Higenamine, also referred to as norcoclaurine, is a chemical compound found in a variety of plants which have a history of use in traditional medicine (mostly extracted from Tinospora crispa). Some of the plants with the highest concentration are: Nandina domestica, Aconitum carmichaelii, Nelumbo nucifera, Aconitum japonicum (root) etc. In vitro and animal studies have shown a variety of effects but its effects in humans are unknown. It is claimed to stimulate β-androgenic receptors and possess lipolytic activity and is therefore quickly making its way into dietary supplement market. Recently, higenamine is receiving attention from the dietary supplement community, as a potential agent for weight loss and sport performance supplements.
Higenamine appears to be rapidly absorbed as it reaches maximum value after 10 mins but has a very short half-life (0.133 h) [12,13]. A study in rabbits reported highly varied bioavailability of orally administered higenamine from approximately 3%–22%, possibly due to differences in degradation, gut metabolism, or gastrointestinal absorption .
Higenamine is usually dosed between 20-40 mg which is similar to Synephrine or Ephedrine. However, some pre-workout supplements go as high as 75 mg. Currently there is no evidence to support the optimal dose.
Replacement to 1,3-Dimethylamylamine (DMAA)?
Since the ban of 1,3-dimethylamylamine many supplements are trying to take its place and norcoclaurine (also known as higenamine) is one of them. Higenamine can be found in many pre-workout supplements for improving athletic performance. At the moment there is no scientific evidence to support these claims. Looking at some en vitro studies it may have the potential to replace famous DMAA.
Higenamine is also used and added to many fat burning supplements. Higenamine is a beta-1 and beta-2 adrenergic receptor agonist (agonist: chemical that binds to receptor) [1,2]. This mechanism is also shared by ephedrine . Beta-2 adrenergic receptor agonists are drugs that act on the beta-2 adrenergic receptor and are primarily used to treat asthma , while the activation of beta-1 receptors leads to increased heart rate and blood pressure , secretion of ghrelin (hunger-stimulating peptide)  from the stomach, and renin (enzyme released when you have decreased salt or low blood volume)  release from the kidneys.
Human studies are lacking but since treatment with beta 2-agonists has been reported to promote fat loss and muscle growth , higenamine shows some promise as a sport supplement. Beta-3 adrenergic receptor agonists have been shown to increase insulin sensitivity and to be very effective thermogenetic and anti-obesity agents . However, higenamines effect on beta-3 adrenoceptors remains to be investigated.
Higenamine Side Effects and Toxicology
Higenamine is possibly unsafe when taken orally. Higenamine containing plant, Aconitum has been shown to cause serious heart-related side effects including arrhythmias and even death when ingested, which may, in part, be caused by the higenamine. 
A very recent safety study  has been conducted in forty-eight men who ingest either a placebo, higenamine, caffeine, or higenamine + caffeine + yohimbe bark extract daily for a period of 8 weeks. Data collected indicated that daily higenamine supplementation, either alone or in conjunction with caffeine and yohimbe bark extract, does not result in a statistically significant change in any of the measured outcome variables. Intravenous administration of 22.5 μg/kg higenamine was reported to be well-tolerated in healthy volunteers. More large-scale studies are needed to better asses its safety.
Higenamine also seems to share some of the side effects with 1,3-dimethylamylamine such as increased blood pressure and heart rate [9,5]. However, it has been observed that at a dose of 22.5 μg/kg, it does not cause a significant change in systolic blood pressure, but it slightly decreases diastolic blood pressure . In the same study, heart rate increased rapidly, occurring within 2 min after drug administration.
(Other common names: 1-[(4-Hydroxyphenyl)methyl]-1,2,3,4-tetrahydroisoquinoline-6,7-diol, benzyltetrahydroisoquinoline, Higenamine HCL; Higenamine Oxalate, Higenamine Hydrobromide, Higenamine Tartrate; Norcoclaurine; O-Demethylcoclaurine, dl-Demethylcoclaurine, demethylcoclaurine, DMC, Aconite root)
Note: All selective and non-selective beta-2 agonists are prohibited in sports. Since 2017, higenamine is expressly added to The World Anti-Doping Agency’s (WADA) prohibition list. 
Tsukiyama, Muneo, et al. “β2-Adrenoceptor-Mediated Tracheal Relaxation Induced by Higneamin from Nandina domestica Thunberg.” Planta medica 75.13 (2009): 1393-1399.
Kimura, Ikuko, et al. “Positive chronotropic and inotropic effects of higenamin and its enhancing action on the aconitine-induced tachyarrhythmia in isolated murine atria.” Japanese journal of pharmacology 66.1 (1994): 75-80.
Liu, Y. L., et al. “Contribution of beta 3-adrenoceptor activation to ephedrine-induced thermogenesis in humans.” International journal of obesity and related metabolic disorders: journal of the International Association for the Study of Obesity 19.9 (1995): 678-685.
Ullman, A. N. D. E. R. S., and N. I. L. S. Svedmyr. “Salmeterol, a new long acting inhaled beta 2 adrenoceptor agonist: comparison with salbutamol in adult asthmatic patients.” Thorax 43.9 (1988): 674-678.
Liu, Jie, et al. “β1-Adrenergic receptor polymorphisms influence the response to metoprolol monotherapy in patients with essential hypertension&ast.” Clinical Pharmacology & Therapeutics 80.1 (2006): 23-32.
Zhao, Tong-Jin, et al. “Ghrelin secretion stimulated by β1-adrenergic receptors in cultured ghrelinoma cells and in fasted mice.” Proceedings of the National Academy of Sciences 107.36 (2010): 15868-15873.
Osborn, J. T. L., G. F. DiBona, and M. D. Thames. “Beta-1 receptor mediation of renin secretion elicited by low-frequency renal nerve stimulation.” Journal of Pharmacology and Experimental Therapeutics 216.2 (1981): 265-269.
Arch, Jonathan RS. “β 3-Adrenoceptor agonists: potential, pitfalls and progress.” European journal of pharmacology 440.2 (2002): 99-107.
Bloomer, Richard J., et al. “Effects of 1, 3-dimethylamylamine and caffeine alone or in combination on heart rate and blood pressure in healthy men and women.” Phys Sportsmed 39.3 (2011): 111-120.
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Bloomer, R. J., J. M. Schriefer, and T. A. Gunnels. “Clinical safety assessment of oral norcoclaurine supplementation in healthy, young men.” Human & experimental toxicology (2015): 0960327114565490.
- Lo, Chi‐Fang, and Chi‐Ming Chen. “Pharmacokinetics of higenamin in rabbits.” Biopharmaceutics & drug disposition 17.9 (1996): 791-803.
- Feng, Sheng, et al. “A phase I study on pharmacokinetics and pharmacodynamics of higenamin in healthy Chinese subjects.” Acta Pharmacologica Sinica 33.11 (2012): 1353-1358.
- Astrup, Arne, et al. “The effect of ephedrine/caffeine mixture on energy expenditure and body composition in obese women.” Metabolism 41.7 (1992): 686-688.