Theacrine

Theacrine supports wakefulness and various dimensions of cognition. Effects include improved memory, attention, and motivation.
The available evidence suggests it is synthesized from caffeine in certain plants, and evidence suggests that it activates similar signaling pathways.
There appears to be no evidence of a diminishing response to successive doses of theacrine, meaning theacrine maintains its effectiveness without increasing the dose over time.
Theacrine has pain reducing and anti-stress properties that caffeine does not.
Theacrine is generally regarded as safe (GRAS) by the FDA.

Theacrine Sources

Theacrine is found in a camellia assamica variant of Kucha tea, but it is also found in Cupuaçu (Theobroma grandiflorum), a tropical rainforest tree related to cacao.

Common throughout the Amazon basin, Cupuaçu is widely cultivated and consumed in the jungles of South America.

Chemistry

The structure of theacrine is similar to caffeine with an additional methyl group and an additional ketone group.

Theacrine is one of a few compounds to be involved in adenosine signaling. Studies on theacrine have shown that concentrated doses activate the dopaminergic receptors D1 and D2, causing an increase in average dopamine levels while the theacrine is active.[1]

Elevated dopamine levels are commonly associated with improved mood, motivation, focus, and mental clarity. Research has shown theacrine to produce many of these benefits, especially improvements in motivation and focus. [2]

Demonstrated Effects

Recent research has reported increased feelings of energy, reduced fatigue, and strong effects on improving focus, concentration, and motivation while decreasing ratings of anxiety and irritability. [3]

In another 2017 study, researchers demonstrated coadministration of theacrine and caffeine results in a clinically significant pharmacokinetic interaction. Consuming caffeine with theacrine increased maximum plasma concentration and area under the curve of theacrine without altering theacrine half-life.[4]

Side Effects

So far, studies have found no side effects at the doses investigated. It is worth noting that many of the doses investigated far exceed nutritional supplement doses.

Safety

Theacrine is approved as a dietary supplement component under provisions of the Dietary Supplement Health and Education Act of 1994. It is classified as generally recognized as safe (GRAS).

In 2015, an 8-week study on the safety of theacrine demonstrated that clinical safety markers fell within normal limits and no evidence of habituation was noted as baseline values for energy, focus, concentration, anxiety, and motivation remained stable in all groups across the 8-week study protocol.[5]

These findings support the clinical safety and non-habituating neuro-energetic effects of theacrine supplementation over 8 weeks of daily use (up to 300 mg/day). Moreover, there was no evidence of diminishing response to successive doses of theacrine, meaning theacrine maintains its effectiveness without increasing the dose over time.[5]

Published Research

1. Feduccia, A. A., Wang, Y., Simms, J. A., Henry, Y. Y., Li, R., Bjeldanes, L., ... & Bartlett, S. E. (2012). Locomotor activation by theacrine, a purine alkaloid structurally similar to caffeine: involvement of adenosine and dopamine receptors. Pharmacology Biochemistry and Behavior, 102(2), 241-248.

2. Kuhman, D. J., Joyner, K. J., & Bloomer, R. J. (2015). Cognitive performance and mood following ingestion of a theacrine-containing dietary supplement, caffeine, or placebo by young men and women. Nutrients, 7(11), 9618-9632.

3. Ziegenfuss, T. N., Habowski, S. M., Sandrock, J. E., Kedia, A. W., Kerksick, C. M., & Lopez, H. L. (2017). A two-part approach to examine the effects of theacrine (TeaCrine®) supplementation on oxygen consumption, hemodynamic responses, and subjective measures of cognitive and psychometric parameters. Journal of dietary supplements, 14(1), 9-24.

4. He Hui, Ma Dejian, Crone Laura Brooks, Butawan Matthew, Meibohm Bernd, Bloomer Richard J., and Yates Charles R.. Assessment of the Drug–Drug Interaction Potential Between Theacrine and Caffeine in Humans. Journal of Caffeine Research. September 2017, 7(3): 95-102.

5. Taylor, L., Mumford, P., Roberts, M., Hayward, S., Mullins, J., Urbina, S., & Wilborn, C. (2016). Safety of TeaCrine®, a non-habituating, naturally-occurring purine alkaloid over eight weeks of continuous use. Journal of the International Society of Sports Nutrition, 13(1), 2.