IngredientsTheacrine is a purine alkaloid found in Camellia kucha Hung T. Chang (a wild tea plant species, formerly named as Camellia assamica var. kucha); its full name is 1,3,7,9-tetramethyl-1H-purine-2,6,8(3H,7H,9H)-trione, with chemical formula C9H12N4O3 and molecular weight 224.22. It is also referred to in the literature as 1,3,7,9-tetramethyluric acid. Other synonyms include Temurin, Temorine, Tetramethyluric acid, Tetramethyl uric acid, and the IUPAC name 1,3,7,9-tetramethylpurine-2,6,8-trione. Its unique chemical registry number is CAS 2309-49-1.
1,3,7,9-tetramethyluric acid, commonly known as theacrine, was not studied until around 1975; however, it has been known of since about 1937, when it was detected in dry, decaffeinated Camellia sinensis tea leaves.
Theacrine is relatively rare and only found in a few varieties of tea (kucha tea, genus Camellia), the fruit cupuaçu, and other plants related to coffee and cacao (genera Coffea and Theobroma), such as Coffea liberica, Coffea dewevrei, Coffea abeokutae and Theobroma grandiflorum. It was recently also reported that theacrine was detected in Camellia sinensis var. puanensis, Ilex vomitoria, and Camellia gymnogyna.
The content of theacrine in tender shoots with two leaves and a bud of C. kucha was 1.3–3.4% based on dry weight (DW). Theacrine is a specific purine alkaloid in Kucha, and no or little theacrine was detected in the leaf of Camellia sinensis which is usually used for processing green tea or black tea.
Recent studies revealed that caffeine can be converted into non-stimulatory theacrine in the rare tea plant Camellia assamica var. kucha, which involves oxidation at the C8 and methylation at the N9 positions of caffeine. The theacrine synthase CkTcS from Kucha possesses novel N9-methyltransferase activity using 1,3,7-trimethyluric acid but not caffeine as a substrate, confirming that C8 oxidation takes place prior to N9-methylation.
At least ten compounds have been isolated and identified from the leaves of Camellia assamica var. kucha, and they include theacrine, caffeine, theobromine, catechin, epigallocatechin, gallocatechin, epigallocatechin-3-O-gallate, gallocatechin 3-O-gallate, 1,2,6-tri-O-galloyl-β-D-glucose, and gallic acid.
Theacrine is available as a dietary supplement primarily in oral forms, including encapsulated powders and tablet formulations. The branded form TeaCrine® (Compound Solutions, Inc.) is described in clinical research as a nature-identical, chemically equivalent bioactive version of theacrine. Pure theacrine can be obtained by separating it from Kucha leaf through high-speed counter-current chromatography using an eluent solvent system composed of hexane/dichloromethane/methanol/water (1/5/4/2, v/v/v/v). At present, high-purity theacrine can also be separated by HPLC and LC-MS, and obtained by ultrasonic reflux extraction.
The kucha tea plant (Camellia assamica var. kucha Chang et Wang) is regarded as a mutant variety of wild Pu'er tea plant found in a few mountain areas of Yunnan, China. Its fresh young leaves and shoots are picked by the indigenous inhabitants of these local areas to prepare an herbal tea for the empirical treatment of the common cold. Two types of Chinese Kucha (bitter) tea are traditionally consumed for health improvement; one is Kuding tea prepared from leaves of Ligustrum robustum or Ilex kaushue, and the other is Yunnan Kucha tea prepared from young leaves of Camellia assamica var. kucha Chang et Wang.
The tea plant Camellia assamica var. kucha has been used traditionally to prolong life and cure the common cold. It is suggested that theacrine and strictinin are two major ingredients responsible for the anti-influenza activity of Yunnan Kucha tea, traditionally used for the treatment of common cold.
