156-409: Tetrahydrocannabinol ( THC ) is a cannabinoid found in cannabis . It is the principal psychoactive constituent of cannabis and one of at least 113 total cannabinoids identified on the plant. Although the chemical formula for THC (C 21 H 30 O 2 ) describes multiple isomers , the term THC usually refers to the delta-9-THC isomer with chemical name (−)- trans -Δ-tetrahydrocannabinol . It
312-508: A 5-HT 1A 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
468-584: 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 . 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. Medical uses include
624-501: A combination of immunoassay and chromatographic techniques as part of a drug use testing program or in a forensic investigation. There is ongoing research to create devices capable of detecting THC in breath. THC, along with its double bond isomers and their stereoisomers , is one of only three cannabinoids scheduled by the UN Convention on Psychotropic Substances (the other two are dimethylheptylpyran and parahexyl ). It
780-464: A common ancestor that appeared late in the Cryogenian period, 700–650 million years ago, and it has been hypothesized that this common ancestor had the shape of a simple tubeworm with a segmented body. At a schematic level, that basic worm-shape continues to be reflected in the body and nervous system architecture of all modern bilaterians, including vertebrates. The fundamental bilateral body form
936-417: A condition characterized by cyclic nausea, vomiting, and abdominal pain that may persist for months to years after discontinuation. The median lethal dose of THC in humans is not fully known as there is conflicting evidence. A 1972 study gave up to 90 mg/kg of THC to dogs and monkeys without any lethal effects. Some rats died within 72 hours after a dose of up to 36 mg/kg. A 2014 case study based on
1092-471: A gradient of size and complexity that roughly follows the evolutionary sequence. All of these brains contain the same set of basic anatomical structures, but many are rudimentary in the hagfish, whereas in mammals the foremost part ( forebrain , especially the telencephalon ) is greatly developed and expanded. Brains are most commonly compared in terms of their mass . The relationship between brain size , body size and other variables has been studied across
1248-569: A lighter color. Further information can be gained by staining slices of brain tissue with a variety of chemicals that bring out areas where specific types of molecules are present in high concentrations. It is also possible to examine the microstructure of brain tissue using a microscope, and to trace the pattern of connections from one brain area to another. The brains of all species are composed primarily of two broad classes of brain cells : neurons and glial cells . Glial cells (also known as glia or neuroglia ) come in several types, and perform
1404-400: 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
1560-524: A moderately psychoactive cannabinoid, has been isolated from different Radula varieties. Machaeriol A and related compounds are found in plants from the Machaerium family. Most of the phytocannabinoids are nearly insoluble in water but are soluble in lipids , alcohols , and other non-polar organic solvents . Cannabis plants can exhibit wide variation in the quantity and type of cannabinoids they produce. The mixture of cannabinoids produced by
1716-450: A much faster onset of action than oral administration of THC. Inhalation of THC bypasses the first-pass metabolism that occurs with oral administration. The bioavailability of THC with inhalation is increased in heavy users. Transdermal administration of THC is limited by its extreme water insolubility . Efficient skin transport can only be obtained with permeation enhancement. Transdermal administration of THC, as with inhalation, avoids
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#17327723746631872-443: A much larger proportion of the brain for primates than for other species, and an especially large fraction of the human brain. The brain develops in an intricately orchestrated sequence of stages. It changes in shape from a simple swelling at the front of the nerve cord in the earliest embryonic stages, to a complex array of areas and connections. Neurons are created in special zones that contain stem cells , and then migrate through
2028-518: A near 1:1 ratio of CBD and THC. Also included are minor cannabinoids and terpenoids , ethanol and propylene glycol excipients , and peppermint flavoring. The drug, made by GW Pharmaceuticals , was first approved by Canadian authorities in 2005 to alleviate pain associated with multiple sclerosis , making it the first cannabis-based medicine. It is marketed by Bayer in Canada. Sativex has been approved in 25 countries; clinical trials are underway in
2184-491: A neuron is in place, it extends dendrites and an axon into the area around it. Axons, because they commonly extend a great distance from the cell body and need to reach specific targets, grow in a particularly complex way. The tip of a growing axon consists of a blob of protoplasm called a growth cone , studded with chemical receptors. These receptors sense the local environment, causing the growth cone to be attracted or repelled by various cellular elements, and thus to be pulled in
2340-470: A number of critical functions, including structural support, metabolic support, insulation, and guidance of development. Neurons, however, are usually considered the most important cells in the brain. In humans, the cerebral cortex contains approximately 14–16 billion neurons, and the estimated number of neurons in the cerebellum is 55–70 billion. Each neuron is connected by synapses to several thousand other neurons. The property that makes neurons unique
2496-548: A partial agonist at CB 1 , it behaves as a CB 1 antagonist in vivo . In rats, virodhamine was found to be present at comparable or slightly lower concentrations than anandamide in the brain , but 2- to 9-fold higher concentrations peripherally. Lysophosphatidylinositol is the endogenous ligand to novel endocannabinoid receptor GPR55 , making it a strong contender as the sixth endocannabinoid. Endocannabinoids serve as intercellular ' lipid messengers ', signaling molecules that are released from one cell and activating
2652-455: A particular direction at each point along its path. The result of this pathfinding process is that the growth cone navigates through the brain until it reaches its destination area, where other chemical cues cause it to begin generating synapses. Considering the entire brain, thousands of genes create products that influence axonal pathfinding. The synaptic network that finally emerges is only partly determined by genes, though. In many parts of
2808-446: 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
2964-512: A previously existing brain structure. This category includes tardigrades , arthropods , molluscs , and numerous types of worms. The diversity of invertebrate body plans is matched by an equal diversity in brain structures. Two groups of invertebrates have notably complex brains: arthropods (insects, crustaceans , arachnids , and others), and cephalopods (octopuses, squids , and similar molluscs). The brains of arthropods and cephalopods arise from twin parallel nerve cords that extend through
3120-422: 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
3276-520: A status that limits cultivation, manufacture, distribution, clinical research, and therapeutic applications. In April 2014, the American Academy of Neurology found evidence supporting the effectiveness of the cannabis extracts in treating certain symptoms of multiple sclerosis and pain, but there was insufficient evidence to determine effectiveness for treating several other neurological diseases. A 2015 review confirmed that medical marijuana
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#17327723746633432-399: A subpopulation of microglia in the human cerebellum . CB 2 receptors appear to be responsible for immunomodulatory and possibly other therapeutic effects of cannabinoid as seen in vitro and in animal models. 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
