Cannabinoid receptor 1 (CB1), is a

G protein-coupled G protein-coupled receptors (GPCRs), also known as seven-(pass)-transmembrane domain receptors, 7TM receptors, heptahelical receptors, serpentine receptors, and G protein-linked receptors (GPLR), form a large group of evolutionarily related ...

cannabinoid receptor Cannabinoid receptors, located throughout the body, are part of the endocannabinoid system of vertebrates a class of cell membrane receptors in the G protein-coupled receptor superfamily. As is typical of G protein-coupled receptors, the cann ...

that in humans is encoded by the ''CNR1''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. And discovered, by determination and characterization in 1988, and

cloned Cloning is the process of producing individual organisms with identical genomes, either by natural or artificial means. In nature, some organisms produce clones through asexual reproduction; this reproduction of an organism by itself without ...

in 1990 for the first time. The human CB1 receptor is expressed in the

peripheral nervous system The peripheral nervous system (PNS) is one of two components that make up the nervous system of Bilateria, bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of nerves and ganglia, which lie outside t ...

and

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

. It is activated by endogenous cannabinoids called

endocannabinoids 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 (THC) (delta-9-THC), the primary psychoact ...

, a group of retrograde neurotransmitters that include lipids, such as

anandamide Anandamide (ANA), also referred to as ''N''-arachidonoylethanolamine (AEA) is a fatty acid neurotransmitter belonging to the fatty acid derivative group known as N-acylethanolamine (NAE). Anandamide takes its name from the Sanskrit word ''ananda ...

and

2-arachidonoylglycerol 2-Arachidonoylglycerol (2-AG) is an endocannabinoid, an endogenous agonist of the CB1 receptor and the primary endogenous ligand for the CB2 receptor. It is an ester formed from the omega-6 fatty acid arachidonic acid and glycerol. It is pres ...

; plant

phytocannabinoid 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 (THC) (delta-9-THC), the primary psychoac ...

s, such as docosatetraenoylethanolamide found in wild dagga, the compound

tetrahydrocannabinol 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 (C21H30O2) de ...

which is an active constituent of the

psychoactive drug A psychoactive drug, psychopharmaceutical, mind-altering drug, consciousness-altering drug, psychoactive substance, or psychotropic substance is a chemical substance that alters psychological functioning by modulating central nervous system acti ...

cannabis ''Cannabis'' () is a genus of flowering plants in the family Cannabaceae that is widely accepted as being indigenous to and originating from the continent of Asia. However, the number of species is disputed, with as many as three species be ...

; and synthetic analogs of tetrahydrocannabinol. CB1 is antagonized by the phytocannabinoid

tetrahydrocannabivarin Tetrahydrocannabivarin (THCV, THV, O-4394, GWP42004) is a Homologous series, homologue of tetrahydrocannabinol (THC) having a propyl (3-carbon) side chain instead of pentyl (5-carbon), making it non-psychoactive in lower doses. It has been shown ...

at low doses and at higher doses, it activates the CB1 receptor as an

agonist An agonist is a chemical that activates a Receptor (biochemistry), receptor to produce a biological response. Receptors are Cell (biology), cellular proteins whose activation causes the cell to modify what it is currently doing. In contrast, an R ...

, but with less potency than tetrahydrocannabinol. The primary

endogenous agonist In pharmacology, an endogenous agonist for a particular receptor is a compound naturally produced by the body which binds to and activates that receptor. For example, the primary endogenous agonist for serotonin receptors is serotonin, and the p ...

of the human CB1 receptor is

Structure

The CB1 receptor shares the structure characteristic of all G-protein-coupled receptors, possessing seven transmembrane domains connected by three extracellular and three intracellular loops, an extracellular N-terminal tail, and an intracellular C-terminal tail. The receptor may exist as a

homodimer In biochemistry, a protein dimer is a macromolecular complex or protein multimer, multimer formed by two protein monomers, or single proteins, which are usually Non-covalent interaction, non-covalently bound. Many macromolecules, such as proteins ...

or form

heterodimer In biochemistry, a protein dimer is a macromolecular complex or multimer formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ...

s or other

GPCR oligomer A GPCR oligomer is a protein complex that consists of a small number ( ''oligoi'' "a few", ''méros'' "part, piece, component") of G protein-coupled receptors (GPCRs). It is held together by covalent bonds or by intermolecular forces. The subun ...

s with different classes of G-protein-coupled receptors. Observed heterodimers include A_2A–CB1, CB₁– D2, OX₁–CB₁, μOR–CB_1, while many more may only be stable enough to exist in vivo. The CB1 receptor possesses an

allosteric modulator In pharmacology and biochemistry, allosteric modulators are a group of substances that bind to a receptor to change that receptor's response to stimuli. Some of them, like benzodiazepines or alcohol, function as psychoactive drugs. The site that a ...

binding site In biochemistry and molecular biology, a binding site is a region on a macromolecule such as a protein that binds to another molecule with specificity. The binding partner of the macromolecule is often referred to as a ligand. Ligands may includ ...

. The CB1 receptor is encoded by the gene ''CNR1,'' located on human chromosome 6. Two transcript variants encoding different isoforms have been described for this gene. CNR1

orthologs Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a spec ...

have been identified in most

mammals A mammal () is a vertebrate animal of the class Mammalia (). Mammals are characterised by the presence of milk-producing mammary glands for feeding their young, a broad neocortex region of the brain, fur or hair, and three middle e ...

. The CNR1 gene has a structure consisting of a single coding-

exon An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequence ...

and multiple alternative 5' untranslated exons. The CB1 receptor is created by transcription of the last exon on the CNR1 gene.

