cannabinoid cannabinoid cannabinoids (/kəˈnæbənɔɪdzˌ ˈkænəbənɔɪdz/) are several structural classes of compounds found in the cannabis plant primarily and most animal organisms (although insects lack such receptors) 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 also 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 (i.e., thca, cbda, cbca and their common precursor cbga) have been demonstrated to have a biogenetic origin. it was reported in 2020 that phytocannabinoids can be found in other plants such as rhododendron, licorice and liverwort, and earlier in echinacea. part of a series oncannabis artsculture 420 books magu (deity) names religion judaism latter-day saints sikhism smoke-in spiritual use sports stoner film stoner rock terms chemistry cannabinoid receptors cannabinoid receptor type 1 cannabinoid receptor type 2 cannabinoids 2-ag 2-age, noladin ether aea cbc cbl cbd cbdv cbg cbn cbv nada thc thcv virodhamine synthetic cannabinoids am-2201 cp-55940 dimethylheptylpyran hu-210 hu-331 jwh-018 jwh-073 jwh-133 levonantradol sr144528 win 55,212-2 consumption drinks edibles smoking tea vaping adult lifetime cannabis use by country annual cannabis use by country economics coffeeshop cultivation shop social club grow house grow shop head shop marijuana vending machine effects dependence driving drug testing effects of legalized cannabis gateway drug theory long term effects medicine memory pregnancy psychosis time perception forms bhang blunt charas flower essential oil hash oil hashish hemp hemp oil joint kief roach synthetic cannabis thai stick tincture law cannabis rights legality of cannabis timeline of cannabis law legality of cannabis in us legal history of cannabis in us us (medical non-medical timeline) cannabis act of canada legal history of cannabis in canada drug policy of california drug policy of the netherlands drug policy of portugal variants autoflowering cannabis genus cannabis species cannabis sativa cannabis indica cannabis ruderalis strains acapulco gold blue dream charlotte's web kush malawi gold sour diesel related drug culture illegal drug trade psychedelia cannabis portal medicine portal agriculture portal phytocannabinoids are multi-ring phenolic compounds structurally related to thc, but endocannabinoids are fatty acid derivatives. nonclassical synthetic cannabinoids (cannabimimetics) include aminoalkylindoles, 1,5-diarylpyrazoles, quinolines, and arylsulfonamides as well as eicosanoids related to endocannabinoids. uses medical uses include the treatment of nausea due to chemotherapy, spasticity, and possibly neuropathic pain. common side effects include dizziness, sedation, confusion, dissociation, and "feeling high". cannabinoid receptors before the 1980s, cannabinoids were speculated to produce their physiological and behavioral effects via nonspecific interaction with cell membranes, instead of interacting with specific membrane-bound receptors. the discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate. these receptors are common in animals. two known cannabinoid receptors are termed cb1 and cb2, with mounting evidence of more. the human brain has more cannabinoid receptors than any other g protein-coupled receptor (gpcr) type. the endocannabinoid system (ecs) regulates many functions of the human body. the ecs plays an important role in multiple aspects of neural functions, including the control of movement and motor coordination, learning and memory, emotion and motivation, addictive-like behavior and pain modulation, among others. cannabinoid receptor type 1 cb1 receptors are found primarily in the brain, more specifically in the basal ganglia and in the limbic system, including the hippocampus and the striatum. they are also found in the cerebellum and in both male and female reproductive systems. cb1 receptors are absent in the medulla oblongata, the part of the brain stem responsible for 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. while found only in the peripheral nervous system, a report does indicate that cb2 is expressed by a subpopulation of microglia in the human cerebellum. cb2 receptors appear to be responsible for immunomodulatory and possibly other therapeutic effects of cannabinoid as seen in vitro and in animal models. phytocannabinoids the bracts surrounding a cluster of cannabis sativa flowers are coated with cannabinoid-laden trichomes. cannabis indica plant 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. to the right, the main classes of cannabinoids from cannabis are shown. all classes