3588-426: A variety of entities in the brain and body, such as adipose tissue (fat). THC, as well as other cannabinoids that contain a phenol group, possess mild antioxidant activity sufficient to protect neurons against oxidative stress , such as that produced by glutamate -induced excitotoxicity . THC targets receptors in a manner far less selective than endocannabinoid molecules released during retrograde signaling , as
3744-425: A very low solubility in water, but good solubility in lipids and most organic solvents , specifically hydrocarbons and alcohols . A total synthesis of the compound was reported in 1965; that procedure called for the intramolecular alkyl lithium attack on a starting carbonyl to form the fused rings, and a tosyl chloride mediated formation of the ether. As a phytochemical , THC is assumed to be involved in
3900-486: A way that reflects in part the complexity of their behavior. For example, primates have brains 5 to 10 times larger than the formula predicts. Predators , who have to implement various hunting strategies against the ever changing anti-predator adaptations , tend to have larger brains relative to body size than their prey. All vertebrate brains share a common underlying form, which appears most clearly during early stages of embryonic development . In its earliest form,
4056-483: A wide range of vertebrate species. As a rule of thumb , brain size increases with body size, but not in a simple linear proportion. In general, smaller animals tend to have proportionally larger brains, measured as a fraction of body size. For mammals, the relationship between brain volume and body mass essentially follows a power law with an exponent of about 0.75. This formula describes the central tendency, but every family of mammals departs from it to some degree, in
4212-412: A wide variety of biochemical and metabolic processes, most notably the interactions between neurotransmitters and receptors that take place at synapses. Neurotransmitters are chemicals that are released at synapses when the local membrane is depolarised and Ca enters into the cell, typically when an action potential arrives at the synapse – neurotransmitters attach themselves to receptor molecules on
4368-437: Is decarboxylated , producing THC. The pathway for THCA biosynthesis is similar to that which produces the bitter acid humulone in hops . It can also be produced in genetically modified yeast . Cannabidiol was isolated and identified from Cannabis sativa in 1940 by Roger Adams who was also the first to document the synthesis of THC (both Delta-9-THC and Delta-8-THC ) from the acid-based cyclization of CBD in 1942. THC
4524-681: Is a colorless oil. THC, referred to as dronabinol in the pharmaceutical context, is approved in the United States as a capsule or solution to relieve chemotherapy-induced nausea and vomiting and HIV/AIDS -induced anorexia . THC is an active ingredient in nabiximols , a specific extract of Cannabis that was approved as a botanical drug in the United Kingdom in 2010 as a mouth spray for people with multiple sclerosis to alleviate neuropathic pain , spasticity , overactive bladder , and other symptoms. Nabiximols (as Sativex)
4680-463: Is a lack of scientific evidence to support these claims, warranting skepticism on the part of consumers. 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
4836-405: Is a list of some of the most important vertebrate brain components, along with a brief description of their functions as currently understood: Modern reptiles and mammals diverged from a common ancestor around 320 million years ago. The number of extant reptiles far exceeds the number of mammalian species, with 11,733 recognized species of reptiles compared to 5,884 extant mammals. Along with
Tetrahydrocannabinol - Misplaced Pages Continue
4992-436: Is a tube with a hollow gut cavity running from the mouth to the anus, and a nerve cord with an enlargement (a ganglion ) for each body segment, with an especially large ganglion at the front, called the brain. The brain is small and simple in some species, such as nematode worms; in other species, such as vertebrates, it is a large and very complex organ. Some types of worms, such as leeches , also have an enlarged ganglion at
5148-508: Is about as potent as THC at the CB 1 receptor. Anandamide is found in nearly all tissues in a wide range of animals. Anandamide has also been found in plants, including small amounts in chocolate. Two analogs of anandamide, 7,10,13,16-docosatetraenoylethanolamide and homo -γ-linolenoylethanolamine, have similar pharmacology . All of these compounds are members of a family of signalling lipids called N -acylethanolamines , which also includes
5304-460: Is almost always inhibitory. Neurons using these transmitters can be found in nearly every part of the brain. Because of their ubiquity, drugs that act on glutamate or GABA tend to have broad and powerful effects. Some general anesthetics act by reducing the effects of glutamate; most tranquilizers exert their sedative effects by enhancing the effects of GABA. There are dozens of other chemical neurotransmitters that are used in more limited areas of
5460-583: Is also stored in fat in addition to being metabolized in the liver. Δ -THC is metabolized to 11-hydroxy-Δ -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
5616-540: Is available as a prescription drug in Canada. In 2021, nabiximols was approved for medical use in Ukraine . Side effects of THC include red eyes , dry mouth , drowsiness , short-term memory impairment , difficulty concentrating, ataxia , increased appetite , anxiety , paranoia , psychosis (i.e., hallucinations , delusions ), decreased motivation , and time dilation , among others. Chronic usage of THC may result in cannabinoid hyperemesis syndrome (CHS),
5772-787: 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 . 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
5928-412: Is by visual inspection, but many more sophisticated techniques have been developed. Brain tissue in its natural state is too soft to work with, but it can be hardened by immersion in alcohol or other fixatives , and then sliced apart for examination of the interior. Visually, the interior of the brain consists of areas of so-called grey matter , with a dark color, separated by areas of white matter , with
6084-414: Is complex, and various molecular mechanisms have been proposed, including direct effects on mitochondrial membranes and receptor-mediated effects. However, an integrated hypothesis of cannabinoids' actions on these processes has yet to be formulated due to conflicting data and the complexity of the pathways involved. Nabiximols (brand name Sativex) is an aerosolized mist for oral administration containing
6240-582: Is critical at key periods of development. Additionally, the quantity and quality of experience are important. For example, animals raised in enriched environments demonstrate thick cerebral cortices, indicating a high density of synaptic connections, compared to animals with restricted levels of stimulation. The functions of the brain depend on the ability of neurons to transmit electrochemical signals to other cells, and their ability to respond appropriately to electrochemical signals received from other cells. The electrical properties of neurons are controlled by
6396-463: Is due to variation in factors including product matrix, ignition temperature, and inhalational dynamics (e.g., number, duration, and intervals of inhalations, breath hold time, depth and volume of inhalations, size of inhaled particles, deposition site in the lungs). THC is detectable within seconds with inhalation and peak levels of THC occur after 3 to 10 minutes. Smoking or inhaling THC results in greater blood levels of THC and its metabolites and
Tetrahydrocannabinol - Misplaced Pages Continue
6552-448: Is formed by CYP2C9 and is psychoactive similarly to THC. This metabolite is further oxidized to 11-nor-9-carboxy-THC (THC-COOH). In animals, more than 100 metabolites of THC could be identified, but 11-OH-THC and THC-COOH are the predominant metabolites. More than 55% of THC is excreted in the feces and approximately 20% in the urine . The main metabolite in urine is the ester of glucuronic acid and 11-OH-THC and free THC-COOH. In