Mechanism

The CB1 receptor is a pre-synaptic

heteroreceptor A heteroreceptor is a Receptor (biochemistry), receptor located in the cell membrane of a neuron, regulating the synthesis and/or the release of mediators other than its own Ligand (biochemistry), ligand. Heteroreceptors play a crucial role in modu ...

that modulates neurotransmitter release when activated in a dose-dependent, stereoselective and

pertussis toxin Pertussis toxin (PT) is a protein-based AB5-type exotoxin produced by the bacterium '' Bordetella pertussis'', which causes whooping cough. PT is involved in the colonization of the respiratory tract and the establishment of infection. ...

-sensitive manner. The CB1 receptor is activated by

cannabinoids 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 (THC) (delta-9-THC), the primary psychoa ...

, generated naturally inside the body (

) or exogenously, normally through

or a related

synthetic Synthetic may refer to: Science * Synthetic biology * Synthetic chemical or compound, produced by the process of chemical synthesis * Synthetic elements, chemical elements that are not naturally found on Earth and therefore have to be created in ...

compound. Research suggests that the majority of CB1 receptors are coupled through G_i/o proteins. Upon activation, CB1 receptor exhibits its effects mainly through activation of G_i, which decreases intracellular cAMP concentration by inhibiting its production

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

adenylate cyclase Adenylate cyclase (EC 4.6.1.1, also commonly known as adenyl cyclase and adenylyl cyclase, abbreviated AC) is an enzyme with systematic name ATP diphosphate-lyase (cyclizing; 3′,5′-cyclic-AMP-forming). It catalyzes the following reaction: :A ...

, and increases

mitogen-activated protein kinase A mitogen-activated protein kinase (MAPK or MAP kinase) is a type of serine/threonine-specific protein kinases involved in directing cellular responses to a diverse array of stimuli, such as mitogens, osmotic stress, heat shock and proinflamma ...

(MAP kinase) concentration. Alternatively, in some rare cases CB1 receptor activation may be coupled to G_s proteins, which stimulate

. cAMP is known to serve as a second messenger coupled to a variety of ion channels, including the positively influenced inwardly rectifying potassium channels (=Kir or IRK), and

calcium channel A calcium channel is an ion channel which shows selective permeability to calcium ions. It is sometimes synonymous with voltage-gated calcium channel, which are a type of calcium channel regulated by changes in membrane potential. Some calcium chan ...

s, which are activated by cAMP-dependent interaction with such molecules as

protein kinase A In cell biology, protein kinase A (PKA) is a family of serine-threonine kinases whose activity is dependent on cellular levels of cyclic AMP (cAMP). PKA is also known as cAMP-dependent protein kinase (). PKA has several functions in the cell, in ...

(PKA),

protein kinase C In cell biology, protein kinase C, commonly abbreviated to PKC (EC 2.7.11.13), is a family of protein kinase enzymes that are involved in controlling the function of other proteins through the phosphorylation of hydroxyl groups of serine and t ...

(PKC), Raf-1, ERK,

JNK c-Jun N-terminal kinases (JNKs), were originally identified as kinases that bind and phosphorylate c-Jun on Ser-63 and Ser-73 within its transcriptional activation domain. They belong to the mitogen-activated protein kinase family, and are r ...

, p38,

c-fos Protein c-Fos is a proto-oncogene that is the human homolog of the retroviral oncogene v-fos. It is encoded in humans by the ''FOS'' gene. It was first discovered in rat fibroblasts as the transforming gene of the FBJ MSV (Finkel–Biskis–Ji ...

c-jun Transcription factor Jun is a protein that in humans is encoded by the ''JUN'' gene. c-Jun, in combination with protein c-Fos, forms the AP-1 early response transcription factor. It was first identified as the Fos-binding protein p39 and only l ...

, and others. In terms of function, the inhibition of intracellular cAMP expression shortens the duration of pre-synaptic action potentials by prolonging the rectifying potassium A-type currents, which is normally inactivated upon phosphorylation by PKA. This inhibition grows more pronounced when considered with the effect of activated CB1 receptors to limit calcium entry into the cell, which does not occur through cAMP but by a direct G-protein-mediated inhibition. As presynaptic calcium entry is a requirement for vesicle release, this function will decrease the transmitter that enters the synapse upon release. The relative contribution of each of these two inhibitory mechanisms depends on the variance of ion channel expression by cell type. The CB1 receptor can also be

allosteric In the fields of biochemistry and pharmacology an allosteric regulator (or allosteric modulator) is a substance that binds to a site on an enzyme or receptor distinct from the active site, resulting in a conformational change that alters the p ...

ally modulated by synthetic ligands in a positive and negative manner. ''

In vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, an ...

'' exposure to tetrahydrocannabinol impairs

long-term potentiation In neuroscience, long-term potentiation (LTP) is a persistent strengthening of synapses based on recent patterns of activity. These are patterns of synaptic activity that produce a long-lasting increase in signal transmission between two neuron ...

and leads to a reduction of phosphorylated

CREB CREB-TF (CREB, cAMP response element-binding protein) is a cellular transcription factor. It binds to certain DNA sequences called cAMP response elements (CRE), thereby increasing or decreasing the transcription of the genes. CREB was first des ...

. The signaling properties of activated CB1 are furthermore modified by the presence of

SGIP1 SH3-containing GRB2-like protein 3-interacting protein 1 is a protein that in humans is encoded by the ''SGIP1'' gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a seque ...

, that hinders receptor internalization and decreases ERK1/2 signalling while augmenting the interaction with

GRK3 G-protein-coupled receptor kinase 3 (GRK3) is an enzyme that in humans is encoded by the ''ADRBK2'' gene. GRK3 was initially called Beta-adrenergic receptor kinase 2 (βARK-2), and is a member of the G protein-coupled receptor kinase subfamily o ...

, β-arrestin-2. In summary, CB1 receptor activity has been found to be coupled to certain ion channels, in the following manner: * Positively to inwardly rectifying and A-type outward potassium channels. * Negatively to D-type outward potassium channels * Negatively to N-type and P/Q-type calcium channels.

