Phytocannabinoids

Phytocannabinoids are a family of chemical compounds produced by plants, most notably Cannabis species, that interact with the endocannabinoid system in animals. They are lipophilic, phenolic molecules synthesized in glandular trichomes and commonly occur as acidic precursors in fresh plant material, which decarboxylate to active neutral forms when heated or aged.

The best known phytocannabinoids include delta-9-tetrahydrocannabinol (THC), the primary psychoactive agent; tetrahydrocannabinolic acid (THCA), the non-psychoactive precursor; cannabidiol (CBD), which has little affinity for CB1/CB2 receptors and modulates other targets; cannabidiolic acid (CBDA); cannabigerol (CBG); cannabichromene (CBC); and cannabinol (CBN), along with numerous minor cannabinoids.

Biosynthesis occurs in the plant’s glandular trichomes, producing the acidic carboxylated forms THCA, CBDA, and CBCA. Upon heating or aging, these acids decarboxylate to THC, CBD, and related neutral cannabinoids. The chemistry of phytocannabinoids involves a phenolic core linked to a terpenoid side chain, contributing to their lipophilicity and diverse biological activity.

Pharmacology is characterized by polypharmacology: THC activates CB1 receptors in the central nervous system, producing psychoactive effects, while CB2 receptors are primarily in the immune system. CBD has low CB1/CB2 affinity but interacts with multiple targets, including TRP channels and PPARs, contributing to anti-inflammatory, analgesic, anticonvulsant, and neuroprotective properties. Some phytocannabinoids are studied for therapeutic uses, and CBD is an approved treatment for certain seizure disorders in some jurisdictions.

Occurrence and applications: phytocannabinoids occur mainly in cannabis but can be present in other plants in smaller amounts. They are investigated for pain, epilepsy, neurodegenerative diseases, and other conditions, and are used in medical cannabis and hemp products. Regulation varies by country and region.