derive from cannabigerol-type (cbg) compounds and differ mainly in the way this precursor is cyclized. the classical cannabinoids are derived from their respective 2-carboxylic acids (2-cooh) by decarboxylation (catalyzed by heat, light, or alkaline conditions). well known cannabinoids the best studied cannabinoids include tetrahydrocannabinol (thc), cannabidiol (cbd) and cannabinol (cbn). tetrahydrocannabinol main article: tetrahydrocannabinol tetrahydrocannabinol (thc) is the primary psychoactive component of the cannabis plant. delta-9-tetrahydrocannabinol (δ9-thc, thc) and delta-8-tetrahydrocannabinol (δ8-thc), through intracellular cb1 activation, induce anandamide and 2-arachidonoylglycerol synthesis produced naturally in the body and brain. these cannabinoids produce the effects associated with cannabis by binding to the cb1 cannabinoid receptors in the brain. cannabidiol main article: cannabidiol cannabidiol (cbd) is mildly psychotropic. evidence shows that the compound counteracts cognitive impairment associated with the use of cannabis. cannabidiol has little affinity for cb1 and cb2 receptors but acts as an indirect antagonist of cannabinoid agonists. it was found to be an antagonist at the putative new cannabinoid receptor, gpr55, a gpcr expressed in the caudate nucleus and putamen. cannabidiol has also been shown to act as a 5-ht1a receptor agonist. cbd can interfere with the uptake of adenosine, which plays an important role in biochemical processes, such as energy transfer. it may play a role in promoting sleep and suppressing arousal. cbd shares a precursor with thc and is the main cannabinoid in cbd-dominant cannabis strains. cbd has been shown to play a role in preventing the short-term memory loss associated with thc. there is tentative evidence that cbd has an anti-psychotic effect, but research in this area is limited. cannabinol main article: cannabinol cannabinol (cbn) is a mildly psychoactive cannabinoid that acts as a low affinity partial agonist at both cb1 and cb2 receptors. through its mechanism of partial agonism at the cb1r, cbn is thought to interact with other kinds of neurotransmission (e.g., dopaminergic, serotonergic, cholinergic, and noradrenergic). cbn was the first cannabis compound to be isolated from cannabis extract in the late 1800s. its structure and chemical synthesis were achieved by 1940, followed by some of the first pre-clinical research studies to determine the effects of individual cannabis-derived compounds in vivo. although cbn shares the same mechanism of action as other more well-known phytocannabinoids (e.g., delta-9 tetrahydrocannabinol or d9thc), it has a lower affinity for cb1 receptors, meaning that much higher doses of cbn are required in order to experience physiologic effects (e.g., mild sedation) associated with cb1r agonism. although scientific reports are conflicting, the majority of findings suggest that cbn has a slightly higher affinity for cb2 as compared to cb1. although cbn has been marketed as a sleep aid in recent years, there is a lack of scientific evidence to support these claims, warranting skepticism on the part of consumers. biosynthesis cannabinoid production starts when an enzyme causes geranyl pyrophosphate and olivetolic acid to combine and form cbga. next, cbga is independently converted to either cbg, thca, cbda or cbca by four separate synthase, fad-dependent dehydrogenase enzymes. there is no evidence for enzymatic conversion of cbda or cbd to thca or thc. for the propyl homologues (thcva, cbdva and cbcva), there is an analogous pathway that is based on cbgva from divarinolic acid instead of olivetolic acid. double bond position in addition, each of the compounds above may be in different forms depending on the position of the double bond in the alicyclic carbon ring. there is potential for confusion because there are different numbering systems used to describe the position of this double bond. under the dibenzopyran numbering system widely used today, the major form of thc is called δ9-thc, while the minor form is called δ8-thc. under the alternate terpene numbering system, these same compounds are called δ1-thc and δ6-thc, respectively. length most classical cannabinoids are 21-carbon compounds. however, some do not follow this rule, primarily because of variation in the length of the side-chain attached to the aromatic ring. in thc, cbd, and cbn, this side-chain is a pentyl (5-carbon) chain. in the most common homologue, the pentyl chain is replaced with a propyl (3-carbon) chain. cannabinoids