mg/day TeaCrine®. No habituation or tachyphylaxis detected. No group × time interactions on energy, focus, anxiety, POMS. s12970-016-0113-3

  • Theacrine's stimulant effects are mediated by adenosine A₁ and A₂A receptor antagonism and downstream dopaminergic activation, demonstrated through pharmacological blocking studies and nucleus accumbens infusion experiments in rodentssupported

    Theacrine significantly enhances locomotor activity via adenosinergic (A1/A2A antagonism) and dopaminergic (D1/D2) mechanisms in rats. Nucleus accumbens implicated. j.pbb.2012.04.014

  • Oral theacrine at 200–300 mg/day produces no clinically significant changes in heart rate, blood pressure, or hematological markers over eight weeks of continuous usesupported

    8-week RCT (n=60): 200-300 mg/day TeaCrine®. All clinical safety markers within normal limits. s12970-016-0113-3

  • Doses at or above 6 mg/kg (~420 mg for a 70 kg individual) elevate resting blood pressure and produce gastrointestinal discomfort, tachycardia perception, and tremor in some individualssupported

    6 mg/kg increased resting systolic and diastolic BP. Reported side effects: GI discomfort, perceived tachycardia, dizziness, headache, head pressure, hand tremor, lack of disposition. apnm-2024-0442

neuroscience7 · 6 ok
  • Claim in neuroscience — inconclusiveinconclusiveworking →

  • However, the absence of locomotor sensitization or tolerance in chronic rodent exposure suggests that theacrine's dopaminergic modulation does not produce the progressive neuroadaptation characteristic of stimulants with high abuse liability.supported

    No locomotor sensitization or tolerance after chronic exposure. j.pbb.2012.04.014

  • PDE4/cAMP/CREB/BDNF/TrkB pathway. In chronic unpredictable mild stress mouse models, theacrine promotes adult hippocampal neurogenesis and counters stress-induced serotonergic dysregulation through this signaling cascadesupported

    Mechanism: PDE4/cAMP/CREB/BDNF/TrkB pathway; promotes hippocampal neurogenesis. acs.jafc.1c01514

  • SIRT3/FOXO3a/Parkin pathway. Theacrine protects dopaminergic neurons in Parkinson's disease models via SIRT3 activation, and the same pathway mediates anti-inflammatory effects in psoriasis modelspartially supported

    Animal study: theacrine protects dopaminergic neurons in PD model via SIRT3 activation; anti-oxidative neuroprotection mechanism. j.phymed.2020.153281

  • Separately, a theacrine-containing supplement increased SIRT1 mRNA, global sirtuin activity, and NAD⁺ levels approximately 2-fold in C2C12 muscle cells in vitro.supported

    NAD3 (theacrine-based) increased Sirt1 mRNA at 3h, global sirtuin activity at 3 and 24h, NAD+ levels elevated ~2-fold at 24h. nu12123727

  • Nrf2/Rac1 pathway. In ischemic stroke models (middle cerebral artery occlusion in rats) and human endothelial cells, theacrine activates the Nrf2 antioxidant pathway and inhibits Rac1, reducing oxidative stress, apoptosis, and vascular injury.supported

    MCAO rat model and HUVECs: theacrine reduces oxidative stress, apoptosis, and vascular injury. Inhibits Rac1 and activates Nrf2/ARE pathway. j.intimp.2025.115951

  • Gut-brain axis. Theacrine-containing Kucha black tea modulated gut microbiota composition and increased brain serotonin, dopamine, and BDNF while decreasing pro-inflammatory cytokines IL-6 and TNF-α in chronic stress depression models.supported

    Modified gut microbiota; increased 5-HT, DA, BDNF; decreased IL-6, TNF-α. j.foodres.2024.115306

chemistry5 · 3 ok
  • This distinguishes theacrine from the methylxanthine class (which includes caffeine, theobromine, and theophylline) by the presence of a C8 carbonyl rather than C8-H, representing a single oxidation step beyond the xanthine scaffold.supported

    C8 oxidation precedes N9-methylation. s41467-020-15324-7

  • Theacrine is the direct biosynthetic product of caffeine (1,3,7-trimethylxanthine) via C8 oxidation to 1,3,7-trimethyluric acid followed by N9 methylationsupported

    Theacrine synthesized from adenosine via caffeine in a three-step pathway; 1,3,7-methyluric acid is intermediate. pmid:12009315