6708-450: Is involved in the sense of smell, and the dentate gyrus of the hippocampus, where there is evidence that the new neurons play a role in storing newly acquired memories. With these exceptions, however, the set of neurons that is present in early childhood is the set that is present for life. Glial cells are different: as with most types of cells in the body, they are generated throughout the lifespan. There has long been debate about whether
6864-627: Is only responsible for the respective body segment ) of the ventral nerve cord , vertebrate brains develop axially from the midline dorsal nerve cord as a vesicular enlargement at the rostral end of the neural tube , with centralized control over all body segments. All vertebrate brains can be embryonically divided into three parts: the forebrain (prosencephalon, subdivided into telencephalon and diencephalon ), midbrain ( mesencephalon ) and hindbrain ( rhombencephalon , subdivided into metencephalon and myelencephalon ). The spinal cord , which directly interacts with somatic functions below
7020-432: Is related to control of movements, neurotransmitters and neuromodulators responsible for integrating inputs and transmitting outputs are present, sensory systems, and cognitive functions. The avian brain is the central organ of the nervous system in birds. Birds possess large, complex brains, which process , integrate , and coordinate information received from the environment and make decisions on how to respond with
7176-491: Is responsible for the cognitive functions of birds. The pallium is made up of several major structures: the hyperpallium, a dorsal bulge of the pallium found only in birds, as well as the nidopallium, mesopallium, and archipallium. The bird telencephalon nuclear structure, wherein neurons are distributed in three-dimensionally arranged clusters, with no large-scale separation of white matter and grey matter , though there exist layer-like and column-like connections. Structures in
7332-413: Is subsequently equilibrated into less vascularized tissue. It is extensively distributed into and sequestered by fat tissue due to its high lipid solubility, from which it is slowly released. THC is able to cross the placenta and is excreted in human breast milk . The metabolism of THC occurs mainly in the liver by cytochrome P450 enzymes CYP2C9 , CYP2C19 , and CYP3A4 . CYP2C9 and CYP3A4 are
7488-488: Is tentative evidence that CBD has an anti-psychotic effect, but research in this area is limited. 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
7644-496: Is the brain's primary mechanism for learning and memory. Most of the space in the brain is taken up by axons, which are often bundled together in what are called nerve fiber tracts . A myelinated axon is wrapped in a fatty insulating sheath of myelin , which serves to greatly increase the speed of signal propagation. (There are also unmyelinated axons). Myelin is white, making parts of the brain filled exclusively with nerve fibers appear as light-colored white matter , in contrast to
7800-470: Is the primary psychoactive component of the Cannabis plant. Delta -9- tetrahydrocannabinol (Δ -THC, THC) and delta-8-tetrahydrocannabinol (Δ -THC), through intracellular CB 1 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 CB 1 cannabinoid receptors in
7956-456: Is the primary psychoactive component), with the exception of Georgia, Idaho, Indiana, Iowa, Kansas, Nebraska, North Carolina, South Carolina, Tennessee, Texas, Wisconsin, and Wyoming. As of 2022, the U.S. federal government maintains cannabis as a schedule I controlled substance, while dronabinol is classified as Schedule III in capsule form (Marinol) and Schedule II in liquid oral form (Syndros). As of October 2018 when recreational use of cannabis
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#17327723746638112-438: Is their ability to send signals to specific target cells, sometimes over long distances. They send these signals by means of an axon , which is a thin protoplasmic fiber that extends from the cell body and projects, usually with numerous branches, to other areas, sometimes nearby, sometimes in distant parts of the brain or body. The length of an axon can be extraordinary: for example, if a pyramidal cell (an excitatory neuron) of
8268-493: Is typically located in the head ( cephalization ), usually near organs for special senses such as vision , hearing and olfaction . Being the most specialized organ, it is responsible for receiving information from the sensory nervous system , processing those information ( thought , cognition , and intelligence ) and the coordination of motor control ( muscle activity and endocrine system ). While invertebrate brains arise from paired segmental ganglia (each of which
8424-400: Is used to compare brain sizes across species. It takes into account the nonlinearity of the brain-to-body relationship. Humans have an average EQ in the 7-to-8 range, while most other primates have an EQ in the 2-to-3 range. Dolphins have values higher than those of primates other than humans, but nearly all other mammals have EQ values that are substantially lower. Most of the enlargement of
8580-439: Is yet to be solved. Recent models in modern neuroscience treat the brain as a biological computer , very different in mechanism from a digital computer , but similar in the sense that it acquires information from the surrounding world, stores it, and processes it in a variety of ways. This article compares the properties of brains across the entire range of animal species, with the greatest attention to vertebrates. It deals with
8736-506: The Cannabis plant. 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). The best studied cannabinoids include tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN). Tetrahydrocannabinol (THC)
8892-496: The Anandamide -like alkylamides from Echinacea species, most notably the cis/trans isomers of 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 CB 2 -receptor. In some Echinacea species, cannabinoids are found throughout the plant structure, but are most concentrated in the roots and flowers. Yangonin found in
9048-471: The Cambrian period , and may have resembled the modern jawless fish ( hagfish and lamprey ) in form. Jawed vertebrates appeared by 445 Mya, tetrapods by 350 Mya, amniotes by 310 Mya and mammaliaforms by 200 Mya (approximately). Each vertebrate clade has an equally long evolutionary history, but the brains of modern fish , amphibians , reptiles , birds and mammals show
9204-684: The Controlled Substances Act for having "no accepted medical use" and "lack of accepted safety". However, dronabinol , a pharmaceutical form of THC, has been approved by the FDA as an appetite stimulant for people with AIDS and an antiemetic for people receiving chemotherapy under the trade names Marinol and Syndros. In 2003, the World Health Organization Expert Committee on Drug Dependence recommended transferring THC to Schedule IV of
9360-463: The Food and Drug Administration for treatment of two rare and severe forms of epilepsy , Dravet and Lennox-Gastaut syndromes. Nabilone (Cesamet) is an FDA approved synthetic analog of THC, prescribed for the treatment of nausea and vomiting induced by chemotherapy treatment in people who have failed to respond adequately to conventional antiemetic treatments. Cannabinoids can be separated from
9516-699: 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. 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
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#17327723746639672-499: The barbiturate pentobarbital has been found to increase by 4 hours when concomitantly administered with oral THC. The actions of Δ-THC result from its partial agonist activity at the cannabinoid receptor CB 1 (K i = 40.7 nM), located mainly in the central nervous system , and the CB 2 receptor (K i = 36 nM), mainly expressed in cells of the immune system . The psychoactive effects of THC are primarily mediated by