with the propyl side chain are named using the suffix varin and are designated thcv, cbdv, or cbnv, while those with the heptyl side chain are named using the suffix phorol and are designated thcp and cbdp. cannabinoids in other plants phytocannabinoids are known to occur in several plant species besides cannabis. these include echinacea purpurea, echinacea angustifolia, acmella oleracea, helichrysum umbraculigerum, and radula marginata. the best-known cannabinoids that are not derived from cannabis are the lipophilic alkamides (alkylamides) from echinacea species, most notably the cis/trans isomers dodeca-2e,4e,8z,10e/z-tetraenoic-acid-isobutylamide. at least 25 different alkylamides have been identified, and some of them have shown affinities to the cb2-receptor. in some echinacea species, cannabinoids are found throughout the plant structure, but are most concentrated in the roots and flowers. yangonin found in the kava plant has significant affinity to the cb1 receptor. tea (camellia sinensis) catechins have an affinity for human cannabinoid receptors. a widespread dietary terpene, beta-caryophyllene, a component from the essential oil of cannabis and other medicinal plants, has also been identified as a selective agonist of peripheral cb2-receptors, in vivo. black truffles contain anandamide. perrottetinene, a moderately psychoactive cannabinoid, has been isolated from different radula varieties. most of the phytocannabinoids are nearly insoluble in water but are soluble in lipids, alcohols, and other non-polar organic solvents. cannabis plant profile cannabis plants can exhibit wide variation in the quantity and type of cannabinoids they produce. the mixture of cannabinoids produced by a plant is known as the plant's cannabinoid profile. selective breeding has been used to control the genetics of plants and modify the cannabinoid profile. for example, strains that are used as fiber (commonly called hemp) are bred such that they are low in psychoactive chemicals like thc. strains used in medicine are often bred for high cbd content, and strains used for recreational purposes are usually bred for high thc content or for a specific chemical balance. quantitative analysis of a plant's cannabinoid profile is often determined by gas chromatography (gc), or more reliably by gas chromatography combined with mass spectrometry (gc/ms). liquid chromatography (lc) techniques are also possible and, unlike gc methods, can differentiate between the acid and neutral forms of the cannabinoids. there have been systematic attempts to monitor the cannabinoid profile of cannabis over time, but their accuracy is impeded by the illegal status of the plant in many countries. pharmacology cannabinoids can be administered by smoking, vaporizing, oral ingestion, transdermal patch, intravenous injection, sublingual absorption, or rectal suppository. once in the body, most cannabinoids are metabolized in the liver, especially by cytochrome p450 mixed-function oxidases, mainly cyp 2c9. thus supplementing with cyp 2c9 inhibitors leads to extended intoxication. some is also stored in fat in addition to being metabolized in the liver. δ9-thc is metabolized to 11-hydroxy-δ9-thc, which is then metabolized to 9-carboxy-thc. some cannabis metabolites can be detected in the body several weeks after administration. these metabolites are the chemicals recognized by common antibody-based "drug tests"; in the case of thc or others, these loads do not represent intoxication (compare to ethanol breath tests that measure instantaneous blood alcohol levels), but an integration of past consumption over an approximately month-long window. this is because they are fat-soluble, lipophilic molecules that accumulate in fatty tissues. research shows the effect of cannabinoids might be modulated by aromatic compounds produced by the cannabis plant, called terpenes. this interaction would lead to the entourage effect. modulation of mitochondrial activity recent evidence has shown that cannabinoids play a role in the modulation of various mitochondrial processes, including intracellular calcium regulation, activation of apoptosis, impairment of electron transport chain activity, disruption of mitochondrial respiration and atp production, and regulation of mitochondrial dynamics. these processes contribute to various aspects of cellular biology and can be modified in response to external stimuli. the interaction between cannabinoids and mitochondria is complex, and various molecular mechanisms have been proposed,