Expression

CB1 receptors are localized throughout the central and peripheral nervous systems, particularly on axon terminals in the cerebellum, hippocampus, basal ganglia, frontal cortex, amygdala, hypothalamus, and midbrain. The CB1 receptor is primarily expressed in the presynaptic terminals of GABAergic (amygdala and cerebellum), glutamatergic (cortex, hippocampus and amygdala), dopaminergic, GABAergic interneurons, cholinergic neurons, noradrenergic, and serotonergic neurons. Acting as a neuromodulator, the CB1 receptor inhibits the release of both excitatory and inhibitory neurotransmitters including acetylcholine, glutamate, GABA, noradrenaline, 5-HT, dopamine, D-aspartate, and cholecystokinin. Repeated administration of receptor agonists may result in receptor internalization and/or a reduction in receptor protein signaling. The

inverse agonist In pharmacology, an inverse agonist is a drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist. A neutral antagonist has no activity in the absence of an agonist or inverse agon ...

MK-9470 makes it possible to produce ''in vivo'' images of the distribution of CB₁ receptors in the human brain with

positron emission tomography Positron emission tomography (PET) is a functional imaging technique that uses radioactive substances known as radiotracers to visualize and measure changes in metabolic processes, and in other physiological activities including blood flow, r ...

Brain

The CB1 receptor is recognized as the most abundant

metabotropic receptor A metabotropic receptor, also referred to by the broader term G-protein-coupled receptor, is a type of membrane receptor that initiates a number of metabolic steps to modulate cell activity. The nervous system utilizes two types of receptors: me ...

in the brain. CB1 receptors are found moderately to highly expressed within the

cerebral cortex The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. It is the largest site of Neuron, neural integration in the central nervous system, and plays ...

(

cingulate gyrus The cingulate cortex is a part of the brain situated in the medial aspect of the cerebral cortex. The cingulate cortex includes the entire cingulate gyrus, which lies immediately above the corpus callosum, and the continuation of this in the cin ...

prefrontal cortex In mammalian brain anatomy, the prefrontal cortex (PFC) covers the front part of the frontal lobe of the cerebral cortex. It is the association cortex in the frontal lobe. The PFC contains the Brodmann areas BA8, BA9, BA10, BA11, BA12, ...

, and

hippocampus The hippocampus (: hippocampi; via Latin from Ancient Greek, Greek , 'seahorse'), also hippocampus proper, is a major component of the brain of humans and many other vertebrates. In the human brain the hippocampus, the dentate gyrus, and the ...

periaqueductal gray The periaqueductal gray (PAG), also known as the central gray, is a brain region that plays a critical role in autonomic function, motivated behavior and behavioural responses to threatening stimuli. PAG is also the primary control center for ...

hypothalamus The hypothalamus (: hypothalami; ) is a small part of the vertebrate brain that contains a number of nucleus (neuroanatomy), nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrin ...

amygdala The amygdala (; : amygdalae or amygdalas; also '; Latin from Greek language, Greek, , ', 'almond', 'tonsil') is a paired nucleus (neuroanatomy), nuclear complex present in the Cerebral hemisphere, cerebral hemispheres of vertebrates. It is c ...

cerebellum The cerebellum (: cerebella or cerebellums; Latin for 'little brain') is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as it or eve ...

, and

basal ganglia The basal ganglia (BG) or basal nuclei are a group of subcortical Nucleus (neuroanatomy), nuclei found in the brains of vertebrates. In humans and other primates, differences exist, primarily in the division of the globus pallidus into externa ...

(

globus pallidus The globus pallidus (GP), also known as paleostriatum or dorsal pallidum, is a major component of the Cerebral cortex, subcortical basal ganglia in the brain. It consists of two adjacent segments, one external (or lateral), known in rodents simpl ...

substantia nigra The substantia nigra (SN) is a basal ganglia structure located in the midbrain that plays an important role in reward and movement. ''Substantia nigra'' is Latin for "black substance", reflecting the fact that parts of the substantia nigra a ...

). Varying levels of CB1 can also be detected in the

olfactory bulb The olfactory bulb (Latin: ''bulbus olfactorius'') is a neural structure of the vertebrate forebrain involved in olfaction, the sense of smell. It sends olfactory information to be further processed in the amygdala, the orbitofrontal cortex (OF ...

, cortical regions (

neocortex The neocortex, also called the neopallium, isocortex, or the six-layered cortex, is a set of layers of the mammalian cerebral cortex involved in higher-order brain functions such as sensory perception, cognition, generation of motor commands, ...

pyriform cortex The piriform cortex, or pyriform cortex, is a region in the brain, part of the rhinencephalon situated in the cerebrum. The function of the piriform cortex relates to the sense of smell. Structure The piriform cortex is part of the rhinencephal ...

), parts of

thalamic The thalamus (: thalami; from Greek θάλαμος, "chamber") is a large mass of gray matter on the lateral wall of the third ventricle forming the dorsal part of the diencephalon (a division of the forebrain). Nerve fibers project out of the ...

, hypothalamic, and

brainstem The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is conti ...

nuclei, as well as in subcortical regions (e.g., the septal region), and

cerebellar cortex The cerebellum (: cerebella or cerebellums; Latin for 'little brain') is a major feature of the hindbrain of all vertebrates. Although usually smaller than the cerebrum, in some animals such as the mormyrid fishes it may be as large as it or e ...