Kucha (Camellia sinensis) is a unique wild tea resource in southwest China, containing sizeable amounts of theacrine and having a special bitter taste both in fresh leaves and made tea. Theacrine has good healthy function locally. The characteristic bitterness of theacrine is well documented: the special purine alkaloid 1,3,7,9-tetramethyluric acid exists in the Kucha leaves and is significantly related to the formation of bitter taste.
Historically, the leaves containing theacrine have been brewed into traditional teas, often referred to as "kucha tea," prized for their invigorating properties. In traditional Chinese medicine, kucha tea was valued as a remedy to combat fatigue, enhance mental clarity, and promote overall vitality.
Theacrine is thought to act through both the adenosine and dopamine systems to provide a mild stimulant effect, as well as a calming effect. It is structurally similar to caffeine and has been reported to have antioxidant, anti-inflammatory/analgesic, anti-depressive, locomotor, and sedative/hypnotic properties.
In rats, the administration of theacrine reversed the motor depression induced by adenosine receptor (AR) agonists, whereas theacrine-induced hyperlocomotion was reversed by dopamine receptor antagonists, suggesting that theacrine's psychostimulatory mechanism of action involves modulation of the adenosinergic and dopaminergic pathways.
Administration of selective dopamine D1 and D2 receptor antagonists (D1R SCH23390 and D2R eticlopride) significantly reduced theacrine-stimulated locomotor activity, indicating that this behavioral response, at least in part, is mediated by dopamine receptors. When theacrine was infused bilaterally into the nucleus accumbens (NAc), it enhanced activity levels in a dose-dependent manner, implicating a role of the NAc in modulating theacrine's effects on locomotion.
Theacrine did not induce locomotor sensitization or tolerance after chronic exposure. Taken together, these findings demonstrate that theacrine significantly enhances activity, an effect which is mediated by both the adenosinergic and dopaminergic systems.
Theacrine has a half-life of 30 to 33 hours. When combined with caffeine, caffeine diminished theacrine's oral clearance without altering its half-life, which suggested that the most likely mechanism for the observed interaction was that caffeine increased theacrine's oral bioavailability. The lack of an effect of theacrine on caffeine clearance implied that theacrine, while it may be a CYP1A2 substrate, is not a clinically significant CYP1A2 inhibitor.
Evidence level: Preliminary; limited number of small human trials with mostly subjective outcomes.
The initial two-part pilot study involving 15 human subjects found that theacrine (Teacrineâ„¢) delivered at an acute dose of 200 mg promoted a significant increase in energy, a reduction in fatigue, and a trend (p = 0.07) towards improved concentration (based on a subjective questionnaire) compared to a placebo group.
To compare the effects of a theacrine-containing dietary supplement with caffeine and placebo on energy and mood and objective measures of cognitive performance, 10 healthy men (20.8 ± 0.7 years) and 10 healthy women (22.2 ± 1.1 years) ingested the dietary supplement TheaTrim (containing a branded form of theacrine and caffeine at 150 mg), caffeine only (150 mg), or a placebo on three different days, separated by approximately one week. Before, and for up to 4 hours following ingestion, subjects completed a subjective assessment of energy and mood, as well as tests of cognitive performance. Heart rate and blood pressure were largely unaffected by treatment. These data indicate that TheaTrim treatment does not result in a statistically significant improvement in cognitive performance but may favorably impact multiple subjective feelings related to energy and mood.
In another clinical study, 24 men and 26 women ingested a placebo, theacrine at 25 mg, theacrine at 125 mg, caffeine at 150 mg, or a combination of 125 mg theacrine and 150 mg caffeine on five separate occasions separated by approximately one week. Subjects rated their subjective feelings at 30 minutes and 1, 2, 3, 4, and 5 hours post ingestion and performed the Trail Making Test (TMT) of cognitive performance. Subjective feelings of attentiveness, sense of focus, and sense of energy improved with all active treatments.