9828-580: 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 100 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
9984-456: The cerebral cortex and the cerebellar cortex, are folded into convoluted gyri and sulci in order to maximize surface area within the available intracranial space . Other parts, such as the thalamus and hypothalamus, consist of many small clusters of nuclei known as "ganglia". Thousands of distinguishable areas can be identified within the vertebrate brain based on fine distinctions of neural structure, chemistry, and connectivity. Although
10140-448: The diencephalon (which will contain the thalamus and hypothalamus). At about the same time, the hindbrain splits into the metencephalon (which will contain the cerebellum and pons) and the myelencephalon (which will contain the medulla oblongata ). Each of these areas contains proliferative zones where neurons and glial cells are generated; the resulting cells then migrate, sometimes for long distances, to their final positions. Once
10296-423: The environment . Some basic types of responsiveness such as reflexes can be mediated by the spinal cord or peripheral ganglia , but sophisticated purposeful control of behavior based on complex sensory input requires the information integrating capabilities of a centralized brain. The operations of individual brain cells are now understood in considerable detail but the way they cooperate in ensembles of millions
10452-505: The gastrointestinal tract . However, due to first-pass metabolism in the liver and the high lipid solubility of THC, only about 5 to 20% reaches circulation. Following oral administration, concentrations of THC and its major active metabolite 11-hydroxy-THC (11-OH-THC) peak after 0.5 to 4 hours, with median time to peak of 1.0 to 2.5 hours at different doses. In some cases, peak levels may not occur for as long as 6 hours. Concentrations of THC and 11-hydroxy-THC in
10608-441: The human brain insofar as it shares the properties of other brains. The ways in which the human brain differs from other brains are covered in the human brain article. Several topics that might be covered here are instead covered there because much more can be said about them in a human context. The most important that are covered in the human brain article are brain disease and the effects of brain damage . The shape and size of
10764-481: 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 CB 2 -receptors, in vivo . Black truffles contain anandamide. Perrottetinene ,
10920-438: The lymphatic system and allows it to bypass first-pass metabolism. Consequently, a high-fat meal increases levels of 11-hydroxy-THC by only 25% and most of the increase in bioavailability is due to increased levels of THC. The bioavailability of THC when smoking or inhaling is approximately 25%, with a range of 2% to 56% (although most commonly between 10 and 35%). The large range and marked variability between individuals
11076-401: 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. CB 2 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 CB 2 is expressed by
11232-450: The neural tube , a hollow cord of cells with a fluid-filled ventricle at the center. At the front end, the ventricles and cord swell to form three vesicles that are the precursors of the prosencephalon (forebrain), mesencephalon (midbrain), and rhombencephalon (hindbrain). At the next stage, the forebrain splits into two vesicles called the telencephalon (which will contain the cerebral cortex, basal ganglia, and related structures) and
11388-423: The skull from the brain. Cerebral arteries pierce the outer two layers of the meninges, the dura and arachnoid mater , into the subarachnoid space and perfuse the brain parenchyma via arterioles perforating into the innermost layer of the meninges, the pia mater . The endothelial cells in the cerebral blood vessel walls are joined tightly to one another, forming the blood–brain barrier , which blocks
11544-539: The stereochemistry of CBD. The following year, in 1964, Mechoulam and his team identified the stereochemistry of Tetrahydrocannabinol (THC). Due to molecular similarity and ease of synthetic conversion, CBD was originally believed to be a natural precursor to THC. However, it is now known that CBD and THC are produced independently in the Cannabis plant from the precursor CBG. The Agriculture Improvement Act of 2018 has been interpreted as allowing any hemp-derived product not exceeding 0.3% Δ -THC to be sold legally in
11700-480: The CB 1 receptor, and only weakly to the CB 2 receptor. Discovered in 2000, NADA preferentially binds to the CB 1 receptor. Like anandamide, NADA is also an agonist for the vanilloid receptor subtype 1 (TRPV1), a member of the vanilloid receptor family. A fifth endocannabinoid, virodhamine, or O -arachidonoyl-ethanolamine (OAE), was discovered in June 2002. Although it is a full agonist at CB 2 and
11856-613: The US. Because the law limited only Δ -THC levels, many other cannabinoids are generally considered legal to sell and are widely available in stores and online, including Δ -THC , Δ -THC , HHC , and THCP , but have not had the same in-depth research that the Δ isomer has on the human body; carrying potential risks in the short- or long-term. Other concerns include difficulties for drug testing due to novel metabolites , or high potency/ binding affinity of isomers for cannabinoid receptors showing potential for abuse (i.e., THCP, which has 33×
12012-537: The United States to gain FDA approval. In 2007, it was approved for treatment of cancer pain. In Phase III trials, the most common adverse effects were dizziness, drowsiness and disorientation; 12% of subjects stopped taking the drug because of the side effects. Dronabinol (brand names Marinol and Syndros) is a delta-9-THC containing drug for treating HIV/AIDS -induced anorexia and chemotherapy-induced nausea and vomiting . The CBD drug Epidiolex has been approved by
12168-443: The activation of (mostly G-coupled) cannabinoid receptors, which result in a decrease in the concentration of the second messenger molecule cAMP through inhibition of adenylate cyclase . The presence of these specialized cannabinoid receptors in the brain led researchers to the discovery of endocannabinoids , such as anandamide and 2-arachidonoyl glyceride ( 2-AG ). THC is a lipophilic molecule and may bind non-specifically to
12324-402: The animal is actively engaged in a task, called beta and gamma waves . During an epileptic seizure , the brain's inhibitory control mechanisms fail to function and electrical activity rises to pathological levels, producing EEG traces that show large wave and spike patterns not seen in a healthy brain. Relating these population-level patterns to the computational functions of individual neurons
12480-477: The animal. The tegmentum receives incoming sensory information and forwards motor responses to and from the forebrain. The isthmus connects the hindbrain with midbrain. The forebrain region is particularly well developed, is further divided into diencephalon and telencephalon. Diencephalon is related to regulation of eye and body movement in response to visual stimuli, sensory information, circadian rhythms , olfactory input, and autonomic nervous system .Telencephalon
12636-403: The back end of the nerve cord, known as a "tail brain". There are a few types of existing bilaterians that lack a recognizable brain, including echinoderms and tunicates . It has not been definitively established whether the existence of these brainless species indicates that the earliest bilaterians lacked a brain, or whether their ancestors evolved in a way that led to the disappearance of
12792-425: The binding affinity of Δ -THC) From 2021 to 2023, the Δ -THC market generated US$ 2 billion in revenue. Many substances are scheduled at the state level under various synonyms owing to the different dibenzopyran and monoterpenoid naming conventions. Delta-1, Delta-6, and Delta 3,4-Tetrahydrocannabinol are alternative names for Delta-9, Delta-8, and Delta-6a10a Tetrahydrocannabinol, respectively. A 2023 paper seeking
