Cannabinoids are a structurally diverse class of compounds that bind to cannabinoid receptors in the endocannabinoid system — a ubiquitous neuromodulatory system present throughout the vertebrate nervous system and in many peripheral tissues. The term encompasses three distinct categories: endocannabinoids (endogenous ligands produced by the body, including anandamide and 2-arachidonoylglycerol), phytocannabinoids (plant-derived compounds, primarily from Cannabis sativa, including Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD)), and synthetic cannabinoids (man-made compounds designed to interact with cannabinoid receptors, ranging from research tools to drugs of abuse).
The endocannabinoid system plays a fundamental regulatory role in the central nervous system, modulating neurotransmitter release through retrograde signaling — postsynaptic neurons release endocannabinoids that travel backwards across the synapse to suppress presynaptic activity. This system regulates pain perception, appetite, memory formation, emotional processing, immune function, and many other physiological processes. Its widespread anatomical distribution explains both the broad range of cannabis's psychological and physical effects, and the potential therapeutic breadth of cannabinoid-based medicines.
Phytocannabinoids in cannabis have been used by humans for at least 5,000 years — for medicinal purposes, in religious and spiritual contexts, and recreationally. THC, identified and synthesized by Raphael Mechoulam in 1964, is primarily responsible for the plant's intoxicating effects. CBD, now the subject of extensive clinical research, is non-intoxicating and has demonstrated efficacy in several neurological conditions. Synthetic cannabinoids, developed initially as research tools, became drugs of abuse in the NPS market beginning in the late 2000s, with substantially higher potency and toxicity than natural cannabis.