A more recent investigation examined the influence of dose and timing of theacrine consumption on cognitive performance and subsequent sleep using conditions that replicate a low (100 mg) and high (400 mg) dose consumed in the morning (12 h prior to bedtime), afternoon (8 hours prior to bedtime), and evening (4 hours prior to bedtime). The study found no significant effect of the low or high theacrine dose on subsequent sleep, although the high dose showed small non-significant effects on sleep efficiency and wake after sleep onset. Participants perceived a significantly longer sleep onset latency when consuming the 400 mg dose of theacrine 12 hours prior to bedtime compared to placebo, despite no significant effect when assessed objectively.
Previous studies investigating theacrine have shown mixed effects on self-reported level of arousal. For example, an acute dose of 200 mg significantly increased energy and reduced fatigue when assessed using visual analogue scales, while the acute intake of 300 mg had no significant effect on arousal when assessed using visual analogue scales or an adapted Profile of Moods States questionnaire.
Evidence level: Preliminary; small, randomized controlled studies; some industry funding noted.
Theacrine, a methylurate class purine alkaloid, triggers diverse pharmacologic responses, including psychostimulatory activity by modulation of adenosinergic and dopaminergic pathways. In a double-blind, placebo-controlled study, theacrine increased energy, concentration, and mood while reducing fatigue. Eight healthy adults received theacrine as TeaCrine® (25 or 125 mg), caffeine (150 mg), or a combination of theacrine (125 mg) and caffeine (150 mg) in a randomized, double-blind crossover study; blood samples were collected over 24 hours. Co-administration of theacrine and caffeine resulted in a clinically significant pharmacokinetic interaction — increased theacrine exposure. Enhanced oral bioavailability is the most likely mechanism by which caffeine alters theacrine exposure; however, further studies examining presystemic elimination mechanisms are needed to confirm the exact mechanism. Hemodynamic parameters were unaltered despite the pharmacokinetic interaction, suggesting that co-administration of caffeine and theacrine is safe at the doses administered.
In humans, co-administration of theacrine (125 mg) and caffeine (150 mg), compared to caffeine alone (275 mg) or placebo, resulted in sustained focus and concentration under fatigue-inducing conditions as well as enhanced alertness, attention, and information processing. It should be noted that several studies in this area were funded by Compound Solutions, Inc., the manufacturer of TeaCrine®. Researchers who received research funding from Compound Solutions, Inc., disclosed that these contracts paid for direct and indirect costs as well as salary, and that this study was funded by Compound Solutions, Inc., who was consulted in the design of the study.
Evidence level: Preliminary; one published randomized controlled trial in athletes; mixed findings.
The purpose of one study was to determine and compare the effects of TeaCrine® and caffeine on cognitive performance and time-to-exhaustion during a simulated soccer game in high-level male and female athletes. Theacrine is a pure alkaloid with a similar structure to caffeine and acts comparably as an adenosine receptor antagonist. Male and female soccer players (N = 24; mean age 20.96 ± 2.05 years) completed a 90-minute simulated treadmill soccer match over four randomized sessions (TeaCrine®, caffeine, TeaCrine® + caffeine, or placebo). Caffeine and caffeine+theacrine periods showed significant improvements versus placebo for cognitive tests, with the biggest differences at match end. Time-to-exhaustion showed 27–38% improvements (P=0.052) for theacrine and caffeine+theacrine periods, lasting from 194 seconds during placebo to 246, 255, and 267 seconds for theacrine, caffeine, and caffeine+theacrine periods respectively.
Studies have shown no adverse effects on heart rate or blood pressure compared to either supplement independently, suggesting this combination is safe to be administered in doses of 125 mg theacrine/150 mg caffeine.
Evidence level: Animal and in vitro data only; no human clinical trials conducted for these specific effects.