12948-508: The body of the animal. Arthropods have a central brain, the supraesophageal ganglion , with three divisions and large optical lobes behind each eye for visual processing. Cephalopods such as the octopus and squid have the largest brains of any invertebrates. There are several invertebrate species whose brains have been studied intensively because they have properties that make them convenient for experimental work: The first vertebrates appeared over 500 million years ago ( Mya ) during
13104-416: The body. Neuroanatomists usually divide the vertebrate brain into six main subregions: the telencephalon (the cerebral hemispheres ), diencephalon ( thalamus and hypothalamus ), mesencephalon (midbrain), cerebellum , pons and medulla oblongata , with the midbrain, pons and medulla often collectively called the brainstem . Each of these areas has a complex internal structure. Some parts, such as
13260-461: The body. The mechanisms and enzymes underlying the biosynthesis of endocannabinoids remain elusive and continue to be an area of active research. The endocannabinoid 2-AG has been found in bovine and human maternal milk. Brain The brain is an organ that serves as the center of the nervous system in all vertebrate and most invertebrate animals . It consists of nervous tissue and
13416-498: The brain appears as three vesicular swellings at the front end of the neural tube ; these swellings eventually become the forebrain ( prosencephalon ), midbrain ( mesencephalon ) and hindbrain ( rhombencephalon ), respectively. At the earliest stages of brain development, the three areas are roughly equal in size. In many aquatic / semiaquatic vertebrates such as fish and amphibians, the three parts remain similar in size in adults , but in terrestrial tetrapods such as mammals,
13572-509: The brain but are not as ubiquitously distributed as glutamate and GABA. As a side effect of the electrochemical processes used by neurons for signaling, brain tissue generates electric fields when it is active. When large numbers of neurons show synchronized activity, the electric fields that they generate can be large enough to detect outside the skull, using electroencephalography (EEG) or magnetoencephalography (MEG). EEG recordings, along with recordings made from electrodes implanted inside
13728-401: The brain in reptiles and mammals, with shared neuronal clusters enlightening brain evolution. Conserved transcription factors elucidate that evolution acted in different areas of the brain by either retaining similar morphology and function, or diversifying it. Anatomically, the reptilian brain has less subdivisions than the mammalian brain, however it has numerous conserved aspects including
13884-445: The brain or distant parts of the body. The prefrontal cortex , which controls executive functions , is particularly well developed in humans. Physiologically , brains exert centralized control over a body's other organs. They act on the rest of the body both by generating patterns of muscle activity and by driving the secretion of chemicals called hormones . This centralized control allows rapid and coordinated responses to changes in
14040-468: The brain than anandamide, and there is some controversy over whether 2-AG rather than anandamide is chiefly responsible for endocannabinoid signalling in vivo . In particular, one in vitro study suggests that 2-AG is capable of stimulating higher G-protein activation than anandamide, although the physiological implications of this finding are not yet known. In 2001, a third, ether -type endocannabinoid, 2-arachidonyl glyceryl ether (noladin ether),
14196-511: The brain to the spinal cord. The most obvious difference between the brains of mammals and other vertebrates is their size. On average, a mammal has a brain roughly twice as large as that of a bird of the same body size, and ten times as large as that of a reptile of the same body size. Size, however, is not the only difference: there are also substantial differences in shape. The hindbrain and midbrain of mammals are generally similar to those of other vertebrates, but dramatic differences appear in
14352-467: The brain varies greatly between species, and identifying common features is often difficult. Nevertheless, there are a number of principles of brain architecture that apply across a wide range of species. Some aspects of brain structure are common to almost the entire range of animal species; others distinguish "advanced" brains from more primitive ones, or distinguish vertebrates from invertebrates. The simplest way to gain information about brain anatomy
14508-402: The brain, axons initially "overgrow", and then are "pruned" by mechanisms that depend on neural activity. In the projection from the eye to the midbrain, for example, the structure in the adult contains a very precise mapping, connecting each point on the surface of the retina to a corresponding point in a midbrain layer. In the first stages of development, each axon from the retina is guided to
14664-439: The brain, often areas dedicated to a particular function. Serotonin , for example—the primary target of many antidepressant drugs and many dietary aids—comes exclusively from a small brainstem area called the raphe nuclei . Norepinephrine , which is involved in arousal, comes exclusively from a nearby small area called the locus coeruleus . Other neurotransmitters such as acetylcholine and dopamine have multiple sources in
14820-478: The brain. Cannabidiol (CBD) is mildly psychotropic . Evidence shows that the compound counteracts cognitive impairment associated with the use of cannabis. Cannabidiol has little affinity for CB 1 and CB 2 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
14976-431: The brains of animals such as rats, show that the brain of a living animal is constantly active, even during sleep. Each part of the brain shows a mixture of rhythmic and nonrhythmic activity, which may vary according to behavioral state. In mammals, the cerebral cortex tends to show large slow delta waves during sleep, faster alpha waves when the animal is awake but inattentive, and chaotic-looking irregular activity when
15132-522: The cannabinoid profile of cannabis over time, but their accuracy is impeded by the illegal status of the plant in many countries. 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
15288-476: The cannabinoid receptors present on other nearby cells. Although in this intercellular signaling role they are similar to the well-known monoamine neurotransmitters such as dopamine , endocannabinoids differ in numerous ways from them. For instance, they are used in retrograde signaling between neurons. Furthermore, endocannabinoids are lipophilic molecules that are not very soluble in water. They are not stored in vesicles and exist as integral constituents of
15444-549: The cerebral cortex were magnified so that its cell body became the size of a human body, its axon, equally magnified, would become a cable a few centimeters in diameter, extending more than a kilometer. These axons transmit signals in the form of electrochemical pulses called action potentials, which last less than a thousandth of a second and travel along the axon at speeds of 1–100 meters per second. Some neurons emit action potentials constantly, at rates of 10–100 per second, usually in irregular patterns; other neurons are quiet most of
15600-503: The cerebral cortex. The cerebellum of mammals contains a large portion (the neocerebellum ) dedicated to supporting the cerebral cortex, which has no counterpart in other vertebrates. In placental mammals , there is a wide nerve tract connecting the cerebral hemispheres called the corpus callosum . The brains of humans and other primates contain the same structures as the brains of other mammals, but are generally larger in proportion to body size. The encephalization quotient (EQ)
15756-507: The circulation are approximately equal with oral administration. There is a slight increase in dose proportionality in terms of peak and area-under-the-curve levels of THC with increasing oral doses over a range of 2.5 to 10 mg. A high-fat meal delays time to peak concentrations of oral THC by 4 hours on average and increases area-under-the-curve exposure by 2.9-fold, but peak concentrations are not significantly altered. A high-fat meal additionally increases absorption of THC via
