Cannabinoid
Cannabinoids are several structural classes of compounds found primarily in the Cannabis plant or as synthetic compounds. The most notable cannabinoid is the phytocannabinoid tetrahydrocannabinol , the primary psychoactive compound in cannabis. Cannabidiol 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 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 include aminoalkylindoles, 1,5-diarylpyrazoles, quinolines, and arylsulfonamides, as well as eicosanoids related to endocannabinoids.
Uses
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".Parkinson's Disease
Cannabis may provide limited relief for some Parkinson's disease symptoms, such as pain, sleep issues, or anxiety, based on small human studies, but it does not improve motor symptoms like tremors or stiffness. A 2023 US survey found 46% of PD patients reported benefits for pain or sleep. Raw Cannabis contains tetrahydrocannabinolic acid and cannabidiolic acid, which are non-psychoactive. Animal studies suggest THCA and CBDA may reduce inflammation and protect brain cells in PD models, acting on CB2 receptors and other pathways, unlike tetrahydrocannabinol and cannabidiol, which form when cannabis is heated. 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 and potential interactions with PD medications like levodopa.Cannabinoid receptors
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 type.The endocannabinoid system regulates multiple functions, including movement, motor coordination, learning, memory, emotion, motivation, addictive-like behavior, and pain modulation.
Cannabinoid receptor type 1
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.Cannabinoid receptor type 2
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.Phytocannabinoids
The classical cannabinoids are concentrated in a viscous resin produced in structures known as glandular trichomes. At least 113 different cannabinoids have been isolated from the Cannabis plant.All classes derive from cannabigerol-type compounds and differ mainly in the way this precursor is cyclized. The classical cannabinoids are derived from their respective 2-carboxylic acids by decarboxylation.
Well known cannabinoids
The best-studied cannabinoids include tetrahydrocannabinol, cannabidiol, and cannabinol.Tetrahydrocannabinol
Tetrahydrocannabinol is the primary psychoactive component of the Cannabis plant. Delta-9-tetrahydrocannabinol and delta-8-tetrahydrocannabinol induce anandamide and 2-arachidonoylglycerol synthesis through intracellular CB1 activation. These cannabinoids produce the psychoactive effects of cannabis by binding to CB1 receptors in the brain.Cannabidiol
Cannabidiol is mildly psychotropic and counteracts cognitive impairment associated with cannabis use. CBD has low affinity for CB1 and CB2 receptors but acts as an indirect antagonist of cannabinoid agonists. It is an agonist at the 5-HT1A receptor and may promote sleep and suppress arousal by interfering with adenosine uptake. CBD shares a precursor with THC and is the main cannabinoid in CBD-dominant Cannabis strains, potentially reducing short-term memory loss associated with THC. Tentative evidence suggests CBD may have anti-psychotic effects, though research is limited. CBD and other cannabinoids have shown antimicrobial properties, potentially addressing antimicrobial resistance.Cannabinol
Cannabinol is a mildly psychoactive cannabinoid acting as a low-affinity partial agonist at CB1 and CB2 receptors. CBN interacts with other neurotransmitter systems, requiring higher doses for physiologic effects like mild sedation compared to THC. Isolated in the late 1800s, its structure was elucidated in the 1930s, and chemical synthesis was achieved by 1940.Biosynthesis
Cannabinoid production begins with an enzyme combining geranyl pyrophosphate and olivetolic acid to form CBGA. CBGA is converted to CBG, THCA, CBDA, or CBCA by four separate synthase, FAD-dependent dehydrogenase enzymes. There is no enzymatic conversion of CBDA or CBD to THCA or THC. Propyl homologues follow an analogous pathway from divarinolic acid.Double bond position
Each cannabinoid may exist in different forms depending on the double bond position in the alicyclic carbon ring. Under the dibenzopyran numbering system, the major form of THC is Δ9-THC, and the minor form is Δ8-THC. In the alternate terpene numbering system, these are Δ1-THC and Δ6-THC, respectively.Length
Most classical cannabinoids are 21-carbon compounds, but variations in the side-chain length attached to the aromatic ring exist. In THC, CBD, and CBN, the side-chain is a pentyl chain. Propyl chain variants are named with the suffix varin, while heptyl chain variants are named phorol.Cannabinoids in other plants
Phytocannabinoids occur in plants like Echinacea purpurea, Echinacea angustifolia, Acmella oleracea, Helichrysum umbraculigerum, and Radula marginata. Echinacea species contain Anandamide-like alkylamides, with at least 25 identified, some showing affinity for CB2 receptors. These are concentrated in roots and flowers. Yangonin in kava has significant CB1 receptor affinity. Tea catechins show affinity for human cannabinoid receptors. Beta-caryophyllene, a terpene in cannabis and other plants, is a selective CB2 receptor agonist. Black truffles contain anandamide. Perrottetinene, a moderately psychoactive cannabinoid, is found in Radula varieties. Machaeriol A and related compounds occur in Machaerium plants.Most phytocannabinoids are nearly insoluble in water but soluble in lipids, alcohols, and other non-polar organic solvents.