  • Claim in chemistry — inconclusiveinconclusiveworking →

  • Theacrine occurs at pharmacologically meaningful concentrations in the leaves of Camellia assamica var. kucha (Kucha tea), where young leaves accumulate approximately 2.8% by dry weight — replacing caffeine as the dominant purine alkaloidsupported

    Endogenous levels: ~2.8% dry weight in young kucha leaves. pmid:12009315

  • Claim in chemistry — not_supportednot supportedworking →

comparative-pharmacology5 · 5 ok
  • The absence of tolerance over 8 weeks is theacrine's most pharmacologically distinctive property relative to caffeinesupported

    No habituation or tachyphylaxis detected. s12970-016-0113-3

  • Tartar and colleagues found that caffeine alone increased self-reported anxiety while a caffeine-theacrine-methylliberine combination increased alertness without anxiety, suggesting theacrine may buffer caffeine's anxiogenic effects — though the presence of methylliberine confounds direct attribution.supported

    Caffeine alone increased anxiety but CDT did not. cureus.20534

  • The pharmacokinetic interaction is well characterized: caffeine enhances theacrine's oral bioavailability (Cmax and AUC) without altering its elimination ratesupported

    Caffeine co-admin increases theacrine Cmax and AUC without altering half-life. Enhanced oral bioavailability hypothesized mechanism. jcr.2017.0006

  • Pharmacodynamically, the combination appears synergistic for cognitive outcomes under fatiguing conditions and during sustained athletic performancesupported

    Combination with caffeine provided greater cognitive benefits than either independently. s12970-019-0287-6

  • Cardiovascular parameters are not additively elevated at typical supplementation doses.supported

    No hemodynamic effects. jcr.2017.0006

history4 · 3 ok
  • Young Kucha leaves contain approximately 2.8% theacrine by dry weight.supported

    Endogenous levels: ~2.8% dry weight in young kucha leaves. pmid:12009315

  • Claim in history — inconclusiveinconclusiveworking →

  • Zhu and colleagues cloned the caffeine oxidase gene CsCDH in 2025, establishing it as the rate-limiting enzyme in theacrine productionsupported

    CsCDH is rate-limiting enzyme in theacrine synthesis pathway. j.ijbiomac.2025.140429

  • Wu and colleagues identified a second theacrine synthase, CsTcS2, regulated by the CsTINY-CsWRKY33 transcription factor module.supported

    Identified CsTcS2 as novel theacrine synthase; CsTINY-CsWRKY33 transcription factor module regulates CsTcS2. pbi.70665

effects-overview3 · 3 ok
  • Caffeine co-consumption meaningfully modulates intensity via pharmacokinetic enhancement of theacrine's systemic exposuresupported

    Caffeine co-admin increases theacrine Cmax and AUC without altering half-life. Enhanced oral bioavailability hypothesized mechanism. jcr.2017.0006

  • Theacrine occupies a position between caffeine and prescription wakefulness-promoting agents in the stimulant landscape — more sustained than caffeine (21-hour vs 3–6-hour half-life) with a cleaner anxiety-sparing profile, but without the potent wakefulness-promoting efficacy of modafinilsupported

    Theacrine elimination t1/2 = 21.00 ± 7.55 hours. j.ijpx.2025.100442

  • Its closest experiential analog is caffeine at moderate doses, minus the tolerance development and with reduced sleep disruption.supported

    100mg and 400mg theacrine: no significant sleep disruption (minor non-significant effects at 400mg). s41598-024-79046-2

pharmacokinetic-detail3 · 1 ok
  • Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →

  • Claim in pharmacokinetic-detail — inconclusiveinconclusiveworking →

  • Tartar and colleagues genotyped participants for the CYP1A2*1F polymorphism — associated with variable caffeine metabolism rates — in a study of the caffeine-theacrine-methylliberine combinationsupported

    CYP1A2*1F allele status did not moderate effects. cureus.20534

receptor-pharmacology3 · 3 ok
  • The low-dose sedative/hypnotic effect observed in rodents (3 mg/kg intragastric) suggests possible partial agonist activity or dose-dependent switching between agonism and antagonism at adenosine receptors — a pharmacological profile that would be unusual among xanthine-derived compounds and warrants formal characterization.supported

    A1 and A2A receptor antagonists reversed sleep effect. Increased adenosine in hippocampus. j.neulet.2017.08.063

  • Theacrine-stimulated locomotion is blocked by both D₁ (SCH23390) and D₂ (eticlopride) receptor antagonists, and bilateral infusion into the nucleus accumbens (10–20 µg) produces dose-dependent locomotor activationsupported