15912-450: The control of movement and motor coordination, learning and memory, emotion and motivation, addictive-like behavior and pain modulation, among others. CB 1 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 . CB 1 receptors are absent in
16068-690: The convention, citing its medical uses and low abuse and addiction potential. In 2019, the Committee recommended transferring Δ-THC to Schedule I of the Single Convention on Narcotic Drugs of 1961 , but its recommendations were rejected by the United Nations Commission on Narcotic Drugs . As of 2023, 38 states, four territories, and the District of Columbia in the United States allow medical use of cannabis (in which THC
16224-512: The darker-colored grey matter that marks areas with high densities of neuron cell bodies. Except for a few primitive organisms such as sponges (which have no nervous system) and cnidarians (which have a diffuse nervous system consisting of a nerve net ), all living multicellular animals are bilaterians , meaning animals with a bilaterally symmetric body plan (that is, left and right sides that are approximate mirror images of each other). All bilaterians are thought to have descended from
16380-420: The developing brain, and apparently exist solely to guide development. In humans and many other mammals, new neurons are created mainly before birth, and the infant brain contains substantially more neurons than the adult brain. There are, however, a few areas where new neurons continue to be generated throughout life. The two areas for which adult neurogenesis is well established are the olfactory bulb, which
16536-415: The dibenzopyran numbering system widely used today, the major form of THC is called Δ -THC, while the minor form is called Δ -THC. Under the alternate terpene numbering system, these same compounds are called Δ -THC and Δ -THC, respectively. 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
16692-481: The drug has a relatively low cannabinoid receptor affinity. THC is also limited in its efficacy compared to other cannabinoids due to its partial agonistic activity, as THC appears to result in greater downregulation of cannabinoid receptors than endocannabinoids . Furthermore, in populations of low cannabinoid receptor density, THC may even act to antagonize endogenous agonists that possess greater receptor efficacy. However while THC's pharmacodynamic tolerance may limit
16848-412: The early stages of neural development are similar across all species. As the embryo transforms from a round blob of cells into a wormlike structure, a narrow strip of ectoderm running along the midline of the back is induced to become the neural plate , the precursor of the nervous system. The neural plate folds inward to form the neural groove , and then the lips that line the groove merge to enclose
17004-434: The edge of the neocortex, including the hippocampus and amygdala , are also much more extensively developed in mammals than in other vertebrates. The elaboration of the cerebral cortex carries with it changes to other brain areas. The superior colliculus , which plays a major role in visual control of behavior in most vertebrates, shrinks to a small size in mammals, and many of its functions are taken over by visual areas of
17160-419: The effects of THC on inflammation and neurological diseases, since autotaxin is responsible of LPA generation, a key lipid mediator involved in numerous diseases and physiological processes. However, clinical trials need to be performed in order to assess the importance of ATX inhibition by THC during medicinal cannabis consumption. With oral administration of a single dose, THC is almost completely absorbed by
17316-447: The extraction of these compounds. The first discovery of an individual cannabinoid was made, when British chemist Robert S. Cahn reported the partial structure of Cannabinol (CBN), which he later identified as fully formed in 1940. Two years later, in 1942, American chemist, Roger Adams , made history when he discovered Cannabidiol (CBD). Progressing from Adams research, in 1963 Israeli professor Raphael Mechoulam later identified
17472-488: The feces, mainly 11-OH-THC was detected. Estimates of the elimination half-life of THC are variable. THC was reported to have a fast initial half-life of 6 minutes and a long terminal half-life of 22 hours in a population pharmacokinetic study. Conversely, the Food and Drug Administration label for dronabinol reports an initial half-life of 4 hours and a terminal half-life of 25 to 36 hours. Many studies report an elimination half-life of THC in
17628-488: The first cannabinoid receptors in the 1980s helped to resolve this debate. These receptors are common in animals. Two known cannabinoid receptors are termed CB 1 and CB 2 , 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
17784-483: The first-pass metabolism that occurs with oral administration. The volume of distribution of THC is large and is approximately 10 L/kg (range 4–14 L/kg), which is due to its high lipid solubility. The plasma protein binding of THC and its metabolites is approximately 95 to 99%, with THC bound mainly to lipoproteins and to a lesser extent albumin . THC is rapidly distributed into well-vascularized organs such as lung , heart , brain , and liver , and
17940-467: The forebrain becomes much larger than the other parts, the hindbrain develops a bulky dorsal extension known as the cerebellum , and the midbrain becomes very small as a result. The brains of vertebrates are made of very soft tissue. Living brain tissue is pinkish on the outside and mostly white on the inside, with subtle variations in color. Vertebrate brains are surrounded by a system of connective tissue membranes called meninges , which separate
18096-424: The forebrain, which is greatly enlarged and also altered in structure. The cerebral cortex is the part of the brain that most strongly distinguishes mammals. In non-mammalian vertebrates, the surface of the cerebrum is lined with a comparatively simple three-layered structure called the pallium . In mammals, the pallium evolves into a complex six-layered structure called neocortex or isocortex . Several areas at
18252-707: The head, can be considered a caudal extension of the myelencephalon enclosed inside the vertebral column . Together, the brain and spinal cord constitute the central nervous system in all vertebrates. In humans , the cerebral cortex contains approximately 14–16 billion neurons, and the estimated number of neurons in the cerebellum is 55–70 billion. Each neuron is connected by synapses to several thousand other neurons, typically communicating with one another via cytoplasmic processes known as dendrites and axons . Axons are usually myelinated and carry trains of rapid micro-electric signal pulses called action potentials to target specific recipient cells in other areas of
18408-441: The map, leaving it finally in its precise adult form. Similar things happen in other brain areas: an initial synaptic matrix is generated as a result of genetically determined chemical guidance, but then gradually refined by activity-dependent mechanisms, partly driven by internal dynamics, partly by external sensory inputs. In some cases, as with the retina-midbrain system, activity patterns depend on mechanisms that operate only in
18564-484: The maximal effects of certain drugs, evidence suggests that this tolerance mitigates undesirable effects, thus enhancing the drug's therapeutic window. Recently, it has been shown that THC is also a partial autotaxin inhibitor, with an apparent IC50 of 407 ± 67 nM for the ATX-gamma isoform. THC was also co-crystallized with autotaxin, deciphering the binding interface of the complex. These results might explain some of