. CB1 receptors are expressed most densely in the central nervous system and are largely responsible for mediating the effects of cannabinoid binding in the brain. Endocannabinoids released by a depolarized neuron bind to CB1 receptors on pre-synaptic glutamatergic and GABAergic neurons, resulting in a respective decrease in either glutamate or GABA release. Limiting glutamate release causes reduced excitation, while limiting GABA release suppresses inhibition, a common form of short-term

plasticity Plasticity may refer to: Science * Plasticity (physics), in engineering and physics, the propensity of a solid material to undergo permanent deformation under load * Behavioral plasticity, change in an organism's behavior in response to exposur ...

in which the depolarization of a single neuron induces a reduction in

GABA GABA (gamma-aminobutyric acid, γ-aminobutyric acid) is the chief inhibitory neurotransmitter in the developmentally mature mammalian central nervous system. Its principal role is reducing neuronal excitability throughout the nervous system. GA ...

-mediated inhibition, in effect exciting the postsynaptic cell.

Brainstem

High expression of CB1 is found in brainstem medullary nuclei, including the nucleus of the solitary tract and area postrema. CB1 receptor is relatively low in medullary respiratory brainstem control centers.

Hippocampal formation

CB1

mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...

transcripts are abundant in

ergic interneurons of the

, indirectly reflecting the expression of these receptors and elucidating the established effect of cannabinoids on

memory Memory is the faculty of the mind by which data or information is encoded, stored, and retrieved when needed. It is the retention of information over time for the purpose of influencing future action. If past events could not be remembe ...

. These receptors are densely located in cornu ammonis pyramidal cells, which are known to release

glutamate Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a Essential amino acid, non-essential nutrient for humans, meaning that ...

. Cannabinoids suppress the induction of LTP and

LTD In a limited company, the liability of members or subscribers of the company is limited to what they have invested or guaranteed to the company. Limited companies may be limited by shares or by guarantee. In a company limited by shares, the li ...

in the hippocampus by inhibiting these glutamatergic neurons. By reducing the concentration of glutamate released below the threshold necessary to depolarize the postsynaptic

NMDA receptor The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and predominantly Ca2+ ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other ...

, a receptor known to be directly related to the induction of LTP and LTD, cannabinoids are a crucial factor in the selectivity of memory. These receptors are highly expressed by GABAergic interneurons as well as glutamatergic principal neurons. However, a higher density is found within GABAergic cells. This means that, although synaptic strength/frequency, and thus potential to induce LTP, is lowered, net hippocampal activity is raised. In addition, CB₁ receptors in the hippocampus indirectly inhibit the release of

acetylcholine Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Par ...

. This serves as the modulatory axis opposing GABA, decreasing neurotransmitter release. Cannabinoids also likely play an important role in the development of memory through their neonatal promotion of

myelin Myelin Sheath ( ) is a lipid-rich material that in most vertebrates surrounds the axons of neurons to insulate them and increase the rate at which electrical impulses (called action potentials) pass along the axon. The myelinated axon can be lik ...

formation, and thus the individual segregation of axons.

Basal ganglia

CB1 receptors are expressed throughout the

and have well-established effects on movement in

rodents Rodents (from Latin , 'to gnaw') are mammals of the order Rodentia ( ), which are characterized by a single pair of continuously growing incisors in each of the upper and lower jaws. About 40% of all mammal species are rodents. They are n ...

. As in the

, these receptors inhibit the release of

transmitter, resulting in decreased excitation or reduced inhibition based on the cell they are expressed in. Consistent with the variable expression of both excitatory glutamate and inhibitory GABA interneurons in both the basal ganglia's direct and indirect motor loops,

synthetic cannabinoids Synthetic cannabinoids, or neocannabinoids, are a class of designer drug molecules that bind to the same receptors to which cannabinoids ( THC, CBD and many others) in cannabis plants attach. These novel psychoactive substances should not be co ...

are known to influence this system in a dose-dependent triphasic pattern. Decreased locomotor activity is seen at both higher and lower concentrations of applied

, whereas an enhancement of movement may occur upon moderate dosages. However, these dose-dependent effects have been studied predominately in rodents, and the physiological basis for this triphasic pattern warrants future research in humans. Effects may vary based on the site of cannabinoid application, input from higher cortical centers, and whether drug application is unilateral or bilateral.

Cerebellum and neocortex

The role of the CB1 receptor in the regulation of motor movements is complicated by the additional expression of this receptor in the

and

, two regions associated with the coordination and initiation of movement. Research suggests that anandamide is synthesized by

Purkinje cells Purkinje cells or Purkinje neurons, named for Czech physiologist Jan Evangelista Purkyně who identified them in 1837, are a unique type of prominent, large neuron located in the cerebellar cortex of the brain. With their flask-shaped cell bo ...

and acts on presynaptic receptors to inhibit glutamate release from granule cells or

release from the terminals of basket cells. In the neocortex, these receptors are concentrated on local interneurons in cerebral layers II-III and V-VI. Compared to rat brains, humans express more CB₁ receptors in the cerebral cortex and amygdala and less in the cerebellum, which may help explain why motor function seems to be more compromised in rats than humans upon cannabinoid application.

Spine

Many of the documented analgesic effects of cannabinoids are based on the interaction of these compounds with CB1 receptors on

spinal cord The spinal cord is a long, thin, tubular structure made up of nervous tissue that extends from the medulla oblongata in the lower brainstem to the lumbar region of the vertebral column (backbone) of vertebrate animals. The center of the spinal c ...

interneurons in the superficial levels of the dorsal horn, known for its role in nociceptive processing. In particular, the CB1 is heavily expressed in layers 1 and 2 of the spinal cord dorsal horn and in lamina 10 by the central canal. Dorsal root ganglion also express these receptors, which target a variety of peripheral terminals involved in nociception. Signals on this track are also transmitted to the

(PAG) of the midbrain. Endogenous cannabinoids are believed to exhibit an analgesic effect on these receptors by limiting both GABA and glutamate of PAG cells that relate to nociceptive input processing, a hypothesis consistent with the finding that anandamide release in the PAG is increased in response to pain-triggering stimuli.