    Theacrine significantly enhances locomotor activity via adenosinergic (A1/A2A antagonism) and dopaminergic (D1/D2) mechanisms in rats. Nucleus accumbens implicated. j.pbb.2012.04.014

  • Functional antagonism at adenosine A₁ and A₂A receptors is established through behavioral pharmacology: theacrine pre-treatment attenuates motor depression induced by the A₁-selective agonist CPA and the A₂A-selective agonist CGS-21680 in ratssupported

    Theacrine significantly enhances locomotor activity via adenosinergic (A1/A2A antagonism) and dopaminergic (D1/D2) mechanisms in rats. j.pbb.2012.04.014

3Sources

33 consumed · sorted by year · feeds = sections resting on it

Sources 1 to 30
yearsourcetierstatusfeeds
2026Assessing the impact of high theacrine doses on hemodynamic measures, cognitive performance, and physiological stress.Stoke C, Chandler M, Madzima T · Applied Physiology, Nutrition, and Metabolismdoi:10.1139/apnm-2025-0380strongconsumed2 sections
2026Theacrine protects vascular endothelial cells against oxidative damage after ischemic stroke by inhibiting Rac1 and activating Nrf2 pathway.Zhang Y, Li Y, Li X, Liao P, Chen W, Feng Y, Zhang X, Chen Y, Nan L, Li H, Yan G · International Immunopharmacologydoi:10.1016/j.intimp.2025.115951moderateconsumed1 section
2026Transcriptional Regulation of the Novel Theacrine Synthase Gene CsTcS2 by the CsTINY-CsWRKY33 Module Underpins Theacrine Biosynthesis in Camellia sinensis.Wu T, Zhu L, Shao C, Xie S, Li N, Li X, Wang F, Peng L, Jin H, Shang F, Huang J, Liu Z, Tian N, Liu S · Plant Biotechnology Journaldoi:10.1111/pbi.70665moderateconsumed1 section
2025A caffeine and theacrine combination improves cognitive performance in tactical personnel under physically fatiguing conditions.Lints BS, Harrison AT, Stray-Gundersen SO, Mastrofini GF, Romersi RF, Nakagawa NK, Yoder MB, Martin-Diala CE, Chandler AJ, Moore RD, Arent SM · Journal of the International Society of Sports Nutritiondoi:10.1080/15502783.2025.2536146strongconsumed1 section
2025A comparison of theacrine and methylliberine with caffeine as salivary markers for determining gastric emptying.Wildgrube T, Senekowitsch S, Krüger R, Winter F, Grimm M, Weitschies W, Schick P · International Journal of Pharmaceutics: Xdoi:10.1016/j.ijpx.2025.100442strongconsumed4 sections
2025Cloning and functional characterization of the caffeine oxidase gene CsCDH from Camellia sinensis.Zhu L, Wu T, Shao C, Li X, Zhou B, Peng L, Jin Q, Jin H, Xie S, Shang F, Liu Z, Huang J, Liu S, Tian N · International Journal of Biological Macromoleculesdoi:10.1016/j.ijbiomac.2025.140429moderateconsumed1 section
2025Different doses of theacrine do not improve 4 km cycling time trial performance.Vieira-Cavalcante V, Schamne J, Gonçalves F, Bertuzzi R, Pierucci A, Boari D, Lima-Silva A, Silva RG · Applied Physiology, Nutrition, and Metabolismdoi:10.1139/apnm-2024-0442strongconsumed3 sections
2025Metabolomic insights into the Arabica-like flavour of stenophylla coffee and the chemistry of quality coffee.Jan-Smith E, Downes H, Davis AP, Richard-Bollans A, Haggar J, Sarmu D, Kite GC, Howes MR · NPJ Science of Fooddoi:10.1038/s41538-025-00398-8moderateconsumedcited only
2025Theacrine as a novel ergogenic aid: impact on canoe sprint performance.Jovanov P, Vranes M, Barak O, Rapaić M, Maravić N, Marić A, Obradović B · Journal of the International Society of Sports Nutritiondoi:10.1080/15502783.2025.2590097strongconsumedcited only
2024CAS 2309-49-1 Theacrine - Chemical Identity Referenceurl:eb845896fcab29c2weakconsumedcited only
2024Dose response effects of theacrine on cognitive performance and subsequent sleep.Gardiner CL, Weakley J, Leota J, Burke LM, Karagounis LG, Russell S, Johnston RD, Townshend A, Halson SL · Scientific Reportsdoi:10.1038/s41598-024-79046-2strongconsumed2 sections
2024Exploration of the mechanism of temperature influence on bitter taste of theacrine by activating human bitter taste receptor hTAS2R14.Xie J, Wen H, Shi Y, Wei F, Jiang J, Luo L, Zeng L · Food Research Internationaldoi:10.1016/j.foodres.2024.114857moderateconsumedcited only
2024Jianghua Kucha black tea containing theacrine attenuates depression-like behavior in CUMS mice by regulating gut microbiota-brain neurochemicals and cytokines.Jia W, Ma Q, Xing R, Yang X, Liu D, Zeng H, Liu Z, Liu S, Xu W, Liu Z, Wu W · Food Research Internationaldoi:10.1016/j.foodres.2024.115306moderateconsumed1 section
2024Theacrine enhances autophagy and inhibits inflammation via regulating SIRT3/FOXO3a/Parkin pathway.Li J, Yan W, Yuan H, Ren F · International Journal of Rheumatic Diseasesdoi:10.1111/1756-185x.15085moderateconsumedcited only
2024Theacrine PubChem Entry (CID 75324)PubChempmid:75324moderateconsumed1 section