18720-510: The membrane bilayers that make up cells. They are believed to be synthesized 'on-demand' rather than made and stored for later use. As hydrophobic molecules, endocannabinoids cannot travel unaided for long distances in the aqueous medium surrounding the cells from which they are released and therefore act locally on nearby target cells. Hence, although emanating diffusely from their source cells, they have much more restricted spheres of influence than do hormones , which can affect cells throughout
18876-407: The membrane of the synapse's target cell (or cells), and thereby alter the electrical or chemical properties of the receptor molecules. With few exceptions, each neuron in the brain releases the same chemical neurotransmitter, or combination of neurotransmitters, at all the synaptic connections it makes with other neurons; this rule is known as Dale's principle . Thus, a neuron can be characterized by
19032-440: The membrane of the target cell. Synapses are the key functional elements of the brain. The essential function of the brain is cell-to-cell communication , and synapses are the points at which communication occurs. The human brain has been estimated to contain approximately 100 trillion synapses; even the brain of a fruit fly contains several million. The functions of these synapses are very diverse: some are excitatory (exciting
19188-494: The neurotransmitters that it releases. The great majority of psychoactive drugs exert their effects by altering specific neurotransmitter systems. This applies to drugs such as cannabinoids , nicotine , heroin , cocaine , alcohol , fluoxetine , chlorpromazine , and many others. The two neurotransmitters that are most widely found in the vertebrate brain are glutamate , which almost always exerts excitatory effects on target neurons, and gamma-aminobutyric acid (GABA), which
19344-449: The noncannabimimetic palmitoylethanolamide and oleoylethanolamide , which possess anti-inflammatory and anorexigenic effects, respectively. Many N -acylethanolamines have also been identified in plant seeds and in molluscs. Another endocannabinoid, 2-arachidonoylglycerol, binds to both the CB 1 and CB 2 receptors with similar affinity, acting as a full agonist at both. 2-AG is present at significantly higher concentrations in
19500-722: The organization of the spinal cord and cranial nerve, as well as elaborated brain pattern of organization. Elaborated brains are characterized by migrated neuronal cell bodies away from the periventricular matrix, region of neuronal development, forming organized nuclear groups. Aside from reptiles and mammals , other vertebrates with elaborated brains include hagfish , galeomorph sharks , skates , rays , teleosts , and birds . Overall elaborated brains are subdivided in forebrain, midbrain, and hindbrain. The hindbrain coordinates and integrates sensory and motor inputs and outputs responsible for, but not limited to, walking, swimming, or flying. It contains input and output axons interconnecting
19656-406: The pallium are associated with perception , learning , and cognition . Beneath the pallium are the two components of the subpallium, the striatum and pallidum . The subpallium connects different parts of the telencephalon and plays major roles in a number of critical behaviours. To the rear of the telencephalon are the thalamus , midbrain , and cerebellum . The hindbrain connects the rest of
19812-430: The passage of many toxins and pathogens (though at the same time blocking antibodies and some drugs, thereby presenting special challenges in treatment of diseases of the brain). As a result of the osmotic restriction by the blood-brain barrier, the metabolites within the brain are cleared mostly by bulk flow of the cerebrospinal fluid within the glymphatic system instead of via venules like other parts of
19968-491: The plant by extraction with organic solvents . Hydrocarbons and alcohols are often used as solvents. However, these solvents are flammable and many are toxic. Butane may be used, which evaporates extremely quickly. Supercritical solvent extraction with carbon dioxide is an alternative technique. Once extracted, isolated components can be separated using wiped film vacuum distillation or other distillation techniques. Also, techniques such as SPE or SPME are found useful in
20124-424: The plant's evolutionary adaptation against insect predation , ultraviolet light , and environmental stress . In the Cannabis plant, THC occurs mainly as tetrahydrocannabinolic acid (THCA, 2-COOH-THC). Geranyl pyrophosphate and olivetolic acid react, catalysed by an enzyme to produce cannabigerolic acid , which is cyclized by the enzyme THC acid synthase to give THCA. Over time, or when heated, THCA
20280-399: The primary enzymes involving in metabolizing THC. Pharmacogenomic research has found that oral THC exposure is 2- to 3-fold greater in people with genetic variants associated with reduced CYP2C9 function. When taken orally, THC undergoes extensive first-pass metabolism in the liver, primarily via hydroxylation . The principal active metabolite of THC is 11-hydroxy-THC (11-OH-THC), which
20436-564: The primate brain comes from a massive expansion of the cerebral cortex, especially the prefrontal cortex and the parts of the cortex involved in vision . The visual processing network of primates includes at least 30 distinguishable brain areas, with a complex web of interconnections. It has been estimated that visual processing areas occupy more than half of the total surface of the primate neocortex. The prefrontal cortex carries out functions that include planning , working memory , motivation , attention , and executive control . It takes up
20592-432: The propyl homologues (THCVA, CBDVA and CBCVA), there is an analogous pathway that is based on CBGVA from divarinolic acid instead of olivetolic acid. 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
20748-439: The qualities of mind , personality, and intelligence can be attributed to heredity or to upbringing . Although many details remain to be settled, neuroscience shows that both factors are important. Genes determine both the general form of the brain and how it reacts to experience, but experience is required to refine the matrix of synaptic connections, resulting in greatly increased complexity. The presence or absence of experience
20904-426: The range of 20 to 30 hours. 11-Hydroxy-THC appears to have a similar terminal half-life to that of THC, for instance 12 to 36 hours relative to 25 to 36 hours in one study. The elimination half-life of THC is longer in heavy users. This may be due to slow redistribution from deep compartments such as fatty tissues, where THC accumulates with regular use. As with many aromatic terpenoids , THC has
21060-464: The receptors. Anandamide was the first such compound identified as arachidonoyl ethanolamine. The name is derived from ananda , the Sanskrit word for bliss. It has a pharmacology similar to THC , although its structure is quite different. Anandamide binds to the central (CB 1 ) and, to a lesser extent, peripheral (CB 2 ) cannabinoid receptors, where it acts as a partial agonist. Anandamide
21216-415: The regulation of cannabinoid terminology coined the term "derived psychoactive cannabis products" to accurately and usefully distinguish said products whilst excluding unrelated substances. Endocannabinoids are substances produced from within the body that activate cannabinoid receptors . After the discovery of the first cannabinoid receptor in 1988, scientists began searching for endogenous ligands for
21372-413: The rest of the body. Like in all chordates , the avian brain is contained within the skull bones of the head . The bird brain is divided into a number of sections, each with a different function. The cerebrum or telencephalon is divided into two hemispheres , and controls higher functions. The telencephalon is dominated by a large pallium , which corresponds to the mammalian cerebral cortex and
21528-433: The right general vicinity in the midbrain by chemical cues, but then branches very profusely and makes initial contact with a wide swath of midbrain neurons. The retina, before birth, contains special mechanisms that cause it to generate waves of activity that originate spontaneously at a random point and then propagate slowly across the retinal layer. These waves are useful because they cause neighboring neurons to be active at