Other

CB₁ is expressed on several types of cells in

pituitary gland The pituitary gland or hypophysis is an endocrine gland in vertebrates. In humans, the pituitary gland is located at the base of the human brain, brain, protruding off the bottom of the hypothalamus. The pituitary gland and the hypothalamus contr ...

thyroid gland The thyroid, or thyroid gland, is an endocrine gland in vertebrates. In humans, it is a butterfly-shaped gland located in the neck below the Adam's apple. It consists of two connected lobes. The lower two thirds of the lobes are connected by ...

, and possibly in the

adrenal gland The adrenal glands (also known as suprarenal glands) are endocrine glands that produce a variety of hormones including adrenaline and the steroids aldosterone and cortisol. They are found above the kidneys. Each gland has an outer adrenal corte ...

. CB1 is also expressed in several cells relating to metabolism, such as

fat cells Adipocytes, also known as lipocytes and fat cells, are the cell (biology), cells that primarily compose adipose tissue, specialized in storing energy as fat. Adipocytes are derived from mesenchymal stem cells which give rise to adipocytes through ...

muscle cells A muscle cell, also known as a myocyte, is a mature contractile cell in the muscle of an animal. In humans and other vertebrates there are three types: skeletal, smooth, and cardiac (cardiomyocytes). A skeletal muscle cell is long and threadli ...

liver cells A hepatocyte is a cell of the main parenchymal tissue of the liver. Hepatocytes make up 80% of the liver's mass. These cells are involved in: * Protein synthesis * Protein storage * Transformation of carbohydrates * Synthesis of cholesterol, bile ...

(and also in the

endothelial cells The endothelium (: endothelia) is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the res ...

Kupffer cell Kupffer cells, also known as stellate macrophages and Kupffer–Browicz cells, are specialized cells localized in the liver within the lumen of the liver sinusoids and are adhesive to their endothelial cells which make up the blood vessel walls. K ...

s and

stellate cells Stellate cells are neurons in the central nervous system, named for their star-like shape formed by dendritic processes radiating from the cell body. These cells play significant roles in various brain functions, including inhibition in the cer ...

of the

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

), and in the

digestive tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the Digestion, digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascula ...

. It is also expressed in the

lungs The lungs are the primary organs of the respiratory system in many animals, including humans. In mammals and most other tetrapods, two lungs are located near the backbone on either side of the heart. Their function in the respiratory syste ...

and the

kidney In humans, the kidneys are two reddish-brown bean-shaped blood-filtering organ (anatomy), organs that are a multilobar, multipapillary form of mammalian kidneys, usually without signs of external lobulation. They are located on the left and rig ...

. CB1 is present on

Leydig cells Leydig cells, also known as interstitial cells of the testes and interstitial cells of Leydig, are found adjacent to the seminiferous tubules in the testicle and produce testosterone in the presence of luteinizing hormone (LH). They are polyhedral ...

and human sperms. In

females An organism's sex is female (symbol: ♀) if it produces the ovum (egg cell), the type of gamete (sex cell) that fuses with the male gamete (sperm cell) during sexual reproduction. A female has larger gametes than a male. Females and male ...

, it is present in the

ovaries The ovary () is a gonad in the female reproductive system that produces ova; when released, an ovum travels through the fallopian tube/oviduct into the uterus. There is an ovary on the left and the right side of the body. The ovaries are endocr ...

oviduct The oviduct in vertebrates is the passageway from an ovary. In human females, this is more usually known as the fallopian tube. The eggs travel along the oviduct. These eggs will either be fertilized by spermatozoa to become a zygote, or will dege ...

myometrium The myometrium is the middle layer of the uterine wall, consisting mainly of uterine smooth muscle cells (also called uterine myocytes) but also of supporting stromal and vascular tissue. Its main function is to induce uterine contractions. Stru ...

decidua The decidua is the modified mucosal lining of the uterus (that is, modified endometrium) that forms every month, in preparation for pregnancy. It is shed off each month when there is no fertilized egg to support. The decidua is under the influe ...

, and

placenta The placenta (: placentas or placentae) is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas, and waste exchange between ...

. It has also been implicated in the proper development of the

embryo An embryo ( ) is the initial stage of development for a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male sp ...

. CB1 is also expressed in the

retina The retina (; or retinas) is the innermost, photosensitivity, light-sensitive layer of tissue (biology), tissue of the eye of most vertebrates and some Mollusca, molluscs. The optics of the eye create a focus (optics), focused two-dimensional ...

. In the retina, they are expressed in the photoreceptors, inner plexiform, outer plexiform, bipolar cells, ganglion cells, and retinal pigment epithelium cells. In the visual system, cannabinoids agonist induce a dose dependent modulation of calcium, chloride and potassium channels. This alters vertical transmission between photoreceptor, bipolar and ganglion cells. Altering vertical transmission in turn results in the way vision is perceived.

Physiological and pathological conditions

The activation of CB1 in the human body generally inhibits neurotransmitter release, controls pain, regulates metabolism, and monitors the

cardiovascular system In vertebrates, the circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the body. It includes the cardiovascular system, or vascular system, that consists of the heart a ...

. CB1 receptors are implicated in a number of physiological processes related to the

(CNS) including brain development, learning and memory, motor behavior, regulation of appetite, body temperature, pain perception, and inflammation. The localization of CB1 receptors is expressed in several neuronal types, including

GABAergic In molecular biology and physiology, something is GABAergic or GABAnergic if it pertains to or affects the neurotransmitter gamma-aminobutyric acid (GABA). For example, a synapse is GABAergic if it uses GABA as its neurotransmitter, and a GABAergic ...

glutamatergic Glutamatergic means "related to glutamate". A glutamatergic agent (or drug) is a chemical that directly modulates the excitatory amino acid (glutamate/aspartate) system in the body or brain. Examples include excitatory amino acid receptor agonist ...

