Ephedrae Herba and Ephedrine on Nervous System: A Comprehensive Review of Pharmacology and Neurotoxicity

Since Ephedra Herba (ephedra) and its major alkaloid ephedrine were prohibited as dietary supplements due to their adverse effects on the cardiovascular and central nervous system (CNS), most studies have focused on their amphetamine-like effects and neurotoxicity. However, ephedra also has a long history of use in the treatment of various CNS diseases (known as "Zhong Feng" syndrome) according to two thousand years of traditional Chinese medicine (TCM) records. Pharmacokinetic reports have also demonstrated that alkaloids of ephedra can quickly penetrate the blood-brain barrier (BBB) once absorbed into the blood and there are multiple alkaloids derived from ephedra which have been identified as natural sympathomimetic drugs. These drugs are capable of interfering with several types of neurotransmitter, and have an especially potent effect on monoamine neurotransmitters. The effects of ephedra on CNS therefore remain both contradictory and confusing. In this review, we summarized the available evidence of pharmacology and toxicology of ephedra and ephedrine on CNS, and aimed to clarify their effects. Given the unmet need for more efficient treatments of neurological disorders, ephedra is potentially valuable herbal medicine which may provide a promising avenue for development of treatments and encourage further drug research and development (R&D).