21684-588: The same basic components are present in all vertebrate brains, some branches of vertebrate evolution have led to substantial distortions of brain geometry, especially in the forebrain area. The brain of a shark shows the basic components in a straightforward way, but in teleost fishes (the great majority of existing fish species), the forebrain has become "everted", like a sock turned inside out. In birds, there are also major changes in forebrain structure. These distortions can make it difficult to match brain components from one species with those of another species. Here
21840-400: The same time; that is, they produce a neural activity pattern that contains information about the spatial arrangement of the neurons. This information is exploited in the midbrain by a mechanism that causes synapses to weaken, and eventually vanish, if activity in an axon is not followed by activity of the target cell. The result of this sophisticated process is a gradual tuning and tightening of
21996-605: The smallest. Turtles have the largest diencephalon per body weight whereas crocodilians have the smallest. On the other hand, lizards have the largest mesencephalon. Yet their brains share several characteristics revealed by recent anatomical, molecular, and ontogenetic studies. Vertebrates share the highest levels of similarities during embryological development, controlled by conserved transcription factors and signaling centers , including gene expression, morphological and cell type differentiation. In fact, high levels of transcriptional factors can be found in all areas of
22152-483: The sole federally-legal source of cannabis for researchers. Despite an August 2016 announcement that licenses would be provided to growers for supplies of medical marijuana, no such licenses were ever issued, despite dozens of applications. Although cannabis is legalized for medical uses in more than half of the states of the United States, no products have been approved for federal commerce by the Food and Drug Administration,
22308-500: The species diversity, reptiles have diverged in terms of external morphology, from limbless to tetrapod gliders to armored chelonians , reflecting adaptive radiation to a diverse array of environments. Morphological differences are reflected in the nervous system phenotype , such as: absence of lateral motor column neurons in snakes, which innervate limb muscles controlling limb movements; absence of motor neurons that innervate trunk muscles in tortoises; presence of innervation from
22464-419: The spinal cord, midbrain and forebrain transmitting information from the external and internal environments. The midbrain links sensory, motor, and integrative components received from the hindbrain, connecting it to the forebrain. The tectum, which includes the optic tectum and torus semicircularis, receives auditory, visual, and somatosensory inputs, forming integrated maps of the sensory and visual space around
22620-423: The target cell); others are inhibitory; others work by activating second messenger systems that change the internal chemistry of their target cells in complex ways. A large number of synapses are dynamically modifiable; that is, they are capable of changing strength in a way that is controlled by the patterns of signals that pass through them. It is widely believed that activity-dependent modification of synapses
22776-440: The time, but occasionally emit a burst of action potentials. Axons transmit signals to other neurons by means of specialized junctions called synapses . A single axon may make as many as several thousand synaptic connections with other cells. When an action potential, traveling along an axon, arrives at a synapse, it causes a chemical called a neurotransmitter to be released. The neurotransmitter binds to receptor molecules in
22932-427: The tissue to reach their ultimate locations. Once neurons have positioned themselves, their axons sprout and navigate through the brain, branching and extending as they go, until the tips reach their targets and form synaptic connections. In a number of parts of the nervous system, neurons and synapses are produced in excessive numbers during the early stages, and then the unneeded ones are pruned away. For vertebrates,
23088-519: The toxicology reports and relative testimony in two separate cases gave the median lethal dose in humans at 30 mg/kg (2.1 grams THC for a person who weighs 70 kg; 154 lb; 11 stone), observing cardiovascular death in the one otherwise healthy subject of the two cases studied. A different 1972 study gave the median lethal dose for intravenous THC in mice and rats at 30–40 mg/kg. Formal drug–drug interaction studies with THC have not been conducted and are limited. The elimination half-life of
23244-431: The treatment of nausea due to chemotherapy , spasticity , and possibly neuropathic pain . Common side effects include dizziness, sedation, confusion, dissociation, and "feeling high". 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
23400-413: The trigeminal nerve to pit organs responsible to infrared detection in snakes. Variation in size, weight, and shape of the brain can be found within reptiles. For instance, crocodilians have the largest brain volume to body weight proportion, followed by turtles, lizards, and snakes. Reptiles vary in the investment in different brain sections. Crocodilians have the largest telencephalon, while snakes have
23556-613: Was legalized in Canada , some 220 dietary supplements and 19 veterinary health products containing not more than 10 parts per million of THC extract were approved with general health claims for treating minor conditions. The status of THC as an illegal drug in most countries imposes restrictions on research material supply and funding, such as in the United States where the National Institute on Drug Abuse and Drug Enforcement Administration continue to control
23712-679: Was effective for treating spasticity and chronic pain, but caused numerous short-lasting adverse events , such as dizziness. Preliminary research indicates that prolonged exposure to high doses of THC may interfere with chromosomal stability, which may be hereditary as a factor affecting cell instability and cancer risk. The carcinogenicity of THC in the studied populations of so-called "heavy users" remains dubious due to various confounding variables, most significantly concurrent tobacco use. Cannabinoid Cannabinoids ( / k ə ˈ n æ b ə n ɔɪ d z ˌ ˈ k æ n ə b ə n ɔɪ d z / ) are several structural classes of compounds found in
23868-485: Was first isolated from Cannabis by Raphael Mechoulam in 1964. Female cannabis plants contain at least 113 cannabinoids, including cannabidiol (CBD), thought to be the major anticonvulsant that helps people with multiple sclerosis , and cannabichromene (CBC), an anti-inflammatory which may contribute to the pain-killing effect of cannabis. THC and its 11-OH-THC and THC-COOH metabolites can be detected and quantified in blood, urine, hair, oral fluid or sweat using
24024-508: Was isolated from porcine brain. Prior to this discovery, it had been synthesized as a stable analog of 2-AG; indeed, some controversy remains over its classification as an endocannabinoid, as another group failed to detect the substance at "any appreciable amount" in the brains of several different mammalian species. It binds to the CB 1 cannabinoid receptor ( K i = 21.2 nmol /L) and causes sedation, hypothermia, intestinal immobility, and mild antinociception in mice. It binds primarily to
24180-498: Was listed under Schedule I in 1971, but reclassified to Schedule II in 1991 following a recommendation from the WHO . Based on subsequent studies, the WHO has recommended the reclassification to the less-stringent Schedule III. Cannabis as a plant is scheduled by the Single Convention on Narcotic Drugs (Schedule I and IV). It is specifically still listed under Schedule I by US federal law under
24336-442: 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
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