Ephedrine

Ephedrine is a stimulant that activates the sympathetic nervous system. It is chemically synthesized for use as a drug in clinical practice, but ephedrine is also one of the ephedrine-type alkaloids that are extracted from plants in the Ephedra genus and have effects on the heart, vascular system, and other organs.^[79] Supplements derived from Ephedra plants (e.g., the Chinese botanical Ma Huang) are often referred to as “ephedra” and are marketed for many uses, including weight loss.^[80] Due to ephedra’s serious side effects, the Food and Drug Administration (FDA) has banned the sale of dietary supplements containing ephedra and ephedrine-type alkaloids in the United States.^[81]

Ephedrine and supplements derived from Ephedra plants can cause weight loss^[80][82] and improve blood lipid profiles (increased HDL cholesterol and decreased LDL cholesterol and triglycerides).^[82] Some studies show that ephedrine and ephedra supplements can improve exercise performance,^{[80][83][84][85]} but these effects are not consistent and are often found only when ephedrine is taken in combination with caffeine.^{[80][83][86][87]}

Ephedrine and supplements derived from Ephedra plants can cause autonomic hyperactivity (e.g., heart palpitations, tremors, twitching, insomnia, and sweating), gastrointestinal problems (e.g., nausea, vomiting, reflux, and heartburn), and psychiatric symptoms (e.g., agitation, lowered mood, irritability, and anxiety).^[82][80] Ephedra supplements have also been implicated in adverse cardiovascular and cerebrovascular outcomes including stroke, heart attack, and death.^[88][80]

Furthermore, ephedrine and its derivatives (pseudoephedrine, methylephedrine, etc.) are currently included on the prohibited list of substances issued by the World Anti-Doping Agency (WADA). Therefore, athletes who use ephedra supplements or over-the-counter drugs containing ephedrine (e.g., decongestants) must ensure that they are following the rules of their sport and holding the necessary therapeutic use exemptions (TUE).

The exact mechanisms are not fully understood but both ephedrine^[89][90] (the drug) and ephedrine-type alkaloids^[79][91] (from Ephedra plants) activate various adrenergic receptors in multiple tissues (heart, lungs, blood vessels, adipose tissue, muscles, etc.). This increases sympathetic nervous system activity, causing heart rate and blood pressure to rise and bronchioles in the lungs to dilate. The role of ephedrine and ephedra supplements in weight loss is likely related to increased fatty acid release from fat stores (adipose) and increased whole-body fat oxidation and energy expenditure.^[92][93][94] Because a rise in energy expenditure would increase heat production (thermogenesis), this likely explains the increased sweating caused by ephedrine and ephedra supplements.