, and serotonergic neurons. CB1 receptors localized in GABAergic neurons can modulate food intake, learning and memory processes, drug addiction, and related behaviors. CB1 receptors localized in glutamatergic neurons are capable of mediating olfactory processes,

neuroprotection Neuroprotection refers to the relative preservation of neuronal structure and/or function. In the case of an ongoing insult (a neurodegenerative insult) the relative preservation of neuronal integrity implies a reduction in the rate of neuronal l ...

, social behaviors, anxiety, and fear memories. The localization of CB1 receptors in serotonergic neurons can regulate emotional responses. Clinically, CB1 is a direct drug target for

addiction Addiction is a neuropsychological disorder characterized by a persistent and intense urge to use a drug or engage in a behavior that produces natural reward, despite substantial harm and other negative consequences. Repetitive drug use can ...

, pain,

epilepsy Epilepsy is a group of Non-communicable disease, non-communicable Neurological disorder, neurological disorders characterized by a tendency for recurrent, unprovoked Seizure, seizures. A seizure is a sudden burst of abnormal electrical activit ...

, and

obesity Obesity is a medical condition, considered by multiple organizations to be a disease, in which excess Adipose tissue, body fat has accumulated to such an extent that it can potentially have negative effects on health. People are classifi ...

. CB1 receptor function is involved with several

psychiatric Psychiatry is the medical specialty devoted to the diagnosis, treatment, and prevention of deleterious mental conditions. These include matters related to cognition, perceptions, mood, emotion, and behavior. Initial psychiatric assessment of ...

neurological Neurology (from , "string, nerve" and the suffix -logia, "study of") is the branch of medicine dealing with the diagnosis and treatment of all categories of conditions and disease involving the nervous system, which comprises the brain, the s ...

neurodevelopmental The development of the nervous system, or neural development (neurodevelopment), refers to the processes that generate, shape, and reshape the nervous system of animals, from the earliest stages of embryonic development to adulthood. The field ...

, and

neurodegenerative A neurodegenerative disease is caused by the progressive loss of neurons, in the process known as neurodegeneration. Neuronal damage may also ultimately result in their death. Neurodegenerative diseases include amyotrophic lateral sclerosis, mul ...

disorders including

Huntington's disease Huntington's disease (HD), also known as Huntington's chorea, is an incurable neurodegenerative disease that is mostly Genetic disorder#Autosomal dominant, inherited. It typically presents as a triad of progressive psychiatric, cognitive, and ...

(HD),

multiple sclerosis Multiple sclerosis (MS) is an autoimmune disease resulting in damage to myelinthe insulating covers of nerve cellsin the brain and spinal cord. As a demyelinating disease, MS disrupts the nervous system's ability to Action potential, transmit ...

(MS), and

Alzheimer's disease Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...

(AD). Major loss of CB1 receptors is reported in patients with HD. However, stimulation of the CB1 receptor has potential to reduce the progression of HD. Improvements from use of CB agonist in MS are associated with the activation of CB1 and CB2 receptors, leading to dual anti-inflammatory and neuroprotective effects throughout the CNS. Similarly, activation of CB1 and CB2 receptors could provide neuroprotective effects against

amyloid-β Amyloid beta (Aβ, Abeta or beta-amyloid) denotes peptides of 36–43 amino acids that are the main component of the amyloid plaques found in the brains of people with Alzheimer's disease. The peptides derive from the amyloid-beta precursor prot ...

(Aβ) toxicity in AD. In several brain regions, including the

dorsolateral prefrontal cortex The dorsolateral prefrontal cortex (DLPFC or DL-PFC) is an area in the prefrontal cortex of the primate brain. It is one of the most recently derived parts of the human brain. It undergoes a prolonged period of maturation which lasts into adulthoo ...

(DLPFC) and

, dysregulation of the CB1 receptor is implicated in the development of

schizophrenia Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...

. Abnormal functioning of the CB1 receptor compromises intricate neural systems that are responsible for controlling cognition and memory, which contributes to the pathology.

PET A pet, or companion animal, is an animal kept primarily for a person's company or entertainment rather than as a working animal, livestock, or a laboratory animal. Popular pets are often considered to have attractive/ cute appearances, inte ...

imaging modalities implicate that alterations of CB1 levels in certain brain systems are strongly associated with schizophrenia symptoms. Neurobehavioral disorders, such as

attention deficit hyperactivity disorder Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by symptoms of inattention, hyperactivity, impulsivity, and emotional dysregulation that are excessive and pervasive, impairing in multiple con ...

(ADHD), are associated with genetic variants of CNR1 in rat models of ADHD.

Use of antagonists

Selective CB1 agonists may be used to isolate the effects of the receptor from the CB2 receptor, as most cannabinoids and endocannabinoids bind to both receptor types. CB1 selective antagonists such as

rimonabant Rimonabant (also known as SR141716; trade names Acomplia, Zimulti) is an anorectic antiobesity drug approved in Europe in 2006 but was withdrawn worldwide in 2008 due to serious psychiatric side effects; it was never approved in the United State ...

are used for weight reduction and

smoking cessation Smoking cessation, usually called quitting smoking or stopping smoking, is the process of discontinuing tobacco smoking. Tobacco smoke contains nicotine, which is Addiction, addictive and can cause Substance dependence, dependence. As a resu ...

. A substantial number of antagonists of the CB1 receptor have been discovered and characterized. TM38837 has been developed as a CB1 receptor antagonist that is restricted to targeting only peripheral CB1 receptors.

Ligands

Agonists

Minocycline Minocycline, sold under the brand name Minocin among others, is a tetracycline antibiotic medication used to treat a number of bacterial infections such as some occurring in certain forms of pneumonia. It is generally (but not always) less pre ...

Dronabinol Dronabinol (), sold under the brand names Marinol and Syndros, is the generic name for the molecule of (−)-trans-Δ9-tetrahydrocannabinol (THC) in the pharmaceutical context. It has indications as an appetite stimulant, antiemetic, and sleep ...