2021A Combination of Caffeine, TeaCrine® (Theacrine), and Dynamine® (Methylliberine) Increases Cognitive Performance and Reaction Time Without Interfering With Mood in Adult Male Egamers.Tartar JL, Banks JB, Marang M, Pizzo F, Antonio J · Cureusdoi:10.7759/cureus.20534strongconsumed4 sections
2021Theacrine, a Potent Antidepressant Purine Alkaloid from a Special Chinese Tea, Promotes Adult Hippocampal Neurogenesis in Stressed Mice.Ouyang SH, Zhai YJ, Wu YP, Xie G, Wang GE, Mao ZF, Hu HH, Luo XH, Sun WY, Liang L, Duan WJ, Kurihara H, Li YF, He RR · Journal of Agricultural and Food Chemistrydoi:10.1021/acs.jafc.1c01514moderateconsumed1 section
2020A Theacrine-Based Supplement Increases Cellular NAD+ Levels and Affects Biomarkers Related to Sirtuin Activity in C2C12 Muscle Cells In Vitro.Mumford PW, Osburn SC, Fox CD, Godwin JS, Roberts MD · Nutrientsdoi:10.3390/nu12123727moderateconsumed1 section
2020Identification and characterization of N9-methyltransferase involved in converting caffeine into non-stimulatory theacrine in tea.Zhang YH, Li YF, Wang Y, Tan L, Cao Z · Nature Communicationsdoi:10.1038/s41467-020-15324-7moderateconsumed2 sections
2020Theacrine, a purine alkaloid from kucha, protects against Parkinson's disease through SIRT3 activation.Duan WJ, Liang L, Pan MH, Lu DH, Wang TM, Li SB, Zhong HB, Yang XJ, Cheng Y, Liu B, Li WX, Kurihara H, Bi W, Li YF, He RR · Phytomedicinedoi:10.1016/j.phymed.2020.153281moderateconsumed1 section
2019The effects of a caffeine-like supplement, TeaCrine®, on muscular strength, endurance and power performance in resistance-trained men.Cesareo KR, Mason JR, Saracino PG, Morrissey MC, Ormsbee MJ · Journal of the International Society of Sports Nutritiondoi:10.1186/s12970-019-0316-5strongconsumed1 section
2019The effects of TeaCrine® and caffeine on endurance and cognitive performance during a simulated match in high-level soccer players.Bello ML, Walker AJ, McFadden BA, Sanders DJ, Arent SM · Journal of the International Society of Sports Nutritiondoi:10.1186/s12970-019-0287-6strongconsumed2 sections
2019US Patent US10272091B2 - Theacrine-based supplement and method of use thereofurl:51fcbe75ce02e07cweakconsumedcited only
2018Theacrine protects against nonalcoholic fatty liver disease by regulating acylcarnitine metabolism.Wang GE, Li YF, Zhai YJ, Gong L, Tian JY, Hong M, Yao N, Wu YP, Kurihara H, He RR · Metabolismdoi:10.1016/j.metabol.2018.04.011moderateconsumed1 section
2017A Two-Part Approach to Examine the Effects of Theacrine (TeaCrine®) Supplementation on Oxygen Consumption, Hemodynamic Responses, and Subjective Measures of Cognitive and Psychometric Parameters.Ziegenfuss TN, Habowski SM, Sandrock JE, Kedia AW, Kerksick CM, Lopez HL · Journal of Dietary Supplementsdoi:10.1080/19390211.2016.1178678strongconsumed2 sections
2017Assessment of the Drug-Drug Interaction Potential Between Theacrine and Caffeine in Humans.He H, Ma D, Crone LB, Butawan M, Meibohm B, Bloomer RJ, Yates CR · Journal of Caffeine Researchdoi:10.1089/jcr.2017.0006strongconsumed6 sections
2017Theacrine: A purine alkaloid from Camellia assamica var. kucha with a hypnotic property via the adenosine system.Qiao H, Ye X, Bai X, He J, Li T, Zhang J, Zhang W, Xu J · Neuroscience Lettersdoi:10.1016/j.neulet.2017.08.063moderateconsumed2 sections
2016Safety of TeaCrine®, a non-habituating, naturally-occurring purine alkaloid over eight weeks of continuous use.Taylor L, Mumford P, Roberts M, Hayward S, Mullins J, Urbina S, Wilborn C · Journal of the International Society of Sports Nutritiondoi:10.1186/s12970-016-0113-3strongconsumed5 sections
2015Cognitive Performance and Mood Following Ingestion of a Theacrine-Containing Dietary Supplement, Caffeine, or Placebo by Young Men and Women.Kuhman DJ, Joyner KJ, Bloomer RJ · Nutrientsdoi:10.3390/nu7115484strongconsumed2 sections
2014Compound Solutions Announces Exclusive Distribution License for TeaCrine (2014)url:4d8a9864e8f3af49weakconsumedcited only
Show all 34 sources — 4 more
Sources 31 to 34
yearsourcetierstatusfeeds
2013Theacrine, a purine alkaloid obtained from Camellia assamica var. kucha, attenuates restraint stress-provoked liver damage in mice.Li WX, Li YF, Zhai YJ, Chen WM, Kurihara H, He RR · Journal of Agricultural and Food Chemistrydoi:10.1021/jf400982cmoderateconsumed1 section
2012Locomotor activation by theacrine, a purine alkaloid structurally similar to caffeine: involvement of adenosine and dopamine receptors.Feduccia AA, Wang Y, Simms JA, Yi HY, Li R, Bjeldanes L, Ye C, Bartlett SE · Pharmacology, Biochemistry, and Behaviordoi:10.1016/j.pbb.2012.04.014moderateconsumed5 sections
2002Theacrine (1,3,7,9-tetramethyluric acid) synthesis in leaves of a Chinese tea, kucha (Camellia assamica var. kucha).Zheng XQ, Ye CX, Kato M, Crozier A, Ashihara H · Phytochemistrypmid:12009315moderateconsumed2 sections
—Searched multiple for "insufflated ROA claim in brief vs published literature" — no resultsabsenceno results—