The anti-inflammatory and analgesic effects of theacrine were investigated using xylene-induced ear edema, acetic acid-induced vascular permeability, and λ-carrageenan-induced paw edema for anti-inflammatory activity, and acetic acid-induced writhing and hot-plate tests for analgesic effect. Oral administration of theacrine (8–32 mg/kg) induced dose-related anti-inflammatory and analgesic effects. In contrast, oral caffeine administration (8–32 mg/kg) did not show an inhibitory effect on the inflammatory response or cause analgesia. These findings are from animal models, and their direct applicability to humans has not been established in controlled clinical trials.
Evidence level: Animal studies only.
In the past few years, it was reported that theacrine had a variety of pharmacological activities, including anti-inflammatory and analgesic activities, antidepressant effects, and a protective effect against stress-provoked liver damage. The present study investigated the possible mechanism of the hypnotic activity of theacrine. The results revealed that theacrine significantly enhanced pentobarbital-induced sleep at a dose of 3.0 mg/kg (intragastrically) in mice. Sleep parameter analysis by EEG and EMG showed that theacrine obviously shortened wake time and increased NREM sleep time and that theacrine almost had no effect on REM sleep.
Theacrine speeds up the central nervous system at higher doses and slows down the central nervous system at lower doses. This dose-dependent bidirectional activity has only been systematically demonstrated in animal models.
Evidence level: Animal studies only; no human trials.
Studies have highlighted various pharmacological activities of theacrine, including antidepressant, antioxidant, anti-inflammatory, sedative and hypnotic properties, anticancer properties, cognitive performance effects, and a protective effect on the liver. Specifically, animal research has shown that theacrine attenuates restraint stress-provoked liver damage in mice; however, these findings have not been replicated in human trials.
Evidence level: Animal and in vitro studies; no established human clinical evidence.
In studies in mice, theacrine protected against liver damage by reducing the levels of inflammatory cytokines IL-1β, TNF-α, IL-6, and IFN-γ in the liver. It also increased the antioxidant capacity of the blood and liver of stressed mice. Theacrine increased the production of the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase and reduced the activity of xanthine oxidase. The relevance of these animal findings to human health requires further investigation.
Evidence level: Animal studies; limited, indirect human data from subjective mood assessments.
In mice, theacrine reduces depression-like activity in various tests. A small trial and one animal study are certainly insufficient to show that theacrine can improve mood. More clinical trials including much larger and more varied groups of people are needed to confirm these preliminary findings.
Evidence level: One human study (2024); preliminary.
There is interest in identifying alternative supplements that improve cognitive performance without compromising subsequent sleep. A study investigated the influence of dose and timing of theacrine consumption on cognitive performance and subsequent sleep using conditions replicating a low (100 mg) and high (400 mg) dose consumed in the morning, afternoon, and evening. Participants perceived a significantly longer sleep onset latency when consuming the 400 mg dose of theacrine 12 hours prior to bedtime compared to the placebo, despite no significant effect when assessed objectively.
All human clinical studies to date have administered theacrine orally, either in capsules or as part of a multi-ingredient supplement formulation.
In the 8-week randomized, placebo-controlled safety study, all values for clinical safety markers fell within normal limits and no group × time interactions were noted. No evidence of habituation was noted, as baseline values for energy, focus, concentration, anxiety, motivation to exercise, and POMS remained stable in all groups across the 8-week study protocol. These findings support the clinical safety and non-habituating neuro-energetic effects of TeaCrine® supplementation over 8 weeks of daily use (up to 300 mg/day). Moreover, there was no evidence of a tachyphylactic response that is typical of neuroactive agents such as caffeine and other stimulants.
Primary safety outcomes measured in the 8-week trial included fasting clinical safety markers: heart rate, blood pressure, lipid profiles, hematologic blood counts, and biomarkers of liver, kidney, and immune function.
Theacrine has demonstrated clinical safety and non-habituating effects in healthy humans over eight weeks of daily use at up to 300 mg/day. Moreover, there was no evidence of the tachyphylaxis typical of neuroactive agents like caffeine and other stimulants.
