Caffeine, nicotine, cannabis, and psilocybin: Pharmacology, toxicology, and potential therapeutic uses of four naturally occurring psychoactive substances

Psychoactive substances are compounds that can influence perception, consciousness, cognition, and emotions. The psychoactive substances caffeine, nicotine, cannabis, and psilocybin all originate from natural sources and can be used without complex processing or synthesis. Their natural availability has contributed to a long-standing history of human use and cultural significance. Caffeine and nicotine are freely available and commonly used as everyday stimulants, whereas psilocybin is more strictly regulated and cannabis has been legalised in some countries and regions. Some of these substances have been intensively studied, and their pharmacological and toxicological properties are well known, but ongoing research continues to investigate their therapeutic use for specific diseases and disorders. This narrative review aims to provide an overview of the pharmacology and toxicology of these four naturally occurring psychoactive substances, including a summary of the currently available evidence on their therapeutic potential, health benefits, and associated risks.