4Docket

one filing per activity — decisions, correspondence, reports

  1. 0012026-05-12revisionRevision 1

    Initial LLM generation (v5 pipeline, wiki, prose phase)

    psx:substance/theacrine/version/1
  2. 0022026-06-04proposal27 value proposals approved together

    one review action inferred from a shared reviewer and instant — the graph records one activity per proposal

    27 items in this filing

    • dose_tier · light
    • dose_tier · common
    • dose_tier · strong
    • dose_tier · heavy
    • timeline · oral · onset
    • timeline · oral · come_up
    • timeline · oral · peak
    • timeline · oral · plateau
    • timeline · oral · resolution
    • timeline · oral · afterglow
    • toxicity
    • dependence · full
    • withdrawal
    • tolerance
    • dosage · oral
    • duration · oral · onset
    • duration · oral · come_up
    • duration · oral · peak
    • duration · oral · offset
    • duration · oral · total
    • duration · oral · aftereffects
    • contraindication · cardiovascular
    • contraindication · psychiatric
    • contraindication · metabolic
    • contraindication · other
    • contraindication · pregnancy_breastfeeding
    psx:substance/theacrine/proposal/dose_tier/dbe1f29d-d388-4119-a938-0ee30cd1c355
  3. 0032026-06-04publicationPublication — backfill

5Issued documents

what the notice, info card and emergency page said, by hash

Issued documents
documentcontent hashissuedfrom versionsuperseded
info_cardb72aada2a9bbde3f732d669d…2026-10-19 20:34Revision 1current
emergency777b5863d801327b008f5610…2026-09-04 04:32Revision 1current
info_card76fd8cb9a5d2491bb499aa5b…2026-09-04 04:32Revision 1superseded2026-10-19
noticefb6e5e61c98289464444fa49…2026-09-04 04:32Revision 1current