Alkaloids from the entheogenic plant Peganum harmala

Entheogenic natural products (e.g., psylocybin and dimethyltryptamine) are emerging as effective therapeutics to treat debilitating mood disorders that are unresponsive to conventional treatment. The detailed evaluation of psychotropic plants will conceivably lead to the discovery of structurally distinct entheogens that may offer improved or complementary medicinal properties to the classic entheogens. The plant Peganum harmala has a rich history in traditional medicine, with consumption inducing a host of central nervous system (CNS) symptoms, including hallucinations. Given alkaloids are uniquely capable of altering the CNS physiology owing to their ability to cross the blood–brain barrier, the natural product(s) responsible for the entheogenic properties are likely hidden in its structurally diverse alkaloid profile. Herein, an overview of the 160 alkaloids isolated from P. harmala is provided. Remarkably, bioactivity data is scarce, limited to inhibition of monoamine oxidases and cholinesterases in a few cases, with the majority having no reported bioactivity at all. As none of the classic entheogens have been detected in P. harmala, this collection of alkaloids provides a useful reference point in the search of structurally unique entheogens.