Theacrine

Uncontrolled hypertension, Cardiac arrhythmias, Cardiovascular disease

Oral theacrine at 6 mg/kg significantly elevated resting systolic and diastolic blood pressure in trained cyclists (Vieira-Cavalcante et al. 2025). Perception of tachycardia was reported at both 3 and 6 mg/kg. Individuals with pre-existing cardiovascular conditions face elevated risk from these hemodynamic effects. The 21-hour half-life prolongs the window of cardiovascular stress.

Panic disorder, Generalized anxiety disorder

Although theacrine appears less anxiogenic than caffeine at typical supplementation doses (Tartar et al. 2021 found caffeine-theacrine-methylliberine combination increased alertness without anxiety), its stimulant mechanism warrants caution in individuals with anxiety disorders, particularly at higher doses where cortisol elevation and restlessness may occur.

Cushing's syndrome, Adrenal insufficiency

Stoke et al. (2026) documented elevated salivary cortisol at 120–180 minutes post-dose at 3–9 mg/kg. Individuals with Cushing's syndrome, adrenal insufficiency under glucocorticoid replacement, or other HPA axis pathology should exercise caution. Clinical significance at typical supplementation doses (200–300 mg) has not been directly assessed.

Pregnancy, Lactation

No reproductive toxicity, teratogenicity, or lactation transfer data for theacrine have been published in any species. Standard precautionary avoidance of stimulant compounds during pregnancy and breastfeeding applies. This contraindication is entirely precautionary — neither safety nor harm has been demonstrated.

Cardiac stress testing with adenosine agonists

Theacrine's adenosine receptor antagonism would interfere with exogenous adenosine agonists used in cardiac stress testing, potentially invalidating diagnostic results. The 21-hour elimination half-life (Wildgrube et al. 2025) necessitates a minimum washout period of approximately 4 days (4–5 half-lives) before adenosine-dependent procedures.