Selective

Epigallocatechin Gallocatechol or gallocatechin (GC) is a flavan-3-ol, a type of chemical compound including catechin, with the gallate residue being in an isomeric ''trans'' position. This compound possesses two epimers. The most common, (+)-gallocatechin (GC), ...

Epicatechin Catechin is a flavan-3-ol, a type of secondary metabolite providing antioxidant roles in plants. It belongs to the subgroup of polyphenols called flavonoids. The name of the catechin chemical family derives from '' catechu'', which is the tann ...

* Kavain *

Yangonin Yangonin is one of the six major kavalactones found in the kava plant. It acts as a selective agonist at the CB1 receptor, CB1 cannabinoid receptor, inhibits monoamine oxidase (particularly MAO-B), and modulates GABAA receptor activity. Yangonin s ...

Oleamide Oleamide is an organic compound with the formula . It is the amide derived from the fatty acid oleic acid. It is a colorless waxy solid and occurs in nature. Sometimes labeled as a fatty acid primary amide (FAPA), it is biosynthesized from ''N''- ...

Unspecified efficacy

N-Arachidonoyl dopamine ''N''-Arachidonoyl dopamine (NADA) is an endocannabinoid that acts as an agonist of the CB1 receptor and the transient receptor potential V1 (TRPV1) ion channel. NADA was first described as a putative endocannabinoid (agonist for the CB1 recep ...

Cannabinol Cannabinol (CBN) is a mildly psychoactive phytocannabinoid that acts as a low affinity partial agonist at both CB1 and CB2 receptors. This activity at CB1 and CB2 receptors constitutes interaction of CBN with the endocannabinoid system (ECS) ...

HU-210 HU-210 is a synthetic cannabinoid that was first synthesized in 1988 from (1''R'',5''S'')- myrtenol by a group led by Raphael Mechoulam at the Hebrew University. HU-210 is 100 to 800 times more potent than natural THC from cannabis and has an ...

* 11-Hydroxy-THC *

Levonantradol Levonantradol (CP 50,556-1) is a synthetic cannabinoid analog of dronabinol (Marinol) developed by Pfizer in the 1980s. It is around 30 times more potent than THC, and exhibits antiemetic and analgesic effects via activation of CB1 and CB2 canna ...

Partial

=Endogenous

= * 2-Arachidonyl glyceryl ether

=Phyto

= *

Tetrahydrocannabinol 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 (C21H30O2) de ...

Hexahydrocannabinol Hexahydrocannabinol (HHC) is a phytocannabinoid that has been reported as a trace component of ''Cannabis sativa''. It can also be synthesized by hydrogenation of tetrahydrocannabinol (THC). The synthesis and bioactivity of HHC was first reporte ...

Full

=Endogenous

= *

2-Arachidonoylglycerol 2-Arachidonoylglycerol (2-AG) is an endocannabinoid, an endogenous agonist of the CB1 receptor and the primary endogenous ligand for the CB2 receptor. It is an ester formed from the omega-6 fatty acid arachidonic acid and glycerol. It is pres ...

=Synthetic

= *

JWH-073 JWH-073, a synthetic cannabinoid, is an analgesic chemical from the naphthoylindole family that acts as a full agonist at both the CB1 and CB2 cannabinoid receptors. It is somewhat selective for the CB1 subtype, with affinity at this subtype appro ...

AM-2201 AM-2201 (1-(5-fluoropentyl)-3-(1-naphthoyl)indole) is a recreational designer drug that acts as a potent but nonselective full agonist for the cannabinoid receptor. It is part of the AM series of cannabinoids discovered by Alexandros Makriyann ...

CP 55,940 55,940 is a synthetic cannabinoid which mimics the effects of naturally occurring THC (one of the psychoactive compounds found in cannabis). CP 55,940 was created by Pfizer in 1974 but was never marketed. It is currently used as a research too ...

JWH-018 JWH-018 (1-pentyl-3-(1-naphthoyl)indole, NA-PIMO or AM-678) is an analgesic chemical from the naphthoylindole family that acts as a full agonist at both the CB1 and CB2 cannabinoid receptors, with some selectivity for CB2. It produces effe ...

WIN 55,212-2 WIN 55,212-2 is a chemical described as an aminoalkylindole derivative, which produces effects similar to those of cannabinoids such as tetrahydrocannabinol (THC) but has an entirely different chemical structure. WIN 55,212-2 is a potent cannab ...

Allosteric agonist

* GAT228

Antagonists

* Cannabigerol * Ibipinabant * Otenabant *

Tetrahydrocannabivarin Tetrahydrocannabivarin (THCV, THV, O-4394, GWP42004) is a Homologous series, homologue of tetrahydrocannabinol (THC) having a propyl (3-carbon) side chain instead of pentyl (5-carbon), making it non-psychoactive in lower doses. It has been shown ...

Virodhamine Virodhamine (''O''-arachidonoyl ethanolamine; O-AEA) is an endocannabinoid and a nonclassic eicosanoid, derived from arachidonic acid. ''O''-Arachidonoyl ethanolamine is arachidonic acid and ethanolamine joined by an ester linkage, the opposit ...

(Endogenous CB1 antagonist and CB2 agonist)

Inverse agonists

Rimonabant Rimonabant (also known as SR141716; trade names Acomplia, Zimulti) is an anorectic antiobesity drug approved in Europe in 2006 but was withdrawn worldwide in 2008 due to serious psychiatric side effects; it was never approved in the United State ...

* Taranabant * Zevaquenabant * Monlunabant * INV-202

Allosteric modulators

* Lipoxin A4 – endogenous, PAM * ZCZ-011 – PAM *

Pregnenolone Pregnenolone (P5), or pregn-5-en-3β-ol-20-one, is an endogenous steroid and precursor/metabolic intermediate in the biosynthesis of most of the steroid hormones, including the progestogens, androgens, estrogens, glucocorticoids, and mineraloc ...