The result of the acute toxicity test showed that the LD50 of theacrine was 810.6 mg/kg (769.5–858.0 mg/kg). In animal studies, theacrine has an LD50 of 810 mg/kg, compared to 265 mg/kg for caffeine. This suggests a substantially wider acute safety margin than caffeine in these preclinical models.
A 90-day repeated-dose oral toxicological evaluation was conducted according to GLP and OECD guidelines on theacrine. Four groups of Hsd.Brl.Han Wistar rats (ten per sex per group) were administered theacrine by gavage doses of 0 (vehicle only), 180, 300, and 375 mg/kg bw/day. Two females and one male in the 300 and 375 mg/kg bw/day groups, respectively, died during the study; histological examination revealed centrilobular hepatocellular necrosis as the probable cause of death.
In 375 mg/kg bw/day males, slight reductions in body weight development, food consumption, and feed efficiency, decreased weight of the testes and epididymides, decreased intensity of spermatogenesis in the testes, and lack or decreased amount of mature spermatozoa in the epididymides were detected. At 300 mg/kg bw/day, slight decreases in the weights of the testes and epididymides, along with decreased intensity of spermatogenesis and lack or decreased amount of mature spermatozoa in the epididymides, were also detected in male animals. The NOAEL was considered to be 180 mg/kg bw/day, as at this dose there were no toxicologically relevant treatment-related findings in male or female animals.
Doses of up to 300 mg (approximately 3.8 mg/kg bw/day for a 78 kg human) given to healthy males and females in a previous clinical study did not result in any adverse effects or potential toxicological findings in numerous clinical safety markers. This contextualizes the high animal doses at which harm was observed relative to typical human supplemental doses.
Treatment with theacrine had little impact on heart rate and blood pressure, with only marginal increases noted (~3 bpm; ~3 mmHg). In the pharmacokinetic interaction study with caffeine, there was no difference between treatment groups with regard to heart rate or systolic/diastolic blood pressure.
Caffeine co-administration increased maximum plasma concentration and area under the curve (AUC) of theacrine without altering theacrine's half-life. Theacrine had no impact on caffeine or paraxanthine pharmacokinetics. The lack of an effect of theacrine on caffeine clearance implied that theacrine, while it may be a CYP1A2 substrate, is not a clinically significant CYP1A2 inhibitor.
Although initial studies related to potential efficacy and safety are promising, more research using this agent is needed. Previous studies investigating theacrine have shown mixed effects on self-reported level of arousal. The human clinical trial database for theacrine is limited in number, sample sizes are generally small, study durations rarely exceed 8 weeks, several studies involve multi-ingredient supplements (making attribution to theacrine alone difficult), and a proportion of published research has been industry-funded. No systematic reviews or meta-analyses exclusively focused on theacrine in humans had been published as of the available data.
Health conditions that Theacrine may help support.
Theacrine is a purine alkaloid naturally occurring in kucha tea (Camellia assamica var. kucha), structurally similar to caffeine. A randomized, double-blind, crossover pilot RCT found 200 mg theacrine significantly increased energy (+8.6%) and reduced fatigue (−6.7%) versus placebo, without habituation. It acts via adenosine and dopamine receptor pathways.
Theacrine is a purine alkaloid found in kucha tea (Camellia assamica var. kucha) with structural similarity to caffeine. Clinical trials show it improves energy, alertness, concentration, and mood without causing tolerance or elevating blood pressure, making it a novel non-habituating stimulant.
Theacrine (1,3,7,9-tetramethyluric acid) is a purine alkaloid in kucha tea (Camellia assamica var. kucha) and camu camu with stimulant and thermogenic properties. It activates dopaminergic and adenosinergic pathways similarly to caffeine, increasing energy expenditure and resting metabolic rate, while reportedly demonstrating less rapid tolerance development than caffeine.
Body systems that Theacrine may help support.
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