Theacrine, caffeine like alkaloid without tolerance build-up

Theacrine is a purine alkaloid that is structurally similar to caffeine and uric acid. This alkaloid is usually isolated from Cupuaçu (Theobroma grandiflorum) and Camellia kucha (Camellia assamica variant kucha). It is sometimes regarded as an alternative to caffeine although small doses of theacrine appear to have sedative effects. At least in kucha leaves, theacrine is synthesized from caffeine [1].

Can Theacrine Replace Caffeine?

A recent pilot study partly funded by Compound Solutions, Inc. [2] reported that 200 mg dose of theacrine (as TeaCrine^™) caused significant improvements in energy and reductions in fatigue with a trend towards improved concentration. Rats injected with 24 or 48 mg/kg theacrine exhibited a dose-dependent increase in activity levels, where higher dose significantly increased locomotor activity compared to control while lower dose tended to do so [3]. This significantly enhanced activity levels were shown to be mediated by both the adenosinergic and dopaminergic systems [3]; the same signalling is reported for caffeine [4]. At low oral doses (10 mg/kg) it appears to have potent sedative and hypnotic properties [5].

Unlike caffeine [6], chronic theacrine exposure did not cause any locomotor sensitization or tolerance in mice; [3] the reason for this difference between theacrine and caffeine is currently not known.

For now, there is lack of evidence to support the claim that theacrine might be a replacement for caffeine. However, it seems that effects of theacrine are similar to that of caffeine but without tolerance build up. There are also no toxicological studies in humans.

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Benefits for Exercise

Recently, theacrine has been tested on muscular strength and muscular endurance. While caffeine has been reported to improve exercise performance and strength [11], 200 mg of theacrine failed to provide effective acute aide for improving either muscular strength or muscular endurance [10]. However, as apparent adenosine receptor antagonist, it provided positive effects on mood, energy, motivation, and focus.

Stress-related Liver Damage

Theacrine might also be helpful in the prevention of stress-related diseases and is potential therapeutic candidate for hepatic diseases. In mice subjected to restraint stress, theacrine was found to attenuate markedly elevated levels of ALT and AST, two markers of liver damage, as well as the decreased inflammatory cell infiltration and focal necrosis in the liver [7].

Other Benefits

Experimental animal studies also report antidepressant effect of theacrine probably due to its influence on monoamine neurotransmitter [8]. In mice, theacrine also exhibited anti-inflammatory and exerted dose dependent analgesic properties (reduced pain) [9].

Safety and Side Effects

No adverse effects were reported so far. At high doses side effects would probably be same as with caffeine. Theacrine appears to be well tolerated at small doses and doses typically found in tea. In mice, acute oral LD₅₀ is around 810 mg/kg [9].

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(Other common names: 1,3,7,9-tetramethyluric acid, TeaCrine)

References

1. Zheng, Xin-Qiang, et al. “Teacrine (1, 3, 7, 9-tetramethyluric acid) synthesis in leaves of a Chinese tea, kucha (Camellia assamica var. kucha).” Phytochemistry 60.2 (2002): 129-134.
2. Habowski, S. M., et al. “The effects of TeacrineTM, a nature-identical purine alkaloid, on subjective measures of cognitive function, psychometric and hemodynamic indices in healthy humans: a randomized, double-blinded crossover pilot trial.” Journal of the International Society of Sports Nutrition 11.Suppl 1 (2014): P49.
3. Feduccia, Allison A., et al. “Locomotor activation by theacrine, a purine alkaloid structurally similar to caffeine: involvement of adenosine and dopamine receptors.” Pharmacology Biochemistry and Behavior 102.2 (2012): 241-248.
4. Mukhopadhyay, S., and M. K. Poddar. “Caffeine-induced locomotor activity: possible involvement of GABAergic-dopaminergic-adenosinergic interaction.” Neurochemical research 20.1 (1995): 39-44.
5. Xu, Jie-Kun, et al. “Theacrin, a special purine alkaloid with sedative and hypnotic properties from Cammelia assamica var. kucha in mice.” Journal of Asian natural products research 9.7 (2007): 665-672.
6. Zancheta, Roberta, et al. “Repeated administration of caffeine induces either sensitization or tolerance of locomotor stimulation depending on the environmental context.” Pharmacological Reports 64.1 (2012): 70-77.
7. Li, Wei-Xi, et al. “Thecrine, a purine alkaloid obtained from Camellia assamica var. kucha, attenuates restraint stress-provoked liver damage in mice.” Journal of agricultural and food chemistry 61.26 (2013): 6328-6335.
8. Xie, Guo, et al. “Experimental study of theacine on antidepressant effects.” Chin Pharmacol Bull 9 (2009): 13.
9. Wang, Yuanyuan, et al. “Teacrine, a purine alkaloid with anti-inflammatory and analgesic activities.” Fitoterapia 81.6 (2010): 627-631.
10. Snyder, Caleb J. “Acute effects of teacrine supplementation on muscular strength and muscular endurance.” (2016).
11. Warren, Gordon L., et al. “Effect of caffeine ingestion on muscular strength and endurance: a meta-analysis.” Med Sci Sports Exerc 42.7 (2010): 1375-87.