– endogenous, NAM *

Cannabidiol Cannabidiol (CBD) is a phytocannabinoid, one of 113 identified cannabinoids in ''Cannabis'', along with tetrahydrocannabinol (THC), and accounts for up to 40% of the plant's extract. Medically, it is an anticonvulsant used to treat multiple f ...

– NAM *

Fenofibrate Fenofibrate, sold under the brand name Tricor among others, is an oral medication of the fibrate class used to treat abnormal blood lipid levels. It is less commonly used compared to statins because it treats a different type of cholesterol a ...

– NAM *

GAT100 GAT100 is a negative allosteric modulator of the cannabinoid CB1 receptor. See also * Org 27569 * PSNCBAM-1 PSNCBAM-1 is a negative allosteric modulator of the cannabinoid CB1 receptor Receptor may refer to: * Sensory receptor, in physi ...

– NAM *

PSNCBAM-1 PSNCBAM-1 is a negative allosteric modulator of the cannabinoid CB1 receptor Receptor may refer to: * Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse *Recep ...

– NAM * RVD-Hpα – NAM

Binding affinities

Evolution

The CNR1 gene is used in animals as a

nuclear DNA Nuclear DNA (nDNA), or nuclear deoxyribonucleic acid, is the DNA contained within each cell nucleus of a eukaryotic organism. It encodes for the majority of the genome in eukaryotes, with mitochondrial DNA and plastid DNA coding for the rest. ...

phylogenetic marker. This intronless gene has first been used to explore the phylogeny of the major groups of

, and contributed to reveal that

placental Placental mammals (infraclass Placentalia ) are one of the three extant subdivisions of the class Mammalia, the other two being Monotremata and Marsupialia. Placentalia contains the vast majority of extant mammals, which are partly distinguished ...

orders are distributed into five major clades:

Xenarthra Xenarthra (; from Ancient Greek ξένος, xénos, "foreign, alien" + ἄρθρον, árthron, "joint") is a superorder and major clade of placental mammals native to the Americas. There are 31 living species: the anteaters, tree sloths, and ...

Afrotheria Afrotheria ( from Latin ''Afro-'' "of Africa" + ''theria'' "wild beast") is a superorder of placental mammals, the living members of which belong to groups that are either currently living in Africa or of African origin: golden moles, elephan ...

Laurasiatheria Laurasiatheria (; "Laurasian beasts") is a superorder of Placentalia, placental mammals that groups together true insectivores (eulipotyphlans), bats (chiropterans), carnivorans, pangolins (Pholidota, pholidotes), even-toed ungulates (Artiodacty ...

Euarchonta The Euarchonta are a proposed grandorder of mammals: the order Scandentia (treeshrews), and its sister Primatomorpha mirorder, containing the Dermoptera (colugos) and the primates (Plesiadapiformes and descendants). The term "Euarchonta" (mea ...

, and

Glires Glires (, Latin ''glīrēs'' 'dormice') is a clade (sometimes ranked as a grandorder) consisting of rodents and lagomorphs ( rabbits, hares, and pikas). The hypothesis that these form a monophyletic group has been long debated based on morph ...

. CNR1 has also proven useful at lower

taxonomic 280px, Generalized scheme of taxonomy Taxonomy is a practice and science concerned with classification or categorization. Typically, there are two parts to it: the development of an underlying scheme of classes (a taxonomy) and the allocation ...

levels, such as

, and for the identification of

dermoptera Colugos (), flying lemurs, or cobegos (), are arboreal gliding euarchontogliran mammals that are native to Southeast Asia. Their closest evolutionary relatives are primates. There are just two living species of colugos: the Sunda flying lemur ...

ns as the closest primate relatives.

Paralogues Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a speci ...

Source: * CNR2 * S1PR1 *

LPAR1 Lysophosphatidic acid receptor 1 also known as LPA1 is a protein that in humans is encoded by the ''LPAR1'' gene. LPA1 is a G protein-coupled receptor that binds the lipid signaling molecule lysophosphatidic acid (LPA). Function The integral ...

* S1PR3 * S1PR5 * S1PR2 *

GPR6 G protein-coupled receptor 6, also known as GPR6, is a protein which in humans is encoded by the ''GPR6'' gene. Function GPR6 is a member of the G protein-coupled receptor family of transmembrane receptors. It has been reported that GPR6 is b ...

GPR12 Probable G-protein coupled receptor 12 is a protein that in humans is encoded by the ''GPR12'' gene. The gene product of GPR12 is an orphan receptor, meaning that its endogenous ligand is currently unknown. Gene disruption of GPR12 in mice resul ...

* S1PR4 * LPAR3 * LPAR2 *

GPR3 G-protein coupled receptor 3 is a protein that in humans is encoded by the ''GPR3'' gene. The protein encoded by this gene is a member of the G protein-coupled receptor family of transmembrane receptors and is involved in signal transduction. GPR ...

* MC3R * MC5R * MC2R *

MC1R The melanocortin 1 receptor (MC1R), also known as melanocyte-stimulating hormone receptor (MSHR), melanin-activating peptide receptor, or melanotropin receptor, is a G protein–coupled receptor that binds to a class of pituitary peptide hormon ...

* MC4R *

GPR119 G protein-coupled receptor 119 also known as GPR119 is a G protein-coupled receptor that in humans is encoded by the ''GPR119'' gene. GPR119, along with GPR55 and GPR18, have been implicated as novel cannabinoid receptors. Pharmacology GPR ...

References

External links

*
Cannabinoid receptor 1
(CNR1) Human Protein Atlas {{DEFAULTSORT:Cannabinoid Receptor Type 1 G protein-coupled receptors