Cannabinoid

Cannabinoids (/kəˈnæbənɔɪdzˌ ˈkænəbənɔɪdz/) are several structural classes of compounds found primarily in the Cannabis plant or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tetrahydrocannabinol (THC) (delta-9-THC), the primary psychoactive compound in cannabis. Cannabidiol (CBD) is a major constituent of temperate cannabis plants and a minor constituent in tropical varieties. At least 113 distinct phytocannabinoids have been isolated from cannabis, although only four (THCA, CBDA, CBCA, and their common precursor CBGA) have a confirmed biogenetic origin. Phytocannabinoids are also found in other plants, such as rhododendron, licorice, and liverwort.

Phytocannabinoids are multi-ring phenolic compounds structurally related to THC, while endocannabinoids are fatty acid derivatives. Nonclassical synthetic cannabinoids (cannabimimetics) include aminoalkylindoles, 1,5-diarylpyrazoles, quinolines, and arylsulfonamides, as well as eicosanoids related to endocannabinoids.

Medical uses of cannabinoids include the treatment of nausea due to chemotherapy, spasticity, and possibly neuropathic pain. Common side effects include dizziness, sedation, confusion, dissociation, and "feeling high".

Cannabis may provide limited relief for some Parkinson's disease (PD) symptoms, such as pain, sleep issues, or anxiety, based on small human studies (2023–2024, 10–50 participants), but it does not improve motor symptoms like tremors or stiffness (no significant change in Unified Parkinson's Disease Rating Scale scores). A 2023 US survey found 46% of PD patients reported benefits for pain or sleep. Raw Cannabis contains tetrahydrocannabinolic acid (THCA, 15–30% of the plant) and cannabidiolic acid (CBDA), which are non-psychoactive. Animal studies (2021–2024) suggest THCA and CBDA may reduce inflammation and protect brain cells in PD models, acting on CB2 receptors and other pathways (e.g., TRP channels, PPARγ), unlike tetrahydrocannabinol (THC) and cannabidiol (CBD), which form when cannabis is heated (e.g., smoking, 105–150°C). No human studies have tested THCA or CBDA for PD as of 2025. In regions like India, raw cannabis is used traditionally for tremors, but scientific evidence is lacking. Risks include dizziness from THC (12–20% dropout in studies) and potential interactions with PD medications like levodopa.

Before the 1980s, cannabinoids were thought to produce their effects via nonspecific interaction with cell membranes, rather than specific membrane-bound receptors. The discovery of cannabinoid receptors in the 1980s resolved this debate. These receptors are common in animals, with two primary types, CB₁ and CB₂, and evidence suggests additional receptors may exist. The human brain has more cannabinoid receptors than any other G protein-coupled receptor (GPCR) type.

The endocannabinoid system (ECS) regulates multiple functions, including movement, motor coordination, learning, memory, emotion, motivation, addictive-like behavior, and pain modulation.

CB₁ receptors are found primarily in the brain, particularly in the basal ganglia, limbic system, hippocampus, and striatum. They are also present in the cerebellum, and male and female reproductive systems, but absent in the medulla oblongata, which controls respiratory and cardiovascular functions. CB1 is also found in the human anterior eye and retina.

CB₂ receptors are predominantly found in the immune system or immune-derived cells, with varying expression patterns. A subpopulation of microglia in the human cerebellum expresses CB₂. CB₂ receptors are linked to immunomodulatory effects and potential therapeutic benefits in animal models.